THE OFFICIAL PATIENT’S SOURCEBOOK
on
OSTEOARTHRITIS J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright Ó2003 by ICON Group International, Inc. Copyright Ó2003 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Tiffany LaRochelle Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended as a substitute for consultation with your physician. All matters regarding your health require medical supervision. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation, in close consultation with a qualified physician. The reader is advised to always check product information (package inserts) for changes and new information regarding dose and contraindications before taking any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960The Official Patient’s Sourcebook on Osteoarthritis: A Revised and Updated Directory for the Internet Age/James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary and index. ISBN: 0-597-83543-8 1. Osteoarthritis-Popular works. I. Title.
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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem or as a substitute for consultation with licensed medical professionals. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors or authors. ICON Group International, Inc., the editors, or the authors are not responsible for the content of any Web pages or publications referenced in this publication.
Copyright Notice If a physician wishes to copy limited passages from this sourcebook for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications are copyrighted. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs or other materials, please contact us to request permission (e-mail:
[email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this sourcebook.
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Dedication To the healthcare professionals dedicating their time and efforts to the study of osteoarthritis.
Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this sourcebook which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which directly or indirectly are dedicated to osteoarthritis. All of the Official Patient’s Sourcebooks draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this sourcebook. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany LaRochelle for her excellent editorial support.
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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for the Official Patient’s Sourcebook series published by ICON Health Publications.
Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for the Official Patient’s Sourcebook series published by ICON Health Publications.
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About ICON Health Publications In addition to osteoarthritis, Official Patient’s Sourcebooks are available for the following related topics: ·
The Official Patient's Sourcebook on Arthritis of the Knee
·
The Official Patient's Sourcebook on Arthritis of the Shoulder
·
The Official Patient's Sourcebook on Fibromyalgia
·
The Official Patient's Sourcebook on Gout
·
The Official Patient's Sourcebook on Juvenile Rheumatoid Arthritis
·
The Official Patient's Sourcebook on Lupus
·
The Official Patient's Sourcebook on Polymyalgia Rheumatica
·
The Official Patient's Sourcebook on Reiter's Syndrome
·
The Official Patient's Sourcebook on Rheumatoid Arthritis
To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes & Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health
Contents vii
Table of Contents INTRODUCTION...................................................................................... 1
Overview............................................................................................................... 1 Organization......................................................................................................... 3 Scope ..................................................................................................................... 3 Moving Forward................................................................................................... 4
PART I: THE ESSENTIALS ................................................. 7 CHAPTER 1. THE ESSENTIALS ON OSTEOARTHRITIS: GUIDELINES ...... 9
Overview............................................................................................................... 9 What Is Osteoarthritis? ...................................................................................... 10 Who Is Affected by Osteoarthritis? .................................................................... 11 Osteoarthritis Basics: The Joint and Its Parts .................................................... 12 Cartilage: The Key to Healthy Joints .................................................................. 13 How Do You Know If You Have Osteoarthritis? .............................................. 13 The Warning Signs of Osteoarthritis ................................................................. 14 How Do Doctors Diagnose Osteoarthritis? ....................................................... 15 How Is Osteoarthritis Treated?.......................................................................... 16 Medicines............................................................................................................ 19 Non-Traditional Approaches .............................................................................. 21 Health Professionals Who Treat Osteoarthritis.................................................. 22 Be a Winner! Practice Self-Care and Keep a Good-Health Attitude .................. 23 Current Research ................................................................................................ 25 Comprehensive Treatment Strategies................................................................. 26 Using NSAIDs ................................................................................................... 27 Drugs to Prevent Joint Damage ......................................................................... 27 Acupuncture....................................................................................................... 27 Nutritional Supplements.................................................................................... 28 Hyaluronic Acid ................................................................................................. 28 Estrogen .............................................................................................................. 29 Tissue Engineering............................................................................................. 29 Enzyme Engineering .......................................................................................... 29 Cartilage Cell Replacement................................................................................. 29 Stem Cell Transplantation ................................................................................. 29 Hope for the Future............................................................................................. 30 Additional Resources .......................................................................................... 30 More Guideline Sources ..................................................................................... 31 Vocabulary Builder............................................................................................. 44
CHAPTER 2. SEEKING GUIDANCE ....................................................... 49
Overview............................................................................................................. 49 Associations and Osteoarthritis ......................................................................... 49 Finding More Associations................................................................................. 51 Finding Doctors.................................................................................................. 53
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Finding a Rheumatologist .................................................................................. 54 Selecting Your Doctor ........................................................................................ 55 Working with Your Doctor ................................................................................ 55 Broader Health-Related Resources ..................................................................... 57
CHAPTER 3. CLINICAL TRIALS AND OSTEOARTHRITIS ....................... 59
Overview............................................................................................................. 59 Recent Trials on Osteoarthritis .......................................................................... 62 Benefits and Risks............................................................................................... 73 Keeping Current on Clinical Trials.................................................................... 76 General References.............................................................................................. 77 Vocabulary Builder............................................................................................. 78
PART II: ADDITIONAL RESOURCES AND ADVANCED MATERIAL.................................................. 79 CHAPTER 4. STUDIES ON OSTEOARTHRITIS ........................................ 81
Overview............................................................................................................. 81 The Combined Health Information Database ..................................................... 81 Federally Funded Research on Osteoarthritis .................................................... 90 E-Journals: PubMed Central ............................................................................ 107 The National Library of Medicine: PubMed .................................................... 109 Vocabulary Builder........................................................................................... 128
CHAPTER 5. PATENTS ON OSTEOARTHRITIS ..................................... 133
Overview........................................................................................................... 133 Patents on Osteoarthritis.................................................................................. 134 Patent Applications on Osteoarthritis.............................................................. 145 Keeping Current ............................................................................................... 156 Vocabulary Builder........................................................................................... 157
CHAPTER 6. BOOKS ON OSTEOARTHRITIS ........................................ 161
Overview........................................................................................................... 161 Book Summaries: Federal Agencies .................................................................. 161 Book Summaries: Online Booksellers ............................................................... 163 The National Library of Medicine Book Index ................................................. 167 Chapters on Osteoarthritis ............................................................................... 169 General Home References ................................................................................. 176 Vocabulary Builder........................................................................................... 176
CHAPTER 7. MULTIMEDIA ON OSTEOARTHRITIS .............................. 179
Overview........................................................................................................... 179 Video Recordings .............................................................................................. 179 Bibliography: Multimedia on Osteoarthritis .................................................... 180
CHAPTER 8. PERIODICALS AND NEWS ON OSTEOARTHRITIS ........... 183
Overview........................................................................................................... 183 News Services & Press Releases ....................................................................... 183 Newsletters on Osteoarthritis........................................................................... 193
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Newsletter Articles ........................................................................................... 195 Academic Periodicals covering Osteoarthritis.................................................. 198 Vocabulary Builder........................................................................................... 200
CHAPTER 9. PHYSICIAN GUIDELINES AND DATABASES ................... 201
Overview........................................................................................................... 201 NIH Guidelines................................................................................................. 201 NIH Databases.................................................................................................. 202 Other Commercial Databases ........................................................................... 214 The Genome Project and Osteoarthritis ........................................................... 214 Specialized References....................................................................................... 218 Vocabulary Builder........................................................................................... 220
CHAPTER 10. DISSERTATIONS ON OSTEOARTHRITIS ........................ 221
Overview........................................................................................................... 221 Dissertations on Osteoarthritis ........................................................................ 221 Keeping Current ............................................................................................... 222 Vocabulary Builder........................................................................................... 223
PART III. APPENDICES .................................................. 225 APPENDIX A. RESEARCHING YOUR MEDICATIONS.......................... 227
Overview........................................................................................................... 227 Your Medications: The Basics .......................................................................... 227 Learning More about Your Medications .......................................................... 229 Commercial Databases...................................................................................... 231 Contraindications and Interactions (Hidden Dangers) ................................... 232 A Final Warning .............................................................................................. 233 General References............................................................................................ 233
APPENDIX B. RESEARCHING ALTERNATIVE MEDICINE ................... 235
Overview........................................................................................................... 235 What Is CAM? ................................................................................................. 235 What Are the Domains of Alternative Medicine?............................................ 236 Can Alternatives Affect My Treatment? ......................................................... 239 Finding CAM References on Osteoarthritis..................................................... 240 Additional Web Resources................................................................................ 251 General References............................................................................................ 268 Vocabulary Builder........................................................................................... 269
APPENDIX C. RESEARCHING NUTRITION ......................................... 271
Overview........................................................................................................... 271 Food and Nutrition: General Principles........................................................... 271 Finding Studies on Osteoarthritis.................................................................... 276 Federal Resources on Nutrition........................................................................ 279 Additional Web Resources................................................................................ 280 Vocabulary Builder........................................................................................... 286
APPENDIX D. FINDING MEDICAL LIBRARIES.................................... 289
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Overview........................................................................................................... 289 Preparation ....................................................................................................... 289 Finding a Local Medical Library ...................................................................... 290 Medical Libraries Open to the Public............................................................... 290
APPENDIX E. QUESTIONS AND ANSWERS ABOUT ARTHRITIS PAIN . 297
Overview........................................................................................................... 297 What Is Arthritis? ............................................................................................ 297 What Is Pain? ................................................................................................... 298 What Causes Arthritis Pain? Why Is It So Variable? ..................................... 298 How Do Doctors Measure Arthritis Pain? ...................................................... 299 What Will Happen When You First Visit a Doctor for Your Arthritis Pain? 299 Who Can Treat Arthritis Pain?........................................................................ 300 How Is Arthritis Pain Treated? ....................................................................... 300 Short-Term Relief ............................................................................................. 300 Long-Term Relief .............................................................................................. 301 What Alternative Therapies May Relieve Arthritis Pain? .............................. 303 How Can You Cope with Arthritis Pain? ........................................................ 303 What Research Is Being Conducted on Arthritis Pain?................................... 304 Where Can You Find More Information on Arthritis Pain? ........................... 306
APPENDIX F. MORE ON RHEUMATIC DISEASES AND ARTHRITIS ..... 309
Overview........................................................................................................... 309 What Are Rheumatic Diseases and What Is Arthritis? ................................... 309 Examples of Rheumatic Diseases...................................................................... 310 What Causes Rheumatic Disease?.................................................................... 312 Who Is Affected by Arthritis and Rheumatic Conditions? .............................. 313 What Are the Symptoms of Arthritis? ............................................................. 314 How Are Rheumatic Diseases Diagnosed? ...................................................... 314 Medical History ................................................................................................ 314 Physical Examination....................................................................................... 315 Common Laboratory Tests................................................................................ 315 Work with Your Doctor to Limit Your Pain .................................................... 317 X-Rays and Other Imaging Procedures ........................................................... 318 What Are the Treatments? ............................................................................... 318 Myths about Treating Arthritis ....................................................................... 322 What Can Be Done to Help? ............................................................................ 323 What Is Some of the Current Research Being Done on Arthritis? .................. 323 Where Can I Find More Information about Arthritis? .................................... 326
APPENDIX G. NIH CONSENSUS STATEMENT ON TOTAL HIP REPLACEMENT ................................................................................... 327
Overview........................................................................................................... 327 What Is Total Hip Replacement? ..................................................................... 329 What Are the Current Indications for Total Hip Replacement?...................... 330 What Are the Design and Surgical Considerations Relating to a Replacement Prosthesis? ........................................................................................................ 331
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What Are the Responses of the Biological Environment? ................................ 335 What Are the Expected Outcomes?.................................................................. 337 What Are the Accepted Approaches and Outcomes for Revision of a Total Hip Replacement?.................................................................................................... 340 What Are the Most Productive Directions for Future Research?.................... 342
ONLINE GLOSSARIES.................................................... 345 Online Dictionary Directories.......................................................................... 349
OSTEOARTHRITIS GLOSSARY................................... 351 General Dictionaries and Glossaries ................................................................ 369
INDEX................................................................................... 371
Introduction
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INTRODUCTION Overview Dr. C. Everett Koop, former U.S. Surgeon General, once said, “The best prescription is knowledge.”1 The Agency for Healthcare Research and Quality (AHRQ) of the National Institutes of Health (NIH) echoes this view and recommends that every patient incorporate education into the treatment process. According to the AHRQ: Finding out more about your condition is a good place to start. By contacting groups that support your condition, visiting your local library, and searching on the Internet, you can find good information to help guide your treatment decisions. Some information may be hard to find—especially if you don't know where to look.2 As the AHRQ mentions, finding the right information is not an obvious task. Though many physicians and public officials had thought that the emergence of the Internet would do much to assist patients in obtaining reliable information, in March 2001 the National Institutes of Health issued the following warning: The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading.3
Quotation from http://www.drkoop.com. The Agency for Healthcare Research and Quality (AHRQ): http://www.ahcpr.gov/consumer/diaginfo.htm. 3 From the NIH, National Cancer Institute (NCI): http://cancertrials.nci.nih.gov/beyond/evaluating.html. 1 2
2
Osteoarthritis
Since the late 1990s, physicians have seen a general increase in patient Internet usage rates. Patients frequently enter their doctor's offices with printed Web pages of home remedies in the guise of latest medical research. This scenario is so common that doctors often spend more time dispelling misleading information than guiding patients through sound therapies. The Official Patient’s Sourcebook on Osteoarthritis has been created for patients who have decided to make education and research an integral part of the treatment process. The pages that follow will tell you where and how to look for information covering virtually all topics related to osteoarthritis, from the essentials to the most advanced areas of research. The title of this book includes the word “official.” This reflects the fact that the sourcebook draws from public, academic, government, and peerreviewed research. Selected readings from various agencies are reproduced to give you some of the latest official information available to date on osteoarthritis. Given patients’ increasing sophistication in using the Internet, abundant references to reliable Internet-based resources are provided throughout this sourcebook. Where possible, guidance is provided on how to obtain free-ofcharge, primary research results as well as more detailed information via the Internet. E-book and electronic versions of this sourcebook are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). Hard copy users of this sourcebook can type cited Web addresses directly into their browsers to obtain access to the corresponding sites. Since we are working with ICON Health Publications, hard copy Sourcebooks are frequently updated and printed on demand to ensure that the information provided is current. In addition to extensive references accessible via the Internet, every chapter presents a “Vocabulary Builder.” Many health guides offer glossaries of technical or uncommon terms in an appendix. In editing this sourcebook, we have decided to place a smaller glossary within each chapter that covers terms used in that chapter. Given the technical nature of some chapters, you may need to revisit many sections. Building one’s vocabulary of medical terms in such a gradual manner has been shown to improve the learning process. We must emphasize that no sourcebook on osteoarthritis should affirm that a specific diagnostic procedure or treatment discussed in a research study, patent, or doctoral dissertation is “correct” or your best option. This sourcebook is no exception. Each patient is unique. Deciding on appropriate
Introduction
3
options is always up to the patient in consultation with their physician and healthcare providers.
Organization This sourcebook is organized into three parts. Part I explores basic techniques to researching osteoarthritis (e.g. finding guidelines on diagnosis, treatments, and prognosis), followed by a number of topics, including information on how to get in touch with organizations, associations, or other patient networks dedicated to osteoarthritis. It also gives you sources of information that can help you find a doctor in your local area specializing in treating osteoarthritis. Collectively, the material presented in Part I is a complete primer on basic research topics for patients with osteoarthritis. Part II moves on to advanced research dedicated to osteoarthritis. Part II is intended for those willing to invest many hours of hard work and study. It is here that we direct you to the latest scientific and applied research on osteoarthritis. When possible, contact names, links via the Internet, and summaries are provided. It is in Part II where the vocabulary process becomes important as authors publishing advanced research frequently use highly specialized language. In general, every attempt is made to recommend “free-to-use” options. Part III provides appendices of useful background reading for all patients with osteoarthritis or related disorders. The appendices are dedicated to more pragmatic issues faced by many patients with osteoarthritis. Accessing materials via medical libraries may be the only option for some readers, so a guide is provided for finding local medical libraries which are open to the public. Part III, therefore, focuses on advice that goes beyond the biological and scientific issues facing patients with osteoarthritis.
Scope While this sourcebook covers osteoarthritis, your doctor, research publications, and specialists may refer to your condition using a variety of terms. Therefore, you should understand that osteoarthritis is often considered a synonym or a condition closely related to the following: ·
Arthrosis
·
Degenerative Joint Disease
·
Hypertrophic Osteoarthritis
4
Osteoarthritis
·
Osteoarthrosis
In addition to synonyms and related conditions, physicians may refer to osteoarthritis using certain coding systems. The International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) is the most commonly used system of classification for the world's illnesses. Your physician may use this coding system as an administrative or tracking tool. The following classification is commonly used for osteoarthritis:4 ·
715 osteoarthrosis and allied disorders
·
715.0 osteoarthrosis, generalized
·
715.1 osteoarthrosis, localized, primary
·
715.2 osteoarthrosis, localized, secondary
·
715.3 osteoarthrosis, localized, not specified whether primary or secondary
·
715.8 osteoarthrosis involving, or with mention of more than one site, but not specified as generalized
·
715.9 osteoarthrosis, unspecified whether generalized or localized
For the purposes of this sourcebook, we have attempted to be as inclusive as possible, looking for official information for all of the synonyms relevant to osteoarthritis. You may find it useful to refer to synonyms when accessing databases or interacting with healthcare professionals and medical librarians.
Moving Forward Since the 1980s, the world has seen a proliferation of healthcare guides covering most illnesses. Some are written by patients or their family members. These generally take a layperson's approach to understanding and coping with an illness or disorder. They can be uplifting, encouraging, and highly supportive. Other guides are authored by physicians or other healthcare providers who have a more clinical outlook. Each of these two styles of guide has its purpose and can be quite useful.
This list is based on the official version of the World Health Organization's 9th Revision, International Classification of Diseases (ICD-9). According to the National Technical Information Service, “ICD-9CM extensions, interpretations, modifications, addenda, or errata other than those approved by the U.S. Public Health Service and the Health Care Financing Administration are not to be considered official and should not be utilized. Continuous maintenance of the ICD-9-CM is the responsibility of the federal government.”
4
Introduction
5
As editors, we have chosen a third route. We have chosen to expose you to as many sources of official and peer-reviewed information as practical, for the purpose of educating you about basic and advanced knowledge as recognized by medical science today. You can think of this sourcebook as your personal Internet age reference librarian. Why “Internet age”? All too often, patients diagnosed with osteoarthritis will log on to the Internet, type words into a search engine, and receive several Web site listings which are mostly irrelevant or redundant. These patients are left to wonder where the relevant information is, and how to obtain it. Since only the smallest fraction of information dealing with osteoarthritis is even indexed in search engines, a non-systematic approach often leads to frustration and disappointment. With this sourcebook, we hope to direct you to the information you need that you would not likely find using popular Web directories. Beyond Web listings, in many cases we will reproduce brief summaries or abstracts of available reference materials. These abstracts often contain distilled information on topics of discussion. While we focus on the more scientific aspects of osteoarthritis, there is, of course, the emotional side to consider. Later in the sourcebook, we provide a chapter dedicated to helping you find peer groups and associations that can provide additional support beyond research produced by medical science. We hope that the choices we have made give you the most options available in moving forward. In this way, we wish you the best in your efforts to incorporate this educational approach into your treatment plan. The Editors
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PART I: THE ESSENTIALS
ABOUT PART I Part I has been edited to give you access to what we feel are “the essentials” on osteoarthritis. The essentials of a disease typically include the definition or description of the disease, a discussion of who it affects, the signs or symptoms associated with the disease, tests or diagnostic procedures that might be specific to the disease, and treatments for the disease. Your doctor or healthcare provider may have already explained the essentials of osteoarthritis to you or even given you a pamphlet or brochure describing osteoarthritis. Now you are searching for more in-depth information. As editors, we have decided, nevertheless, to include a discussion on where to find essential information that can complement what your doctor has already told you. In this section we recommend a process, not a particular Web site or reference book. The process ensures that, as you search the Web, you gain background information in such a way as to maximize your understanding.
Guidelines
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CHAPTER 1. THE ESSENTIALS ON OSTEOARTHRITIS: GUIDELINES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines on osteoarthritis. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. The great advantage of guidelines over other sources is that they are often written with the patient in mind. Since new guidelines on osteoarthritis can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.
The National Institutes of Health (NIH)5 The National Institutes of Health (NIH) is the first place to search for relatively current patient guidelines and fact sheets on osteoarthritis. Originally founded in 1887, the NIH is one of the world's foremost medical research centers and the federal focal point for medical research in the United States. At any given time, the NIH supports some 35,000 research grants at universities, medical schools, and other research and training institutions, both nationally and internationally. The rosters of those who have conducted research or who have received NIH support over the years include the world's most illustrious scientists and physicians. Among them are 97 scientists who have won the Nobel Prize for achievement in medicine.
5
Adapted from the NIH: http://www.nih.gov/about/NIHoverview.html.
10 Osteoarthritis
There is no guarantee that any one Institute will have a guideline on a specific disease, though the National Institutes of Health collectively publish over 600 guidelines for both common and rare diseases. The best way to access NIH guidelines is via the Internet. Although the NIH is organized into many different Institutes and Offices, the following is a list of key Web sites where you are most likely to find NIH clinical guidelines and publications dealing with osteoarthritis and associated conditions: ·
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
·
National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc. ) with guidelines available at http://www.nlm.nih.gov/medlineplus/healthtopics.html
·
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines at http://www.nih.gov/niams/healthinfo/
Among those listed above, the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) is especially noteworthy. The mission of NIAMS, a part of the National Institutes of Health (NIH), is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases, the training of basic and clinical scientists to carry out this research, and the dissemination of information on research progress in these diseases. The National Institute of Arthritis and Musculoskeletal and Skin Diseases Information Clearinghouse is a public service sponsored by the NIAMS that provides health information and information sources. The NIAMS provides the following guideline concerning osteoarthritis.6
What Is Osteoarthritis?7 Osteoarthritis (AH-stee-oh-ar-THREYE-tis) is the most common type of arthritis, especially among older people. Sometimes it is called degenerative joint disease or osteoarthrosis. Osteoarthritis is a joint disease that mostly affects the cartilage (KAR-til-uj). Cartilage is the slippery tissue that covers the ends of bones in a joint. 6This
and other passages are adapted from the NIH and NIAMS (http://www.niams.nih.gov/hi/index.htm). “Adapted” signifies that the text is reproduced with attribution, with some or no editorial adjustments. 7 Adapted from The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): http://www.niams.nih.gov/hi/topics/arthritis/oahandout.htm.
Guidelines 11
Healthy cartilage allows bones to glide over one another. It also absorbs energy from the shock of physical movement. In osteoarthritis, the surface layer of cartilage breaks down and wears away. This allows bones under the cartilage to rub together, causing pain, swelling, and loss of motion of the joint. Over time, the joint may lose its normal shape. Also, bone spurs--small growths called osteophytes--may grow on the edges of the joint. Bits of bone or cartilage can break off and float inside the joint space. This causes more pain and damage. People with osteoarthritis usually have joint pain and limited movement. Unlike some other forms of arthritis, osteoarthritis only affects joints, and not internal organs. For example, rheumatoid arthritis--the second most common form of arthritis--affects other parts of the body besides the joints. It begins earlier than osteoarthritis, causes inflammation, and may make people feel sick, tired, and sometimes feverish.
Who Is Affected by Osteoarthritis? Osteoarthritis is one of the most frequent causes of physical disability among adults. More than 20 million people in the United States probably have the disease. Some younger people get osteoarthritis from a joint injury, but osteoarthritis most often occurs in older people. In fact, by age 65, more than half of the population has x-ray evidence of osteoarthritis in at least one joint. Since the number of older Americans is increasing, so is the number of people with osteoarthritis. Both men and women have the disease. Before age 45, more men have it, while after age 45 osteoarthritis is more common in women.
How Does Osteoarthritis Affect People? Osteoarthritis affects each person differently. In some people, it progresses more quickly; in others, the symptoms are more serious. Scientists do not yet know what causes the disease, but they suspect a combination of factors in the body and in the environment. Also, diet, weight, and stresses on the joints from certain jobs affect the disease and how a person reacts to it. Osteoarthritis hurts people in more than their joints--their finances and lifestyles are also affected. Financial effects include: ·
The cost of treatment
12 Osteoarthritis
·
Wages lost because of disability.
Lifestyle effects include: ·
Depression
·
Anxiety
·
Feelings of helplessness
·
Limits on daily activities
·
Job limitations
·
Loss of everyday family joys and responsibilities.
Despite these challenges, most people with osteoarthritis can lead active and productive lives. They succeed by using osteoarthritis treatment strategies such as: ·
Pain relief medications
·
Rest and exercise
·
Patient education and support programs
·
Learning self-care and having a “good-health attitude.”
Osteoarthritis Basics: The Joint and Its Parts Most joints--the place where two moving bones come together--are designed to protect bone ends from wearing away and to absorb shock from movements like walking or repetitive movements. The joint includes: ·
Cartilage. A hard but slippery coating on the end of each bone. Cartilage, which breaks down and wears away in osteoarthritis, is described in more detail in the box below.
·
Joint capsule. A tough membrane sac that holds all the bones and other joint parts together.
·
Synovium (sin-O-vee-um). A thin membrane inside the joint capsule.
·
Synovial fluid. A fluid that lubricates the joint and keeps the cartilage smooth and healthy.
·
Muscles, ligaments, and tendons. Together, muscles and connective tissues keep the bones stable and allow the joint to bend and move. Ligaments are tough, cord-like tissues that connect one bone to another. Tendons are tough, fibrous cords that connect muscles to bones.
Guidelines 13
Cartilage: The Key to Healthy Joints Cartilage is 65 to 80 percent water. Three other substances make up the rest of cartilage tissue: collagen, proteoglycans, and chondrocytes. ·
Collagen (KAHL-uh-jen). A fibrous protein. Collagen is also the building block of skin, tendon, bone, and other connective tissues.
·
Proteoglycans (PRO-tee-uh-GLY-kanz). A combination of proteins and sugars. Strands of proteoglycans and collagen weave together and form a mesh-like tissue. This allows cartilage to flex and absorb physical shock.
·
Chondrocytes (KAHN-druh-sytz). Cells that grow all through the cartilage. They mainly help cartilage stay healthy and grow. Sometimes, however, they release substances called enzymes that destroy collagen and other proteins. Researchers are trying to learn more about chondrocytes.
How Do You Know If You Have Osteoarthritis? Usually, osteoarthritis comes on slowly. Early in the disease, joints may ache after physical work or exercise. Osteoarthritis can occur in any joint. Most often it occurs at the hands, hips, knees, or spine.
Hands Osteoarthritis of the fingers is the one type of the disease that seems to be hereditary; that is, it runs in families. More women than men have it, especially after menopause. Small, bony knobs appear on the end joints of the fingers. They are called Heberden's nodes. Similar knobs (called Bouchard's [boo-SHARDZ] nodes) can appear on the middle joints of the fingers. Fingers can become enlarged and gnarled, and may ache or be stiff and numb. The base of the thumb joint is also commonly affected by osteoarthritis. This kind of osteoarthritis can be helped by medications, splints, or heat treatment.
14 Osteoarthritis
Knees The knees are the body's primary weight-bearing joints. For this reason, they are among the joints most commonly affected by osteoarthritis. They may be stiff, swollen, and painful, making it hard to walk, climb, get in and out of chairs, and use bathtubs. If not treated, osteoarthritis in the knees can lead to disability. Medications, losing weight, exercise, and walking aids can reduce pain and disability. In severe cases, knee replacement surgery may be helpful.
Hips Osteoarthritis in the hip can cause pain, stiffness, and severe disability. People may feel the pain in their hips, or in their groin, inner thigh, or knees. Walking aids such as canes or walkers can reduce stress on the hip. Osteoarthritis in the hip may limit moving and bending. This can make daily activities such as dressing and foot care a challenge. Walking aids, medication, and exercise can help relieve pain and improve motion. The doctor may recommend hip replacement if the pain is severe and not helped by other methods.
Spine Stiffness and pain in the neck or in the lower back can result from osteoarthritis of the spine. Weakness or numbness of the arms or legs can also result. Some people feel better when they sleep on a firm mattress or sit using back support pillows. Others find help from heat treatment or an exercise program to strengthen the back and abdominal muscles. In severe cases, the doctor may suggest surgery to reduce pain and help restore function.
The Warning Signs of Osteoarthritis ·
Steady or intermittent pain in a joint
·
Stiffness after getting out of bed
·
Joint swelling or tenderness in one or more joints
·
A crunching feeling or sound of bone rubbing on bone
Guidelines 15
·
Hot, red, or tender? Probably not osteoarthritis. Check with your doctor about other causes, such as rheumatoid arthritis.
·
Not always pain. Not everyone with osteoarthritis feels pain. In fact, only a third of people with osteoarthritis in their X-rays report pain or other symptoms.
How Do Doctors Diagnose Osteoarthritis? No single test can diagnose osteoarthritis. Most doctors use a combination of the following methods to diagnose the disease and rule out other conditions.
Clinical History The doctor begins by asking the patient to describe the symptoms, and when and how the condition started. Good doctor-patient communication is important. The doctor can give a better assessment if the patient gives a good description of pain, stiffness, and joint function, and how they changed over time. It is also important for the doctor to know how the condition is affecting the patient's work and daily life. Finally, the doctor also needs to know about other medical conditions and whether the patient is taking any medicines.
Physical Examination The doctor will check the patient's general health. Joints bothering the patient will be examined, including checking reflexes and muscle strength. The doctor will also observe the patient's ability to walk, bend, and carry out activities of daily living.
X-Rays Doctors take x rays to see how much joint damage has been done. X rays of the affected joint can show such things as cartilage loss, bone damage, and bone spurs. But there is often a big difference between the severity of osteoarthritis that the x ray shows and the degree of pain and disability the patient has. And x rays may not show early osteoarthritis damage (before much cartilage loss has taken place).
16 Osteoarthritis
Other Tests The doctor may order blood tests to determine the cause of symptoms. Another common test includes “joint aspiration,” where fluid is drawn from the joint for examination. It is usually not difficult to tell if a patient has osteoarthritis. It is more difficult to tell if the disease is causing the patient's symptoms. Osteoarthritis is so common, especially in older people, that other conditions may play a role in the symptoms. The doctor will try to find out what is causing the symptoms, ruling out other disorders and identifying conditions that may make the symptoms worse. The severity of symptoms in osteoarthritis is greatly influenced by the patient's attitudes, anxiety, depression, or daily activity level.
How Is Osteoarthritis Treated? Most successful treatment programs involve a combination of treatments tailored to the patient's needs, lifestyle, and health. Osteoarthritis treatment has four general goals: ·
Control pain through drugs and other measures.
·
Improve joint care through rest and exercise.
·
Maintain an acceptable body weight.
·
Achieve a healthy lifestyle.
Osteoarthritis treatment plans often include ways to manage pain and improve function. Such plans can involve exercise, rest and joint care, pain relief, weight control, medications, surgery, and nontraditional treatment approaches. Treatment approaches to osteoarthritis include: ·
Exercise
·
Rest and joint care
·
Surgery
·
Pain relief techniques
·
Weight control
Guidelines 17
·
Medicines
·
Alternative therapies
Exercise Research shows that one of the best treatments for osteoarthritis is exercise. This activity can improve mood and outlook, decrease pain, increase flexibility, improve the heart and blood flow, maintain weight, and promote general physical fitness. It is also inexpensive and, if done correctly, has few negative side effects. The amount and form of exercise will depend on which joints are involved, how stable the joints are, and whether a joint replacement has already been done. You can use exercises to keep strong and limber, extend your range of movement, and reduce weight. Ask your doctor or physical therapist what exercises are best for you. ·
Strength: Exercise bands are inexpensive devices that add resistance.
·
Aerobics: Activities that keep your lungs and circulation systems in shape.
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Range of Motion: These activities keep the joints limber.
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Agility: Many of these exercises help you to maintain daily living skills.
·
Neck and Back Strength: Don't forget to keep your spine strong and limber.
Ask your doctor or physical therapist what exercises are best for you. Ask for guidelines on exercising when a joint is sore or if swelling is present. Also, check if you should (1) use drugs such as analgesics or anti-inflammatories (NSAIDs) to make exercising easier, or (2) use ice afterwards.
Rest and Joint Care Treatment plans include regularly scheduled rest. Patients must learn to recognize the body's signals, and know when to stop or slow down. This prevents pain caused by overexercising. Some patients find that relaxation techniques, stress reduction, and biofeedback help. Some use canes and splints to protect joints and take pressure off them. Splints or braces provide extra support for weakened joints. They also keep the joint in proper position during sleep or activity. Splints must be used for limited periods because
18 Osteoarthritis
joints and muscles need to be exercised to prevent stiffness and weakness. An occupational therapist or a doctor can help the patient get a properly fitting splint. Surgery For some people, surgery helps relieve the pain and disability of osteoarthritis. Surgery may be performed to: ·
Resurface (smooth out) bones.
·
Reposition bones.
·
Replace joints. Surgeons may replace affected joints with artificial joints called prostheses. These joints can be made from metal alloys, highdensity plastic, and ceramic material, and can be joined to bone surfaces by special cements. Artificial joints can last from 10 to 15 years or more. About 10 percent may need revision. Surgeons choose the design and components of prostheses according to their patient's weight, sex, age, activity level, and other medical conditions.
·
Remove loose pieces of bone or cartilage from the joint to improve joint function.
The decision to use surgery depends on several things. Both surgeon and patient consider the patient's level of disability, intensity of pain, interference with lifestyle, age, and occupation. Currently, more than 80 percent of osteoarthritis surgery cases involve replacing the hip or knee joint. After surgery and rehabilitation, the patient usually feels less pain and swelling, and can move more easily.
Pain Relief People with osteoarthritis may have nonmedical ways to relieve pain. Patients can use warm towels, hot packs, or a warm bath or shower to apply moist heat to the joint. This can relieve pain and stiffness. In some cases, cold packs (a bag of ice or frozen vegetables wrapped in a towel) can relieve pain or numb the sore area. (Check with a doctor or physical therapist to find out if heat or cold is the best treatment.) Water therapy in a heated pool or whirlpool may also relieve pain and stiffness. For osteoarthritis in the knee, patients may wear insoles or cushioned shoes to redistribute weight and reduce joint stress.
Guidelines 19
Weight Control Osteoarthritis patients who are overweight or obese need to lose weight. Weight loss can reduce stress on weight-bearing joints and limit further injury. A dietician can help patients develop healthy eating habits. A healthy diet and regular exercise help reduce weight.
Medicines Doctors use medicines to eliminate or reduce pain and to improve functioning. Doctors consider a number of factors when choosing medicines for their patients with osteoarthritis. Two important factors are the nature of the pain and potential drug side effects. Patients must use medicines carefully and tell doctors about any changes that occur. The following types of medicines are commonly used in treating osteoarthritis.
NSAIDs (Nonsteroidal Anti-Inflammatory Drugs) Many NSAIDs are used to treat osteoarthritis. Patients can buy some over the counter (for example, aspirin, Advil®8, Motrin® IB, Aleve®, ketoprofen). Others need a prescription. These drugs work in a similar way: they fight inflammation or swelling and relieve pain. However, each NSAID is a different chemical, and has slightly different effects in the body. Side effects of NSAIDs include: ·
NSAIDs can cause stomach irritation or affect kidney function. The longer a person uses NSAIDs, the more likely he or she is to have side effects, and the more serious those effects can be.
·
Many other drugs cannot be taken with NSAIDs, because NSAIDs alter the way the body uses or gets rid of these drugs.
·
NSAIDs are associated with serious gastrointestinal problems, including ulcers, bleeding, and perforation. They should be used with caution in
Brand names included in this booklet are provided as examples only. Their inclusion does not mean they are endorsed by the National Institutes of Health or any other Government agency. Also, if a certain brand name is not mentioned, this does not mean or imply that the product is unsatisfactory.
8
20 Osteoarthritis
people over 65 and in those with any history of ulcers or gastrointestinal bleeding.
COX-2 Inhibitors Two new NSAIDs, Celebrex® and Vioxx®, from a class of drugs known as COX-2 inhibitors, are now being used against osteoarthritis. These medicines reduce inflammation like traditional NSAIDs, but cause fewer gastrointestinal side effects.
Acetaminophen A non-anti-inflammatory pain reliever (for example, Tylenol®). This drug does not irritate the stomach and is less likely than NSAIDs to cause longterm side effects. Research has shown that in many patients with osteoarthritis, acetaminophen relieves pain as effectively as NSAIDs.9
Other Medicines Doctors may prescribe several other medicines for osteoarthritis. They include: ·
Topical pain-relieving creams, rubs, and sprays (for example, capsaicin cream) applied directly to the skin.
·
Mild narcotic painkillers, which--while very effective--are addictive and rarely used.
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Corticosteroids, powerful anti-inflammatory hormones made naturally in the body or man made for use as drugs. Corticosteroids are typically injected into affected joints to relieve pain temporarily. This is a shortterm measure, not recommended for more than two or three times per year.
·
Hyaluronic acid, a new medicine for joint injection, used to treat osteoarthritis of the knee. This substance is a normal component of the joint, involved in joint lubrication and nutrition. Many patients experience pain relief after a series of three to five injections.
Warning: Patients with liver disease, heavy alcohol drinkers, and those on blood-thinning medicines should use acetaminophen with caution.
9
Guidelines 21
Questions to Ask Your Doctor or Pharmacist about Medicines ·
How often should I take this medicine?
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Should I take this medicine with food or between meals?
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What side effects can I expect?
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Should I take this medicine with other prescription medicines I take?
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Should I take this medicine with the over-the-counter medicines I take?
Side Effects Most medicines used to treat osteoarthritis have side effects. So it is important for patients to learn about the drugs they are taking. Even nonprescription drugs should be checked. Several groups of patients are at high risk for side effects. Those patients are people with a history of peptic ulcers or digestive tract bleeding, those taking oral corticosteroids or anticoagulants (blood thinners), those who smoke, and those who consume alcohol. Some patients may be able to help reduce side effects by taking some drugs with food. Others should avoid stomach irritants such as alcohol, tobacco, and caffeine. Some patients take other medicines to try to protect their stomachs by coating the stomach or blocking stomach acids. These measures help, but are not always completely effective.
Non-Traditional Approaches Among the alternative therapies for treating osteoarthritis are: ·
Acupuncture
·
Folk remedies
Acupuncture Some people have found pain relief using acupuncture (the use of fine needles inserted at specific points on the skin). Preliminary research shows that acupuncture may be a useful component in an osteoarthritis treatment plan for some patients.
22 Osteoarthritis
Folk Remedies Some patients seek alternative therapies for their pain and disability. Some of these alternative therapies have included wearing copper bracelets, drinking herbal teas, and taking mud baths. While these practices are not harmful, some can be expensive. They also cause delays in seeking medical treatment. To date, no scientific research shows these approaches to be helpful in treating osteoarthritis.
Health Professionals Who Treat Osteoarthritis Many types of health professionals care for people with osteoarthritis: ·
Rheumatologists. Doctors who specialize in treating arthritis and related conditions that affect joints, muscles, and bones.
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Orthopaedists. Doctors who specialize in treatment of and surgery for bone diseases.
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Physical therapists. Health professionals who work with patients to improve joint function.
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Occupational therapists. Health professionals who teach ways to protect joints, minimize pain, and conserve energy.
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Dietitians. Health professionals who teach ways to use a good diet to improve health and maintain a healthy weight.
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Nurse educators. Nurses who specialize in helping patients understand their overall condition and implement their treatment plans.
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Physiatrists (rehabilitation specialists). Doctors who help patients make the most of their physical potential.
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Licensed acupuncture therapists. Health professionals who reduce pain and improve physical functioning by inserting fine needles into the skin at various points on the body.
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Psychologists. Health professionals who help patients cope with difficulties in the home and workplace resulting from their conditions.
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Social workers. Professionals who assist patients with social challenges caused by disability, unemployment, financial hardships, home health care, and other needs resulting from their conditions.
Guidelines 23
Be a Winner! Practice Self-Care and Keep a Good-Health Attitude People with osteoarthritis can enjoy good health despite having the disease. How? By learning self-care skills and developing a good-health attitude. Self-care is central to successfully managing the pain and disability of osteoarthritis. Patients have a much better chance for a rewarding lifestyle when they educate themselves about the disease and take part in their own care. Working actively with a team of health care providers enables people with the disease to minimize pain, share in decision-making about treatment, and feel a sense of control over their lives. Research shows that patients who take part in their own care report less pain and make fewer doctor visits. They also enjoy a better quality of life. Self-Management Programs People with osteoarthritis find that self-management programs help them: ·
Understand the disease
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Reduce pain while remaining active
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Cope physically, emotionally, and mentally
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Have greater control over the disease
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Build confidence in their ability to live an active, independent life.
Self-Help and Education Programs Three kinds of programs help people learn about osteoarthritis, learn selfcare, and improve their good-health attitude. These programs are: ·
Patient education programs
·
Arthritis self-management programs
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Arthritis support groups.
These programs teach about osteoarthritis, its treatments, exercise and relaxation, patient/health care provider communication, and problem solving. Research has shown that these programs have clear and long-lasting benefits.
24 Osteoarthritis
Enjoy a Good-Health Attitude ·
Focus on your abilities instead of disabilities.
·
Focus on your strengths instead of weaknesses.
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Break down activities into small tasks that you can manage.
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Incorporate fitness and nutrition into daily routines.
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Develop methods to minimize and manage stress.
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Balance rest with activity.
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Develop a support system of family, friends, and health professionals.
Exercise Regular physical activity plays a key role in self-care and wellness. Two types of exercise are important in osteoarthritis management. Therapeutic exercises keep joints working as well as possible. Aerobic conditioning exercises improve strength and fitness, and control weight. Patients should be realistic when they start exercising. They should learn how to exercise correctly, because exercising incorrectly can actually cause problems. Most people with osteoarthritis exercise best when pain is least severe. Start with an adequate warmup and begin exercising slowly. Resting frequently ensures a good workout. It also reduces the risk of injury. A physical therapist can evaluate how a patient's muscles are working. This information helps the therapist develop a safe, personalized exercise program to increase strength and flexibility. Many people enjoy sports or other activities in their exercise program. Good activities include swimming and aquatic exercise, walking, running, biking, cross-country skiing, and using exercise machines and exercise videotapes. People with osteoarthritis should check with their doctor or physical therapist before embarking on an exercise program. Health care providers will suggest what exercises are best for you, how to warm up safely, and when to avoid exercising a joint affected by arthritis. Pain medications and ice applications may make exercising easier.
Guidelines 25
Body, Mind, Spirit Making the most of good health requires careful attention to the body, mind, and spirit. People with osteoarthritis must plan and develop daily routines that maximize their quality of life and minimize disability. They also need to evaluate these routines periodically to make sure they are working well. Good health also requires a positive attitude. People must decide to make the most of things when faced with the challenges of osteoarthritis. This attitude--a good-health mindset--doesn't just happen. It takes work, every day. And with the right attitude, you will enjoy it.
Current Research The leading role in osteoarthritis research is played by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), within the National Institutes of Health (NIH). The NIAMS funds many researchers across the United States to study osteoarthritis. It has established a Specialized Center of Research devoted to osteoarthritis. Also, a large number of researchers study arthritis at the NIAMS Multipurpose Arthritis and Musculoskeletal Disease Centers. These centers conduct basic, laboratory, and clinical research aimed at understanding the causes, treatment options, and prevention of arthritis and musculoskeletal diseases. Center researchers also study professional, patient, and public education; epidemiology; and health services. For years, scientists thought that osteoarthritis was simply a disease of “wear and tear” that occurred in joints as people got older. In the last decade, however, research has shown that there is more to the disorder than aging alone. The production, maintenance, and breakdown of cartilage, as well as bone changes in osteoarthritis, are now seen as a series or “cascade” of events. Many researchers are trying to discover where in that cascade of events things go wrong. By understanding what goes wrong, they hope to find new ways to prevent or treat osteoarthritis. Some key areas of research are described below.
Animal Models Animals help researchers understand how diseases work and why they occur. In osteoarthritis, animal models help researchers learn many things about osteoarthritis. They help reveal what happens to cartilage, how
26 Osteoarthritis
treatment strategies might work, and what might prevent the disease. Animal models also help scientists study osteoarthritis in very early stages, before it causes joint damage. Diagnostic Tools Some scientists want to find ways to detect osteoarthritis at earlier stages so that they can treat it earlier. They seek specific abnormalities in the blood, joint fluid, or urine of people with the disease. Other scientists use new technologies to analyze differences in cartilage from different joints. For example, many people have osteoarthritis in the knees or hips, but few have it in their ankles. Can ankle cartilage be different? Does it age differently? Answering these questions will help us understand the disease better.
Genetic Studies Researchers suspect that inheritance plays a role in 25 to 30 percent of osteoarthritis cases. Scientists have identified a mutation (a gene defect) affecting collagen, an important part of cartilage in patients with an inherited kind of osteoarthritis that starts at an early age. The mutation weakens collagen protein, which may break or tear more easily under stress. Scientists are looking for other mutations in osteoarthritis. In the future, a test to determine who carries the genetic defect (or defects) could help people reduce their risk for osteoarthritis with lifestyle adjustments.
Comprehensive Treatment Strategies Effective treatment for osteoarthritis takes more than drugs or surgery. Getting help from a variety of care professionals can often improve patient treatment and self-care. Research shows that adding patient education and social support is a low-cost, effective way to decrease pain and reduce the amount of medicine used. Exercise plays a key part in comprehensive treatment. Researchers are studying exercise in greater detail, finding out just how to use it in treating or preventing osteoarthritis. For example, several scientists have looked at knee osteoarthritis and exercise. They have found that
Guidelines 27
·
The level of muscle strength in the thigh muscle (quadriceps) is very important. Strengthening this muscle can relieve symptoms and prevent more damage.
·
Walking can result in better functioning and increased walking distance.
·
People with knee osteoarthritis who were active in an exercise program feel less pain. They also function better.
Research has shown that losing extra weight can help people with osteoarthritis. Most important, weight loss may reduce the risk of developing osteoarthritis of the knee in overweight or obese people.
Using NSAIDs Many patients have pain that persists despite the use of simple pain relievers like acetaminophen. Some of these patients use NSAIDs instead. Health care providers are concerned about long-term NSAID use because dangerous side effects can result. Scientists are working to design and test new, safer NSAIDs. One example currently available is a class of drugs called COX-2 inhibitors. These medicines relieve symptoms and are less likely to produce serious side effects such as stomach ulcers and bleeding, which are associated with long-term NSAID use.
Drugs to Prevent Joint Damage No treatment actually prevents osteoarthritis or reverses or blocks the disease process once it begins. Present treatments just relieve the symptoms. Researchers are looking for drugs that would prevent, slow down, or reverse joint damage. One experimental antibiotic drug, doxycycline, may stop certain enzymes from damaging cartilage. The drug has responded well in clinical studies, but more studies are needed. Researchers are also studying growth factors or other natural chemical messengers. These potential medicines may be able to stimulate cartilage growth or repair.
Acupuncture Licensed acupuncture therapists insert very fine needles into the skin at various points on the body. Scientists think that the needles stimulate the release of natural, pain-relieving chemicals produced by the brain or the
28 Osteoarthritis
nervous system. Researchers are looking at acupuncture treatment of patients who have knee osteoarthritis. Early findings suggest that traditional Chinese acupuncture is effective in some patients as an additional therapy for osteoarthritis, reducing pain and improving function.
Nutritional Supplements Nutritional supplements are often reported as helpful in treating osteoarthritis. Such reports should be viewed with caution, however, since very few studies have carefully evaluated the role of nutritional supplements in osteoarthritis.
Glucosamine and Chondroitin Sulfate Both of these nutrients are found in small quantities in food and are components of normal cartilage. Scientific studies on these two nutritional supplements have not yet shown that they affect the disease. They may relieve symptoms in some patients, however. The National Center for Complementary and Alternative Medicine at NIH is supporting a clinical trial to test whether either glucosamine or chondroitin sulfate alone, or in combination with each other, reduces pain and improves function. Patients using this therapy should do so only under the supervision of their doctor, as part of an overall treatment program with exercise, relaxation, and pain relief.
Vitamins D and C Progression of the disease appears to be less in patients with high levels of vitamin D or C intake. More studies are needed to confirm these reports.
Hyaluronic Acid Injecting this substance into the knee joint provides long-term pain relief for some people with osteoarthritis. Hyaluronic acid is a natural component of cartilage and joint fluid. It lubricates and absorbs shock in the joint. The Food and Drug Administration (FDA) recently approved this therapy for patients with osteoarthritis of the knee if they do not get relief from exercise, physical
Guidelines 29
therapy, or simple analgesics. Researchers are testing whether hyaluronic acid can slow down the progression of osteoarthritis.
Estrogen In studies of older women, scientists found a lower risk of osteoarthritis in women who had used oral estrogens for hormone replacement therapy. The researchers suspect that low estrogen levels could increase risk for the disease. Further studies are needed to answer this question.
Tissue Engineering This technology involves removing cells from the body and replacing them to improve certain body functions. NIAMS researchers are exploring three types of tissue engineering for use in treating osteoarthritis.
Enzyme Engineering Certain body chemicals called enzymes may help cartilage break down. Scientists are working to genetically engineer cells that would inhibit these enzymes and prevent the damage they cause. Cells are removed from the body, genetically changed, and then injected back into the affected joint. They live in the joint and protect it from damaging enzymes.
Cartilage Cell Replacement Researchers remove cartilage cells from the patient's own joint, clone or grow new cells using tissue culture and other laboratory techniques, and inject the newly grown cells into the patient's joint. Patients with cartilage cell replacement have decreased osteoarthritis symptoms. Actual cartilage repair is limited, however.
Stem Cell Transplantation Stem cells are primitive cells that can transform into other kinds of cells, such as muscle or bone cells. They are usually taken from bone marrow. In the
30 Osteoarthritis
future, researchers hope to insert stem cells into cartilage where they will make new cartilage. If successful, this process could be used to repair damaged cartilage and avoid the need for surgical joint replacements with metal or plastics.
Hope for the Future Research is opening up new avenues of treatment for people with osteoarthritis. A balanced, comprehensive approach is still the key to staying active and healthy with the disease. People with osteoarthritis should combine exercise, relaxation education, social support, and medicines in their treatment strategies. Meanwhile, as scientists unravel the complexities of the disease, new treatments and prevention methods should appear. They will improve the quality of life for people with osteoarthritis and their families.
Additional Resources National Institute of Arthritis and Musculoskeletal and Skin Diseases Information Clearinghouse National Institutes of Health 1 AMS Circle Bethesda, MD 20892-3675 (301) 495-4484 or (877) 22-NIAMS (toll free) TTY: (301) 565-2966 Fax: (301) 718-6366 NIAMS Fast Facts-For health information that is available by fax 24 hours a day, call (301) 881-2731 from a fax machine telephone. http://www.niams.nih.gov/ This clearinghouse, a public service sponsored by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), provides information about various forms of arthritis and rheumatic diseases. The clearinghouse distributes patient and professional education materials and also refers people to other sources of information.
Guidelines 31
Arthritis Foundation 1330 West Peachtree Street Atlanta, GA 30309 (404) 872-7100 (800) 283-7800, or call your local chapter (listed in the telephone directory) http://www.arthritis.org/ This is the main voluntary organization devoted to arthritis. The foundation publishes a free pamphlet on osteoarthritis and a magazine for members on arthritis and related conditions. It also provides up-todate information on research and treatment, nutrition, alternative therapies, and self-management strategies. Chapters nationwide offer exercise programs, classes, support groups, physician referral services, and free literature. American College of Rheumatology 1800 Century Place, Suite 250 Atlanta, GA 30345 (404) 633-3777 Fax: (404) 633-1870 http://www.rheumatology.org/ This association provides referrals to rheumatologists and physical and occupational therapists who have experience working with people who have osteoarthritis. The organization also provides educational materials and guidelines.
More Guideline Sources The guideline above on osteoarthritis is only one example of the kind of material that you can find online and free of charge. The remainder of this chapter will direct you to other sources which either publish or can help you find additional guidelines on topics related to osteoarthritis. Many of the guidelines listed below address topics that may be of particular relevance to your specific situation or of special interest to only some patients with osteoarthritis. Due to space limitations these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly.
32 Osteoarthritis
Topic Pages: MEDLINEplus For patients wishing to go beyond guidelines published by specific Institutes of the NIH, the National Library of Medicine has created a vast and patientoriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages.” You can think of a health topic page as a guide to patient guides. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following as being relevant to osteoarthritis: ·
Guides on Osteoarthritis Osteoarthritis http://www.nlm.nih.gov/medlineplus/osteoarthritis.html Osteoarthritis http://www.nlm.nih.gov/medlineplus/tutorials/osteoarthritisloade r.html
·
Other Guides Arthritis http://www.nlm.nih.gov/medlineplus/arthritis.html Hip Injuries and Disorders http://www.nlm.nih.gov/medlineplus/hipinjuriesanddisorders.htm l Juvenile Rheumatoid Arthritis http://www.nlm.nih.gov/medlineplus/juvenilerheumatoidarthritis. html Knee Injuries and Disorders http://www.nlm.nih.gov/medlineplus/kneeinjuriesanddisorders.ht ml Rheumatoid Arthritis http://www.nlm.nih.gov/medlineplus/rheumatoidarthritis.html
Guidelines 33
Within the health topic page dedicated to osteoarthritis, the following was recently recommended to patients: ·
General/Overviews Osteoarthritis Source: Arthritis Foundation http://www.arthritis.org/conditions/DiseaseCenter/oa.asp Osteoarthritis Source: Patient Education Institute http://www.nlm.nih.gov/medlineplus/tutorials/osteoarthritisloade r.html
·
Diagnosis/Symptoms Bone Radiography Source: American College of Radiology, Radiological Society of North America http://www.radiologyinfo.org/content/bone_radiography.htm
·
Treatment 2003 Drug Guide Source: Arthritis Foundation http://www.arthritis.org/conditions/DrugGuide/default.asp Arthritic Disorders and Treatments Source: American College of Foot and Ankle Surgeons http://www.acfas.org/brarthdis.html Arthritis: Timely Treatments for an Ageless Disease Source: Food and Drug Administration http://www.fda.gov/fdac/features/2000/300_arth.html FDA Approves New Indication and Label Changes for the Arthritis Drug, Vioxx Source: Food and Drug Administration http://www.fda.gov/bbs/topics/ANSWERS/2002/ANS01145.html
34 Osteoarthritis
Help Your Arthritis Treatment Work Source: img src='/medlineplus/images/easyread.gif' width='79' height='17' border=0 alt='Easy-to-Read'> (Food and Drug Administration http://www.fda.gov/opacom/lowlit/arthrtis.html Injections (for Pain Control) Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=PN00046 New Arthritis Drugs for Rheumatoid Arthritis and Osteoarthritis Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases http://www.niams.nih.gov/hi/topics/arthritis/arthrdrugs.htm Osteoarthritis of the Knee: Hyaluronic Acid Injections Source: American Academy of Family Physicians http://familydoctor.org/handouts/616.html Types of Surgery Source: Arthritis Foundation http://www.arthritis.org/conditions/surgerycenter/types.asp Viscosupplementation Treatment for Arthritis Source: American Academy of Orthopaedic Surgeons http://orthoinfo.aaos.org/fact/thr_report.cfm?Thread_ID=245&topc ategory=Knee ·
Alternative Therapy Acupuncture Source: Arthritis Foundation http://www.arthritis.org/resources/arthritistoday/2000_archives/2 000_05_06_acupuncture.asp Ayurvedic Herbs Source: Arthritis Foundation http://www.arthritis.org/resources/arthritistoday/1999_archives/1 999_05_06explorations.asp
Guidelines 35
Glucosamine and Chondroitin Sulfate Source: Arthritis Foundation http://www.arthritis.org/conditions/alttherapies/glucosamine.asp Homeopathy Source: Arthritis Foundation http://www.arthritis.org/resources/arthritistoday/2000_archives/2 000_03_04_homeopathy.asp Meditation Source: Arthritis Foundation http://www.arthritis.org/resources/arthritistoday/2001_archives/2 001_01_02_meditation.asp Nontraditional Arthritis Treatments: Some May Help, But Be Wary Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=HQ01121 Tai Chi Source: Arthritis Foundation http://www.arthritis.org/resources/arthritistoday/2000_archives/2 000_07_08_taichi.asp ·
Specific Conditions/Aspects Arthritis of the Foot and Ankle Source: American Orthopaedic Foot and Ankle Society http://www.aofas.org/arthritis.asp Arthritis of the Knee Source: American Academy of Orthopaedic Surgeons http://orthoinfo.aaos.org/fact/thr_report.cfm?Thread_ID=177&topc ategory=Arthritis Arthritis of the Thumb Source: American Academy of Orthopaedic Surgeons http://orthoinfo.aaos.org/fact/thr_report.cfm?Thread_ID=138&topc ategory=Arthritis
36 Osteoarthritis
Arthritis Patients Receive Effective Care in Nurse-led Clinics Source: American College of Rheumatology http://www.rheumatology.org/press/am2002/pr4.asp Bone Spurs (Osteophytes) Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?objectid=B153EB20-02EF4D54-A1B1FC6DB1C67499 Degenerative Changes in the Spine Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=AN00124 JAMA Patient Page: Osteoarthritis of the Knee Source: American Medical Association http://www.amaassn.org/public/journals/patient/archive/jpg022603.htm Managing Housework with Arthritis Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=AR00010 Osteoarthritis of the Hip Source: American Academy of Orthopaedic Surgeons http://orthoinfo.aaos.org/fact/thr_report.cfm?Thread_ID=208&topc ategory=Arthritis Overuse Injuries Associated with Hobbies Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=AR00020 Questions and Answers about Arthritis and Exercise Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases http://www.niams.nih.gov/hi/topics/arthritis/arthexfs.htm Questions and Answers about Arthritis Pain Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases http://www.niams.nih.gov/hi/topics/arthritis/arthpain.htm
Guidelines 37
Traveling with Arthritis: Plan, Pack and Enjoy Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=HQ01554 ·
From the National Institutes of Health Arthritis Advice Source: National Institute on Aging http://www.nia.nih.gov/health/agepages/arthritis.htm Do I Have Arthritis? http://www.niams.nih.gov/hi/topics/arthritis/tengo/english.htm Glucosamine/Chondroitin Arthritis Intervention Trial Begins Patient Recruitment Source: National Center for Complementary and Alternative Medicine http://nccam.nih.gov/news/19972000/121100/index.htm Handout on Health: Osteoarthritis Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases http://www.niams.nih.gov/hi/topics/arthritis/oahandout.htm Questions and Answers about Arthritis and Rheumatic Disease Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases http://www.niams.nih.gov/hi/topics/arthritis/artrheu.htm
·
Organizations American College of Rheumatology http://www.rheumatology.org/ Arthritis Foundation http://www.arthritis.org/ National Institute of Arthritis and Musculoskeletal and Skin Diseases http://www.niams.nih.gov/
38 Osteoarthritis
·
Prevention/Screening 10 Ways You Can Protect Your Joints Source: Arthritis Foundation http://www.arthritis.org/conditions/tips_jointprotection.asp
·
Research Genetic Regions Linked to Inherited Hand Osteoarthritis Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases http://www.niams.nih.gov/ne/highlights/spotlight/2002/hand.ht m Major Review Reveals That Osteoarthritis is a Complex Disease with New Solutions Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases http://www.niams.nih.gov/ne/press/2001/01_05.htm Progress and Opportunities in Osteoarthritis Source: Arthritis Foundation http://www.arthritis.org/research/research_program/Osteoarthritis /default.asp
If you do not find topics of interest when browsing health topic pages, then you can choose to use the advanced search utility of MEDLINEplus at http://www.nlm.nih.gov/medlineplus/advancedsearch.html. This utility is similar to the NIH Search Utility, with the exception that it only includes material linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search.
The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on osteoarthritis and related conditions. One of the advantages of CHID over other sources is that it offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to
Guidelines 39
http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: ·
Questions and Answers About Arthritis and Rheumatic Diseases Source: Bethesda, MD: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Information Clearinghouse. 2002. 40 p. Contact: Available from National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Information Clearinghouse. 1 AMS Circle, Bethesda, MD 20892-3675. (877) 226-4267 or (301) 495-4484. Fax (301) 718-6366. TTY (301) 565-2966. E-mail:
[email protected]. Website: www.niams.nih.gov. PRICE: 1 to 25 copies free. Order Number: AR-27 QA (booklet), or AR-27L QA (large print). Summary: This booklet uses a question and answer format to provide people who have arthritis and other rheumatic diseases with information on their causes, symptoms, diagnosis, and treatment. Rheumatic diseases cause pain, stiffness, and swelling in joints and other supporting structures of the body. Although many people use arthritis to refer to all rheumatic diseases, the many types of arthritis comprise only a portion of the rheumatic diseases. Examples of rheumatic diseases include osteoarthritis (OA), rheumatic arthritis (RA), fibromyalgia, systemic lupus erythematosus, scleroderma, juvenile rheumatoid arthritis, ankylosing spondylitis, gout, infectious arthritis, reactive arthritis, psoriatic arthritis, bursitis, and tendinitis. The causes of rheumatic disease depend on the type of disease, and the causes of most rheumatic diseases are still being investigated. Common symptoms of arthritis include joint swelling, pain, and stiffness. Diagnosis of rheumatic diseases involves obtaining a medical history, performing a physical examination, and obtaining laboratory tests and X rays or other imaging tests. Common laboratory tests include various blood tests, arthrocentesis, and urinalysis. Treatment options for arthritis include rest and relaxation; exercise; proper diet; medications such as analgesics, nonsteroidal anti-inflammatory drugs, acetaminophen, and corticosteroids; heat and cold therapies; hydrotherapy; mobilization therapy; relaxation therapy; orthotic devices; and surgery. The National Institute of Arthritis and Musculoskeletal and Skin Diseases currently supports research efforts in RA, OA, lupus, and scleroderma. The fact sheet includes a list of additional sources of information and a list of key words to help readers understand the terms used in the fact sheet.
40 Osteoarthritis
·
An Inside Look at Osteoarthritis Source: South Deerfield, MA: Channing L. Bete Co., Inc. 2000. 16 p. Contact: Available from Channing L. Bete Co., Inc. 200 State Road, South Deerfield, MA 01373-0200. (800) 628-7733. Fax (800) 499-6464. E-mail:
[email protected]. PRICE: Contact company for pricing information; available in bulk. Order Number 75324A-02-00. Summary: This illustrated booklet provides people who have osteoarthritis (OA) with an overview of this common degenerative form of arthritis. OA causes morning joint stiffness; joint pain during or after use; a crackling sound or grating sensation during use; and joint tenderness, redness, or swelling. Risk factors for OA include age, heredity, overuse, excess weight, and a previous injury to a bone or joint. Joints commonly affected by OA include the hand, spine, hip, knee, and foot. The booklet describes the anatomy of a normal joint and explains how OA slowly damages joints. Other topics include taking various prescription and nonprescription medications to relieve pain; using heat or cold, massage, relaxation techniques, and complementary therapies to ease pain and stiffness; and undergoing surgery to repair joints. In addition, the booklet discusses the importance of exercise in managing OA, provides examples of good body mechanics to help protect joints, and identifies supportive devices and tools.
·
Osteoarthritis Source: San Bruno, CA: StayWell Company. 1998. 8 p. Contact: Available from StayWell Company. 1100 Grundy Lane, San Bruno, CA 94066-3030. (800) 333-3032. Website: www.staywell.com. PRICE: Call or write for current pricing on single and bulk orders. Summary: This booklet provides people who have osteoarthritis (OA) with information on this degenerative form of arthritis. Although its cause is not completely known, OA is associated with the breakdown of the articular cartilage. Symptoms of OA vary greatly among people. The booklet explains the basic anatomy of the normal, movable joint, focusing on the articular cartilage, the synovial membrane, and the joint capsule. OA occurs when the articular cartilage begins to break down and the smooth sliding surfaces of the bones become pitted and irregular. Sites include the neck, fingers, lower back, hip, and knee. Diagnosis requires a medical history, a physical examination, and laboratory and diagnostic imaging studies. Medical treatment may include taking aspirin, nonsteroidal anti-inflammatory drugs, and corticosteroids, as well as losing excess weight. Physical therapy, including exercise and heat treatments, may also be used to treat OA. Exercises can be performed to
Guidelines 41
increase joint flexibility and strengthen muscles. In addition, surgical treatment, such as hip and knee replacement, may be used for pain that does not respond to conventional treatment and physical therapy. ·
Living With Osteoarthritis: Controlling Joint Pain Source: San Bruno, CA: StayWell Company. 1998. 6 p. Contact: Available from StayWell Company. 1100 Grundy Lane, San Bruno, CA 94066-3030. (800) 333-3032. Website: www.staywell.com. PRICE: Call or write for current pricing on single and bulk orders. Summary: This brochure provides people who have osteoarthritis (OA) with information on controlling joint pain. OA causes the cartilage in the joints to break down. Symptoms include joint pain and stiffness, weak muscles and wobbly joints, and loss of normal joint shape and motion. These symptoms can be controlled by exercising, losing weight and maintaining weight loss, and using special tools and aids to reduce strain and protect joints. Medications may help relieve pain and stiffness. The brochure provides tips on obtaining the best results from medications and comments on the use of surgery to decrease pain and improve movement.
·
Facts About Osteoporosis, Arthritis, and Osteoarthritis Source: Washington, DC: National Osteoporosis Foundation (NOF). 1997. 6 p. Contact: Available from National Osteoporosis Foundation. 1150 17th Street, NW, Suite 500, Washington, DC 20036-4603. (202) 223-2226. Fax (202) 223-2237. Website: www.nof.org. PRICE: Single copy free; bulk orders available at cost. Summary: This pamphlet provides people who have osteoporosis, arthritis, and osteoarthritis with information on these painful chronic diseases. Osteoporosis is characterized by a loss of bone mass and by poor bone quality, which lead to reduced bone strength and increased risk of fractures. The pamphlet lists the risk factors for osteoporosis and highlights prevention and treatment strategies. Osteoarthritis (OA), the most common form of arthritis, is a degenerative joint disease that leads to the thinning or destruction of the cartilage. The pamphlet presents the features of OA, identifies risk factors, and comments on diagnosis and treatment. Rheumatoid arthritis (RA) is an inflammatory disease of the lining of the joints that has no known cause. The pamphlet presents the warning signs of RA and provides information on diagnosis, treatment, and outcomes.
42 Osteoarthritis
The National Guideline Clearinghouse™ The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search their site located at http://www.guideline.gov by using the keyword “osteoarthritis” or synonyms. The following was recently posted: ·
Exercise prescription for older adults with osteoarthritis pain: consensus practice recommendations. Source: American Geriatrics Society.; 2001 June; 16 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 2414&sSearch_string=osteoarthritis
·
Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. Source: American College of Rheumatology.; 2000 September; 11 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 2161&sSearch_string=Arthrosis
Healthfinder™ Healthfinder™ is an additional source sponsored by the U.S. Department of Health and Human Services which offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: ·
Arthritis of the Knee Summary: Three basic types of arthritis may affect the knee joint. Osteoarthritis (OA) is the most common form of knee arthritis.
1.
Source: American Academy of Orthopaedic Surgeons http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=7231
Guidelines 43
·
Celebrex Summary: Celebrex is used to relieve the signs and symptoms of osteoarthritis and rheumatoid arthritis in adults. Source: Center for Drug Evaluation and Research, U.S. Food and Drug Administration http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=6975
·
Celebrex Summary: Celebrex is used to relieve the signs and symptoms of osteoarthritis and rheumatoid arthritis in adults. Source: Center for Drug Evaluation and Research, U.S. Food and Drug Administration http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=6975
·
Handout on Health: Osteoarthritis Summary: This guide discusses osteoarthritis -- the most common type of arthritis, especially among older individuals. Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=5983
·
New Arthritis Drugs for Rheumatoid Arthritis and Osteoarthritis Summary: This fact sheet discusses arthritis drug by category, including biological response modifiers, disease-modifying antirheumatic drugs, and nonsteroidal anti-inflammatory drugs. Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=6691
44 Osteoarthritis
The NIH Search Utility After browsing the references listed at the beginning of this chapter, you may want to explore the NIH Search Utility. This allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEBSPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to osteoarthritis. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html.
Additional Web Sources A number of Web sites that often link to government sites are available to the public. These can also point you in the direction of essential information. The following is a representative sample: ·
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
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drkoop.comÒ: http://www.drkoop.com/conditions/ency/index.html
·
Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
·
Med Help International: http://www.medhelp.org/HealthTopics/A.html
·
Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
·
Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
·
WebMDÒHealth: http://my.webmd.com/health_topics
Vocabulary Builder The material in this chapter may have contained a number of unfamiliar words. The following Vocabulary Builder introduces you to terms used in this chapter that have not been covered in the previous chapter:
Guidelines 45
Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. [NIH] Aerobic: 1. Having molecular oxygen present. 2. Growing, living, or occurring in the presence of molecular oxygen. 3. Requiring oxygen for respiration. [EU] Alloys: A mixture of metallic elements or compounds with other metallic or metalloid elements in varying proportions. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Antibiotic: A chemical substance produced by a microorganism which has the capacity, in dilute solutions, to inhibit the growth of or to kill other microorganisms. Antibiotics that are sufficiently nontoxic to the host are used as chemotherapeutic agents in the treatment of infectious diseases of man, animals and plants. [EU] Anticoagulants: Agents that prevent blood clotting. Naturally occurring agents in the blood are included only when they are used as drugs. [NIH] Anxiety: The unpleasant emotional state consisting of psychophysiological responses to anticipation of unreal or imagined danger, ostensibly resulting from unrecognized intrapsychic conflict. Physiological concomitants include increased heart rate, altered respiration rate, sweating, trembling, weakness, and fatigue; psychological concomitants include feelings of impending danger, powerlessness, apprehension, and tension. [EU] Aspiration: The act of inhaling. [EU] Bursitis: Inflammation of a bursa, occasionally accompanied by a calcific deposit in the underlying supraspinatus tendon; the most common site is the subdeltoid bursa. [EU] Chondrocytes: Polymorphic cells that form cartilage. [NIH] Chronic: Persisting over a long period of time. [EU] Collagen: The protein substance of the white fibres (collagenous fibres) of skin, tendon, bone, cartilage, and all other connective tissue; composed of molecules of tropocollagen (q.v.), it is converted into gelatin by boiling. collagenous pertaining to collagen; forming or producing collagen. [EU] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Contracture: A condition of fixed high resistance to passive stretch of a muscle, resulting from fibrosis of the tissues supporting the muscles or the joints, or from disorders of the muscle fibers. [EU] Doxycycline:
A synthetic tetracycline derivative with a range of
46 Osteoarthritis
antimicrobial activity and mode of action similar to that of tetracycline, but more effective against many species. Animal studies suggest that it may cause less tooth staining than other tetracyclines. [NIH] Enzyme: A protein molecule that catalyses chemical reactions of other substances without itself being destroyed or altered upon completion of the reactions. Enzymes are classified according to the recommendations of the Nomenclature Committee of the International Union of Biochemistry. Each enzyme is assigned a recommended name and an Enzyme Commission (EC) number. They are divided into six main groups; oxidoreductases, transferases, hydrolases, lyases, isomerases, and ligases. [EU] Estrogens: A class of sex hormones associated with the development and maintenance of secondary female sex characteristics and control of the cyclical changes in the reproductive cycle. They are also required for pregnancy maintenance and have an anabolic effect on protein metabolism and water retention. [NIH] Gastrointestinal: Pertaining to or communicating with the stomach and intestine, as a gastrointestinal fistula. [EU] Gout: Hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Irritants: Drugs that act locally on cutaneous or mucosal surfaces to produce inflammation; those that cause redness due to hyperemia are rubefacients; those that raise blisters are vesicants and those that penetrate sebaceous glands and cause abscesses are pustulants; tear gases and mustard gases are also irritants. [NIH] Ketoprofen: An ibuprofen-type anti-inflammatory analgesic and antipyretic. It is used in the treatment of rheumatoid arthritis and osteoarthritis. [NIH] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH]
Membrane: A thin layer of tissue which covers a surface, lines a cavity or divides a space or organ. [EU] Osteoporosis: Reduction in the amount of bone mass, leading to fractures after minimal trauma. [EU] Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] Proteoglycans:
Glycoproteins which have a very high polysaccharide
Guidelines 47
content. [NIH] Rheumatology: A subspecialty of internal medicine concerned with the study of inflammatory or degenerative processes and metabolic derangement of connective tissue structures which pertain to a variety of musculoskeletal disorders, such as arthritis. [NIH] Spondylitis: Inflammation of the vertebrae. [EU] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Synovial: Of pertaining to, or secreting synovia. [EU] Systemic: Pertaining to or affecting the body as a whole. [EU] Tendinitis: Inflammation of tendons and of tendon-muscle attachments. [EU] Topical: Pertaining to a particular surface area, as a topical anti-infective applied to a certain area of the skin and affecting only the area to which it is applied. [EU] Ulcer: A local defect, or excavation, of the surface of an organ or tissue; which is produced by the sloughing of inflammatory necrotic tissue. [EU] Urinalysis: Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. [NIH]
Seeking Guidance 49
CHAPTER 2. SEEKING GUIDANCE Overview Some patients are comforted by the knowledge that a number of organizations dedicate their resources to helping people with osteoarthritis. These associations can become invaluable sources of information and advice. Many associations offer aftercare support, financial assistance, and other important services. Furthermore, healthcare research has shown that support groups often help people to better cope with their conditions.10 In addition to support groups, your physician can be a valuable source of guidance and support. Therefore, finding a physician that can work with your unique situation is a very important aspect of your care. In this chapter, we direct you to resources that can help you find patient organizations and medical specialists. We begin by describing how to find associations and peer groups that can help you better understand and cope with osteoarthritis. The chapter ends with a discussion on how to find a doctor that is right for you.
Associations and Osteoarthritis As mentioned by the Agency for Healthcare Research and Quality, sometimes the emotional side of an illness can be as taxing as the physical side.11 You may have fears or feel overwhelmed by your situation. Everyone has different ways of dealing with disease or physical injury. Your attitude, your expectations, and how well you cope with your condition can all Churches, synagogues, and other houses of worship might also have groups that can offer you the social support you need. 11 This section has been adapted from http://www.ahcpr.gov/consumer/diaginf5.htm. 10
50 Osteoarthritis
influence your well-being. This is true for both minor conditions and serious illnesses. For example, a study on female breast cancer survivors revealed that women who participated in support groups lived longer and experienced better quality of life when compared with women who did not participate. In the support group, women learned coping skills and had the opportunity to share their feelings with other women in the same situation. In addition to associations or groups that your doctor might recommend, we suggest that you consider the following list (if there is a fee for an association, you may want to check with your insurance provider to find out if the cost will be covered): ·
Arthritis Foundation of Australia Address: 33 Bligh Street, Suite 902A, Sydney, New South Wales, 2000, Australia Telephone: 02 221 2456 Fax: 02 232 2538 Web Site: http://www.span.com.au/arthritis/ Background: The Arthritis Foundation of Australia is a not-for-profit organization that is committed to providing care, education, and research for people affected by arthritis and other musculoskeletal disorders. The term arthritis, meaning inflammation of the joints, may encompass several conditions or disease states, such as osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, gout, and others. The Arthritis Foundation of Australia, which was founded in 1949, is dedicated to promoting research into the causes, control, and cure of arthritis; supporting the professional education and training of physicians and allied health professionals; and enhancing community awareness of the needs of those affected by arthritis. The Foundation's additional objectives include representing people with arthritis nationally and internationally, serving as national secretariat of affiliated state and territory foundations, and assisting affiliated foundations in promoting self-management programs for people with arthritis. The Arthritis Foundation of Australia currently consists of eight state and territory affiliates. These affiliated foundations offer a wide range of services to their members and represent their interests to their own state and territory governments. Each affiliated foundation may also provide the addresses of a wide network of branches and self-help groups in each state. Relevant area(s) of interest: Gout, Osteoarthritis, Reiter's Syndrome
Seeking Guidance 51
·
Back Pain Association of America, Inc. Address: P.O. Box 135, Pasadena, MD 21123-0135 Telephone: (410) 255-3633 Fax: (410) 255- 7338 Email:
[email protected] Background: The Back Pain Association of America, Inc. (BPAA) is a national nonprofit organization dedicated to providing information and support to people who are affected by back and neck pain, their family members, friends, and health care professionals. Established in 1991 and consisting of nearly 4,000 members, BPAA offers programs and information to help affected individuals learn more about their spinal disorders and ways to cope with them. The organization also has a program to help individuals prevent back injuries. BPAA publishes a self-titled quarterly newsletter that helps readers stay informed of updated information and new forms of treatment. The organization's 'Friends Across America' networking program enables affected individuals to exchange information and support via telephone. BPAA also has a physician referral service as well as an information service for physicians who treat back and neck pain. In addition, the Association also promotes research and offers a variety of fact sheets including 'The Relationship Between Nerve Damage and Leg Pain,' 'Urinary Problems and Diseases of the Spine,' 'Arachnoiditis, Questions and Answers,' and 'A Guide to Abdominal and Stretching Exercises.'. Relevant area(s) of interest: Fibromyalgia, Osteoarthritis, Reiter's Syndrome
Finding More Associations There are a number of directories that list additional medical associations that you may find useful. While not all of these directories will provide different information than what is listed above, by consulting all of them, you will have nearly exhausted all sources for patient associations.
The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about osteoarthritis. For more information, see the NHIC’s Web site at
52 Osteoarthritis
http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797.
DIRLINE A comprehensive source of information on associations is the DIRLINE database maintained by the National Library of Medicine. The database comprises some 10,000 records of organizations, research centers, and government institutes and associations which primarily focus on health and biomedicine. DIRLINE is available via the Internet at the following Web site: http://dirline.nlm.nih.gov/. Simply type in “osteoarthritis” (or a synonym) or the name of a topic, and the site will list information contained in the database on all relevant organizations.
The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “osteoarthritis”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” By making these selections and typing in “osteoarthritis” (or synonyms) into the “For these words:” box, you will only receive results on organizations dealing with osteoarthritis. You should check back periodically with this database since it is updated every 3 months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by specific diseases. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “osteoarthritis” (or a synonym) in the search box, and click “Submit Query”.
Seeking Guidance 53
Online Support Groups In addition to support groups, commercial Internet service providers offer forums and chat rooms for people with different illnesses and conditions. WebMDÒ, for example, offers such a service at their Web site: http://boards.webmd.com/roundtable. These online self-help communities can help you connect with a network of people whose concerns are similar to yours. Online support groups are places where people can talk informally. If you read about a novel approach, consult with your doctor or other healthcare providers, as the treatments or discoveries you hear about may not be scientifically proven to be safe and effective.
Finding Doctors One of the most important aspects of your treatment will be the relationship between you and your doctor or specialist. All patients with osteoarthritis must go through the process of selecting a physician. While this process will vary from person to person, the Agency for Healthcare Research and Quality makes a number of suggestions, including the following:12 ·
If you are in a managed care plan, check the plan's list of doctors first.
·
Ask doctors or other health professionals who work with doctors, such as hospital nurses, for referrals.
·
Call a hospital’s doctor referral service, but keep in mind that these services usually refer you to doctors on staff at that particular hospital. The services do not have information on the quality of care that these doctors provide.
·
Some local medical societies offer lists of member doctors. Again, these lists do not have information on the quality of care that these doctors provide.
Additional steps you can take to locate doctors include the following: ·
Check with the associations listed earlier in this chapter.
·
Information on doctors in some states is available on the Internet at http://www.docboard.org. This Web site is run by “Administrators in Medicine,” a group of state medical board directors.
This section has been adapted from the AHRQ: http://www.ahrq.gov/consumer/qntascii/qntdr.htm.
12
54 Osteoarthritis
·
The American Board of Medical Specialties can tell you if your doctor is board certified. “Certified” means that the doctor has completed a training program in a specialty and has passed an exam, or “board,” to assess his or her knowledge, skills, and experience to provide quality patient care in that specialty. Primary care doctors may also be certified as specialists. The AMBS Web site is located at 13 http://www.abms.org/newsearch.asp. You can also contact the ABMS by phone at 1-866-ASK-ABMS.
·
You can call the American Medical Association (AMA) at 800-665-2882 for information on training, specialties, and board certification for many licensed doctors in the United States. This information also can be found in “Physician Select” at the AMA's Web site: http://www.amaassn.org/aps/amahg.htm.
Finding a Rheumatologist The American College of Rheumatology (ACR) maintains a geographic directory of member physicians called “Find a Rheumatologist.” To access this database, log on to http://www.rheumatology.org/directory/geo.asp. You will be given the option to search for a rheumatologist by name, by U.S. State, or by country. To contact the ACR, you can use the following information: American College of Rheumatology 1800 Century Place, Suite 250 Atlanta, GA 30345 Phone: (404) 633-3777 Fax: (404) 633-1870 E-mail:
[email protected] If the previous sources did not meet your needs, you may want to log on to the Web site of the National Organization for Rare Disorders (NORD) at http://www.rarediseases.org/. NORD maintains a database of doctors with expertise in various rare diseases. The Metabolic Information Network (MIN), 800-945-2188, also maintains a database of physicians with expertise in various metabolic diseases.
While board certification is a good measure of a doctor's knowledge, it is possible to receive quality care from doctors who are not board certified.
13
Seeking Guidance 55
Selecting Your Doctor14 When you have compiled a list of prospective doctors, call each of their offices. First, ask if the doctor accepts your health insurance plan and if he or she is taking new patients. If the doctor is not covered by your plan, ask yourself if you are prepared to pay the extra costs. The next step is to schedule a visit with your chosen physician. During the first visit you will have the opportunity to evaluate your doctor and to find out if you feel comfortable with him or her. Ask yourself, did the doctor: ·
Give me a chance to ask questions about osteoarthritis?
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Really listen to my questions?
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Answer in terms I understood?
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Show respect for me?
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Ask me questions?
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Make me feel comfortable?
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Address the health problem(s) I came with?
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Ask me my preferences about different kinds of treatments for osteoarthritis?
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Spend enough time with me?
Trust your instincts when deciding if the doctor is right for you. But remember, it might take time for the relationship to develop. It takes more than one visit for you and your doctor to get to know each other.
Working with Your Doctor15 Research has shown that patients who have good relationships with their doctors tend to be more satisfied with their care and have better results. Here are some tips to help you and your doctor become partners: ·
You know important things about your symptoms and your health history. Tell your doctor what you think he or she needs to know.
·
It is important to tell your doctor personal information, even if it makes you feel embarrassed or uncomfortable.
14 This
section has been adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm. 15 This section has been adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm.
56 Osteoarthritis
·
Bring a “health history” list with you (and keep it up to date).
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Always bring any medications you are currently taking with you to the appointment, or you can bring a list of your medications including dosage and frequency information. Talk about any allergies or reactions you have had to your medications.
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Tell your doctor about any natural or alternative medicines you are taking.
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Bring other medical information, such as x-ray films, test results, and medical records.
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Ask questions. If you don't, your doctor will assume that you understood everything that was said.
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Write down your questions before your visit. List the most important ones first to make sure that they are addressed.
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Consider bringing a friend with you to the appointment to help you ask questions. This person can also help you understand and/or remember the answers.
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Ask your doctor to draw pictures if you think that this would help you understand.
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Take notes. Some doctors do not mind if you bring a tape recorder to help you remember things, but always ask first.
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Let your doctor know if you need more time. If there is not time that day, perhaps you can speak to a nurse or physician assistant on staff or schedule a telephone appointment.
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Take information home. Ask for written instructions. Your doctor may also have brochures and audio and videotapes that can help you.
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After leaving the doctor's office, take responsibility for your care. If you have questions, call. If your symptoms get worse or if you have problems with your medication, call. If you had tests and do not hear from your doctor, call for your test results. If your doctor recommended that you have certain tests, schedule an appointment to get them done. If your doctor said you should see an additional specialist, make an appointment.
By following these steps, you will enhance the relationship you will have with your physician.
Seeking Guidance 57
Broader Health-Related Resources In addition to the references above, the NIH has set up guidance Web sites that can help patients find healthcare professionals. These include:16 ·
Caregivers: http://www.nlm.nih.gov/medlineplus/caregivers.html
·
Choosing a Doctor or Healthcare Service: http://www.nlm.nih.gov/medlineplus/choosingadoctororhealthcareserv ice.html
·
Hospitals and Health Facilities: http://www.nlm.nih.gov/medlineplus/healthfacilities.html
You can access this information at: http://www.nlm.nih.gov/medlineplus/healthsystem.html.
16
Clinical Trials 59
CHAPTER 3. CLINICAL TRIALS AND OSTEOARTHRITIS Overview Very few medical conditions have a single treatment. The basic treatment guidelines that your physician has discussed with you, or those that you have found using the techniques discussed in Chapter 1, may provide you with all that you will require. For some patients, current treatments can be enhanced with new or innovative techniques currently under investigation. In this chapter, we will describe how clinical trials work and show you how to keep informed of trials concerning osteoarthritis.
What Is a Clinical Trial?17 Clinical trials involve the participation of people in medical research. Most medical research begins with studies in test tubes and on animals. Treatments that show promise in these early studies may then be tried with people. The only sure way to find out whether a new treatment is safe, effective, and better than other treatments for osteoarthritis is to try it on patients in a clinical trial.
The discussion in this chapter has been adapted from the NIH and the NEI: www.nei.nih.gov/netrials/ctivr.htm.
17
60 Osteoarthritis
What Kinds of Clinical Trials Are There? Clinical trials are carried out in three phases: ·
Phase I. Researchers first conduct Phase I trials with small numbers of patients and healthy volunteers. If the new treatment is a medication, researchers also try to determine how much of it can be given safely.
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Phase II. Researchers conduct Phase II trials in small numbers of patients to find out the effect of a new treatment on osteoarthritis.
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Phase III. Finally, researchers conduct Phase III trials to find out how new treatments for osteoarthritis compare with standard treatments already being used. Phase III trials also help to determine if new treatments have any side effects. These trials--which may involve hundreds, perhaps thousands, of people--can also compare new treatments with no treatment. How Is a Clinical Trial Conducted?
Various organizations support clinical trials at medical centers, hospitals, universities, and doctors' offices across the United States. The “principal investigator” is the researcher in charge of the study at each facility participating in the clinical trial. Most clinical trial researchers are medical doctors, academic researchers, and specialists. The “clinic coordinator” knows all about how the study works and makes all the arrangements for your visits. All doctors and researchers who take part in the study on osteoarthritis carefully follow a detailed treatment plan called a protocol. This plan fully explains how the doctors will treat you in the study. The “protocol” ensures that all patients are treated in the same way, no matter where they receive care. Clinical trials are controlled. This means that researchers compare the effects of the new treatment with those of the standard treatment. In some cases, when no standard treatment exists, the new treatment is compared with no treatment. Patients who receive the new treatment are in the treatment group. Patients who receive a standard treatment or no treatment are in the “control” group. In some clinical trials, patients in the treatment group get a new medication while those in the control group get a placebo. A placebo is a harmless substance, a “dummy” pill, that has no effect on osteoarthritis. In other clinical trials, where a new surgery or device (not a medicine) is being tested, patients in the control group may receive a “sham treatment.” This treatment, like a placebo, has no effect on osteoarthritis and does not harm patients.
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Researchers assign patients “randomly” to the treatment or control group. This is like flipping a coin to decide which patients are in each group. If you choose to participate in a clinical trial, you will not know which group you will be appointed to. The chance of any patient getting the new treatment is about 50 percent. You cannot request to receive the new treatment instead of the placebo or sham treatment. Often, you will not know until the study is over whether you have been in the treatment group or the control group. This is called a “masked” study. In some trials, neither doctors nor patients know who is getting which treatment. This is called a “double masked” study. These types of trials help to ensure that the perceptions of the patients or doctors will not affect the study results. Natural History Studies Unlike clinical trials in which patient volunteers may receive new treatments, natural history studies provide important information to researchers on how osteoarthritis develops over time. A natural history study follows patient volunteers to see how factors such as age, sex, race, or family history might make some people more or less at risk for osteoarthritis. A natural history study may also tell researchers if diet, lifestyle, or occupation affects how a disease or disorder develops and progresses. Results from these studies provide information that helps answer questions such as: How fast will a disease or disorder usually progress? How bad will the condition become? Will treatment be needed? What Is Expected of Patients in a Clinical Trial? Not everyone can take part in a clinical trial for a specific disease or disorder. Each study enrolls patients with certain features or eligibility criteria. These criteria may include the type and stage of disease or disorder, as well as, the age and previous treatment history of the patient. You or your doctor can contact the sponsoring organization to find out more about specific clinical trials and their eligibility criteria. If you are interested in joining a clinical trial, your doctor must contact one of the trial's investigators and provide details about your diagnosis and medical history. If you participate in a clinical trial, you may be required to have a number of medical tests. You may also need to take medications and/or undergo surgery. Depending upon the treatment and the examination procedure, you may be required to receive inpatient hospital care. Or, you may have to
62 Osteoarthritis
return to the medical facility for follow-up examinations. These exams help find out how well the treatment is working. Follow-up studies can take months or years. However, the success of the clinical trial often depends on learning what happens to patients over a long period of time. Only patients who continue to return for follow-up examinations can provide this important long-term information.
Recent Trials on Osteoarthritis The National Institutes of Health and other organizations sponsor trials on various diseases and disorders. Because funding for research goes to the medical areas that show promising research opportunities, it is not possible for the NIH or others to sponsor clinical trials for every disease and disorder at all times. The following lists recent trials dedicated to osteoarthritis.18 If the trial listed by the NIH is still recruiting, you may be eligible. If it is no longer recruiting or has been completed, then you can contact the sponsors to learn more about the study and, if published, the results. Further information on the trial is available at the Web site indicated. Please note that some trials may no longer be recruiting patients or are otherwise closed. Before contacting sponsors of a clinical trial, consult with your physician who can help you determine if you might benefit from participation. ·
Acupuncture Safety/Efficacy in Knee Osteoarthritis Condition(s): Osteoarthritis, Knee Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Complementary and Alternative Medicine (NCCAM) Purpose - Excerpt: The goal of this research is to determine the efficacy and safety of Traditional Chinese Acupuncture (TCA) in patients with osteoarthritis of the knee. A three arm randomized controlled trial (RCT) using sham TCA, true TCA, and an education/attention comparison group with a total sample of 525 is proposed. Primary hypothesis to be tested is that patients randomized to true TCA will have significantly more improvement in pain and function as measured by the Womac Pain & Function Scales and patient global assessments than patients randomized to the sham acupuncture and education/attention control groups. Secondary aims of the study are to 1) determine if improvement with TCA differs between patients below age 65 vs. those aged 65 and above, 2) to determine if improvement with TCA differs by racial/ethnic
18
These are listed at www.ClinicalTrials.gov.
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group (ie., Caucasian, Black, Hispanic), and 3) to determine if improvement with TCA differs by stage of radiographic severity of knee OA at baseline (KL grade 2, 3 or 4) Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00010946;jsessionid=46A2D C309B3A8ECA85AA147CF4449B37 ·
Aerobic Exercise Intervention for Knee Osteoarthritis Condition(s): Osteoarthritis Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: This trial will test if walking or bicycling exercise is effective as a non-surgical treatment option for patients with knee osteoarthritis. Study Type: Interventional Contact(s): Kenton R. Kaufman, Ph.D., P.E.: 507-284-2262,
[email protected]; Christine Hughes: 507-266-0985,
[email protected]; Mayo Clinic, Rochester, Minnesota, 55905, United States Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00049816;jsessionid=46A2D C309B3A8ECA85AA147CF4449B37
·
Efficacy and Safety of PG-530742 in the treatment of Mild to Moderate Knee Osteoarthritis Condition(s): Osteoarthritis, Knee Study Status: This study is currently recruiting patients. Sponsor(s): Procter & Gamble Pharmaceuticals Purpose - Excerpt: Matrix metalloproteinases have been implicated in the cartilage degradation that occurs in osteoarthritis. PG-530742 inhibits some of these matrix metalloproteinases, thus potentially limiting cartilage degradation and disease progression. This study will test the efficacy and safety of PG-530742 in the treatment of mild to moderate knee osteoarthritis.
64 Osteoarthritis
Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00041756;jsessionid=46A2D C309B3A8ECA85AA147CF4449B37 ·
Efficacy of Acupuncture with Physical Therapy for Knee OsteoArthritis Condition(s): Osteoarthritis Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Complementary and Alternative Medicine (NCCAM) Purpose - Excerpt: This study will examine the efficacy of acupuncture in combination with exercise physical therapy for moderate osteoarthritis (OA) of the knee. Phase(s): Phase III Study Type: Interventional Contact(s): Patricia Williams, RN-C: (215) 898-3038
[email protected]; Penn Therapy and Fitness, Philadelphia, Pennsylvania, 19104, United States. Study Chairs or Principal Investigators: John T. Farrar, MD, MSCE, Principal Investigator; University of Pennsylvania; Erin McMenamin, MSN, CRNP, Study Director; University of Pennsylvania Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00035399;jsessionid=46A2D C309B3A8ECA85AA147CF4449B37
·
Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT) Condition(s): knee pain; Osteoarthritis Study Status: This study is currently recruiting patients. Sponsor(s): Department of Veterans Affairs; Department of Veterans Affairs Cooperative Studies Program; National Institutes of Health (NIH); National Center for Complementary and Alternative Medicine (NCCAM) Purpose - Excerpt: This study will determine whether glucosamine, chondroitin sulfate and/or the combination of glucosamine and chondroitin sulfate are more effective than placebo and whether the
Clinical Trials 65
combination is more effective than glucosamine or chondroitin sulfate alone in the treatment of knee pain associated with osteoarthritis (OA) of the knee. These substances, marketed in the United States as nutritional supplements, have been widely touted by the lay press and by anecdotal personal experience as effective in treating OA. To date, however, only a few small studies have been published in the worldwide literature. The study proposed herein has been carefully constructed to definitively determine the efficacy of these agents. Phase(s): Phase III Study Type: Interventional Contact(s): See Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00032890;jsessionid=46A2D C309B3A8ECA85AA147CF4449B37 ·
Prevention of Post-Traumatic Osteoarthritis (OA) Condition(s): Osteoarthritis Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: Joint injury and trauma dramatically increase the risk of developing osteoarthritis (OA). The purpose of this study is to determine what factors lead to decreased pain, improved joint function, and repair of the joint surface in post-traumatic OA. Study Type: Interventional Contact(s): See Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00054821;jsessionid=46A2D C309B3A8ECA85AA147CF4449B37
·
Shoe Insert Study Condition(s): Osteoarthritis, Knee Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: This trial will test shoe inserts for the treatment of knee osteoarthritis, the most common form of knee arthritis. Those with disease on the inner (medial) aspect of the knee will be studied.
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Phase(s): Phase III Study Type: Interventional Contact(s): Boston University Medical Center, Boston, Massachusetts, 02118, United States; Joyce P. Goggins, M.P.H.: 617-638-4462,
[email protected]; Kristin Baker, Ph.D.: 617-638-5452,
[email protected] Principal Investigator: David T. Felson, M.D., M.P.H. Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00032240;jsessionid=46A2D C309B3A8ECA85AA147CF4449B37 ·
Doxycycline and OA Progression Condition(s): Osteoarthritis Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); National Institute on Aging (NIA) Purpose - Excerpt: This study will determine whether doxycycline decreases the severity or rate of progression of osteoarthritis (OA) in the knee. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most popular agents used to treat OA, but elderly women, in whom OA is especially common, are at greatest risk of developing serious side effects from NSAIDs. Our study targets overweight middle-aged women who have OA in one knee. Half of the 432 study participants will receive the treatment (doxycycline) and half will receive a placebo (inactive pill). Treatment with doxycycline (or placebo) will last 30 months, and participants and researchers will not know who is receiving doxycycline and who is receiving placebo until the end of the study. We will look for narrowing of the joint space in the knee that was not affected by OA at the start of the study. Joint space narrowing is a sign of OA. We will also use questionnaires to evaluate participants' symptoms and functioning. Phase(s): Phase III Study Type: Interventional Contact(s): See Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00000403;jsessionid=46A2D C309B3A8ECA85AA147CF4449B37
·
Effects of Strength Training on Knee Osteoarthritis Condition(s): Osteoarthritis, Knee
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Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: To understand the effects of leg strengthening exercise, we will study the effects of strength training of the legs in four groups of people: (1) osteoarthritis (OA) with knee pain; (2) OA without knee pain; (3) no OA but elderly with knee pain; and (4) normal elderly with no OA or knee pain. In each of the first three groups, we will look at whether people who do strength training have less pain and/or slower progression of x-ray signs of OA over 30 months than people who perform nonstrengthening, range-of-motion exercises. We are including the fourth group to find out whether people with OA (groups 1 & 2) have the same response to strength training as healthy elderly people, and whether those with knee pain (groups 1 & 3) have the same response to training as those without joint pain. Phase(s): Phase II Study Type: Interventional Contact(s): National Institute for Fitness and Sport, Indianapolis, Indiana, 46202, United States. Study chairs or principal investigators: Alan Mikesky, Ph.D.; Indiana University School of Medicine Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00000406;jsessionid=46A2D C309B3A8ECA85AA147CF4449B37 ·
Impact of Exercise on Older Persons with Osteoarthritis Condition(s): Osteoarthritis Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); National Institute on Aging (NIA) Purpose - Excerpt: Previous studies have found that exercise can reduce pain, improve endurance for physical activities, and improve cardiovascular fitness over time. However, these studies have not looked at the impact of exercise programs for older adults with osteoarthritis or at how long older adults continue exercising after a program is finished. This study will look at the long-term effects of a structured exercise program for people aged 60 or older who have osteoarthritis of the hip or knee. One goal of the exercise program is to encourage older people with osteoarthritis to continue exercising. We will randomly assign study participants to either the exercise program or a control group that does
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not do the exercise program. We will monitor participants at the start of the study, at 8 weeks, and every 3 months for 2 years after the program is completed. The exercise program lasts for 8 weeks and includes an exercise part and an educational part led by trained physical therapists. We believe that participants in the treatment (exercise) group will show higher rates of continued exercise and higher functional status over time compared to the group of people who do not participate in the exercise program. Phase(s): Phase II Study Type: Interventional Contact(s): Illinois; North Park Village, Chicago, Illinois, 60646, United States; Bernard Horwich Jewish Community Center, Chicago, Illinois, 60659, United States. Study chairs or principal investigators: Susan Hughes, Principal Investigator; Center for Research on Health and Aging Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00000434;jsessionid=46A2D C309B3A8ECA85AA147CF4449B37 ·
Effects of Comprehensive Care for Knee OA Condition(s): Osteoarthritis Study Status: This study is completed. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: We will study 300 people with knee osteoarthritis (OA) who receive their medical care from a large health maintenance organization (HMO) in Indianapolis. Our study will evaluate a comprehensive plan for treatment of knee OA by primary care physicians. Primary care physicians will provide standard care for knee OA to half of the study participants (150 people), and will use the comprehensive treatment plan guidelines to treat the other half. The comprehensive plan includes careful use of medications along with nondrug approaches such as patient education, exercise, and social support. People who participate in the study will receive care for knee OA for 1 year. We will measure the results (outcomes) of treatment at the start of the study and at 3 months, 6 months, and 12 months after patients join the study. The results we will measure include joint pain, physical function, drug side effects, quality of life, satisfaction with OA care, and the cost of medical care. Phase(s): Phase II Study Type: Interventional
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Contact(s): Long Hospital, Room 545, Indianapolis, Indiana, 46202-5103, United States. Study Chairs or Principal Investigators: Steven A. Mazzuca, Ph.D.; Indiana University School of Medicine Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00000404;jsessionid=46A2D C309B3A8ECA85AA147CF4449B37 ·
Genetic and Immune Studies of Rheumatoid Arthritis and Related Conditions Condition(s): Arthritis, Psoriatic; Autoimmune Diseases; Joint Diseases; Osteoarthritis; Rheumatoid Arthritis Study Status: This study is completed. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: This protocol will examine blood, synovial fluid and synovial tissue from patients with rheumatoid arthritis and other chronic inflammatory joint diseases to study genetic and immunologic factors involved in the cause, development and progression of these conditions. Synovial fluid is the lubricating fluid in joints. The synovial membrane is a delicate tissue lining the inner surface of joints, which, in arthritic conditions, thickens and becomes infiltrated with various types of cells. Patients with rheumatoid arthritis and certain patients with other forms of arthritis may be eligible for this study. Those enrolled will be followed periodically for follow-up and disease evaluation. They may undergo the following procedures: 1. Synovial fluid aspiration, when medically indicated (for example, for joint swelling and inflammation). For this procedure, an area of skin around the joint is numbed with an anesthetic, and a needle is inserted into the joint to withdraw a small fluid sample. 2. Periodic blood sampling, not to exceed 450 milliliters (15 ounces) during any 6-week period, for genetic studies of rheumatoid arthritis. The samples are usually taken at the same times that synovial fluid is withdrawn. 3. Synovial tissues, collected by needle biopsy or during surgical procedures for arthroscopy (examination of the interior of the joint and repair of the joint) or total joint replacement. For the needle biopsy, the skin over the biopsy site is washed and anesthetized. A needle is inserted and fluid is aspirated. The biopsy needle is then inserted through the outer needle and a tissue sample is suctioned. Patients who qualify for other research studies may be invited to participate. Study Type: Observational
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Contact(s): Maryland; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), 9000 Rockville Pike, Bethesda, Maryland, 20892, United States Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00001291;jsessionid=46A2D C309B3A8ECA85AA147CF4449B37 ·
Muscle Strengthening Device for Knee Osteoarthritis Condition(s): Osteoarthritis Study Status: This study is completed. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: Studies have shown that isometric strengthening helps people with osteoarthritis of the knee. Isometric strengthening is musclestrengthening exercise without movement, in which a person applies a force against a resistant object--for example, pushing against a brick wall. This study will test the effectiveness of a portable isometric exercise device for home use that guides a person through an exercise program using various forms of feedback. We will look at whether people exercising with the device achieve better outcomes (results) in pain, stiffness, strength, and functional measures compared to people who do not use the device or people exercising according to printed material from arthritis organizations. Phase(s): Phase II Study Type: Interventional Contact(s): See Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00007241;jsessionid=46A2D C309B3A8ECA85AA147CF4449B37
·
Patient Education in Rheumatoid Arthritis and Osteoarthritis Condition(s): Rheumatoid Arthritis; Osteoarthritis Study Status: This study is completed. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: This project will evaluate the effectiveness and general usefulness of two arthritis patient education programs. The first, the Arthritis Self-Management Program, is a 6-week, community-based
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program taught in small groups by peer leaders. The second, the SelfManaged Arthritis Relief Therapy (SMART) Program, is a computerdriven program delivered through the mail. Participants in this project are people with rheumatoid arthritis or osteoarthritis who are taking part in the larger long-term studies being conducted by ARAMIS (the Arthritis, Rheumatism and Aging Medical Information System). Phase(s): Phase III Study Type: Interventional Contact(s): California; Stanford University, Palo Alto, California, 94305, United States; Kansas; Wichita Arthritis Center, Wichita, Kansas, United States; Pennsylvania; University of Pittsburgh, Pittsburgh, Pennsylvania, United States; Tennessee; Vanderbilt University, Nashville, Tennessee, United States; Canada, Alberta; University of Saskatoon, Edmonton, Alberta, Canada. Study Chairs or Principal Investigators: Kate R. Lorig, Dr.P.H.; Stanford University Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00000414;jsessionid=46A2D C309B3A8ECA85AA147CF4449B37 ·
Prevention of Arthritis-Related Work Disability Condition(s): Rheumatoid Arthritis; Systemic Lupus Erythematosus; Osteoarthritis, Knee; Ankylosing Spondylitis Study Status: This study is completed. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: People with rheumatic disorders (arthritis) often have trouble keeping their jobs. This study will look at whether vocational rehabilitation (VR) will improve the ability of employed people with arthritis to keep their jobs. Job retention VR services target key factors that increase the risk of job loss. They aim to modify jobs to reduce barriers caused by functional limitations and disease symptoms, future career planning, and establish a partnership with a VR counselor for ongoing help. We will conduct the study among patients with rheumatic disorders recruited in eastern Massachusetts. We will give 120 study participants job retention services provided by VR counselors. We will give another 120 participants literature about employment- related resources. We will compare the outcomes of the two groups to evaluate the usefulness of job retention services in preventing job loss in people with rheumatic disorders.
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Phase(s): Phase II Study Type: Interventional Contact(s): Boston University School of Medicine, Boston, Massachusetts, 02118, United States. Study Chairs or Principal Investigators: Saralynn J. Allaire, Sc.D.; Boston University School of Medicine Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00000416;jsessionid=46A2D C309B3A8ECA85AA147CF4449B37 ·
Tidal Lavage in Knee Osteoarthritis Condition(s): Osteoarthritis, Knee Study Status: This study is completed. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: This study compared the effects of tidal lavage (washing out) of the knee joint and an imitation lavage procedure in people with knee osteoarthritis. In tidal lavage, the doctor flushes out a knee joint with repeated injections of a mild salt solution, done under local anesthesia. Study participants had to meet standard criteria for diagnosis of osteoarthritis but could have low, medium, or high severity of x-ray changes indicating knee osteoarthritis. We performed the lavage procedure once, and did quarterly followups for 1 year. We permitted patients to use some other osteoarthritis treatments during the study, such as non-narcotic pain relievers, nonsteroidal anti-inflammatory drugs, and physical therapy. Phase(s): Phase II Study Type: Interventional Contact(s): Indiana; Indiana University School of Medicine, Indianapolis, Indiana, 46202, United States. Study Chairs or Principal Investigators: John D. Bradley, M.D.; Indiana University School of Medicine Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00000424;jsessionid=46A2D C309B3A8ECA85AA147CF4449B37
·
Toward Better Outcomes in Osteoarthritis Condition(s): Osteoarthritis
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Study Status: This study is completed. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: This study will determine if there is a difference between commonly used nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen (a pain-reliever that does not prevent inflammation) for treating knee pain in osteoarthritis (OA). The two main results we will look at are disease progression according to x-rays and disability over 3.5 years. Study participants with moderate knee OA and knee pain will continue taking their NSAID or stop taking their NSAID and start taking acetaminophen. Every 6 months we will send the participants questionnaires that ask about pain, medication use, and disability. We will take x-rays of the knees at the start of the study and again at the end of the study. Phase(s): Phase III Study Type: Interventional Contact(s): San Francisco General Hospital, San Francisco, California, 94110, United States. Study Chairs or Principal Investigators: Nancy Lane, M.D., Study Director; UCSF, Division of Rheumatology, SFGH Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00000425;jsessionid=46A2D C309B3A8ECA85AA147CF4449B37
Benefits and Risks19 What Are the Benefits of Participating in a Clinical Trial? If you are interested in a clinical trial, it is important to realize that your participation can bring many benefits to you and society at large: ·
A new treatment could be more effective than the current treatment for osteoarthritis. Although only half of the participants in a clinical trial receive the experimental treatment, if the new treatment is proved to be more effective and safer than the current treatment, then those patients who did not receive the new treatment during the clinical trial may be among the first to benefit from it when the study is over.
This section has been adapted from ClinicalTrials.gov, a service of the National Institutes of Health: http://www.clinicaltrials.gov/ct/gui/c/a1r/info/whatis?JServSessionIdzone_ct=9jmun6f291.
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If the treatment is effective, then it may improve health or prevent diseases or disorders.
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Clinical trial patients receive the highest quality of medical care. Experts watch them closely during the study and may continue to follow them after the study is over.
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People who take part in trials contribute to scientific discoveries that may help other people with osteoarthritis. In cases where certain diseases or disorders run in families, your participation may lead to better care or prevention for your family members. The Informed Consent
Once you agree to take part in a clinical trial, you will be asked to sign an “informed consent.” This document explains a clinical trial's risks and benefits, the researcher’s expectations of you, and your rights as a patient. What Are the Risks? Clinical trials may involve risks as well as benefits. Whether or not a new treatment will work cannot be known ahead of time. There is always a chance that a new treatment may not work better than a standard treatment. There is also the possibility that it may be harmful. The treatment you receive may cause side effects that are serious enough to require medical attention. How Is Patient Safety Protected? Clinical trials can raise fears of the unknown. Understanding the safeguards that protect patients can ease some of these fears. Before a clinical trial begins, researchers must get approval from their hospital's Institutional Review Board (IRB), an advisory group that makes sure a clinical trial is designed to protect patient safety. During a clinical trial, doctors will closely watch you to see if the treatment is working and if you are experiencing any side effects. All the results are carefully recorded and reviewed. In many cases, experts from the Data and Safety Monitoring Committee carefully monitor each clinical trial and can recommend that a study be stopped at any time. You will only be asked to take part in a clinical trial as a volunteer giving informed consent.
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What Are a Patient's Rights in a Clinical Trial? If you are eligible for a clinical trial, you will be given information to help you decide whether or not you want to participate. As a patient, you have the right to: ·
Information on all known risks and benefits of the treatments in the study.
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Know how the researchers plan to carry out the study, for how long, and where.
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Know what is expected of you.
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Know any costs involved for you or your insurance provider.
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Know before any of your medical or personal information is shared with other researchers involved in the clinical trial.
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Talk openly with doctors and ask any questions.
After you join a clinical trial, you have the right to: ·
Leave the study at any time. Participation is strictly voluntary. However, you should not enroll if you do not plan to complete the study.
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Receive any new information about the new treatment.
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Continue to ask questions and get answers.
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Maintain your privacy. Your name will not appear in any reports based on the study.
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Know whether you participated in the treatment group or the control group (once the study has been completed). What about Costs?
In some clinical trials, the research facility pays for treatment costs and other associated expenses. You or your insurance provider may have to pay for costs that are considered standard care. These things may include inpatient hospital care, laboratory and other tests, and medical procedures. You also may need to pay for travel between your home and the clinic. You should find out about costs before committing to participation in the trial. If you have health insurance, find out exactly what it will cover. If you don't have health insurance, or if your insurance company will not cover your costs, talk to the clinic staff about other options for covering the cost of your care.
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What Questions Should You Ask before Deciding to Join a Clinical Trial? Questions you should ask when thinking about joining a clinical trial include the following: ·
What is the purpose of the clinical trial?
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What are the standard treatments for osteoarthritis? Why do researchers think the new treatment may be better? What is likely to happen to me with or without the new treatment?
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What tests and treatments will I need? Will I need surgery? Medication? Hospitalization?
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How long will the treatment last? How often will I have to come back for follow-up exams?
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What are the treatment's possible benefits to my condition? What are the short- and long-term risks? What are the possible side effects?
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Will the treatment be uncomfortable? Will it make me feel sick? If so, for how long?
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How will my health be monitored?
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Where will I need to go for the clinical trial? How will I get there?
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How much will it cost to be in the study? What costs are covered by the study? How much will my health insurance cover?
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Will I be able to see my own doctor? Who will be in charge of my care?
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Will taking part in the study affect my daily life? Do I have time to participate?
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How do I feel about taking part in a clinical trial? Are there family members or friends who may benefit from my contributions to new medical knowledge?
Keeping Current on Clinical Trials Various government agencies maintain databases on trials. The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide patients, family members, and physicians with current information about clinical research across the broadest number of diseases and conditions.
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The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to their Web site (www.clinicaltrials.gov) and search by “osteoarthritis” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: ·
For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/
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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html
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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm
General References The following references describe clinical trials and experimental medical research. They have been selected to ensure that they are likely to be available from your local or online bookseller or university medical library. These references are usually written for healthcare professionals, so you may consider consulting with a librarian or bookseller who might recommend a particular reference. The following includes some of the most readily available references (sorted alphabetically by title; hyperlinks provide rankings, information and reviews at Amazon.com): ·
A Guide to Patient Recruitment : Today's Best Practices & Proven Strategies by Diana L. Anderson; Paperback - 350 pages (2001), CenterWatch, Inc.; ISBN: 1930624115; http://www.amazon.com/exec/obidos/ASIN/1930624115/icongroupinterna
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A Step-By-Step Guide to Clinical Trials by Marilyn Mulay, R.N., M.S., OCN; Spiral-bound - 143 pages Spiral edition (2001), Jones & Bartlett Pub;
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ISBN: 0763715697; http://www.amazon.com/exec/obidos/ASIN/0763715697/icongroupinterna ·
The CenterWatch Directory of Drugs in Clinical Trials by CenterWatch; Paperback - 656 pages (2000), CenterWatch, Inc.; ISBN: 0967302935; http://www.amazon.com/exec/obidos/ASIN/0967302935/icongroupinterna
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The Complete Guide to Informed Consent in Clinical Trials by Terry Hartnett (Editor); Paperback - 164 pages (2000), PharmSource Information Services, Inc.; ISBN: 0970153309; http://www.amazon.com/exec/obidos/ASIN/0970153309/icongroupinterna
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Dictionary for Clinical Trials by Simon Day; Paperback - 228 pages (1999), John Wiley & Sons; ISBN: 0471985961; http://www.amazon.com/exec/obidos/ASIN/0471985961/icongroupinterna
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Extending Medicare Reimbursement in Clinical Trials by Institute of Medicine Staff (Editor), et al; Paperback 1st edition (2000), National Academy Press; ISBN: 0309068886; http://www.amazon.com/exec/obidos/ASIN/0309068886/icongroupinterna
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Handbook of Clinical Trials by Marcus Flather (Editor); Paperback (2001), Remedica Pub Ltd; ISBN: 1901346293; http://www.amazon.com/exec/obidos/ASIN/1901346293/icongroupinterna
Vocabulary Builder The following vocabulary builder gives definitions of words used in this chapter that have not been defined in previous chapters: Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH]
Arthroscopy: Endoscopic examination, therapy and surgery of the joint. [NIH] Biopsy: The removal and examination, usually microscopic, of tissue from the living body, performed to establish precise diagnosis. [EU] Cardiovascular: Pertaining to the heart and blood vessels. [EU] Gait: Manner or style of walking. [NIH]
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PART II: ADDITIONAL RESOURCES AND ADVANCED MATERIAL
ABOUT PART II In Part II, we introduce you to additional resources and advanced research on osteoarthritis. All too often, patients who conduct their own research are overwhelmed by the difficulty in finding and organizing information. The purpose of the following chapters is to provide you an organized and structured format to help you find additional information resources on osteoarthritis. In Part II, as in Part I, our objective is not to interpret the latest advances on osteoarthritis or render an opinion. Rather, our goal is to give you access to original research and to increase your awareness of sources you may not have already considered. In this way, you will come across the advanced materials often referred to in pamphlets, books, or other general works. Once again, some of this material is technical in nature, so consultation with a professional familiar with osteoarthritis is suggested.
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CHAPTER 4. STUDIES ON OSTEOARTHRITIS Overview Every year, academic studies are published on osteoarthritis or related conditions. Broadly speaking, there are two types of studies. The first are peer reviewed. Generally, the content of these studies has been reviewed by scientists or physicians. Peer-reviewed studies are typically published in scientific journals and are usually available at medical libraries. The second type of studies is non-peer reviewed. These works include summary articles that do not use or report scientific results. These often appear in the popular press, newsletters, or similar periodicals. In this chapter, we will show you how to locate peer-reviewed references and studies on osteoarthritis. We will begin by discussing research that has been summarized and is free to view by the public via the Internet. We then show you how to generate a bibliography on osteoarthritis and teach you how to keep current on new studies as they are published or undertaken by the scientific community.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and osteoarthritis, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the
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format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type in “osteoarthritis” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is a sample of what you can expect from this type of search: ·
Osteoarthritis: Diagnosis and Therapeutic Considerations Source: American Family Physician. 65(5): 841-848. March 1, 2002. Contact: Available from American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (800) 274-2237 or (913) 906-6000. E-mail:
[email protected]. Website: www.aafp.org. Summary: This journal article provides health professionals with information on the diagnosis and treatment of osteoarthritis (OA). This common rheumatologic disorder affects men and women equally, but symptoms occur earlier and appear to be more severe in women. Current estimates suggest that 40 million Americans and 70 to 90 percent of persons older than 75 have OA. In addition to age, risk factors include joint injury, obesity, and mechanical stress. The pathophysiology involves a combination of mechanical, cellular, and biochemical processes. The interaction of these processes leads to changes in the composition and mechanical properties of the articular cartilage. The strong association between age and OA may be best explained by age related changes in the matrix composition and a decrease in chondrocyte function and responsiveness to stimuli. These changes can interfere with continued internal remodeling, maintenance of the tissue, and loss of cartilage. This leads to an increased risk for cartilage degradation and injury, including surface defects in the articular cartilage. The abnormal repair process leads to the formation of osteophytes and subchondral cysts as the disease progresses. Diagnosis is largely based on a detailed history and a physical examination because radiographic findings do not always correlate with symptoms. Radiographic findings consistent with OA include joint space narrowing, osteophyte formation, pseudocyst in subchondral bone, and increased density of subchondral bone. Knowledge of the etiology and pathogenesis of the disease process aids in prevention and management. The primary goals of treatment are improved function and quality of life. Acetaminophen and nonsteroidal antiinflammatory drugs remain first line drugs. Agents such as cyclooxygenase 2 inhibitors and sodium hyaluronate joint injections offer
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new treatment alternatives. Use of complementary medications has also increased. Patient education, rehabilitation, exercise, modification of activities of daily living, and surgery are also treatment modalities that should be considered. 1 figure, 6 tables, and 44 references. (AA-M).
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A Controlled Trial of Arthroscopic Surgery for Osteoarthritis of the Knee Source: New England Journal of Medicine. 347(2): 81-88. July 11, 2002. Summary: This journal article provides health professionals with information on a randomized, placebo-controlled trial that assessed the efficacy of arthroscopic surgery of the knee in relieving pain and improving function in patients with osteoarthritis (OA). The study population consisted of 180 patients with knee OA who were randomly assigned to receive arthroscopic debridement, arthroscopic lavage, or placebo surgery. Patients in the placebo group received skin incisions and underwent a simulated debridement without insertion of the arthroscope. Patients and assessors of outcome were blinded to the treatment group assignment. Outcomes were assessed at multiple points over a 24 month period with the use of five self reported scores (three on scales for pain and two on scales for function) and one objective test of walking and stair climbing. A total of 165 patients completed the trial. The study found that at no point did either of the intervention groups report less pain or better function than the placebo group. For example, there was no difference in knee pain between the placebo group and either the lavage group or the debridement group at 1 year or 2 years. Similarly, there was no significant difference in arthritis pain between the placebo group and the lavage group or the debridement group at 1 or 2 years. Furthermore, at no time point did either arthroscopic intervention group have significantly greater improvement in function than the placebo group. For example, there was no significant difference between the placebo group and either the lavage group or the debridement group in the self reported ability to walk and bend at 1 year or at 2 years. In fact, objectively measured walking and stair climbing were poorer in the debridement group than in the placebo group at 2 weeks and 1 year and showed a trend toward worse functioning at 2 years. Lacking evidence of the superiority of the arthroscopic treatments over the placebo procedure in relieving pain or improving function, researchers considered whether the 95 percent confidence intervals for the differences in outcomes between each arthroscopic procedure and the placebo procedure included clinically important differences. At almost all time points during follow up, the confidence intervals excluded the minimal
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important differences used in the study. The article concludes that the outcomes after arthroscopic lavage or arthroscopic debridement were no better than those after a placebo procedure. 2 figures, 3 tables, and 35 references. (AA-M).
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Debridement and Lavage for Osteoarthritis of the Knee Source: New England Journal of Medicine. 347(2): 132-133. July 11, 2002. Summary: This journal article provides health professionals with information on a randomized, placebo-controlled trial that assessed the efficacy of arthroscopic surgery of the knee in relieving pain and improving function in patients with osteoarthritis (OA). The study found no improvement of knee symptoms or knee related function from either arthroscopic debridement or lavage. Among the strengths of this trial are its size, its use of a sham arthroscopy control group with patients and evaluators blinded to the treatment assignment, its limited loss to follow up over a 2 year period, and its use of treatments that are essentially identical to those in widespread use. Weaknesses of the study include its use of an as yet unpublished instrument to measure knee pain, its focus on patients who completed the trial, and its use of a study population consisting mostly of men. The article concludes that the study provides insights into factors that affect and do not affect joint pain and disability over time and suggests that the effects on clinical symptoms of debris in osteoarthritic joints are negligible. 12 references.
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Determining the Efficacy of Glucosamine and Chondroitin for Osteoarthritis Source: Nurse Practitioner, The. 26(6): 44-46,49-52. June 2001. Summary: This journal article provides health professionals with information on the use of glucosamine and chondroitin in the treatment of osteoarthritis (OA). Although OA was once regarded as a simple consequence of aging and cartilage degeneration, researchers now believe that OA may be a group of overlapping diseases rather than a single disorder. The functional properties of articular cartilage are the core of OA pathogenesis. Components of articular cartilage are water, collagen, proteoglycans, chondrocytes, and other matrix components. Over time, the catabolism of proteoglycans and the increased loss of glycosaminoglycans result in the abrasion of cartilage and the formation of new bone within the joint. In healthy people, a balance of cartilage matrix turnover is maintained through synthesis and degradation. The
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failure to maintain this homeostatic balance because of reduced formation or increased catabolism is a possible explanation for OA. Treatment modalities focus on primary and secondary prevention. Primary prevention involves educating patients about joint protection, exercise, weight reduction, and the dangers of repetitive motion. Secondary prevention is mainly palliative and involves both nonpharmacologic and pharmacologic therapies to minimize pain. Glucosamine sulfate and chondroitin sulfate are being used by many patients for the treatment of OA. The article reviews human and animal studies on the use of these agents in treating OA. Despite findings in many of these studies supporting the efficacy of these agents for palliation of joint pain in patients with OA, the American College of Rheumatology Subcommittee on OA believes that it is too early to issue recommendations for use. Currently, the National Institute for Arthritis and Musculoskeletal and Skin Diseases, in collaboration with the National Center for Complementary and Alternative Medicine has begun a pivotal study to thoroughly evaluate these agents. 36 references. (AAM).
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Radiographic Assessment of Osteoarthritis Source: American Family Physician. 64(2): 279-286. July 15, 2001. Contact: American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (800) 274-2237 or (913) 9066000. E-mail:
[email protected]. Website: www.aafp.org. Summary: This journal article provides health professionals with information on the etiology, clinical features, radiographic findings, and disease progression of osteoarthritis (OA). Although OA is common in older adults, its pathology of asymmetric joint cartilage loss, subchondral sclerosis, and marginal osteophytes and subchondral cysts is the same in younger and older adults. OA is primarily diagnosed and assessed through a history and physical examination. The cardinal symptom is pain that worsens during activity and improves with rest. Joint instability is a common finding, especially involving the knees and first carpometacarpal joints. Early morning stiffness is common. Stiffness may also occur following periods of inactivity. Radiographic findings, including asymmetric joint space narrowing, subchondral sclerosis, osteophyte formation, subluxation, and distribution patterns of osteoarthritis changes, can be helpful when the diagnosis is in question. Although followup radiographs are not necessary to evaluate disease progression, they can be helpful if surgical intervention is planned or a fracture is suspected. The article includes guidelines on diagnosing OA of
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the knee, hand, hips, pelvis, spine, and foot. 5 figures, 2 tables, and 20 references. (AA-M).
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Use of Glucosamine and Chondroitin Sulfate in the Management of Osteoarthritis Source: Journal of the American Academy of Orthopaedic Surgeons. 9(2): 71-78. March-April 2001. Summary: This journal article provides health professionals with information on the use of glucosamine and chondroitin sulfate in the management of osteoarthritis (OA). The goals of OA therapy are to decrease pain and to maintain or improve joint function. The pharmacologic treatment of this condition has included the use of aspirin, acetaminophen, and nonsteroidal antiinflammatory drugs. More recently, numerous studies have investigated the potential role of chondroprotective agents, particularly glucosamine and chondroitin sulfate, in repairing articular cartilage and decelerating the degenerative process. Glucosamine is an aminosaccharide that takes part in the synthesis of glycosaminoglycans and proteoglycans by condrocytes. Chondroitin sulfate is a glycosaminoglycan composed of a long, unbranched polysaccharide chain of alternative residues of sulfated or unsulfated residues of glucuronic acid and N-acetylgalactosamine. The reports of limited clinical experience with these two agents, as well as the accompanying publicity in the popular media, have generated controversy. Advocates of these alternative modalities cite reports of progressive and gradual decline of joint pain and tenderness, improved mobility, sustained improvement after drug withdrawal, and a lack of significant toxicity associated with short term use of these agents. Critics point out that in the great majority of the relevant clinical trials, sample sizes were small and follow up was short term. Many unanswered questions remain surrounding the long term effects of these agents, the most effective dosage and route, and product purity. 2 tables and 34 references. (AA-M).
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When To Consider a COX-2 Inhibitor for Osteoarthritis of the Knee Source: JAAPA: Journal of the American Academy of Physician Assistants. 14(3): 13-14. March 2001. Summary: This journal article uses a case study question to provide health professionals with information on the use of cyclooxygenase-2 (COX-2) inhibitors in treating osteoarthritis (OA) of the knee. The patient
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in question is a 64 year old retired schoolteacher who has a history of OA and hypertension. She complains of tenderness and pain in her right knee. She takes nonprescription ibuprofen almost daily but complains that it causes heartburn. She asks about taking the newer COX-2 inhibitors. The article recommends that the patient be given acetaminophen first. Other options include the nonsteroidal antiinflammatory drugs (NSAIDs) etodolac or salsalate, or another agent. If the patient does not tolerate the NSAIDs or they do not relieve her symptoms, one of the COX-2 inhibitors can be considered. Celecoxib is indicated for signs and symptoms of OA, rheumatoid arthritis, and familial adenomatous polyposis, whereas rofecoxib is indicated for acute pain, OA, and primary dysmenorrhea. Although the COX-2 inhibitors have an excellent safety profile, they are quite costly in comparison with NSAIDs. The main adverse effects associated with the COX-2 inhibitors are diarrhea, dyspepsia, nausea, and edema; however, they pose less risk of gastrointestinal bleeding than standard NSAIDs. 1 table and 5 references.
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Glucosamine in the Treatment of Osteoarthritis Source: Rheumatic Disease Clinics of North America. 26(1): 1-11. February 2000. Summary: This journal article provides health professionals with information on the use of glucosamine sulfate in the treatment of osteoarthritis (OA). Glucosamine, an aminomonosaccharide, is found in articular cartilage. Despite its widespread use, little is known about its bioavailability or pharmacokinetics. Various clinical trials have investigated the efficacy of glucosamine sulfate. Available data suggest that glucosamine decreases pain and improves function in OA. Several studies have shown that glucosamine sulfate is as good as ibuprofen for treating OA of the knee. However, most of the glucosamine studies have methodological flaws or used parenteral formulations, making their data difficult to extrapolate into clinical practice. In addition, no data on the long term safety or efficacy of glucosamine are available. Better designed clinical trials of glucosamine are needed to identify its role in the pharmacology of OA. Although glucosamine is frequently sold as a combination product containing chondroitin sulfate, no clinical data are available on the efficacy of the combination. A few studies have compared chondroitin sulfate with placebo or diclofenac sodium OA therapy. Results suggest that chondroitin sulfate may be beneficial. People who chose to take glucosamine should be aware that its safety and efficacy are largely unknown. 1 table and 21 references. (AA M).
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Homeopathy and Rheumatic Disease Source: Rheumatic Disease Clinics of North America. 26(1): 117-123. February 2000. Summary: This journal article provides health professionals with information on the use of homeopathy to treat rheumatic disease. Homeopathy is one of the most frequently sought alternative therapies for treating rheumatic syndromes. Homeopathy was developed by the German physician Samuel Christian Hahnemann in the latter half of the 18th century. There are two main tenets of homeopathy. One is the principle of similars. This principle states that patients with a particular pattern of signs and symptoms can be cured if they are given a drug that produces the same pattern of signs and symptoms when given to a healthy individual. The second tenet in homeopathy is that remedies retain biological activity if they are diluted and agitated or shaken between serial dilutions. This tenet has often led scientists to reject homeopathy out of hand, without looking at evidence for its effects in clinical trials. Unfortunately, the current number of controlled clinical trials on the treatment of rheumatic syndromes with homeopathy is few, and results are mixed. Rheumatic arthritis has been the most studied, and only small studies have been done on osteoarthritis, fibromyalgia, and the myalgias. Overall, it appears that homeopathic remedies work better than a placebo in studies of rheumatic syndromes; however, there are too few studies to draw definitive conclusions about the efficacy of any one type of homeopathic treatment on any one condition. 25 references. (AAM).
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Around-the-Clock, Controlled-Release Oxycodone Therapy for Osteoarthritis-Related Pain Source: Archives of Internal Medicine. 160(6): 853-860. March 27, 2000. Summary: This journal article provides health professionals with information on a study that evaluated the effects of controlled-release oxycodone (OxyContin tablets) treatment on pain and function and its safety versus placebo and in long term use in patients who had moderate to severe osteoarthritis (OA). The study population consisted of 135 patients experiencing persistent OA related pain for at least 1 month who were randomized to double blind treatment with placebo or 10 milligrams or 20 milligrams of controlled-release oxycodone every 12 hours for 14 days. One hundred six patients enrolled in an open label, 6
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month extension trial. Treatment for an additional 12 months was optional. Results indicate that the use of 20 milligrams of controlledrelease oxycodone was superior to placebo in reducing pain intensity and the interference of pain with mood, sleep, and enjoyment of life. During long term treatment, the mean dose remained stable at approximately 40 milligrams per day after titration, and pain intensity was stable. Fiftyeight patients completed 6 months of treatment, 41 completed 12 months, and 15 completed 18 months. Common opioid side effects were reported, several of which decreased in duration as therapy continued. The article concludes that around the clock controlled-release oxycodone therapy seemed to be an effective and safe treatment modality for patients who had chronic, moderate to severe pain associated with OA. 34 references. (AA-M).
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Glucosamine and Chondroitin for Treatment of Osteoarthritis: A Systematic Quality Assessment and Meta-analysis Source: JAMA. Journal of the American Medical Association. 283(11): 1469-1475. March 15, 2000. Summary: This journal article provides health professionals with information on a study that evaluated the benefit of glucosamine and chondroitin preparations for osteoarthritis (OA) symptoms using meta analysis combined with systematic quality assessment of clinical trials of these preparations in knee or hip OA. Clinical trials of glucosamine and chondroitin compounds were identified by using electronic searches of MEDLINE and the Cochrane Controlled Trials Register. 'Osteoarthritis,' 'osteroarthrosis,' 'degenerative arthritis,' 'glucosamine,' 'chondroitin,' and 'glycosaminoglycans' were entered as medical subject heading terms and as textwords. Review articles, manuscripts, and supplements from rheumatology and OA journals were manually searched, and unpublished data were sought by contacting content experts, study authors, and manufacturers of glucosamine and chondroitin. Studies were included if they were published or unpublished double blind, randomized, placebo controlled trials of 4 or more weeks' duration that tested glucosamine or chondroitin for knee or hip OA and reported extractable data on the effect of treatment on symptoms. Fifteen of 37 studies were included in the analysis. Reviewers performed data extraction and scored each trial using a quality assessment instrument. Quality scores ranged from 12.3 percent to 55.4 percent of the maximum, with a mean of 35.5 percent. Only one study described adequate allocation concealment and two reported an intent to treat analysis. Most were supported or performed by a manufacturer. Funnel plots show
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significant asymmetry compatible with publication bias. Tests for heterogeneity were nonsignificant after removing one outlier trial. The aggregated effect sizes were 0.44 for glucosamine and 0.78 for chondroitin, but they were diminished when only high quality or large trials were considered. The effect sizes were relatively consistent for pain and functional outcomes. The article concludes that trials of glucosamine and chondroitin preparations demonstrate moderate to large effects on OA symptoms, but quality issues and likely publication bias suggest that these effects are exaggerated. Nevertheless, some degree of efficacy appears probable for these preparations. 2 figures, 2 tables, and 54 references. (AA-M).
Federally Funded Research on Osteoarthritis The U.S. Government supports a variety of research studies relating to osteoarthritis and associated conditions. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.20 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Visit the CRISP Web site at http://commons.cit.nih.gov/crisp3/Crisp_Query.Generate_Screen. You can perform targeted searches by various criteria including geography, date, as well as topics related to osteoarthritis and related conditions. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore osteoarthritis and related conditions. In some cases, therefore, it may be difficult to understand how some basic or fundamental research could eventually translate into medical practice. The following sample is typical of the type of information found when searching the CRISP database for osteoarthritis: ·
Project Title: AEROBIC EXERCISE INTERVENTION FOR KNEE OSTEOARTHRITIS Principal Investigator & Institution: Kaufman, Kenton R.; Associate Professor; Mayo Clinic, Rochester; 200 1St St SW; Rochester, MN 55905
Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
20
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Timing: Fiscal Year 2002; Project Start 1-SEP-2002; Project End 1-MAR2006 Summary: (provided by applicant): Arthritis is one of the most common causes of functional limitation and dependency in the United States. Individuals with osteoarthritis restrict joint motion and limit activity in order to decrease their symptoms. Traditional, conservative medical treatment of osteoarthritis has been directed at improving functional status through reducing joint pain and inflammation and maintaining or restoring joint function. Exercise as an adjunct therapy in the clinical management of patients with osteoarthritis of the knee, however, is not uniformly accepted. In contrast, exercise has been shown to be effective for prevention and treatment of cardiovascular and metabolic disorders. Standard guidelines exist for aerobic exercise prescriptions. The focus of this study is to determine if these guidelines can also be applied to individuals with knee osteoarthritis. Patients with knee osteoarthritis will be randomized into a control group, a walking exercise group, and a stationary cycling exercise group. The individuals in the exercise groups will be required to exercise three times per week for one year using emerging public health recommendations for aerobic exercise in the adult and aging population. Patient outcome will be assessed using objective gait analysis measurements, knee radiographs to quantify joint space narrowing, magnetic resonance imaging, a general health status questionnaire (SF-36), a disease/site specific questionnaire (WOMAC), and a visual-analog pain scale. All subjects will be studied at 0 and 52 weeks. The central hypothesis of this work is that aerobic exercise can be successfully implemented as an effective nonsurgical option for treatment of patients with early stages of knee osteoarthritis. In order to evaluate this hypothesis, the following specific aims are proposed: Specific Aim 1: Determine the effect of aerobic exercise on patients with knee osteoarthritis. Hypothesis A: Clinical Outcome measures will be better in patients enrolled in exercise programs that in control patients. Hypothesis B: Quantitative measures of lower extremity function will not decline over time in an effective aerobic exercise program. Specific Aim 2: Determine prognostic factors that effect outcome in patients with knee osteoarthritis. Hypothesis: A effective exercise prescription for adults with degenerative joint disease is dependent on knee compartment involvement, CIA stage, BMI, and type of exercise prescribed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BIOMARKERS EPIDEMIOLOGY
OF
OSTEOARTHRITIS--THEIR
Principal Investigator & Institution: Sowers, Maryfran R.; Professor; University of Michigan at Ann Arbor; 3003 South State, Room 1040; Ann Arbor, MI 481091274 Timing: Fiscal Year 2001; Project Start 1-JAN-2001; Project End 1-DEC2002 Summary: Osteoarthritis (OA) is a highly prevalent chronic disease leading to significant functional limitations in both males and females, but particularly women. We propose to characterize the natural history of osteoarthritis (of the knee and hand) using radiographs, interviews and markers of cartilage and bone turnover as well as joint inflammation with this longitudinal study. The specific questions are: 1.Do biochemical markers of osteoarthritis (OA) provide evidence os OA earlier than radiographs.? 2.Can turnover markers be used to define natural history and progression of arthritis? 3.Are bone mineral density(BMD) loss and development/initiation of OA highly regulated? These questions can be addressed efficiently by concatenating historical data from two previously generated population-based groups. One population(Tecumseh Bone Health Study) of 573 women was 25-45 years at their 1992 baseline evaluation (R01-AR-40888--Bone Mineral Density Change and the Climacteric). Hand and knee films were taken two times four years apart (1992 and 1996) along with an annual BMD measurement. Annual urine and serum specimens were collected and are available for analysis of OA markers. The second group, from the SWAN Study (NR-04061), is a population-based group of 300 African-American and 150 Caucasian pre and perimenopausal women, aged 42-52 years at their 1996 baseline when hand and knee films were characterized and serum and urine collected. To the retrospectively available data, we propose to recontract these 1,023 women for radiographs (hand and knee) and interviews in 1998 and 2000 and add annual blood and urine collection with identification of potential markers of arthritis (including turnover on bone/collagen and inflammation). This would allow the examination of the initiation of osteoarthritis using radiographs, interviews and turnover biomarkers. This information about the natural history of osteoarthritis should allow us to consider more appropriate prevention and intervention strategies and offer the potential to identify markers prognostic of disease incidence and of processes involved in its pathobiology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TRANSGENE RESCUE OF CHONDRODYSPLASIA AND OSTEOARTHRITIS Principal Investigator & Institution: Bridgewater, Laura C.; Zoology; Brigham Young University; Provo, UT 84602 Timing: Fiscal Year 2001; Project Start 0-SEP-1999; Project End 1-OCT2002 Summary: Cartilage collagen fibrils are composed of type II, type IX and type XI collagen. Mutations in the genes for any of these collagens produce cartilage disorders, which range in severity from mild dwarfism with osteoarthritis to neonatal lethal chondrodysplasias. In addition to these syndromic cartilage disorders, a growing body of evidence suggests that cartilage collagen mutations also play a role in some of the estimated 20.7 million cases of osteoarthritis in America today. Little is currently known about the etiology of the vast majority of osteoarthritis cases. But in cases where the genetic cause is known, and the mutation is not dominant negative therapeutic expression of a healthy version of the mutant gene in the affected joint may be an effective treatment. The feasibility of such a treatment for cartilage disorders has not yet been tested, but we propose to begin testing it in this project. The chondrodysplasia (cho) mouse line provides a model system in which the rescue of both chondrodysplasia and osteoarthritis by ectopic expression of a gene can be studied. The cho mutation is a single base pair deletion in Col11a1 which leads to premature termination of its protein product, the type XI collagen subunit alpha1 (XI). Mice that are homozygous for the cho mutation have severe abnormalities of all cartilaginous structures and die at birth. Mice that are heterozygous for the mutation appear normal at birth, but develop osteoarthritis within six months. The goal of this proposal is to express a Col11a1 transgene in homozygous and heterozygous cho mice, in an effort to rescue the chondrodysplasia and osteoarthritis phenotypes. Enhancer elements which are capable of directing reporter gene expression specifically to cartilage in transgenic mice have already been characterized and tested. These elements will be used to construct a transgene vector that expresses Col11a1 specifically in cartilage and at levels that approximate the expression level of the endogenous Col11a1 gene. The vector will then be used to insert the transgene in homozygous and heterozygous cho mice. Our hypothesis is that the Col11a1 transgene will rescue or ameliorate the neonatal lethal homozygous cho phenotype, allowing mice to survive beyond birth. But whether or not the mice survive beyond birth, they will be thoroughly analyzed by skeletal preparations histology, immunofluorescence, and electron microscopy. Our hypothesis in the case of the heterozygous cho mice which develop osteoarthritis by 6 months of age, is that the Col11a1
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transgene will prevent or delay the onset of osteoarthritis. Histological and electron microscopic analyses of articular cartilage and intervertebral discs will be performed to assess the effects of the transgene on these mice. The overall goal of this proposal is to determine whether the chondrodysplasia and osteoarthritis phenotypes in cho mice can be rescued by the ectopic expression of a transgene, and to thereby shed light on the feasibility of one day using gene therapy protocols to treat similar disorders in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: WEDGED INSOLE OSTEOARTHRITIS OF THE KNE
FOR
TREATMENT
OF
Principal Investigator & Institution: Felson, David T.; Professor and Chair; Boston University; 715 Albany St, 560; Boston, MA 02118 Timing: Fiscal Year 2001; Project Start 4-SEP-2001; Project End 1-AUG2006 Summary: Osteoarthritis is a highly prevalent and often disabling disorder and its treatment is often frustrating. Most osteoarthritis of the knee affects the medial compartment of the knee which even in an unaffected persons bears 60-70% of loading during walking. With the development of disease in the medial compartment, increased loading of the medial compartment is likely to be one source of localized pain. An operation in which realignment unloads the medial compartment provides excellent pain relief for patients with medial osteoarthritis. One way to lessen load across the medial compartment would be to insert an insole into the shoe that alters the distribution of load in the foot which, in turn, alters load in the knee. Japanese investigators have tested such a wedged insole and have suggested in an uncontrolled study that knee symptoms are improved. No randomized controlled trials of this treatment have been reported but if it is efficacious, it is likely to be safe and inexpensive. The overall objective of this project is to perform a randomized clinical trial of a wedged insole in patients with medial knee osteoarthritis to determine whether the use of these insoles alleviates pain. We will test that hypothesis, that compared to a neutral insert, the provision of a wedged shoe insert alleviates pain in medial knee osteoarthritis. The specific aims are: 1) to undertake a 16-week randomized crossover clinical trial in patients with medial knee osteoarthritis to determine whether prevision of the valgus wedged insert into the shoe leads to lower pain scores during the time of this treatment than during the use of a neutral insert made of the same material and 2) to perform an open label follow-up to track use and effectiveness of
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inserts. We are recruiting 80-90 patients from clinics at Boston Medical Center and by advertisements in the media, who meet criteria for medial joint osteoarthritis of the knee (roughly 60% of patients with osteoarthritis). Our protocol includes a pre-randomization visit at which time subjects undergo radiographs to evaluate their eligibility and then randomization to either the neutral shoe insert or the wedged insert with a total of six weeks of treatment after which there is a four week washout period followed by six weeks randomized to the other treatment. Our main outcome measure will be the WOMAC, a well validated tool for evaluating knee symptoms and knee related disability. At the end of the study we will be able to test whether provision of a valgus shoe insole relives pain when compared to a prevision of a neutral insole. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EFFICACY OF ACUPUNCTURE WITH PT FOR KNEE OSTEO-ARTHRITIS Principal Investigator & Institution: Farrar, John T.; Senior Scholar; Anesthesia; University of Pennsylvania; 3451 Walnut Street; Philadelphia, PA 19104 Timing: Fiscal Year 2001; Project Start 5-JUL-2001; Project End 1-MAR2006 Summary: Acupuncture is an ancient Chinese technique of using a fine needle to stimulate points along theoretical meridians of energy to correct imbalances thought to be responsible for specific disease states. In the United States, acupuncture is often used for the treatment of painful conditions. The 1997 NIH Consensus Conference concluded that there was adequate evidence of efficacy in an acute dental pain model and in nausea. In chronic pain, most studies were too small, poorly designed, poorly executed, or improperly controlled to adequately demonstrate that needle acupuncture worked better than sham acupuncture, placebo, standard medical therapy, or even no treatment. Osteoarthritis (OA) of the knee has been proposed as a good model to test the efficacy of acupuncture in a chronic pain condition because it is an extremely common, well defined, and disabling condition with well established outcome measures for symptoms and functional status. There is clinical trial evidence of efficacy for the standard treatments of acetaminophen and NSAIDs, and exercise physical therapy (EPT), which is usually added when the patient develops functional limitations. One high quality study of acupuncture for knee OA, demonstrated moderate benefit in an unblinded comparison to a usual care control group. As such, a major question remains about whether acupuncture, used in addition to
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exercise therapy, will provide a clinically meaningful improvement in pain and function. Since pain can be the primary limiting factor in improved exercise capacity, if acupuncture has any efficacy in reducing the pain of knee OA, then the combination with an EPT program should be substantially more effective than EPT alone. Another major concern is that the effect of the acupuncture may be predominantly mediated by non- specific placebo effects rather than the specific effects of the placement of a needle. Another important component of this proposal is our use of a validated blinded placebo needle instead of sham acupuncture points. Therefore, the primary goal of this proposal is to use a properly designed randomized blinded clinical trial, using American College of Rheumatology (ACR) criteria and Food and Drug Administration (FDA) recommended outcome measures, to determine whether the addition of acupuncture to standard EPT provides an overall clinically important benefit to patients with symptomatic knee OA compared to placebo acupuncture. As a secondary goal, we will use the clinical trial data to develop prognostic and etiologic models for the patients that are most likely to respond to acupuncture. If a clinically important benefit for acupuncture is found, a broader application of this technique would be justified. However, if the results are negative, then the addition of acupuncture to EPT should be generally curtailed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HUMAN CARTILAGE BIOMECHANICS: AGING AND OSTEORTHRITIS Principal Investigator & Institution: Sah, Robert L.; Professor and ViceChairman; Scripps Research Institute; 10550 N Torrey Pines Rd; San Diego, CA 92037 Timing: Fiscal Year 2002; Project Start 1-JUL-1997; Project End 1-MAR2007 Summary: Articular cartilage normally serves as a wear resistant, low friction, load- bearing surface in diarthrodial joints. However, during aging and osteoarthritic cartilage degeneration in adult humans, biomechanical properties deteriorate. The long-term goal of this project is to elucidate the cellular and molecular basis for the biomechanical dysfunction of human articular cartilage during "aging" and "osteoarthritis", and also to develop diagnostic assays of this dysfunction. During the current grant period, we found that articular cartilage (1) has (a) compressive and tensile moduli that vary markedly with depth from the articular surface, (b) tensile properties that diminish modestly with normal aging (defined by gross morphology and histopathology) in a
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site-specific manner in adult humans, and (c) properties that appear dependent on both fixed charge and collagen network properties, (2) becomes more brittle with controlled aging by in vitro glycation, (3) has marked increases in intrinsic fluorescence during aging that needs to be accounted for in assessing DNA content, and (4)allows attachment of exogenous cells in a time-dependent manner. We now propose to further analyze the extent and mechanisms of biomechanical dysfunction in adult human articular cartilage during "aging" and "osteoarthritis". In particular, we propose the following. (1) To expand the biomechanical analysis of depth-dependent properties of human articular cartilage to osteoarthritic tissue in order to assess how both "aging" and "osteoarthritis" each contribute to altered material and structural mechanical properties, (2) To determine if distinct matrix metabolic pathways of "aging" and "osteoarthritis" are evident in human cartilage, as well as cartilage treated in vitro, and contribute to altered biomechanical properties. (3) To determine if cell density, organization, and phenotype are altered in "aging" and "osteoarthritis", as well as cartilage treated in vitro, and also contribute to altered biomechanical properties. Elucidation of depth-varying tissue-scale properties of cartilage are critical to an overall understanding of cartilage biomechanical function. Determination of the sensitivity of structural biomechanical testing in specific regions of human articular cartilage will help evaluate a diagnostic modality. Elucidation of mechanistic pathways leading to cartilage biomechanical dysfunction in aging and osteoarthritis may ultimately suggest therapeutic interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HUMAN RETROVIRUS-5 AND ARTHRITIS Principal Investigator & Institution: Patel, Robin; Assistant Professor of Medicine; Mayo Clinic, Rochester; 200 1St St SW; Rochester, MN 55905 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 1-AUG2003 Summary: Osteoarthritis and rheumatoid arthritis are the most common joint diseases of mankind. To date, no infectious agent has been convincingly associated with rheumatoid arthritis or osteoarthritis, although preliminary data ,suggest an association with human retrovirus-5, a newly identified retrovirus. That human retrovirus-5 is associated with both rheumatoid arthritis and osteoarthritis is, on initial consideration, striking, because these diseases are felt to be epidemiologically, clinically and pathologically distinct. However, it is possible that rheumatoid arthritis and osteoarthritis are both associated
98 Osteoarthritis
with human retrovirus-5, but that the immunologic response to the infection differs in each instance. The response may depend on the genetic background of the patient. Alternatively, genetic polymorphisms amongst human retrovirus-5 isolates may account for its association with two, seemingly unrelated, disease processes. The purpose of this proposal is to establish the association of human retrovirus-5 with rheumatoid arthritis and osteoarthritis, and to further characterize human retrovirus-5 by sequencing the entire viral genome and culturing the putative retrovirus. To achieve these goals, three specific aims are proposed. Specific Aim 1: Study the association of human retrovirus-5 with rheumatoid arthritis and osteoarthritis. Specific Aim 2: Sequence the entire viral genome of human retrovirus-5. Specific Aim 3: Culture human retrovirus-5. Intraoperative synovial tissue and whole blood specimens from 50 patients with rheumatoid arthritis and 50 patients with osteoarthritis, and synovial tissue specimens from 15 patients with normal joints will be collected and tested by nested polymerase chain reaction for human retrovirus-5 proviral DNA. Positive samples will be sequenced. The frequency of detection of human retrovirus-5 proviral DNA in synovial tissues and blood from rheumatoid arthritis and osteoarthritis patients will be compared to that in patients with no known joint disease. These samples will be used as sources of human retrovirus5 in experiments to extend the known sequence of the human retrovirus5 genome and culture the novel virus. Identification of a specific infectious agent associated with these arthritides would potentially allo for the development of preventive strategies such as vaccination and novel therapeutic approaches. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: JOB-RELATED ARTHRITIS AND DISABILITY IN RETIREMENT Principal Investigator & Institution: Leigh, Paul; Epidemiology and Prev Medicine; University of California, Davis; Sponsored Programs, 118 Everson Hall; Davis, CA 95616 Timing: Fiscal Year 2001; Project Start 0-SEP-2000; Project End 9-SEP-2002 Summary: Two widely-shared medical views motivate the proposed study: 1) Injuries to joints at some time in life can produce osteoarthritis in those joints later in life. 2) Perhaps the best predictor of future lowback pain is prior low-back pain. For our purposes, the time dimension is important. The initial injury or pain could occur on-the-job whereas the subsequent osteoarthritis or pain could occur much later, perhaps during retirement years. These subsequent osteoarthritis and pain events will
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generate direct costs (doctor visits, hospitalizations, drugs) and indirect costs (lost productivity on-the-job and in the home). Aim 1 is to estimate the costs of job-related osteoarthritis. Current estimates of all job-related injuries and illnesses ignore these costs. Aim 2 is to investigate the connection between employment in injury-producing jobs prior to retirement and functional disability after retirement. Costs of job-related osteoarthritis and functional disability in retirement are important for at least three reasons. First, ignoring them leads to a significant underestimate of the overall costs of job-related injuries and illnesses. Second, these costs were largely borne by victims, families, and taxpayers, not by workers' compensation (WC) systems. Third, current economic evaluations of some Occupational Safety and Health (OSHA) standards, such as those pertaining to ergonomics, also ignore these costs. If these standards reduce initial disorders and injuries, then they should also reduce the subsequent costs. The implication is that current ergonomic standards may be more cost-effective than is commonly believed. Prevalence and costs of osteoarthritis will be estimated with primary data from the National Health Interview Surveys, National Center for Health Statistics, the Bureau of Labor Statistics, and the Agency for Healthcare Research and Quality and with secondary data from published studies. We will present a range of estimates under clearly- stated assumptions so readers can select the scenario they find most reasonable. The connection between employment in injuryproducing jobs and subsequent functional disability will be investigated with the National Health and Nutrition Examination Survey III (NHANES III). The NHANES III has information on the functional disability (Activities of Daily Living) of retirees, as well as information on subjects' longest held jobs prior to retirement. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MIDCAREER INVESTIGATOR AWARD PATIENTORIENTED RESEARCH Principal Investigator & Institution: Lane, Nancy E.; Associate Professor; Medicine; University of California, San Francisco; 500 Parnassus Ave.; San Francisco, CA 94122 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 30-JUN2007 Summary: (provided by applicant): Nancy E. Lane, MD is an Associate Professor of Medicine at the University of California, San Francisco (UCSF). She is an established clinical investigator in musculoskeletal diseases with a special emphasis on osteoporosis and osteoarthritis. She
100 Osteoarthritis
is currently an NIH-funded investigator conducting a study to determine if PTH can reverse glucocorticoid-induced osteoporosis and to determine risk factors for the development and progression of hip OA. The purpose of this K24 award is to mentor and teach clinical research in osteoporosis and osteoarthritis at UCSF by 1) Developing an interdisciplinary clinical research seminars in osteoporosis and osteoarthritis that both topical lectures and work in progress research presentations by junior investigators; 2) Meeting individually with all junior clinical investigators UCSF in the field of osteoporosis and osteoarthritis to review research progress, provide study design analysis suggestions, and to establish additional resources for the investigators; 3) Becoming a core faculty member in the Master's in Clinical Research Program at UCSF by teaching a seminar on Developing a Clinical Research Protocol and mentoring master's students on research methodology; 4) Mentoring junior investigators in clinical research with my currently funded NIH grants on glucocorticoid-osteoporosis and on the epidemiology of hip OA. The specific aims of the currently funded NIH proposal to determine if PTH can reverse glucocorticoid-induced osteoporosis are to: l) To determine the changes in BMD caused by two years of treatment with hPTH (1-34) or placebo in postmenopausal women with GC-induced osteoporosis who are taking estrogen, calcium, vitamin D and chronic low doses of GCs; 2) To determine if estrogen or alendronate will preserve the high bone mass state created by two years of hPTH (1-34) treatment; 3) To determine the association of biochemical markers of bone turnover with hPTH (1-34) both during and after treatment. Monitoring for specific aim 3 will be accomplished by obtaining serum bone specific alkaline phosphates, serum osteocalcin, and urinary deoxypyridinoline cross-links at 3-month intervals; 4) To compare, as possible, the fracture incidence between the hPTH (1-34) and placebo treatment groups. Monitoring for specific aims I and 2 will be accomplished by annual spinal and proximal femur trabecular bone mineral content by quantitative computed tomography (QCT) and semiannual dual x-ray absorptiometry (DXA) of the spine, hip, and forearm. The specific aims for the natural history of hip CA are to identify cases of new or worsening radiographic osteoarthritis (OA) of the hip by obtaining a second x-ray of the pelvis after an average of 8 years of follow-up in order to describe the natural history of radiographic hip OA and to determine the risk factors for hip OA. This Study of Osteoporotic Fractures cohort of elderly Caucasian women age - 65 have had radiographs of the pelvis obtained at baseline and after 8 years of followup in addition to bone mass measurements and other questionnaire and medication information. The data have been obtained and analyses are required. Dr. Lane has the enthusiastic support of her department of
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medicine and epidemiology at UCSF to pursue both her mentoring and continued research efforts in-patient oriented clinical research goals. She will strengthen her role senior mentor to young clinical investigators, she will teach clinical research methodology and develop a strong interdisciplinary clinical research group for musculoskeletal disease oriented research at UCSF. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOLECULAR MEDIATORS OF CHONDROCYTE FUNCTION IN AGING/OA Principal Investigator & Institution: Amiel, David; Professor of Orthopedics; Scripps Research Institute; 10550 N Torrey Pines Rd; San Diego, CA 92037 Timing: Fiscal Year 2002; Project Start 1-JUL-1997; Project End 1-MAR2007 Summary: Aging and associated age-related diseases are becoming increasingly important as the percentage of the population comprised by the elderly increases. Osteoarthritis (OA) is a chronic disease which affects diarthrodial joints predominantly in older individuals and is manifested by loss of articular cartilage which often progresses to the point of total joint destruction. Among various parameters which determine the onset and progression of osteoarthritis, age appears to be the greatest risk factor. At present, however, it is still unclear whether aging and osteoarthritis are a continuum or whether this disease is precipitated by biological factors not directly tied to aging. There remain important questions as to what defines "normal" aging, and how much of the pathogenesis of osteoarthritis results from non-age-related causative mechanisms. Studies from our laboratories and others suggest that osteoarthritis pathology is characterized by decreased cellularity and/or cell viability and increased fibrillation. These changes are regulated by molecules that mediate both catabolic and anabolic responses in chondrocytes. Employing an experimentally induced osteoarthritis model in mature rabbits, we demonstrated an up-regulation of catabolic mediators such as MMP-3, IL-1beta and nitric oxide in cartilage and meniscus. These changes correlated with the observed development of OA pathology. To date, however, a systematic correlation of specific molecular mediators with age-related OA pathology has yet to be elucidated. We propose that changes in cartilage cellularity/viability, and in expression of matrix metalloproteinases (MMPs), metabolic and apoptotic regulators (i.e. cytokines and nitric oxide), and extracellular matrix (ECM) structural molecules play a leading role in the induction
102 Osteoarthritis
and maintenance of osteoarthritis during aging. To delineate the role of these molecules in the pathology of developing OA and distinguish between age-related and non-age-related effects, we will study mature and aged rabbits in an animal model of experimentally induced OA, i.e. anterior cruciate ligament transection. In a parallel study we will document human age-related joint pathology which will help us differentiate age-related osteoarthritic changes from experimentally induced effects. We also propose to characterize the role of a specific anabolic (TGF-beta1) and a catabolic (PTHrP) mediator on chondrocyte metabolism and function in an in vivo aged-animal model of osteochondral defect repair. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NMES FOR OLDER INDIVIDUALS AFTER TOTAL KNEE ARTHROPLASTY Principal Investigator & Institution: Snyder-Mackler, Lynn; Professor; Physical Therapy; University of Delaware; Newark, DE 19716 Timing: Fiscal Year 2002; Project Start 5-MAR-2002; Project End 8-FEB2007 Summary: Reduced muscle strength from illness or injuries often leads to loss of function and independence in the elderly. The recovery of muscle strength and function in disabled elderly individuals is a major challenge in rehabilitation. The etiology of the muscle weakness with injury or age is fully elucidated. Training programs designed to maximize strength gains in young individuals may not be optimal in the elderly because the cause of the weakness and the morphology of the muscle may be different for young vs. old people. The overall goal of this work is to determine if physiologically and morphologically based rehabilitation programs are more effective than traditional rehabilitation to counter changes in muscle strength and function in older individuals. Neuromuscular electrical stimulation (NMES) may be used to improve strength and function following injury or surgery. This study provides motivation for exploring the use of NMES with the elderly. We posit that using NMES to augment a traditional rehabilitation program for elderly patients with osteoarthritis following total knee arthroplasties (TKA) will result in greater strength and functional gains than using only traditional rehabilitation. Elderly patients with osteoarthritis who undergo TKAs serve as ideal subjects for testing the effectiveness of rehabilitation programs become those patients almost always exhibit marked quadriceps weakness that is resistant to traditional physical rehabilitation. More than 300,000 TKAs are performed each year in the
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United States to treat osteoarthritis of the knee in older individuals. Neuromuscular electrical stimulation (NMES) may be used to improve strength and function following injury or surgery. This study provides motivation for exploring the use of NMES with the elderly, We posit that using NMES to augment a traditional rehabilitation program for elderly patients with osteoarthritis following total knee arthroplasties (TKA) will result in greater strength and functional gains than using only traditional rehabilitation. Elderly patients with osteoarthritis who undergo TKAs serve as ideal subjects for testing the effectiveness of rehabilitation programs become those patients almost always exhibit marked quadriceps weakness that is resistant to traditional physical rehabilitation. More than 300,000 TKAs are performed each year in the United States to treat osteoarthritis of the knee in older individuals. So, the successful rehabilitation of elder patients following TKA is an important and challenging problem. The specific aims of this proposal are: 1) To assess the effectiveness of high-level neuromuscular electrical stimulation is an adjunct to ongoing intensive, early rehabilitation in restoring quadriceps strength and improving the functional outcome after primary TKA, and 2) To identify the physiological and morphological bases for improvements in quadriceps strength and functional outcome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SYMPTOMATIC HAND OA IN CHINESE AND CAUCASIANS Principal Investigator & Institution: Zhang, Yuqing; Medicine; Boston University; 715 Albany St, 560; Boston, MA 02118 Timing: Fiscal Year 2001; Project Start 1-AUG-2001; Project End 1-JUL2002 Summary: (provided by applicant): Epidemiologic studies of disease in different racial groups have frequently revealed major difference in disease occurrence. These observations often provide the first important clues to disease etiology. Over the last several decades, evidence on racial difference in the prevalence of radiographic osteoarthritis (OA) has accumulated. Several studies also found that prevalence of symptomatic OA, mainly in hip and knee joints, varies among different racial groups, yet relatively few studies have incorporated an evaluation of symptomatic disease in their design, even though symptomatic disease has public health and clinical importance. To our knowledge, no population-based study has been conducted to assess differences in symptomatic hand OA among different racial groups. The overall
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objective of this study is to compare the prevalence of symptomatic hand OA, the pattern of joint involvement, and its impact on upper extremity functional limitations using the data collected from two population-based studies, i.e., the Framingham Osteoarthritis Study and the Beijing Osteoarthritis Study. We will analyze the data collected from 1,099 subjects from the Framingham Osteoarthritis Study and 2,500 subjects from the Beijing Osteoarthritis Study. These two studies used identical protocols to obtain and read the hand radiographs, and identical questionnaire to assess hand symptoms and functional limitations. All information, including hand x-ray reading, hand symptoms, grip strength, and functional limitation, has been collected. The principal investigator has been actively involved in both studies, and played an important role in the study design, operation and data analysis. The results of this study will generate important information on the descriptive epidemiology of symptomatic hand OA among different racial groups. First, this is the first study that incorporated into its design a standardized and identical evaluation of the prevalence of symptomatic hand OA so that valid comparisons between Chinese and Caucasians can be made. Second, participants in both studies were randomly selected from the population, thus, difference in prevalence, joint involvement pattern of symptomatic hand OA are more likely attributable to genetic and/or environment factors between two racial groups rather than to sampling bias; Finally, the study will examine the association between symptomatic hand OA and upper extremity functional limitation in two racial groups so that we will be able to estimate and compare the impact of this disease on functional limitation among the elderly. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: THE EFFECT OF EXERCISE ON PROGRESSION OF KNEE OA Principal Investigator & Institution: Concoff, Andrew L.; Internal Medicine; University of Texas Hlth Sci Ctr; Box 20036; Houston, TX 77225 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 1-AUG2006 Summary: (Taken from the applicants abstract): In order to gain the requisite skills to design and conduct clinical investigations regarding the interrelationship between exercise and osteoarthritis (OA), this application proposes that a physician with formal Rheumatology and Sports Medicine fellowship training engage in a five-year program of combining didactic lectures in Clinical Investigation with the conduction of an arthroscopically-based trial of the effect of exercise on the
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progression of knee OA. Specific emphasis will be placed upon the development of new outcome measures, large scale trial methodology and management, in addition to statistical data analysis. The proposed research study will investigate whether a weight-resistance exercise intervention yields slower progression of knee OA than a control group that receives only education regarding self-management techniques in knee osteoarthritis. A novel, arthroscopic outcome measure that assesses cartilage damage and synovial inflammation, the American College of Rheumatology Knee Arthroscopy Osteoarthritis Scale (ACR/KAOS), will serve as the primary outcome measure. A blinded observer trained in arthroscopy will score videotapes of arthroscopies performed on each patient prior to and following the assigned intervention using the ACR/KAOS. The rate of progression according to the ACR/KAOS will then be compared between those randomized to the exercise and education groups. The sensitivity to change of the ACR/KAOS will be compared to that of the gold-standard for knee OA disease progression, semiflexed (MTP) plain radiographs of the knee. The short-term goal will be to complete the courses required to achieve a Masters of Science degree in Clinical Investigation. The goals of this didactic portion of the program will be to gain knowledge of biostatistics, epidemiology, study design, and a detailed understanding of the moral and legal limitations to the inclusion of human subjects in clinical studies. In order to achieve this goal, the first year of the proposed plan would include participation in classes in the UCLA School of Public Health. Approximately 50% of the first year will be devoted to these classes, with the remaining 50% devoted to the conduction of the trial. This research plan will provide the training required to establish the principal investigator as an independent researcher in osteoarthritis. The long-term goal of the plan is to systematically apply the state of the art, aggressive training methods from sports medicine to those afflicted with OA and to monitor the impact through the use of comprehensive rheumatologic outcomes. Eventually, optimal exercise regimens will be sought for both primary and secondary prevention of OA at various joints and stages. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: THE ROLE CARTILAGE INTEGRITY
OF
SEDLIN
IN
MAINTAINING
Principal Investigator & Institution: Tiller, George E.; Pediatrics; Vanderbilt University; 2201 West End Ave; Nashville, TN 37240 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 1-AUG2006
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Summary: (provided by applicant): Osteoarthritis is a chronic debilitating disease that affects up to 1/3 of the adult population. Growing evidence suggests that genetic factors influence its development, and a better understanding of inherited chondrodysplasias will undoubtedly shed light on the processes common to all degenerative joint disease. Spondyloepiphyseal dysplasia tarda (SEDL) is a chondrodysplasia that is characterized by disproportionate short stature, X-linked inheritance, and early-onset osteoarthritis. We have recently identified the gene responsible for this disorder, and have characterized numerous mutations responsible for the SEDL phenotype--However, the function of the SEDL gene product, "sedlin," remains to be elucidated. In order to determine the role played by the sedlin protein in maintaining cartilage integrity, the following goals are proposed: 1) to determine the biochemical structure and properties of sedlin, 2) to determine the subcellular localization of sedlin and its expression pattern throughout murine chondrogenesis, 3) to determine the proteins with which sedlin associates, 4) to establish an animal model for SEDL, and 5) to test the genes of proteins associated with sedlin as candidate osteciarthritis susceptibility genes. To fulfill these aims, we propose to 1) express native sedlin in vitro and study its structure by NMR spectroscopy and X-ray crystallography, 2) determine its subcellular localization using subcellular fractionation, Western blotting, and immunoelectron microscopy; follow its expression during murine chondrogenesis, 3) identify sedlin-associated proteins by immunoprecipitation and find polymorphisms in their genes, 4) create knockout mice for the SEDL locus and examine their histologic phenotype from embryo through senescence, and 5) test the genes identified in (3) as candidate genes for osteoarthritis susceptibility within a case-control cohort with idiopathic osteoarthritis. Elucidation of the expression pattern and function of the SEDL gene may provide clues for designing therapeutic modalities for individuals affected with SEDL. Moreover, we anticipate that these studies will yield valuable insight into the role of the sedlin pathway in maintaining cartilage integrity and its derangement in osteoarthritis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: WOMEN'S FUNCTIONAL ACTIVITIES
KNEE
MOTION
PATTERNS
IN
Principal Investigator & Institution: Yu, Bing; University of North Carolina, Chapel Hill; Box 2688, 910 Raleigh Rd; Chapel Hill, NC 27515 Timing: Fiscal Year 2001
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Summary: Women have a greater prevalence rate of knee osteoarthritis than men do. Although some risk factors for knee osteoarthritis in women have been qualitatively identified, limited studies exist regarding the quantitative nature of risk factors for knee osteoarthritis. Particularly limited are the studies addressing the differences in lower extremity motion patterns between women and men in daily functional activities, and the effects of the motion patterns on the risk of knee osteoarthritis in women. Our recent studies suggest that women may have different knee motion patterns from men, and that stair climbing may be a more sensitive evaluation procedure for knee disorders. The objective of our long-term research project is to identify modifiable motion related risk factors for knee osteoarthritis in women and develop corresponding prevention strategies. The purpose of the proposed study is to obtain basic understanding of the differences in knee motion patterns between women and men in selected daily functional activities such as level walking and stair climbing, and the effects of estrogen level on women's knee motion patterns in these activities. The knee flexion angle, valgusvarus angle, internal rotation angle, flexion-extension moment, and valgus-varus moment will be used as knee motion measures. Knee static alignment angle will also be measured. The specific aims of this study are: Specific Aim l: To compare the knee motion patterns between women and men during the stance phases of level walking and stair climbing including ascending and descending. Specific Aim 2: To determine the effect of women's estrogen level on the women's knee motion patterns in level walking and stair climbing. Specific Aim 3: To compare static knee alignment angle with weight bearing between women and men. Specific Aim 4: To determine the relationship between static knee alignment angle with weight bearing and maximum knee valgus or varus angle in level walking and stair climbing. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
E-Journals: PubMed Central21 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).22 Access Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html. 22 With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 21
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to this growing archive of e-journals is free and unrestricted.23 To search, go to http://www.pubmedcentral.nih.gov/search, and type “osteoarthritis” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for osteoarthritis in the PubMed Central database: ·
Articular cartilage and changes in Arthritis: Cell biology of osteoarthritis. by Sandell LJ, Aigner T.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&arti d=128887
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Assessment of a genetic contribution to osteoarthritis of the hip: sibling study. by Lanyon P, Muir K, Doherty S, Doherty M.; 2000 Nov 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&arti d=27520
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Body mass indices in patients with disabling hip osteoarthritis. by Marks R, Allegrante JP.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&arti d=83842
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Cardiovascular risk in rheumatoid arthritis versus osteoarthritis: acute phase response related decreased insulin sensitivity and high-density lipoprotein cholesterol as well as clustering of metabolic syndrome features in rheumatoid arthritis. by Dessein PH, Stanwix AE, Joffe BI.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&arti d=125299
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Cellular Immunity in Osteoarthritis: Novel Concepts for an Old Disease. by Liossis SN, Tsokos GC.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&ren dertype=external&artid=95594
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Efficacy, tolerability, and upper gastrointestinal safety of celecoxib for treatment of osteoarthritis and rheumatoid arthritis: systematic review of randomised controlled trials. by Deeks JJ, Smith LA, Bradley MD.; 2002 Sep 21; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&arti d=126301
The value of PubMed Central, in addition to its role as an archive, lies the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.
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Home based exercise programme for knee pain and knee osteoarthritis: randomised controlled trial. by Thomas KS, Muir KR, Doherty M, Jones AC, O'Reilly SC, Bassey EJ.; 2002 Oct 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&arti d=128377
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Mosaic chromosomal aberrations in synovial fibroblasts of patients with rheumatoid arthritis, osteoarthritis, and other inflammatory joint diseases. by Kinne RW, Liehr T, Beensen V, Kunisch E, Zimmermann T, Holland H, Pfeiffer R, Stahl HD, Lungershausen W, Hein G, Roth A, Emmrich F, Claussen U, Froster UG.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&arti d=64845
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Osteoarthritis Associated with Mild Chondrodysplasia in Transgenic Mice Expressing [alpha]1(IX) Collagen Chains with a Central Deletion. by Nakata K, Ono K, Miyazaki J, Olsen BR, Muragaki Y, Adachi E, Yamamura K, Kimura T.; 1993 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&ren dertype=abstract&artid=46198
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Single Base Mutation in the Type II Procollagen Gene (COL2A1) as a Cause of Primary Osteoarthritis Associated with a Mild Chondrodysplasia. by Ala-Kokko L, Baldwin CT, Moskowitz RW, Prockop DJ.; 1990 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&ren dertype=abstract&artid=54577
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T Cells and T-Cell Cytokine Transcripts in the Synovial Membrane in Patients with Osteoarthritis. by Sakkas LI, Scanzello C, Johanson N, Burkholder J, Mitra A, Salgame P, Katsetos CD, Platsoucas CD.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&ren dertype=external&artid=95595
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What can we do about osteoarthritis? by Lohmander LS.; 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&arti d=129992
The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine. The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign
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references. It is also free to the public.24 If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with osteoarthritis, simply go to the PubMed Web site at www.ncbi.nlm.nih.gov/pubmed. Type “osteoarthritis” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for “osteoarthritis” (hyperlinks lead to article summaries): ·
A 12-month, multicenter, prospective, open-label trial of radiographic analysis of disease progression in osteoarthritis of the knee or hip in patients receiving celecoxib. Author(s): Tindall EA, Sharp JT, Burr A, Katz TK, Wallemark CB, Verburg K, Lefkowith JB. Source: Clinical Therapeutics. 2002 December; 24(12): 2051-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12581544&dopt=Abstract
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A home-based pedometer-driven walking program to increase physical activity in older adults with osteoarthritis of the knee: a preliminary study. Author(s): Talbot LA, Gaines JM, Huynh TN, Metter EJ. Source: Journal of the American Geriatrics Society. 2003 March; 51(3): 387-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12588583&dopt=Abstract
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A hyaluronan preparation (500-730 kDa) in the treatment of osteoarthritis: a review of clinical trials with Hyalgan. Author(s): Maheu E, Ayral X, Dougados M. Source: Int J Clin Pract. 2002 December; 56(10): 804-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12510956&dopt=Abstract
PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
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A randomized, double blind, placebo controlled trial of a topical cream containing glucosamine sulfate, chondroitin sulfate, and camphor for osteoarthritis of the knee. Author(s): Cohen M, Wolfe R, Mai T, Lewis D. Source: The Journal of Rheumatology. 2003 March; 30(3): 523-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12610812&dopt=Abstract
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A report of two cases treated with Pauwels' femoral osteotomy for advanced osteoarthritis resulting from a sequela of infectious coxitis in childhood. Author(s): Ohsawa S, Matsushita S, Norimatsu H, Ueno R. Source: Archives of Orthopaedic and Trauma Surgery. 2003 February; 123(1): 39-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12582795&dopt=Abstract
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Advanced glycation endproducts and osteoarthritis. Author(s): Saudek DM, Kay J. Source: Curr Rheumatol Rep. 2003 February; 5(1): 33-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12590883&dopt=Abstract
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Algo-functional assessment of knee osteoarthritis: comparison of the test-retest reliability and construct validity of the WOMAC and Lequesne indexes. Author(s): Faucher M, Poiraudeau S, Lefevre-Colau MM, Rannou F, Fermanian J, Revel M. Source: Osteoarthritis and Cartilage / Oars, Osteoarthritis Research Society. 2002 August; 10(8): 602-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12479381&dopt=Abstract
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American pain society pain questionnaire and other pain measures in the assessment of osteoarthritis pain: a pooled analysis of three celecoxib pivotal studies. Author(s): Moskowitz RW, Sunshine A, Brugger A, Lefkowith JB, Zhao WW, Geis GS.
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Source: American Journal of Therapeutics. 2003 January-February; 10(1): 12-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12522515&dopt=Abstract ·
Arthroscopic evaluation of potential structure-modifying drug in osteoarthritis of the knee. A multicenter, randomized, double-blind comparison of tenidap sodium vs piroxicam. Author(s): Ayral X, Mackillop N, Genant HK, Kirkpatrick J, Beaulieu A, Pippingskiold P, Will RK, Alava S, Dougados M. Source: Osteoarthritis and Cartilage / Oars, Osteoarthritis Research Society. 2003 March; 11(3): 198-207. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12623291&dopt=Abstract
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Arthroscopic lavage or debridement did not reduce pain more than placebo did in patients with osteoarthritis. Author(s): Moseley JB, O'Malley K, Petersen NJ, Menke TJ, Brody BA, Kuykendall DH, Hollingsworth JC, Ashton CM, Wray NP. Source: The Journal of Bone and Joint Surgery. American Volume. 2003 February; 85-A(2): 387. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12571329&dopt=Abstract
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Arthroscopic surgery for osteoarthritis of the knee. Author(s): Morse LJ. Source: The New England Journal of Medicine. 2002 November 21; 347(21): 1717-9; Author Reply 1717-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12448433&dopt=Abstract
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Arthroscopic surgery was not effective for relieving pain or improving function in osteoarthritis of the knee. Author(s): Gillespie WJ. Source: Acp Journal Club. 2003 March-April; 138(2): 49. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12614134&dopt=Abstract
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Arthroscopic treatment of osteoarthritis of the knee. Author(s): Wray NP, Moseley JB, O'Malley K.
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Source: The Journal of Bone and Joint Surgery. American Volume. 2003 February; 85-A(2): 381. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12571321&dopt=Abstract ·
Association of Heterozygous Hemochromatosis C282Y Gene Mutation with Hand Osteoarthritis. Author(s): Ross JM, Kowalchuk RM, Shaulinsky J, Ross L, Ryan D, Phatak PD. Source: The Journal of Rheumatology. 2003 January; 30(1): 121-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12508400&dopt=Abstract
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Balance impairments in individuals with symptomatic knee osteoarthritis: a comparison with matched controls using clinical tests. Author(s): Hinman RS, Bennell KL, Metcalf BR, Crossley KM. Source: Rheumatology (Oxford, England). 2002 December; 41(12): 138894. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12468818&dopt=Abstract
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Cancellous bone microdamage in the proximal femur: influence of age and osteoarthritis on damage morphology and regional distribution. Author(s): Fazzalari NL, Kuliwaba JS, Forwood MR. Source: Bone. 2002 December; 31(6): 697-702. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12531564&dopt=Abstract
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Cardiovascular thrombotic events and COX-2 inhibitors: results in patients with osteoarthritis receiving rofecoxib. Author(s): Bannwarth B, Dougados M. Source: The Journal of Rheumatology. 2003 February; 30(2): 421-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12583353&dopt=Abstract
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Coexisting chondrocalcinosis, osteoarthritis and popliteal cyst. Author(s): Zandman-Goddard G, Tal S, Levy Y, Korat A. Source: Isr Med Assoc J. 2003 January; 5(1): 74-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12592969&dopt=Abstract
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Comparison of a computer based method and the classical manual method for radiographic joint space width assessment in hip osteoarthritis. Author(s): Maillefert JF, Sharp JT, Aho LS, Dougados M. Source: The Journal of Rheumatology. 2002 December; 29(12): 2592-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12465158&dopt=Abstract
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Comparison of low-dose rofecoxib versus 1000 mg naproxen in patients with osteoarthritis. Results of two randomized treatment trals of six weeks duration. Author(s): Myllykangas-Luosujarvi R, Lu HS, Chen SL, Choon D, Amante C, Chow CT, Pasero G, Genti G, Sarembock B, Zerbini CA, Vrijens F, Moan A, Rodgers DB, De Tora L, Laurenzi M. Source: Scandinavian Journal of Rheumatology. 2002; 31(6): 337-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12492248&dopt=Abstract
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Correlation between radiographic severity of knee osteoarthritis and future disease progression. Results from a 3-year prospective, placebocontrolled study evaluating the effect of glucosamine sulfate. Author(s): Bruyere O, Honore A, Ethgen O, Rovati LC, Giacovelli G, Henrotin YE, Seidel L, Reginster JY. Source: Osteoarthritis and Cartilage / Oars, Osteoarthritis Research Society. 2003 January; 11(1): 1-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12505481&dopt=Abstract
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C-reactive protein as a biomarker of emergent osteoarthritis. Author(s): Sowers M, Jannausch M, Stein E, Jamadar D, Hochberg M, Lachance L. Source: Osteoarthritis and Cartilage / Oars, Osteoarthritis Research Society. 2002 August; 10(8): 595-601. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12479380&dopt=Abstract
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Criteria for selection and application of molecular markers for clinical studies of osteoarthritis. Author(s): Otterness IG, Swindell AC.
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Source: Osteoarthritis and Cartilage / Oars, Osteoarthritis Research Society. 2003 March; 11(3): 153-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12623286&dopt=Abstract ·
Crosslinking of fibrinogen and fibronectin by free radicals: a possible initial step in adhesion formation in osteoarthritis of the temporomandibular joint. Author(s): Dijkgraaf LC, Zardeneta G, Cordewener FW, Liem RS, Schmitz JP, de Bont LG, Milam SB. Source: Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons. 2003 January; 61(1): 101-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12524616&dopt=Abstract
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Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) in early knee osteoarthritis. Author(s): Tiderius CJ, Olsson LE, Leander P, Ekberg O, Dahlberg L. Source: Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. 2003 March; 49(3): 488-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12594751&dopt=Abstract
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Detection of radiographic joint space narrowing in subjects with knee osteoarthritis: longitudinal comparison of the metatarsophalangeal and semiflexed anteroposterior views. Author(s): Mazzuca SA, Brandt KD, Buckwalter KA. Source: Arthritis and Rheumatism. 2003 February; 48(2): 385-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12571847&dopt=Abstract
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Do glucosamine or chondriotin cause regeneration of cartilage in osteoarthritis? Author(s): Priebe D, McDiarmid T, Mackler L, Tudiver F. Source: The Journal of Family Practice. 2003 March; 52(3): 237-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12620182&dopt=Abstract
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Does structural worsening of osteoarthritis predict clinical worsening? Author(s): Chevalier X.
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Source: Joint, Bone, Spine : Revue Du Rhumatisme. 2002 October; 69(5): 430-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12477225&dopt=Abstract ·
Economic evaluation of osteoarthritis treatment in Europe. Author(s): Gillette JA, Tarricone R. Source: Expert Opinion on Pharmacotherapy. 2003 March; 4(3): 327-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12614185&dopt=Abstract
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Effect of arthroscopic debridement for osteoarthritis of the knee on health-related quality of life. Author(s): Dervin GF, Stiell IG, Rody K, Grabowski J. Source: The Journal of Bone and Joint Surgery. American Volume. 2003 January; 85-A(1): 10-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12533566&dopt=Abstract
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Effectiveness and safety of strengthening, aerobic, and coordination exercises for patients with osteoarthritis. Author(s): Bischoff HA, Roos EM. Source: Current Opinion in Rheumatology. 2003 March; 15(2): 141-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12598802&dopt=Abstract
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Enhanced lipid peroxidation in synoviocytes from patients with osteoarthritis. Author(s): Grigolo B, Roseti L, Fiorini M, Facchini A. Source: The Journal of Rheumatology. 2003 February; 30(2): 345-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12563693&dopt=Abstract
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Epidemiology of osteoarthritis and enthesopathies in a European population dating back 7700 years. Author(s): Crubezy E, Goulet J, Bruzek J, Jelinek J, Rouge D, Ludes B. Source: Joint, Bone, Spine : Revue Du Rhumatisme. 2002 December; 69(6): 580-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12537266&dopt=Abstract
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Epigallocatechin-3-gallate selectively inhibits interleukin-1betainduced activation of mitogen activated protein kinase subgroup c-Jun N-terminal kinase in human osteoarthritis chondrocytes. Author(s): Singh R, Ahmed S, Malemud CJ, Goldberg VM, Haqqi TM. Source: Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society. 2003 January; 21(1): 102-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12507586&dopt=Abstract
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Erythema annulare centrifugum and osteoarthritis treated with hyaluronic acid. Author(s): Ioannidou D, Krasagakis K, Stefanidou M, Tosca A. Source: Clinical and Experimental Dermatology. 2002 November; 27(8): 720-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12472560&dopt=Abstract
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Ethnic and sex differences in serum levels of cartilage oligomeric matrix protein: the Johnston County Osteoarthritis Project. Author(s): Jordan JM, Luta G, Stabler T, Renner JB, Dragomir AD, Vilim V, Hochberg MC, Helmick CG, Kraus VB. Source: Arthritis and Rheumatism. 2003 March; 48(3): 675-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12632420&dopt=Abstract
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Evaluation of locally induced osteoarthritis by the complete and incomplete Freund's adjuvant in mice. The application of DEXA measurements. Author(s): Wlodarski KH, Dickson GR. Source: Folia Biol (Praha). 2002; 48(5): 192-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12448767&dopt=Abstract
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Evidence for increased bone resorption in patients with progressive knee osteoarthritis: longitudinal results from the Chingford study. Author(s): Bettica P, Cline G, Hart DJ, Meyer J, Spector TD. Source: Arthritis and Rheumatism. 2002 December; 46(12): 3178-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12483721&dopt=Abstract
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Ex-professional association footballers have an increased prevalence of osteoarthritis of the hip compared with age matched controls despite
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not having sustained notable hip injuries. Author(s): Shepard GJ, Banks AJ, Ryan WG. Source: British Journal of Sports Medicine. 2003 February; 37(1): 80-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12547750&dopt=Abstract ·
Feasibility of a dyadic intervention for management of osteoarthritis: a pilot study with older patients and their spousal caregivers. Author(s): Martire LM, Schulz R, Keefe FJ, Starz TW, Osial Jr TA, Dew MA, Reynolds III CF. Source: Aging & Mental Health. 2003 February; 7(1): 53-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12554315&dopt=Abstract
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German short musculoskeletal function assessment questionnaire (SMFA-D): comparison with the SF-36 and WOMAC in a prospective evaluation in patients with primary osteoarthritis undergoing total knee arthroplasty. Author(s): Kirschner S, Walther M, Bohm D, Matzer M, Heesen T, Faller H, Konig A. Source: Rheumatology International. 2003 January; 23(1): 15-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12548437&dopt=Abstract
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Growth-related oncogene alpha induction of apoptosis in osteoarthritis chondrocytes. Author(s): Borzi RM, Mazzetti I, Magagnoli G, Paoletti S, Uguccioni M, Gatti R, Orlandini G, Cattini L, Facchini A. Source: Arthritis and Rheumatism. 2002 December; 46(12): 3201-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12483724&dopt=Abstract
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Hip disability and osteoarthritis outcome score. An extension of the Western Ontario and McMaster Universities Osteoarthritis Index. Author(s): Klassbo M, Larsson E, Mannevik E. Source: Scandinavian Journal of Rheumatology. 2003; 32(1): 46-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12635946&dopt=Abstract
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History of acute knee injury and osteoarthritis of the knee: a prospective epidemiological assessment. The Clearwater Osteoarthritis
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Study. Author(s): Wilder FV, Hall BJ, Barrett JP Jr, Lemrow NB. Source: Osteoarthritis and Cartilage / Oars, Osteoarthritis Research Society. 2002 August; 10(8): 611-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12479382&dopt=Abstract ·
HLA class II is associated with distal interphalangeal osteoarthritis. Author(s): Riyazi N, Spee J, Huizinga TW, Schreuder GM, De Vries RR, Dekker FW, Kloppenburg M. Source: Annals of the Rheumatic Diseases. 2003 March; 62(3): 227-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12594107&dopt=Abstract
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Hydroxypyridinium collagen crosslinks in serum, urine, synovial fluid and synovial tissue in patients with rheumatoid arthritis compared with osteoarthritis. Author(s): Kaufmann J, Mueller A, Voigt A, Carl HD, Gursche A, Zacher J, Stein G, Hein G. Source: Rheumatology (Oxford, England). 2003 February; 42(2): 314-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12595629&dopt=Abstract
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Hylan G-F 20 was safe and effective in knee osteoarthritis and had a relatively low cost-utility ratio. Author(s): Symmons D. Source: Acp Journal Club. 2003 January-February; 138(1): 20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12511132&dopt=Abstract
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Idiopathic osteoarthritis of the hip: incidence, classification, and natural history of 272 cases. Author(s): Hartofilakidis G, Karachalios T. Source: Orthopedics. 2003 February; 26(2): 161-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12597220&dopt=Abstract
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Imaging and osteoarthritis: what is the predictive value? Author(s): Mazzuca SA.
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Source: Curr Rheumatol Rep. 2003 February; 5(1): 27-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12590882&dopt=Abstract ·
Immunologic intervention in the pathogenesis of osteoarthritis. Author(s): Yuan GH, Masuko-Hongo K, Kato T, Nishioka K. Source: Arthritis and Rheumatism. 2003 March; 48(3): 602-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12632410&dopt=Abstract
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Increased femoral neck cancellous bone and connectivity in coxarthrosis (hip osteoarthritis). Author(s): Jordan GR, Loveridge N, Bell KL, Power J, Dickson GR, Vedi S, Rushton N, Clarke MT, Reeve J. Source: Bone. 2003 January; 32(1): 86-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12584040&dopt=Abstract
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Induction of matrix metalloproteinase 1 gene expression is regulated by inflammation-responsive transcription factor SAF-1 in osteoarthritis. Author(s): Ray A, Kuroki K, Cook JL, Bal BS, Kenter K, Aust G, Ray BK. Source: Arthritis and Rheumatism. 2003 January; 48(1): 134-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12528113&dopt=Abstract
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Influence of preoperative factors on outcome of shoulder arthroplasty for glenohumeral osteoarthritis. Author(s): Iannotti JP, Norris TR. Source: The Journal of Bone and Joint Surgery. American Volume. 2003 February; 85-A(2): 251-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12571302&dopt=Abstract
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Interposition arthroplasty for osteoarthritis of trapezio metacarpal joint: results of a modified incision and technique of interposing with early mobilisation. Author(s): Maqsood M, Chenthil Kumar NR, Noorpuri BS.
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Source: Hand Surgery : an International Journal Devoted to Hand and Upper Limb Surgery and Related Research : Journal of the Asia-Pacific Federation of Societies for Surgery of the Hand. 2002 December; 7(2): 2016. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12596280&dopt=Abstract ·
Investigation of linkage on chromosome 2q and hand and knee osteoarthritis. Author(s): Gillaspy E, Spreckley K, Wallis G, Doherty M, Spector TD. Source: Arthritis and Rheumatism. 2002 December; 46(12): 3386-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12483746&dopt=Abstract
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Is there any rationale for prescribing hormone replacement therapy (HRT) to prevent or to treat osteoarthritis? Author(s): Reginster JY, Kvasz A, Bruyere O, Henrotin Y. Source: Osteoarthritis and Cartilage / Oars, Osteoarthritis Research Society. 2003 February; 11(2): 87-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12554124&dopt=Abstract
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Isometric muscle force measurement for clinicians treating patients with osteoarthritis of the knee. Author(s): Fransen M, Crosbie J, Edmonds J. Source: Arthritis and Rheumatism. 2003 February 15; 49(1): 29-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12579591&dopt=Abstract
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JAMA patient page. Osteoarthritis of the knee. Author(s): Parmet S, Lynm C, Glass RM. Source: Jama: the Journal of the American Medical Association. 2003 February 26; 289(8): 1068. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12597762&dopt=Abstract
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Joint distraction as an alternative for the treatment of osteoarthritis. Author(s): van Roermund PM, Marijnissen AC, Lafeber FP. Source: Foot Ankle Clin. 2002 September; 7(3): 515-27. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12512407&dopt=Abstract
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Joint irrigation as treatment for osteoarthritis. Author(s): Bradley JD. Source: Curr Rheumatol Rep. 2003 February; 5(1): 20-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12590881&dopt=Abstract
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Joint-Specific Multidimensional Assessment of Pain (J-MAP): Factor Structure, Reliability, Validity, and Responsiveness in Patients with Knee Osteoarthritis. Author(s): O'Malley KJ, Suarez-Almazor M, Aniol J, Richardson P, Kuykendall DH, Moseley JB Jr, Wray NP. Source: The Journal of Rheumatology. 2003 March; 30(3): 534-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12610814&dopt=Abstract
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Knee Osteoarthritis Compromises Early Mobility Function: The Women's Health and Aging Study II. Author(s): Ling SM, Fried LP, Garrett ES, Fan MY, Rantanen T, Bathon JM. Source: The Journal of Rheumatology. 2003 January; 30(1): 114-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12508399&dopt=Abstract
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Lack of efficacy of acetaminophen in treating symptomatic knee osteoarthritis: a randomized, double-blind, placebo-controlled comparison trial with diclofenac sodium. Author(s): Case JP, Baliunas AJ, Block JA. Source: Archives of Internal Medicine. 2003 January 27; 163(2): 169-78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12546607&dopt=Abstract
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Laser-Doppler imaging of osteoarthritis in proximal interphalangeal joints. Author(s): Ng EY, How TJ. Source: Microvascular Research. 2003 January; 65(1): 65-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12535875&dopt=Abstract
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Mechanism of cartilage destruction in osteoarthritis. Author(s): Ishiguro N, Kojima T, Pool AR.
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Source: Nagoya J Med Sci. 2002 November; 65(3-4): 73-84. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12580533&dopt=Abstract ·
Medial opening-wedge high tibial osteotomy with use of porous hydroxyapatite to treat medial compartment osteoarthritis of the knee. Author(s): Koshino T, Murase T, Saito T. Source: The Journal of Bone and Joint Surgery. American Volume. 2003 January; 85-A(1): 78-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12533576&dopt=Abstract
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Medial torsion of the tibia in Japanese patients with osteoarthritis of the knee. Author(s): Nagamine R, Miyanishi K, Miura H, Urabe K, Matsuda S, Iwamoto Y. Source: Clinical Orthopaedics and Related Research. 2003 March; 408: 218-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12616062&dopt=Abstract
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Men's Shoes and Knee Joint Torques Relevant to the Development and Progression of Knee Osteoarthritis. Author(s): Kerrigan DC, Karvosky ME, Lelas JL, Riley PO. Source: The Journal of Rheumatology. 2003 March; 30(3): 529-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12610813&dopt=Abstract
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Microarray analysis reveals the involvement of beta-2 microglobulin (B2M) in human osteoarthritis. Author(s): Zhang H, Liew CC, Marshall KW. Source: Osteoarthritis and Cartilage / Oars, Osteoarthritis Research Society. 2002 December; 10(12): 950-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12464555&dopt=Abstract
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New directions in symptomatic therapy for patients with osteoarthritis and rheumatoid arthritis. Author(s): Hochberg MC.
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Source: Seminars in Arthritis and Rheumatism. 2002 December; 32(3 Suppl 1): 4-14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12528069&dopt=Abstract ·
New radiographic-based surrogate outcome measures for osteoarthritis of the knee. Author(s): Duryea J, Zaim S, Genant HK. Source: Osteoarthritis and Cartilage / Oars, Osteoarthritis Research Society. 2003 February; 11(2): 102-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12554126&dopt=Abstract
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No loss of cartilage volume over three years in patients with knee osteoarthritis as assessed by magnetic resonance imaging. Author(s): Gandy SJ, Dieppe PA, Keen MC, Maciewicz RA, Watt I, Waterton JC. Source: Osteoarthritis and Cartilage / Oars, Osteoarthritis Research Society. 2002 December; 10(12): 929-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12464553&dopt=Abstract
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Nonrandom evolution of end-stage osteoarthritis of the lower limbs. Author(s): Shakoor N, Block JA, Shott S, Case JP. Source: Arthritis and Rheumatism. 2002 December; 46(12): 3185-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12483722&dopt=Abstract
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Obesity and hip osteoarthritis: the weight of the evidence is increasing. Author(s): Gelber AC. Source: The American Journal of Medicine. 2003 February 1; 114(2): 158-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12586240&dopt=Abstract
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Obesity outcomes in disease management: clinical outcomes for osteoarthritis. Author(s): Nevitt MC. Source: Obesity Research. 2002 November; 10 Suppl 1: 33S-7S. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12446856&dopt=Abstract
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Osteoarthritis of finger joints in Finns aged 30 or over: prevalence, determinants, and association with mortality. Author(s): Haara MM, Manninen P, Kroger H, Arokoski JP, Karkkainen A, Knekt P, Aromaa A, Heliovaara M. Source: Annals of the Rheumatic Diseases. 2003 February; 62(2): 151-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12525385&dopt=Abstract
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Osteoarthritis of the Hands, Hips and Knees in an Australian Twin Sample-Evidence of Association with the Aggrecan VNTR Polymorphism. Author(s): Kirk KM, Doege KJ, Hecht J, Bellamy N, Martin NG. Source: Twin Research : the Official Journal of the International Society for Twin Studies. 2003 February; 6(1): 62-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12626230&dopt=Abstract
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Osteoarthritis of the peripheral joints. Author(s): Petersson IF, Jacobsson LT. Source: Best Practice & Research. Clinical Rheumatology. 2002 December; 16(5): 741-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12473271&dopt=Abstract
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Osteoarthritis. Author(s): Chard J, Lohmander S, Smith C, Scott D. Source: Clin Evid. 2002 December; (8): 1212-37. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12603937&dopt=Abstract
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Osteoarthritis: biological markers for the future? Author(s): Garnero P. Source: Joint, Bone, Spine : Revue Du Rhumatisme. 2002 December; 69(6): 525-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12537257&dopt=Abstract
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Osteoarthritis: MR imaging findings in different stages of disease and correlation with clinical findings. Author(s): Link TM, Steinbach LS, Ghosh S, Ries M, Lu Y, Lane N, Majumdar S.
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Source: Radiology. 2003 February; 226(2): 373-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12563128&dopt=Abstract ·
Osteoprotegerin expression in synovial tissue from patients with rheumatoid arthritis, spondyloarthropathies and osteoarthritis and normal controls. Author(s): Haynes DR, Barg E, Crotti TN, Holding C, Weedon H, Atkins GJ, Zannetino A, Ahern MJ, Coleman M, Roberts-Thomson PJ, Kraan M, Tak PP, Smith MD. Source: Rheumatology (Oxford, England). 2003 January; 42(1): 123-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12509625&dopt=Abstract
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Peripheral-type benzodiazepine receptors in human mononuclear cells of patients affected by osteoarthritis, rheumatoid arthritis or psoriasic arthritis. Author(s): Bazzichi L, Betti L, Giannaccini G, Rossi A, Lucacchini A. Source: Clinical Biochemistry. 2003 January; 36(1): 57-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12554061&dopt=Abstract
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Pharmacologic therapy for osteoarthritis. Author(s): Goldberg SH, Von Feldt JM, Lonner JH. Source: Am J Orthop. 2002 December; 31(12): 673-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12498526&dopt=Abstract
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Posterior-anterior weight-bearing radiograph in 15 degrees knee flexion in medial osteoarthritis. Author(s): Yamanaka N, Takahashi T, Ichikawa N, Yamamoto H. Source: Skeletal Radiology. 2003 January; 32(1): 28-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12525941&dopt=Abstract
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Preoperative predictors of locomotor ability two months after total knee arthroplasty for severe osteoarthritis. Author(s): Parent E, Moffet H. Source: Arthritis and Rheumatism. 2003 February 15; 49(1): 36-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12579592&dopt=Abstract
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Prevention of disability in daily activities in older persons with knee osteoarthritis. Author(s): McCormack R. Source: Clinical Journal of Sport Medicine : Official Journal of the Canadian Academy of Sport Medicine. 2002 November; 12(6): 405. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12650157&dopt=Abstract
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Procollagen II C propeptide level in the synovial fluid as a predictor of radiographic progression in early knee osteoarthritis. Author(s): Sugiyama S, Itokazu M, Suzuki Y, Shimizu K. Source: Annals of the Rheumatic Diseases. 2003 January; 62(1): 27-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12480665&dopt=Abstract
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Protein kinase signals activate interleukin 16 encoding transcripts in rheumatoid arthritis versus osteoarthritis synovial fibroblasts. Author(s): Schuler MK, Sell S, Aicher WK. Source: Annals of the Rheumatic Diseases. 2003 February; 62(2): 182-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12525392&dopt=Abstract
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Pulsed magnetic field therapy for osteoarthritis of the knee--a doubleblind sham-controlled trial. Author(s): Nicolakis P, Kollmitzer J, Crevenna R, Bittner C, Erdogmus CB, Nicolakis J. Source: Wiener Klinische Wochenschrift. 2002 August 30; 114(15-16): 67884. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12602111&dopt=Abstract
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Quality of life after several treatments for osteoarthritis of the hip. Author(s): Kawasaki M, Hasegawa Y, Sakano S, Torii Y, Warashina H. Source: Journal of Orthopaedic Science : Official Journal of the Japanese Orthopaedic Association. 2003; 8(1): 32-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12560883&dopt=Abstract
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Quality of well-being in older people with osteoarthritis. Author(s): Groessl EJ, Kaplan RM, Cronan TA.
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Source: Arthritis and Rheumatism. 2003 February 15; 49(1): 23-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12579590&dopt=Abstract
Vocabulary Builder Acetylgalactosamine: The N-acetyl derivative of galactosamine. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Allopurinol: A xanthine oxidase inhibitor that decreases uric acid production. [NIH] Antidepressant: An agent that stimulates the mood of a depressed patient, including tricyclic antidepressants and monoamine oxidase inhibitors. [EU] Arthroplasty: Surgical reconstruction of a joint to relieve pain or restore motion. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Catabolism: Any destructive metabolic process by which organisms convert substances into excreted compounds. [EU] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cyst: Any closed cavity or sac; normal or abnormal, lined by epithelium, and especially one that contains a liquid or semisolid material. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Dysmenorrhea: Painful menstruation. [NIH] Dyspepsia: Impairment of the power of function of digestion; usually applied to epigastric discomfort following meals. [EU] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Etodolac: A nonsteroidal anti-inflammatory agent with potent analgesic and antiarthritic properties. It has been shown to be effective in the treatment of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and in the alleviation of postoperative pain. [NIH]
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Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Flexion: In gynaecology, a displacement of the uterus in which the organ is bent so far forward or backward that an acute angle forms between the fundus and the cervix. [EU] Gadolinium: An element of the rare earth family of metals. It has the atomic symbol Gd, atomic number 64, and atomic weight 157.25. Its oxide is used in the control rods of some nuclear reactors. [NIH] Glycosaminoglycans: Heteropolysaccharides which contain an Nacetylated hexosamine in a characteristic repeating disaccharide unit. The repeating structure of each disaccharide involves alternate 1,4- and 1,3linkages consisting of either N-acetylglucosamine or N-acetylgalactosamine. [NIH]
Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Hypertension: Persistently high arterial blood pressure. Various criteria for its threshold have been suggested, ranging from 140 mm. Hg systolic and 90 mm. Hg diastolic to as high as 200 mm. Hg systolic and 110 mm. Hg diastolic. Hypertension may have no known cause (essential or idiopathic h.) or be associated with other primary diseases (secondary h.). [EU] Ibuprofen: A nonsteroidal anti-inflammatory agent with analgesic properties used in the therapy of rheumatism and arthritis. [NIH] Immunity: The condition of being immune; the protection against infectious disease conferred either by the immune response generated by immunization or previous infection or by other nonimmunologic factors (innate i.). [EU] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulindependent diabetes mellitus. [NIH] Irrigation: Washing by a stream of water or other fluid. [EU] Lipid: Any of a heterogeneous group of flats and fatlike substances characterized by being water-insoluble and being extractable by nonpolar (or fat) solvents such as alcohol, ether, chloroform, benzene, etc. All contain as a major constituent aliphatic hydrocarbons. The lipids, which are easily stored in the body, serve as a source of fuel, are an important constituent of cell structure, and serve other biological functions. Lipids may be considered to
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include fatty acids, neutral fats, waxes, and steroids. Compound lipids comprise the glycolipids, lipoproteins, and phospholipids. [EU] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Naproxen: An anti-inflammatory agent with analgesic and antipyretic properties. Both the acid and its sodium salt are used in the treatment of rheumatoid arthritis and other rheumatic or musculoskeletal disorders, dysmenorrhea, and acute gout. [NIH] Orthopedics: A surgical specialty which utilizes medical, surgical, and physical methods to treat and correct deformities, diseases, and injuries to the skeletal system, its articulations, and associated structures. [NIH] Osteonecrosis: Death of a bone or part of a bone, either atraumatic or posttraumatic. [NIH] Osteotomy: The surgical cutting of a bone. [EU] Oxycodone: Semisynthetic derivative of codeine that acts as a narcotic analgesic more potent and addicting than codeine. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Pharmacokinetics: The action of drugs in the body over a period of time, including the processes of absorption, distribution, localization in tissues, biotransformation, and excretion. [EU] Piroxicam: 4-Hydroxy-2-methyl-N-2-pyridyl-2H-1,2-benzothiazine-3carboxamide 1,1-dioxide. A non-steroidal anti-inflammatory agent that is well established in the treatment of rheumatoid arthritis and osteoarthritis. Its usefulness has also been demonstrated in the treatment of musculoskeletal disorders, dysmenorrhea, and postoperative pain. Its long half-life enables it to be administered once daily. The drug has also been shown to be effective if administered rectally. Gastrointestinal complaints are the most frequently reported side effects. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Probenecid: The prototypical uricosuric agent. It inhibits the renal excretion of organic anions and reduces tubular reabsorption of urate. Probenecid has
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also been used to treat patients with renal impairment, and, because it reduces the renal tubular excretion of other drugs, has been used as an adjunct to antibacterial therapy. [NIH] Procollagen: A biosynthetic precursor of collagen containing additional amino acid sequences at the amino-terminal ends of the three polypeptide chains. Protocollagen, a precursor of procollagen consists of procollagen peptide chains in which proline and lysine have not yet been hydroxylated. [NIH]
Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Receptor: 1. A molecular structure within a cell or on the surface characterized by (1) selective binding of a specific substance and (2) a specific physiologic effect that accompanies the binding, e.g., cell-surface receptors for peptide hormones, neurotransmitters, antigens, complement fragments, and immunoglobulins and cytoplasmic receptors for steroid hormones. 2. A sensory nerve terminal that responds to stimuli of various kinds. [EU] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU]
Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Sclerosis: A induration, or hardening; especially hardening of a part from inflammation and in diseases of the interstitial substance. The term is used chiefly for such a hardening of the nervous system due to hyperplasia of the connective tissue or to designate hardening of the blood vessels. [EU] Sequela: Any lesion or affection following or caused by an attack of disease. [EU]
Serum: 1. The clear portion of any body fluid; the clear fluid moistening serous membranes. 2. Blood serum; the clear liquid that separates from blood on clotting. 3. Immune serum; blood serum from an immunized animal used for passive immunization; an antiserum; antitoxin, or antivenin. [EU]
Sulfinpyrazone: A uricosuric drug that is used to reduce the serum urate levels in gout therapy. It lacks anti-inflammatory, analgesic, and diuretic properties. [NIH] Symptomatic: 1. Pertaining to or of the nature of a symptom. 2. Indicative (of a particular disease or disorder). 3. Exhibiting the symptoms of a particular disease but having a different cause. 4. Directed at the allying of symptoms, as symptomatic treatment. [EU] Tophus: A chalky deposit of sodium urate occurring in gout; tophi form most often around joints in cartilage, bone, bursae, and subcutaneous tissue
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and in the external ear, producing a chronic foreign-body inflammatory response. [EU] Torsion: 1. A type of mechanical stress, whereby the external forces (load) twist an object about its axis. 2. In ophthalmology any rotation of the vertical corneal meridians. [EU] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Uricosuric: 1. Pertaining to, characterized by, or promoting uricosuria (= the excretion of uric acid in the urine). 2. An agent that promotes uricosuria. [EU] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substancespecific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU]
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CHAPTER 5. PATENTS ON OSTEOARTHRITIS Overview You can learn about innovations relating to osteoarthritis by reading recent patents and patent applications. Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.25 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available to patients with osteoarthritis within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available to patients with osteoarthritis. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information.
25Adapted
from The U. S. Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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Patents on Osteoarthritis By performing a patent search focusing on osteoarthritis, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an example of the type of information that you can expect to obtain from a patent search on osteoarthritis: ·
Solution and the method of making the same for the treatment of osteoarthritis Inventor(s): Lee; Troy J. (17 Daniel Rd., Asheville, NC 28806) Assignee(s): none reported Patent Number: 6,537,590 Date filed: February 19, 2002 Abstract: A solution and the method of making the same for the treatment of osteoarthritis for treating symptoms of osteoarthritic conditions. The solution and the method of making the same for the treatment of osteoarthritis includes magnesium oxide; ethylenediaminetetraacetic acid; glycerin; and water, all of which are heated and added in a mixture which, after being cooled, is applied to the affected areas for treatment of the osteoarthritic condition. Excerpt(s): The present invention relates to osteoarthritic treatment lotions and more particularly pertains to a new solution and the method of making the same for the treatment of osteoarthritis for treating symptoms of osteoarthritic conditions. ... While these devices fulfill their respective, particular objectives and requirements, the aforementioned patents do not disclose a new solution and the method of making the same for the treatment of osteoarthritis. The prior art describes solutions and medicated products for various ailment treatments. ... The general purpose of the present invention, which will be described subsequently in greater detail, is to provide a new solution and the method of making the same for the treatment of osteoarthritis which has many of the advantages of the osteoarthritic treatment lotions mentioned heretofore and many novel features that result in a new solution and the method of making the same for the treatment of osteoarthritis which is not
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anticipated, rendered obvious, suggested, or even implied by any of the prior art osteoarthritic treatment lotions, either alone or in any combination thereof. The present invention includes magnesium oxide; ethylenediaminetetraacetic acid; glycerin; and water, all of which are heated and added in a mixture which, after being cooled, is applied to the affected areas for treatment of the osteoarthritic condition. None of the prior art uses the combination of ingredients of the present invention in the treatment of osteoarthritis. Web site: http://www.delphion.com/details?pn=US06537590__ ·
Composition for the treatment of osteoarthritis Inventor(s): Graus; Ivo Maria Franciscus (Wg Ede, NL), Smit; Hobbe Friso (As Utrecht, NL) Assignee(s): N.V. Nutricia (Zoetermeer, NL) Patent Number: 6,492,429 Date filed: September 14, 2000 Abstract: Osteoarthritis is treated by a composition containing both apocynin and an inhibitor of inducible nitric oxide synthase such as curcumin. Further components such as boswellic acids, glucosamine, acetylcysteine and boron further enhance the beneficial effect of apocynin and curcumin. Excerpt(s): The invention is concerned with compositions for the treatment of osteoarthritis and related diseases and with methods for treating osteoarthritis. ... Osteoarthritis (OA) is a degenerative joint disease, which develops by wear and tear of the joints during aging. OA mostly affects the weight-bearing joints such as spine, knees and hips, but thumb and finger joints may also be affected. Repetitive mechanical injury of the cartilage eventually results in loss of cartilage and damage to joint surfaces and adjacent bone. As a result of the tissue destruction, inflammatory cells invade the joint and the synovial membrane which is manifested by pain, swelling and stiffness of the affected joints. The repetitive mechanical injury leads to pathological changes that result in loss of proteoglycans and collagen from the cartilage matrix, which in turn leads to surface erosion and decreased loading capacity, In OA, chondro-cytes show a reduced potential to synthesize matrix constituents (proteoglycans and collagen fibers) and the expression of proteolytic enzymes (called matrix metallo-proteases, MNMP's) contributes to cartilage destruction and release of proteoglycan fragments in the synovial fluid. The inflammatory responses to the mechanical insults further contribute to cartilage destruction. The inflammatory mediator
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interleukin I (IL-1) is considered as the principal mediator of cartilage destruction. It induces a number of changes in chondrocytes, including the concurrent generation of significant amounts of NO (nitrogen oxide) and superoxide radicals by inducible NO synthase (iNOS) and NADPH oxidase, respectively. NO reacts with superoxide to form peroxynitrite, which is largely responsible for the decrease in proteoglycan synthesis induced by IL-1. The role of superoxide was further demonstrated by the ability of superoxide dismutase to reverse the decrease in proteoglycan synthesis. The prevention of peroxynitrite formation via selective inhibition of iNOS and thus NO formation in vivo resulted in a marked decrease of MMP's. In addition, intra-articular treatment of OA patients with superoxide dismutase reduces symptoms of OA for prolonged periods. These studies demonstrate that induction of catabolic enzymes (MMP's) and cartilage destruction is mediated via the formation of NO and O.sub.2.sup.- radicals by chondrocytes or inflammatory cells. While the primary cause of OA is mechanical damage, rheumatoid arthritis (RA) is mainly the result of an autoimmune response that leads to chronic inflammation in the joint. Contrary to OA, typical manifestations of RA are an increase of parameters that are associated with inflammation, such as haematocrite and white blood cell count and pannus formation or hyperplasia of the joint capsule that leads to deformed joints. This in turn leads to morning stiffness. Although the (primary) aetiology of RA and OA are different, the pathological processes at a later stage result in some manifestations that are similar such as joint pain, cartilage degradation and general joint disability. ... It was found that osteoarthritis can be effectively treated by administration of a suitable amount of apocynin or its functional and structural analogues, preferably in the form of an extract from a Picrorhiza plant, and preferably together with further components enhancing the beneficial effect of the apocynin. Thus, the invention in a first aspect provides compositions for the treatment of osteoarthritis, containing an effective amount of apocynin or its analogues. Web site: http://www.delphion.com/details?pn=US06492429__ ·
Combined use of diclofenac and tribenoside to treat osteoarthritis Inventor(s): Chayen; Joseph (Surrey, GB), Bitensky, deceased; Lucille (late of Surrey, GB), Kagan, executor; by Martin Roy (Teddington, GB) Assignee(s): KS Biomedix Ltd. (Surrey, GB) Patent Number: 6,034,122 Date filed: January 5, 1998
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Abstract: Diclofenac sodium and tribenoside, or more generally (i) a compound that acts on the chondrocytes and (ii) a compound that reduces the water content of the chondrocyte matrix, are useful in the treatment of osteoarthritis. Excerpt(s): This invention relates to compositions for use in the treatment of osteoarthritis (OA). ... Many drugs are known for the treatment of osteoarthritis, but in general their effectiveness is low, especially if sideeffects are to be avoided. A known drug of this type is diclofenac sodium. ... Compositions of this invention are suitable for use in the treatment of osteoarthritis in humans and in animals, e.g. domesticated and farm animals such as dogs, cats and horses. Web site: http://www.delphion.com/details?pn=US06034122__ ·
Method of treatment of osteoarthritis with interleuken-1 receptor antagonist Inventor(s): Pelletier; Jean-Pierre (St-Lambert, CA), Martel-Pelletier; Johanne (St-Lambert, CA) Assignee(s): Arthro Lab Inc. (Sherbrooke, CA) Patent Number: 5,972,880 Date filed: March 7, 1996 Abstract: A method and a composition for the preventative treatment of osteoarthritis comprising the periodic administration to a mammal suffering of this disease of a composition comprising an amount of Human recombinant Interleukin-1 receptor antagonist effective for reducing the progression of lesions and cartilage degradation. Excerpt(s): The invention relates to a method and a composition for the preventive treatment of osteoarthritis. More particularly the invention relates to a method and a composition for reducing the progression of lesion and cartilage degradation in osteoarthritis. ... Osteoarthritis, which is also called "degenerative joint disease", is the most common rheumatic disease and is characterized by a chronic inflammation of the articulation and a progressive depletion of articular cartilage matrix macromolecules. Together with the cartilage degeneracy, osteophytes (small abnormal body outgrowths) occur and develop on the stripped part of the articular bones. Symptoms of osteoarthritis occur in many people over the age of 65, and women are affected twice as often as men. These symptoms are pain, swelling and stiffness of the articulation. In a further stage of the disease, movement of articulations is limited and becomes painfil. ... The most commonly used drugs for the treatment of osteoarthritis are the
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nonsteroidal anti-inflammatory agents (NSAID). Even though these drugs have proved effectiveness in relieving the symptoms of osteoarthritis and in decreasing osteoarthritis cartilage catabolism, some of them, like sodium salicylate, have shown inhibiting properties of the proteoglycan synthesis which may jeopardize the cartilage repair process. Other drugs, such as tiaprofenic acid, which do not inhibit the proteoglycan synthesis and have shown in vitro that they are able to decrease osteoarthritis cartilage catabolism, (Jean-Pierre Pelletier et al. The Journal of Rheumatology 1989;16:5, 646-655), have been unable to provide any preventing effect in development of osteoarthritis when administrated to patients suffering from the latter, (Edward C. Huskisson et al. The Journal of Rheumatology 1995; 22:10-1941-1946). Doxycycline, a member of the tetracycline family, was also shown to reduce, in vivo, the severity of osteoarthritis lesions in the dog ACL model while reducing metalloprotease activity, (Yu LP Jr et al. Arthritis Rheum 35:1150-1159, 1992). Recent data suggests that the action of corticosteroids is associated with a reduction in the synthesis of stromelysin-1 by chondrocytes. (see: Pelletier et al., J Arthritis Rheum 37:414-423, 1994; and Pelletier et al., J Lab Invest 72:578-586, 1995). Web site: http://www.delphion.com/details?pn=US05972880__ ·
Methods of diagnosing a predisposition for osteoarthritis via detection of vitamin D receptor gene polymorphisms Inventor(s): Spector; Timothy David (London, GB), Keen; Richard William (London, GB) Assignee(s): Gemini International Holdings Limited (MC) Patent Number: 5,939,260 Date filed: April 21, 1997 Abstract: A method of diagnosing a disease associated with a genetic polymorphism in a vitamin D receptor gene comprises determining the genotype of said vitamin D receptor gene in an animal. The method can be used to diagnose predisposition or susceptibility to osteoarthritis. Compositions for said diagnosis are provided. Methods of treatment of osteoarthritis are provided, comprising identifying an individual having a predisposition or susceptibility to the disease and subsequently treating that individual. Excerpt(s): Osteoarthritis, or degenerative joint disease as it is also known, is one of the most common types of arthritis. It is characterised by the breakdown of the joint's cartilage, causing bone to rub against bone causing pain and loss of movement. Osteoarthritis can range from
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very mild to very severe and most commonly affects middle-aged and older people. It affects hands and weight-bearing joints, such as the knees, hips, feet and back. ... Although age is a leading risk factor, at present the aetiology and pathogenesis of this condition remain largely unknown. Many environmental factors and other independent conditions have been associated with osteoarthritis, including obesity, previous injury and/or menisectomy, knee bending occupations, smoking, sex hormones, gynaecological disorders and other metabolic factors. Obesity may lead to osteoarthritis of the knees. Also, people with injuries to the joints because of sports, repeated movements, or accidents may be at increased risk of developing osteoarthritis. ... At present accurate diagnosis of osteoarthritis is in general possible only when the disease has progressed significantly. Physicians can do little more than make a diagnosis of osteoarthritis based on a physical examination and history of symptoms. X-ray is typically used only to confirm diagnosis. Web site: http://www.delphion.com/details?pn=US05939260__ ·
Osteoarthritis-associated inducable isoform of nitric oxide synthetase Inventor(s): Amin; Ashok R. (Union, NJ), Abramson; Steven B. (Rye, NY) Assignee(s): Hospital For Joint Diseases (New York, NY) Patent Number: 5,759,836 Date filed: March 27, 1995 Abstract: An novel isoform of inducible nitric oxide synthase (OA-NOS) has been identified in osteoarthritis-affected articular cartilage. Some properties, including molecular weight, are similar to the constitutive isoform of neuronal nitric oxide synthase (ncnos) while other properties share similarity with the previously identified inducible nitric oxide (iNOS). Acetylating agents, such as aspirin and N-acetylimidazole act on both iNOS and OA-NOS by inhibiting their catalytic activities. A method is provided to screen for acetylating agents that inhibit OA-NOS, and the selective inhibition of OA-NOS by inhibitory agents is determined by comparison to a panel of different isoforms of nitric oxide synthase. Excerpt(s): The expression and function of iNOS and COX2, known to be involved in inflammatory processes in vivo (Stadler et al., J. Leukocyte Biol. 53:165-172, 1993; Vane et al., 1994, supra), are regulated by the local production of cytokines (Curran et al., J. Exp. Med. 170:1769-1774, 1989; Nussler and Billiar, J. Leukocyte. Biol. 54:171-178, 1993; Schini et al., Eur. J. Pharmacol. 216, 379-383, 1992). This is further substantiated by the observation that the upregulation of iNOS can be reduced by antiinflammatory cytokines such as IL-4, IL-8, IL-10, TGF-.beta.-1, -2, and -3,
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and macrophage deactivating factor (Nussler and Billiar, 1993, supra). COX-2 is induced in a number of cell types by EGF (Bailey et al., J. Lipid Res. 26:54-61, 1985), FGF (Goddard et al., Cytokine 4:377-384, 1992), PDGF (Lin et al., J. Biol. Chem. 264:17379-17383, 1989), IL-1 (Raz et al., Proc. Natl. Acad. Sci. USA 86:1657-1661, 1989) and TGF-.beta. (Bailey and Verma, Anal. Biochem. 196:11-18, 1991). PGE.sub.2 inhibits the production of cytokines (Ferreri et al., J. Biol. Chem. 267:9443-9449, 1992) and cytokine-induced proliferation in a number of cell types in vitro, (Albina and Henry, J. Surg. Res. 50:403-409, 1991). However, the actions of PGs in vivo are more complex, in that COX inhibitors exacerbate cartilage erosion but reduce bone loss (Willoughby et al., J. Lipid Mediators 6:298-293, 1993). Expression of COX-1 and COX-2 is influenced by IL-1 in rheumatoid synovial tissue (Crofford et al., J. Clin. Inv. 93:10951101, 1992). IL-1 is also known to modulate the activity of COX-2 in chondrocytes, and to affect chondrocyte function by inhibiting proteoglycan and collagen (Type II) synthesis and promoting matrix degradation by stimulating neutral and metalloproteases (LyonsGiordano et al., Exp. Cell Res. 206:58-62, 1993). Differing levels of NO (induced by cytokines or endotoxin) have stimulatory as well as inhibitory effects on PGE.sub.2 and the synthesis of neutral proteases in chondrocytes (Stadler et al., J. Immunol. 147:3915-3920, 1991). IL-1 has been reported to be a strong inducer of IL-6 synthesis and secretion in human chondrocytes, and has been shown to have a protective effect on extracellular matrix of human articular chondrocytes (Gunther et al., Arthritis Rheum. 37:395-405, 1994). Recently, Venn et al. (Arthritis Rheum 36:819-826, 1993) have reported elevated levels of IL-6 and TNF-.alpha. in synovial fluid of canine osteoarthritis. ... Classically, osteoarthritis (OA), unlike rheumatoid arthritis (RA), is defined as an inherently noninflammatory disorder of movable joints characterized by deterioration of articular cartilage and the formation of new bone at the joint surfaces and margins (Hough, in Arthritis and Allied Conditions, D. J. McCarty and W. J. Koopman, eds., Lea & Febiger, Philadelphia and London, 1699-1723, 1993). In contrast to RA, the synovial fluid in OA typically contains few neutrophils (
