Fosamax - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

FOSAMAX A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES J AMES N. P ...

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FOSAMAX A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES

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 ©2003 by ICON Group International, Inc. Copyright ©2003 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: Philip Parker, Ph.D. 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 for the diagnosis or treatment of a health problem. 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. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing 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., 1960Fosamax: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-83917-4 1. Fosamax-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. 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, and 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 book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. 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 book.

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on Fosamax. Books in this series 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 book. 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 Freeman 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 health books 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 ICON Health Publications.

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About ICON Health Publications 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

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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON FOSAMAX .................................................................................................. 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Fosamax ........................................................................................ 4 E-Journals: PubMed Central ......................................................................................................... 6 The National Library of Medicine: PubMed .................................................................................. 6 CHAPTER 2. NUTRITION AND FOSAMAX ........................................................................................ 23 Overview...................................................................................................................................... 23 Finding Nutrition Studies on Fosamax ....................................................................................... 23 Federal Resources on Nutrition ................................................................................................... 24 Additional Web Resources ........................................................................................................... 24 CHAPTER 3. ALTERNATIVE MEDICINE AND FOSAMAX .................................................................. 27 Overview...................................................................................................................................... 27 National Center for Complementary and Alternative Medicine.................................................. 27 Additional Web Resources ........................................................................................................... 32 General References ....................................................................................................................... 33 CHAPTER 4. CLINICAL TRIALS AND FOSAMAX............................................................................... 35 Overview...................................................................................................................................... 35 Recent Trials on Fosamax ............................................................................................................ 35 Keeping Current on Clinical Trials ............................................................................................. 41 CHAPTER 5. PATENTS ON FOSAMAX ............................................................................................... 43 Overview...................................................................................................................................... 43 Patents on Fosamax ..................................................................................................................... 43 Patent Applications on Fosamax.................................................................................................. 49 Keeping Current .......................................................................................................................... 51 CHAPTER 6. BOOKS ON FOSAMAX .................................................................................................. 53 Overview...................................................................................................................................... 53 The National Library of Medicine Book Index ............................................................................. 53 Chapters on Fosamax ................................................................................................................... 54 CHAPTER 7. PERIODICALS AND NEWS ON FOSAMAX ..................................................................... 55 Overview...................................................................................................................................... 55 News Services and Press Releases................................................................................................ 55 Academic Periodicals covering Fosamax...................................................................................... 57 CHAPTER 8. RESEARCHING MEDICATIONS .................................................................................... 59 Overview...................................................................................................................................... 59 U.S. Pharmacopeia....................................................................................................................... 59 Commercial Databases ................................................................................................................. 60 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 63 Overview...................................................................................................................................... 63 NIH Guidelines............................................................................................................................ 63 NIH Databases............................................................................................................................. 65 Other Commercial Databases....................................................................................................... 67 APPENDIX B. PATIENT RESOURCES ................................................................................................. 69 Overview...................................................................................................................................... 69 Patient Guideline Sources............................................................................................................ 69 Finding Associations.................................................................................................................... 71 APPENDIX C. FINDING MEDICAL LIBRARIES .................................................................................. 73 Overview...................................................................................................................................... 73 Preparation................................................................................................................................... 73 Finding a Local Medical Library.................................................................................................. 73

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Medical Libraries in the U.S. and Canada ................................................................................... 73 ONLINE GLOSSARIES.................................................................................................................. 79 Online Dictionary Directories ..................................................................................................... 79 FOSAMAX DICTIONARY............................................................................................................. 81 INDEX .............................................................................................................................................. 107

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FORWARD 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."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with Fosamax is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about Fosamax, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to Fosamax, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on Fosamax. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to Fosamax, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on Fosamax. The Editors

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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.

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CHAPTER 1. STUDIES ON FOSAMAX Overview In this chapter, we will show you how to locate peer-reviewed references and studies on Fosamax.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and Fosamax, 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 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 “Fosamax” (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 what you can expect from this type of search: •

Fosamax Recently Approved in Canada for the Treatment of Paget 's Disease Source: Update. (18)1:4-5. Spring 1996. Contact: Paget Foundation for Paget 's Disease of Bone and Related Disorders. 200 Varick Street, Suite 1004. New York, NY 10014-4810. (212) 229-1582 or Fax (212) 2291502. Price: Free. Summary: Fosamax , a newly-approved Canadian aminobisphosphonate , decreases the rate of bone resorption, therefore reducing the abnormal bone resorption associated with Paget 's disease. Clinical trials show a 60 percent or more success rate in normalizing alkaline phosphatase levels while maintaining normal quality in reformed bone and without discrimination as to race, sex, or age of patient. Fosamax absorption requires a 30-minute wait, subsequent to taking a dose, before ingesting any food or

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liquids (other than plain water). Side effects are reported to be mild and not significantly affecting quality of life. Fosamax has been approved in the U.S., Canada, and 18 other countries.

Federally Funded Research on Fosamax The U.S. Government supports a variety of research studies relating to Fosamax. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 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. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to Fosamax. 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 Fosamax. The following is typical of the type of information found when searching the CRISP database for Fosamax: •

Project Title: BISPHOSPHONATE THERAPY IN ALCOHOL-INDUCED BONE DISEASE Principal Investigator & Institution: Wezeman, Frederick H.; Professor; Orthopaedic Surgery and Rehab; Loyola University Medical Center Lewis Towers, 13Th Fl Chicago, Il 60611 Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 28-FEB-2005 Summary: Alcohol abuse is a major public health problem in the United States and world-wide, and alcohol consumption by young individuals is rising. The direct effects of alcohol on the skeleton lead to reduced bone formation. In adults, alcohol- related osteopenia increases fracture incidence; fracture incidences rise in postmenopausal estrogen-deficient females who also use alcohol. There are no current therapeutic approaches to restore bone loss due to alcohol-induced damage. We will therefore test the hypothesis that bisphosphonate therapy during chronic alcohol ingestion reduces alcohol-induced damage to bone. Our preliminary results indicate that for one bisphosponate, alendronate (Fosamax) trabecular bone mineral density is increased during chronic alcohol ingestion in male rats. These preliminary data suggest that the bisphosphonates may be ideal therapeutic agents in restoring bone loss associated with alcohol-induced osteopenia. We will test our hypothesis for the bisphosphonates alendronate, clodronate, ibandronate and pamidronate at both a high and low dose. These in vivo studies will compare the effects of bisphosphonates in age- and genderrelated experiments. In Specific Aim number 1 we will test these bisphosphonates in adolescent male and female rats during skeletal modeling during chronic alcohol intake. In Specific Aim number 2 we will test these bisphosphonates in adult male and female adult rats undergoing skeletal remodeling during chronic alcohol ingestion. In Specific

2 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).

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Aim number 3 we will test these bisphosphonates in parallel with parathyroid hormone in sham-operated and ovariectomized adult female rats to determine their effectiveness in estrogen-depleted animals during chronic alcohol ingestion. We will compare the dose-related therapeutic interventions by measuring serum hormonal changes for IGF-1, testosterone, luteinizing hormone (ICSH), estradiol, and osteocalcin, for trabecular and cortical bone mineral density by quantitative computerized tomography, for metaphyseal bone gene expression of type I collagen, osteocalcin, and bone-specific alkaline phosphatase, for cortical bone biomechanical properties, and for trabecular and cortical bone histomorphometric parameters. We expect that the various types and doses of the bisphosphonates (chosen on the basis of their antiresorptive potencies) will differ in their effects on these skeletal tissues during chronic alcohol ingestion. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMPAIRMENTS AND BONE REMODELING IN AGING PAGETS PATIENTS Principal Investigator & Institution: Lyles, Kenneth W.; Professor; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001; Project Start 01-DEC-2000; Project End 30-NOV-2001 Summary: Purpose: The purpose of this study is to determine if pamidroante will improve mobility impairments, functional status, pain, and psychosocial performance in patients with Paget's disease of bone. Methods: In order to determine if pamidronate will improve mobility impairments, functional status, pain, and psychosocial performance, we propose to use a randomized, double-blind, placebo-controlled trial in which 66 patients with active Paget's disease of femur, tibia, and/or acetabular portion of the ilium will be treated (pamidronate or placebo) and then followed for 6 months. All patients who enter the trial must have documented impairments in mobility, defined as an abnormal mobility measure (ten foot walk time, 360 degree turn, mobility skills protocol score, or 6 minute walk distance) and bone resorption or formation markers that are at least twice the normal level. When patients who have Paget's disease enter the study, they will have baseline measures performed and then be randomized to receive pamidronate 90mg intravenously over six hours or placebo. Measurements will be made at one, three and six months post therapy. Changes in mobility impairments will be assessed by measuring changes in ten foot walk time, (primary response variable), mobility skills protocol score, steps to make a 360 degree turn, or six minute walk distance. Changes in functional status impairments will be assessed with the Functional Status Questionnaire (FSQ). The primary response variable for functional status will be the instrumental activities of daily living scale of the FSQ. Changes in pain will be assessed by the West Haven Pain Inventory. Changes in impairments in psychosocial performance will be measured with the Rosenberg Self-Esteem Scale, the Beck Depression Scale and the Hopkins Symptom Checklist 90 Revised. Changes in bone remodeling activity will be followed by measuring serum alkaline phosphatase levels and urinary hydroxyproline and N-Telepeptide excretion. Results: Patients continue to be actively recruited and enrolled in this trial. Over the past year on the GCRC twenty-six patients were evaluated who were potential candidates for the study. Of the twenty-six, six were enrolled and two more have been offered a chance to participate in the study but have not yet been consented. We have treated the six patients with pamidronate, a second generation bisphosphonate, and shown improvement in mobility and functional status impairments as well as bone remodeling activity. Significance: Paget's disease of bone is a chronic skeletal disease that affects elderly people and is characterized by areas of increased skeletal remodeling which can

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lead to pain, deformity, secondary arthritis, fractures and rarely malignant degeneration. Several studies suggest that Paget's disease affects 1.8-5% of people over 60 years of age and 10% of people at 90 years of age. Improved therapy will enhance the ability of these patients to function in normal life activities. Future plans: Since the trial was started, two new bisphosphonates have been approved by the FDA to treat Paget's disease of bone: Alendronate (Fosamax) and Risedronate (Actonel). Both of these drugs are oral preparations and some patients have wished to receive oral medication rather than an intravenous preparation. More importantly, these drugs give many patients sustained biochemical and clinical remissions of their Paget's disease lasting 24 to 36 months. This means that many of the patients referred for evaluation of their Paget's disease do not need treatment of their disease as frequently as we had initially planned for this study. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

E-Journals: PubMed Central3 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).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “Fosamax” (or synonyms) into the search box. This search gives you access to fulltext articles. The following is a sample of items found for Fosamax in the PubMed Central database: •

Alendronate mechanism of action: geranylgeraniol, an intermediate in the mevalonate pathway, prevents inhibition of osteoclast formation, bone resorption, and kinase activation in vitro. by Fisher JE, Rogers MJ, Halasy JM, Luckman SP, Hughes DE, Masarachia PJ, Wesolowski G, Russell RG, Rodan GA, Reszka AA.; 1999 Jan 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=15105

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Protein-Tyrosine Phosphatase Activity Regulates Osteoclast Formation and Function: Inhibition by Alendronate. by Schmidt A, Rutledge SJ, Endo N, Opas EE, Tanaka H, Wesolowski G, Leu CT, Huang Z, Ramachandaran C, Rodan SB, Rodan GA.; 1996 Apr 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39762

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.6 3 4

Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.

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. 5 The value of PubMed Central, in addition to its role as an archive, lies in 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. 6 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

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The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. 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 Fosamax, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “Fosamax” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for Fosamax (hyperlinks lead to article summaries): •

14 day endoscopy study comparing risedronate and alendronate in postmenopausal women stratified by Helicobacter pylori status. Author(s): Thomson AB, Marshall JK, Hunt RH, Provenza JM, Lanza FL, Royer MG, Li Z, Blank MA; Risedronate Endoscopy Study Group. Source: The Journal of Rheumatology. 2002 September; 29(9): 1965-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12233894&dopt=Abstract

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A cost effectiveness analysis of calcium and vitamin D supplementation, etidronate, and alendronate in the prevention of vertebral fractures in women treated with glucocorticoids. Author(s): Buckley LM, Hillner BE. Source: The Journal of Rheumatology. 2003 January; 30(1): 132-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12508402&dopt=Abstract

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A urine midmolecule osteocalcin assay shows higher discriminatory power than a serum midmolecule osteocalcin assay during short-term alendronate treatment of osteoporotic patients. Author(s): Srivastava AK, Mohan S, Singer FR, Baylink DJ. Source: Bone. 2002 July; 31(1): 62-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12110414&dopt=Abstract

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Additional beneficial effects of alendronate in growth hormone (GH)-deficient adults with osteoporosis receiving long-term recombinant human GH replacement therapy: a randomized controlled trial. Author(s): Biermasz NR, Hamdy NA, Janssen YJ, Roelfsema F. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 July; 86(7): 3079-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11443170&dopt=Abstract

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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Additive effects of raloxifene and alendronate on bone density and biochemical markers of bone remodeling in postmenopausal women with osteoporosis. Author(s): Johnell O, Scheele WH, Lu Y, Reginster JY, Need AG, Seeman E. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 March; 87(3): 98592. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11889149&dopt=Abstract

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Alendronate and etidronate do not regulate interleukin 6 and 11 synthesis in normal human osteoblasts in culture. Author(s): Engel E, Serrano S, Marinoso ML, Lloreta J, Ulloa F, Nogues X, Diez-Perez A, Carbonell J. Source: Calcified Tissue International. 2003 March; 72(3): 228-35. Epub 2003 January 15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12522661&dopt=Abstract

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Alendronate and risedronate: what you need to know about their upper gastrointestinal tract toxicity. Author(s): Baker DE. Source: Reviews in Gastroenterological Disorders. 2002; 2(1): 20-33. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12122976&dopt=Abstract

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Alendronate daily, weekly in conventional tablets and weekly in enteric tablets: preliminary study on the effects in bone turnover markers and incidence of side effects. Author(s): Blumel JE, Castelo-Branco C, de la Cuadra G, Maciver L, Moreno M, Haya J. Source: Journal of Obstetrics and Gynaecology : the Journal of the Institute of Obstetrics and Gynaecology. 2003 May; 23(3): 278-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12850861&dopt=Abstract

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Alendronate does not interfere with 99mTc-methylene diphosphonate bone scanning. Author(s): Carrasquillo JA, Whatley M, Dyer V, Figg WD, Dahut W. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 2001 September; 42(9): 1359-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11535725&dopt=Abstract

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Alendronate improves bone mineral density in elderly women with osteoporosis residing in long-term care facilities. A randomized, double-blind, placebo-controlled trial. Author(s): Greenspan SL, Schneider DL, McClung MR, Miller PD, Schnitzer TJ, Bonin R, Smith ME, DeLucca P, Gormley GJ, Melton ME. Source: Annals of Internal Medicine. 2002 May 21; 136(10): 742-6. Summary for Patients In: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12020142&dopt=Abstract

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Alendronate in the prevention of bone loss after a fracture of the lower leg. Author(s): van der Poest Clement E, van Engeland M, Ader H, Roos JC, Patka P, Lips P. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2002 December; 17(12): 2247-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12469919&dopt=Abstract

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Alendronate in the treatment of avascular necrosis of the hip. Author(s): Agarwala S, Sule A, Pai BU, Joshi VR. Source: Rheumatology (Oxford, England). 2002 March; 41(3): 346-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11934975&dopt=Abstract

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Alendronate in the treatment of Paget's disease of bone. Author(s): Reid IR, Siris E. Source: Int J Clin Pract Suppl. 1999 April; 101: 62-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12669742&dopt=Abstract

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Alendronate in the treatment of postmenopausal osteoporosis. Author(s): Hosking DJ, Favus M, Yates AJ. Source: Int J Clin Pract Suppl. 1999 April; 101: 27-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12669738&dopt=Abstract

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Alendronate in the treatment of primary hyperparathyroid-related osteoporosis: a 2year study. Author(s): Parker CR, Blackwell PJ, Fairbairn KJ, Hosking DJ. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 October; 87(10): 4482-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12364423&dopt=Abstract

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Alendronate increases bone density in chronic spinal cord injury: a case report. Author(s): Sniger W, Garshick E. Source: Archives of Physical Medicine and Rehabilitation. 2002 January; 83(1): 139-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11782844&dopt=Abstract

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Alendronate increases bone mass and reduces bone markers in postmenopausal African-American women. Author(s): Bell NH, Bilezikian JP, Bone HG 3rd, Kaur A, Maragoto A, Santora AC; MK063 Study Group. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 June; 87(6): 2792-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12050252&dopt=Abstract

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Alendronate increases bone mineral density in long-term renal transplant recipients. Author(s): Koc M, Tuglular S, Arikan H, Ozener C, Akoglu E. Source: Transplantation Proceedings. 2002 September; 34(6): 2111-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12270333&dopt=Abstract

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Alendronate increases degree and uniformity of mineralization in cancellous bone and decreases the porosity in cortical bone of osteoporotic women. Author(s): Roschger P, Rinnerthaler S, Yates J, Rodan GA, Fratzl P, Klaushofer K. Source: Bone. 2001 August; 29(2): 185-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11502482&dopt=Abstract

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Alendronate inhibits invasion of PC-3 prostate cancer cells by affecting the mevalonate pathway. Author(s): Virtanen SS, Vaananen HK, Harkonen PL, Lakkakorpi PT. Source: Cancer Research. 2002 May 1; 62(9): 2708-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11980672&dopt=Abstract

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Alendronate inhibits lysophosphatidic acid-induced migration of human ovarian cancer cells by attenuating the activation of rho. Author(s): Sawada K, Morishige K, Tahara M, Kawagishi R, Ikebuchi Y, Tasaka K, Murata Y. Source: Cancer Research. 2002 November 1; 62(21): 6015-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12414621&dopt=Abstract

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Alendronate interacts with the inhibitory effect of 1,25(OH)2D3 on parathyroid hormone-related protein expression in human osteoblastic cells. Author(s): Gomez-Garcia L, Esbrit P, Carreno L, Sabando P, Garcia-Flores M, Martinez ME. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2003 January; 18(1): 78-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12510808&dopt=Abstract

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Alendronate prevents loss of bone density associated with discontinuation of hormone replacement therapy: a randomized controlled trial. Author(s): Ascott-Evans BH, Guanabens N, Kivinen S, Stuckey BG, Magaril CH, Vandormael K, Stych B, Melton ME. Source: Archives of Internal Medicine. 2003 April 14; 163(7): 789-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12695269&dopt=Abstract

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Alendronate reduces the risk of multiple symptomatic fractures: results from the fracture intervention trial. Author(s): Levis S, Quandt SA, Thompson D, Scott J, Schneider DL, Ross PD, Black D, Suryawanshi S, Hochberg M, Yates J; FIT Research Group. Source: Journal of the American Geriatrics Society. 2002 March; 50(3): 409-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11943033&dopt=Abstract

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Alendronate treatment for infants with osteogenesis imperfecta: demonstration of efficacy in a mouse model. Author(s): McCarthy EA, Raggio CL, Hossack MD, Miller EA, Jain S, Boskey AL, Camacho NP. Source: Pediatric Research. 2002 November; 52(5): 660-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12409511&dopt=Abstract

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Alendronate treatment for osteoporosis in patients infected with human immunodeficiency virus. Author(s): Guaraldi G, Ventura P, Albuzza M, Orlando G, Bedini A, Esposito R. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2001 August 1; 33(3): 414-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11438917&dopt=Abstract

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Alendronate: an update of its use in osteoporosis. Author(s): Sharpe M, Noble S, Spencer CM. Source: Drugs. 2001; 61(7): 999-1039. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11434454&dopt=Abstract

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Alendronate: suspected pancreatitis. Author(s): Cadario B. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2002 January 8; 166(1): 86-7, 91-2. English, French. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11800261&dopt=Abstract

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Alendronate-induced lichen planus. Author(s): Lazarov A, Moss K, Plosk N, Cordoba M, Baitelman L. Source: Isr Med Assoc J. 2002 May; 4(5): 389-90. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12040836&dopt=Abstract

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Bilateral acute anterior uveitis after alendronate. Author(s): Ann Intern Med. 2002 Dec 3;137(11):I31 Source: The British Journal of Ophthalmology. 2002 December; 86(12): 1443. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12459003

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Bisphosphonates for the treatment of postmenopausal osteoporosis: clinical studies of etidronate and alendronate. Author(s): Harris ST. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2001 December; 12 Suppl 3: S11-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11846336&dopt=Abstract

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Bones and Crohn's: should we treat Crohn's disease patients with alendronate? Author(s): Bailen LS. Source: Inflammatory Bowel Diseases. 2001 May; 7(2): 175-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11383592&dopt=Abstract

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By the way, doctor. I recently heard that I can take Fosamax once a week for osteoporosis, rather than every day. Is it really effective when taken this way? Is there a downside? Author(s): Robb-Nicholson C. Source: Harvard Women's Health Watch. 2001 May; 8(9): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11410457&dopt=Abstract

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By the way, doctor. My doctor prescribed Fosamax to me for osteoporosis prevention, but it upsets my stomach. Are there any other proven medications for osteoporosis prevention? Author(s): Robb-Nicholson C. Source: Harvard Women's Health Watch. 2000 August; 7(12): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10927664&dopt=Abstract

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Changes in bone mineral density following discontinuation or continuation of alendronate therapy in glucocorticoid-treated patients: a retrospective, observational study. Author(s): Emkey R, Delmas PD, Goemaere S, Liberman UA, Poubelle PE, Daifotis AG, Verbruggen N, Lombardi A, Czachur M. Source: Arthritis and Rheumatism. 2003 April; 48(4): 1102-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687554&dopt=Abstract

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Changes in markers of bone turnover and inflammatory variables during alendronate therapy in pediatric patients with rheumatic diseases. Author(s): Cimaz R, Gattorno M, Sormani MP, Falcini F, Zulian F, Lepore L, Bardare M, Chiesa S, Corona F, Dubini A, Lenhardt A, Martini G, Masi L, Bianchi ML. Source: The Journal of Rheumatology. 2002 August; 29(8): 1786-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12180745&dopt=Abstract

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Combination therapy with hormone replacement and alendronate for prevention of bone loss in elderly women: a randomized controlled trial. Author(s): Greenspan SL, Resnick NM, Parker RA. Source: Jama : the Journal of the American Medical Association. 2003 May 21; 289(19): 2525-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12759324&dopt=Abstract

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Comparison of bone and total alkaline phosphatase and bone mineral density in postmenopausal osteoporotic women treated with alendronate. Author(s): Watts NB, Jenkins DK, Visor JM, Casal DC, Geusens P. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2001; 12(4): 279-88. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11420777&dopt=Abstract

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Cost effectiveness of alendronate (fosamax) for the treatment of osteoporosis and prevention of fractures. Author(s): Johnell O, Jonsson B, Jonsson L, Black D. Source: Pharmacoeconomics. 2003; 21(5): 305-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12627984&dopt=Abstract

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Determination of alendronate in human urine as 9-fluorenylmethyl derivative by high-performance liquid chromatography. Author(s): Ptacek P, Klima J, Macek J. Source: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. 2002 February 5; 767(1): 111-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11863282&dopt=Abstract

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Dispensing error leading to alendronate ingestion. Author(s): Carriere B, Bailey B, Chabot G, Lebel D. Source: The Annals of Pharmacotherapy. 2003 January; 37(1): 87-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12503941&dopt=Abstract

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Drug eruption due to alendronate sodium hydrate. Author(s): Kimura M, Kawada A, Murayama Y, Murayama M. Source: Contact Dermatitis. 2003 February; 48(2): 116. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12694218&dopt=Abstract

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Early response to alendronate after treatment with etidronate in postmenopausal women with osteoporosis. Author(s): Iwamoto J, Takeda T, Ichimura S, Uzawa M. Source: Keio J Med. 2003 June; 52(2): 113-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12862363&dopt=Abstract

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Effect of alendronate on bone mineral density in male idiopathic osteoporosis. Author(s): Weber TJ, Drezner MK. Source: Metabolism: Clinical and Experimental. 2001 August; 50(8): 912-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11474478&dopt=Abstract

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Effect of alendronate on periprosthetic bone loss after total knee arthroplasty: a oneyear, randomized, controlled trial of 19 patients. Author(s): Soininvaara TA, Jurvelin JS, Miettinen HJ, Suomalainen OT, Alhava EM, Kroger PJ. Source: Calcified Tissue International. 2002 December; 71(6): 472-7. Epub 2002 October 10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12370800&dopt=Abstract

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Effect of daily hormone therapy and alendronate use on bone mineral density in postmenopausal women. Author(s): Davas I, Altintas A, Yoldemir T, Varolan A, Yazgan A, Baksu B. Source: Fertility and Sterility. 2003 September; 80(3): 536-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12969694&dopt=Abstract

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Effect of estrogen replacement plus low-dose alendronate treatment on bone density in surgically postmenopausal women with osteoporosis. Author(s): Palomba S, Orio F Jr, Colao A, di Carlo C, Sena T, Lombardi G, Zullo F, Mastrantonio P. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 April; 87(4): 1502-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11932272&dopt=Abstract

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Effect of two forms of alendronate administration upon bone mass after two years of treatment. Author(s): Sosa M, Hernandez D, Segarra MC, Gomez A, de la Pena E, Betancor P. Source: Journal of Clinical Densitometry : the Official Journal of the International Society for Clinical Densitometry. 2002 Spring; 5(1): 27-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11940726&dopt=Abstract

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Effectiveness of alendronate treatment in postmenopausal women with osteoporosis: relationship with BsmI vitamin D receptor genotypes. Author(s): Palomba S, Numis FG, Mossetti G, Rendina D, Vuotto P, Russo T, Zullo F, Nappi C, Nunziata V. Source: Clinical Endocrinology. 2003 March; 58(3): 365-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12608943&dopt=Abstract

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Effects of hormone therapy and alendronate on C-reactive protein, E-selectin, and sex hormone-binding globulin in osteoporotic women. Author(s): Ylikorkala O, Evio S, Valimaki M, Tiitinen A. Source: Fertility and Sterility. 2003 September; 80(3): 541-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12969695&dopt=Abstract

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Efficacy and safety of alendronate for the treatment of osteoporosis in diffuse connective tissue diseases in children. Author(s): Stuart M. Source: Clinical Pediatrics. 2002 June; 41(5): 362-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12086205&dopt=Abstract

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Efficacy of teriparatide and alendronate on nonvertebral fractures. Author(s): Watts NB. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 March; 88(3): 14023; Author Reply 1403. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12629137&dopt=Abstract

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Gastric and duodenal safety of daily alendronate. Author(s): Donahue JG, Chan KA, Andrade SE, Beck A, Boles M, Buist DS, Carey VJ, Chandler JM, Chase GA, Ettinger B, Fishman P, Goodman M, Guess HA, Gurwitz JH, LaCroix AZ, Levin TR, Platt R. Source: Archives of Internal Medicine. 2002 April 22; 162(8): 936-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11966346&dopt=Abstract

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Heel ultrasonography in monitoring alendronate therapy: a four-year longitudinal study. Author(s): Gonnelli S, Cepollaro C, Montagnani A, Martini S, Gennari L, Mangeri M, Gennari C. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2002 May; 13(5): 415-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12086353&dopt=Abstract

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I am 51 years old, perimenopausal, have irritable bowel syndrome and a family history of breast cancer, and am told my bones are thinning. These conditions would seem to rule out my use of estrogen or Fosamax. I weight train and take 1,500 mg of calcium a day to stave off osteoporosis. What's left? Author(s): Robb-Nicholson C. Source: Harvard Women's Health Watch. 1998 November; 6(3): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9814138&dopt=Abstract

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Intravenous pamidronate compared with oral alendronate for the treatment of postmenopausal osteoporosis. Author(s): Heijckmann AC, Juttmann JR, Wolffenbuttel BH. Source: The Netherlands Journal of Medicine. 2002 September; 60(8): 315-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12481878&dopt=Abstract

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Long-term predictions of the therapeutic equivalence of daily and less than daily alendronate dosing. Author(s): Hernandez CJ, Beaupre GS, Marcus R, Carter DR. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2002 September; 17(9): 1662-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12211437&dopt=Abstract

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Meta-analyses of therapies for postmenopausal osteoporosis. II. Meta-analysis of alendronate for the treatment of postmenopausal women. Author(s): Cranney A, Wells G, Willan A, Griffith L, Zytaruk N, Robinson V, Black D, Adachi J, Shea B, Tugwell P, Guyatt G; Osteoporosis Methodology Group and The Osteoporosis Research Advisory Group. Source: Endocrine Reviews. 2002 August; 23(4): 508-16. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12202465&dopt=Abstract

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Month 3 and month 6 measurements of bone mineral density predict the annual outcome in postmenopausal women with osteoporosis in whom alendronate was added to long-term HRT. Author(s): Pines A, Eckstein N, Kopernik G, Ayalon D, Comaneshter D, Frenkel Y. Source: Maturitas. 2003 April 25; 44(4): 287-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12697369&dopt=Abstract

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No major effect of estrogen receptor beta gene RsaI polymorphism on bone mineral density and response to alendronate therapy in postmenopausal osteoporosis. Author(s): Arko B, Prezelj J, Komel R, Kocijancic A, Marc J. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2002 June; 81(2): 147-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12137804&dopt=Abstract

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Nongranulomatous anterior uveitis associated with alendronate therapy. Author(s): Salmen S, Berrueta L, Sanchez N, Montes H, Borges L. Source: Invest Clin. 2002 March; 43(1): 49-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11921747&dopt=Abstract

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Nonhealing gastric ulcer caused by chronic alendronate administration. Author(s): Malnick SD, Gottesfeld F, Walpart A, Keter D, Lurie Y, Beergabel M. Source: Medgenmed [electronic Resource] : Medscape General Medicine. 2002 May 22; 4(2): 3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12145563&dopt=Abstract

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Oral alendronate increases bone mineral density in postmenopausal women with primary hyperparathyroidism. Author(s): Chow CC, Chan WB, Li JK, Chan NN, Chan MH, Ko GT, Lo KW, Cockram CS. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 February; 88(2): 581-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12574184&dopt=Abstract

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Parathyroid hormone plus alendronate--a combination that does not add up. Author(s): Khosla S. Source: The New England Journal of Medicine. 2003 September 25; 349(13): 1277-9. Epub 2003 Sep 20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14500803&dopt=Abstract

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Patient preference for once-weekly alendronate 70 mg versus once-daily alendronate 10 mg: a multicenter, randomized, open-label, crossover study. Author(s): Simon JA, Lewiecki EM, Smith ME, Petruschke RA, Wang L, Palmisano JJ. Source: Clinical Therapeutics. 2002 November; 24(11): 1871-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12501880&dopt=Abstract

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Pharmacokinetics of alendronate: an overview. Author(s): Lin JH, Russell G, Gertz B. Source: Int J Clin Pract Suppl. 1999 April; 101: 18-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12669737&dopt=Abstract

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Pharmacovigilance study of alendronate in England. Author(s): Biswas PN, Wilton LV, Shakir SA. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2003 July; 14(6): 507-14. Epub 2003 April 23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12730757&dopt=Abstract

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Placebo-controlled multicenter study of oral alendronate in postmenopausal osteoporotic women. FOSIT-Study-Group. Fosamax International Trial. Author(s): Felsenberg D, Alenfeld F, Bock O, Hammermeister C, Gowan W. Source: Maturitas. 1998 November 30; 31(1): 35-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10091203&dopt=Abstract

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Preclinical evidence of normal bone with alendronate. Author(s): Hayes WC, Shea M, Rodan GA. Source: Int J Clin Pract Suppl. 1999 April; 101: 9-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12669735&dopt=Abstract

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Preclinical safety profile of alendronate. Author(s): Peter C, Rodan GA. Source: Int J Clin Pract Suppl. 1999 April; 101: 3-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12669734&dopt=Abstract

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Progression of coronary artery calcification in patients taking alendronate for osteoporosis. Author(s): Hill JA, Goldin JG, Gjertson D, Emerick AM, Greaser LD, Yoon HC, Khorrami S, Aziz D, Adams JS. Source: Academic Radiology. 2002 October; 9(10): 1148-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12385509&dopt=Abstract

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Re: Famularo--esophageal perforation in a patient with esophageal diverticulum on daily alendronate. Author(s): Daifotis AG. Source: The American Journal of Gastroenterology. 2002 October; 97(10): 2678; Author Reply 2678. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12385463&dopt=Abstract

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Re: Lanza et al.--Endoscopic comparison of alendronate and risedronate. Author(s): Blank MA, Thomson AB. Source: The American Journal of Gastroenterology. 2001 June; 96(6): 1938-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11419858&dopt=Abstract

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Response to alendronate in osteoporotic women previously treated with pamidronate. Author(s): Peretz A, Siderova V, Body JJ, Dumon JC, Rozenberg S, Fellemans C, Fuss M, Bergmann P; Interdisciplinary Group for the Study of Bone Diseases and Calcium metabolism (GIPOB). Source: Maturitas. 2003 February 25; 44(2): 111-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12590006&dopt=Abstract

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Results of special studies with alendronate. Author(s): McClung M. Source: Int J Clin Pract Suppl. 1999 April; 101: 67-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12669743&dopt=Abstract

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Seizures after alendronate. Author(s): Maclsaac RJ, Seeman E, Jerums G. Source: Journal of the Royal Society of Medicine. 2002 December; 95(12): 615-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12461152&dopt=Abstract

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Significant differential effects of alendronate, estrogen, or combination therapy on the rate of bone loss after discontinuation of treatment of postmenopausal osteoporosis. A randomized, double-blind, placebo-controlled trial. Author(s): Greenspan SL, Emkey RD, Bone HG, Weiss SR, Bell NH, Downs RW, McKeever C, Miller SS, Davidson M, Bolognese MA, Mulloy AL, Heyden N, Wu M, Kaur A, Lombardi A. Source: Annals of Internal Medicine. 2002 December 3; 137(11): 875-83. Summary for Patients In: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12458987&dopt=Abstract

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Study of alendronate in avascular necrosis of bone. Author(s): Agarwala S, Sule A, Pai BU, Joshi VR. Source: J Assoc Physicians India. 2001 September; 49: 949-50. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11837783&dopt=Abstract

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Superficial gyrate erythema as a cutaneous reaction to alendronate for osteoporosis. Author(s): High WA, Cohen JB, Wetherington W, Cockerell CJ. Source: Journal of the American Academy of Dermatology. 2003 June; 48(6): 945-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12789190&dopt=Abstract

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The antifracture efficacy of alendronate. Author(s): Seeman E. Source: Int J Clin Pract Suppl. 1999 April; 101: 40-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12675021&dopt=Abstract

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The clinical tolerability profile of alendronate. Author(s): Watts N, Freedholm D, Daifotis A. Source: Int J Clin Pract Suppl. 1999 April; 101: 51-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12669741&dopt=Abstract

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The effect of alendronate (Fosamax) and implant surface on bone integration and remodeling in a canine model. Author(s): Frenkel SR, Jaffe WL, Valle CD, Jazrawi L, Maurer S, Baitner A, Wright K, Sala D, Hawkins M, Di Cesare PE. Source: Journal of Biomedical Materials Research. 2001; 58(6): 645-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11745516&dopt=Abstract

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The effect of alendronate sodium on alveolar bone loss in periodontitis (clinical trial). Author(s): El-Shinnawi UM, El-Tantawy SI. Source: J Int Acad Periodontol. 2003 January; 5(1): 5-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12666950&dopt=Abstract

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The effect of alendronate therapy on osteoporotic fracture in the vertebral fracture arm of the Fracture Intervention Trial. Author(s): Black DM, Thompson DE. Source: Int J Clin Pract Suppl. 1999 April; 101: 46-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12669740&dopt=Abstract

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The effects of alendronate and calcitonin on cytokines in postmenopausal osteoporosis: a 6-month randomized and controlled study. Author(s): Gur A, Denli A, Cevik R, Nas K, Karakoc M, Sarac AJ. Source: Yonsei Medical Journal. 2003 February; 44(1): 99-109. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12619182&dopt=Abstract

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The effects of alendronate in postmenopausal women with osteoporosis. Author(s): Yaniv I. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2003 January; 14(1): 90-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12577190&dopt=Abstract

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The effects of alendronate on bone turnover and bone quality. Author(s): Meunier PJ, Arlot M, Chavassieux P, Yates AJ. Source: Int J Clin Pract Suppl. 1999 April; 101: 14-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12669736&dopt=Abstract

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The effects of alendronate on stature and the spine deformity index. Author(s): Minne HW, Pollhane W, Karpf DB. Source: Int J Clin Pract Suppl. 1999 April; 101: 36-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12669739&dopt=Abstract

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The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis. Author(s): Black DM, Greenspan SL, Ensrud KE, Palermo L, McGowan JA, Lang TF, Garnero P, Bouxsein ML, Bilezikian JP, Rosen CJ; PaTH Study Investigators. Source: The New England Journal of Medicine. 2003 September 25; 349(13): 1207-15. Epub 2003 Sep 20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14500804&dopt=Abstract

Studies

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•

The effects of parathyroid hormone, alendronate, or both in men with osteoporosis. Author(s): Finkelstein JS, Hayes A, Hunzelman JL, Wyland JJ, Lee H, Neer RM. Source: The New England Journal of Medicine. 2003 September 25; 349(13): 1216-26. Epub 2003 Sep 20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14500805&dopt=Abstract

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The upper GI safety and tolerability of oral alendronate at a dose of 70 milligrams once weekly: a placebo-controlled endoscopy study. Author(s): Lanza F, Sahba B, Schwartz H, Winograd S, Torosis J, Quan H, Reyes R, Musliner T, Daifotis A, Leung A. Source: The American Journal of Gastroenterology. 2002 January; 97(1): 58-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11808969&dopt=Abstract

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The values of urinary NTx in postmenopausal women undergoing HRT; the role of additional alendronate therapy. Author(s): Posaci C, Altunyurt S, Islekel H, Saygili U, Altekin E, Onvural A, Onvural B. Source: Maturitas. 2002 August 30; 42(4): 281-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12191850&dopt=Abstract

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Therapeutic equivalence of alendronate 35 milligrams once weekly and 5 milligrams daily in the prevention of postmenopausal osteoporosis. Author(s): Luckey MM, Gilchrist N, Bone HG, Davie MW, de Villiers TJ, Wu M, Daifotis AG, Santora AC, Orloff JJ. Source: Obstetrics and Gynecology. 2003 April; 101(4): 711-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12681875&dopt=Abstract

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Tolerability of once-weekly alendronate in patients with osteoporosis: a randomized, double-blind, placebo-controlled study. Author(s): Greenspan S, Field-Munves E, Tonino R, Smith M, Petruschke R, Wang L, Yates J, de Papp AE, Palmisano J. Source: Mayo Clinic Proceedings. 2002 October; 77(10): 1044-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12374248&dopt=Abstract

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Tolerability of risedronate in postmenopausal women intolerant of alendronate. Author(s): Adachi JD, Adami S, Miller PD, Olszynski WP, Kendler DL, Silverman SL, Licata AA, Li Z, Gomez-Panzani E. Source: Aging (Milano). 2001 October; 13(5): 347-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11820707&dopt=Abstract

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Treatment of male osteoporosis: recent advances with alendronate. Author(s): Ringe JD, Orwoll E, Daifotis A, Lombardi A. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2002 March; 13(3): 195-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11991437&dopt=Abstract

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Treatment of osteoporosis and osteopenia in long-term renal transplant patients with alendronate. Author(s): Cruz DN, Brickel HM, Wysolmerski JJ, Gundberg CG, Simpson CA, Kliger AS, Lorber MI, Basadonna GP, Friedman AL, Insogna KL, Bia MJ. Source: American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2002 January; 2(1): 62-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12095058&dopt=Abstract

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Two-year results of once-weekly administration of alendronate 70 mg for the treatment of postmenopausal osteoporosis. Author(s): Rizzoli R, Greenspan SL, Bone G 3rd, Schnitzer TJ, Watts NB, Adami S, Foldes AJ, Roux C, Levine MA, Uebelhart B, Santora AC 2nd, Kaur A, Peverly CA, Orloff JJ; Alendronate Once-Weekly Study Group. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2002 November; 17(11): 1988-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12412806&dopt=Abstract

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Use of alendronate in treatment of secondary osteoporosis from hypopituitarism: a case report. Author(s): Maugeri D, Bonanno MR, Russo MS, Speciale S, Santangelo A, Curasi MP, Panebianco P. Source: Eur Rev Med Pharmacol Sci. 2000 July-August; 4(4): 89-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11550759&dopt=Abstract

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Use of phalangeal bone mineral density and multi-site speed of sound conduction to monitor therapy with alendronate in postmenopausal women. Author(s): Drake WM, Brown JP, Banville C, Kendler DL. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2002 March; 13(3): 249-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11991446&dopt=Abstract

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CHAPTER 2. NUTRITION AND FOSAMAX Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and Fosamax.

Finding Nutrition Studies on Fosamax The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail: [email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “Fosamax” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

7 Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

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The following information is typical of that found when using the “Full IBIDS Database” to search for “Fosamax” (or a synonym): •

By the way, doctor. My doctor prescribed Fosamax to me for osteoporosis prevention, but it upsets my stomach. Are there any other proven medications for osteoporosis prevention? Source: Robb Nicholson, C Harv-Womens-Health-Watch. 2000 August; 7(12): 8 1070910X

•

I am 51 years old, perimenopausal, have irritable bowel syndrome and a family history of breast cancer, and am told my bones are thinning. These conditions would seem to rule out my use of estrogen or Fosamax. I weight train and take 1,500 mg of calcium a day to stave off osteoporosis. What's left? Source: Robb Nicholson, C Harv-Womens-Health-Watch. 1998 November; 6(3): 8 1070910X

Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •

healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

Nutrition

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Google: http://directory.google.com/Top/Health/Nutrition/

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Healthnotes: http://www.healthnotes.com/

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Open Directory Project: http://dmoz.org/Health/Nutrition/

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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/

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WebMD®Health: http://my.webmd.com/nutrition

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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The following is a specific Web list relating to Fosamax; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

Minerals Calcium Source: Healthnotes, Inc.; www.healthnotes.com Calcium Source: Integrative Medicine Communications; www.drkoop.com Magnesium Source: Healthnotes, Inc.; www.healthnotes.com Magnesium Source: Integrative Medicine Communications; www.drkoop.com

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CHAPTER 3. ALTERNATIVE MEDICINE AND FOSAMAX Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to Fosamax. At the conclusion of this chapter, we will provide additional sources.

National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to Fosamax and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “Fosamax” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to Fosamax: •

A 73-year-old woman with osteoporosis. Author(s): Greenspan SL. Source: Jama : the Journal of the American Medical Association. 1999 April 28; 281(16): 1531-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10227324&dopt=Abstract

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A cost effectiveness analysis of calcium and vitamin D supplementation, etidronate, and alendronate in the prevention of vertebral fractures in women treated with glucocorticoids. Author(s): Buckley LM, Hillner BE. Source: The Journal of Rheumatology. 2003 January; 30(1): 132-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12508402&dopt=Abstract

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Alendronate improves bone mineral density in elderly women with osteoporosis residing in long-term care facilities. A randomized, double-blind, placebo-controlled

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trial. Author(s): Greenspan SL, Schneider DL, McClung MR, Miller PD, Schnitzer TJ, Bonin R, Smith ME, DeLucca P, Gormley GJ, Melton ME. Source: Annals of Internal Medicine. 2002 May 21; 136(10): 742-6. Summary for Patients In: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12020142&dopt=Abstract •

Alendronate inhibition of protein-tyrosine-phosphatase-meg1. Author(s): Opas EE, Rutledge SJ, Golub E, Stern A, Zimolo Z, Rodan GA, Schmidt A. Source: Biochemical Pharmacology. 1997 September 15; 54(6): 721-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9310349&dopt=Abstract

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Alendronate prevents cyclosporin A-induced osteopenia in the rat. Author(s): Sass DA, Bowman AR, Yuan Z, Ma Y, Jee WS, Epstein S. Source: Bone. 1997 July; 21(1): 65-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9213009&dopt=Abstract

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American Association of Clinical Endocrinologists 2001 Medical Guidelines for Clinical Practice for the Prevention and Management of Postmenopausal Osteoporosis. Author(s): Hodgson SF, Watts NB, Bilezikian JP, Clarke BL, Gray TK, Harris D W, Johnston CC, Kleerekoper M, Lindsay R, Luckey MM, McClung MR, Nankin HR, Petak SM, Recker RR; American Association of Clinical Endocrinologists. Source: Endocrine Practice : Official Journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2001 July-August; 7(4): 293312. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11508261&dopt=Abstract

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Bisphosphonate therapy for Paget's disease in a patient with hypoparathyroidism: profound hypocalcemia, rapid response, and prolonged remission. Author(s): Stuckey BG, Lim EM, Kent GN, Ward LC, Gutteridge DH. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2001 September; 16(9): 1719-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11547843&dopt=Abstract

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Bisphosphonates and tetracycline: experimental models for their evaluation in calcium-related disorders. Author(s): Cohen H, Solomon V, Alferiev IS, Breuer E, Ornoy A, Patlas N, Eidelman N, Hagele G, Golomb G. Source: Pharmaceutical Research. 1998 April; 15(4): 606-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9587958&dopt=Abstract

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Bisphosphonates in prostate carcinoma. Author(s): Adami S.

Alternative Medicine 29

Source: Cancer. 1997 October 15; 80(8 Suppl): 1674-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9362435&dopt=Abstract •

Combining herbal supplements with prescription drugs. Author(s): Annfinsen SL, Pick M, Woodward JA. Source: Adv Nurse Pract. 1998 May; 6(5): 28. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9633286&dopt=Abstract

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Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial. Author(s): Cummings SR, Black DM, Thompson DE, Applegate WB, Barrett-Connor E, Musliner TA, Palermo L, Prineas R, Rubin SM, Scott JC, Vogt T, Wallace R, Yates AJ, LaCroix AZ. Source: Jama : the Journal of the American Medical Association. 1998 December 23-30; 280(24): 2077-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9875874&dopt=Abstract

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Effectiveness of local delivery of alendronate in reducing alveolar bone loss following periodontal surgery in rats. Author(s): Binderman I, Adut M, Yaffe A. Source: J Periodontol. 2000 August; 71(8): 1236-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10972639&dopt=Abstract

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Effects of a bisphosphonate on experimental periodontitis in monkeys. Author(s): Brunsvold MA, Chaves ES, Kornman KS, Aufdemorte TB, Wood R. Source: J Periodontol. 1992 October; 63(10): 825-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1328593&dopt=Abstract

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Effects of alendronate and taxol on PC-3 ML cell bone metastases in SCID mice. Author(s): Stearns ME, Wang M. Source: Invasion & Metastasis. 1996; 16(3): 116-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9186547&dopt=Abstract

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From the Food and Drug Administration. Author(s): Nightingale SL. Source: Jama : the Journal of the American Medical Association. 1996 May 22-29; 275(20): 1534. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8622234&dopt=Abstract

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How does alendronate inhibit protein-tyrosine phosphatases? Author(s): Skorey K, Ly HD, Kelly J, Hammond M, Ramachandran C, Huang Z, Gresser MJ, Wang Q.

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Source: The Journal of Biological Chemistry. 1997 September 5; 272(36): 22472-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9278398&dopt=Abstract •

Local delivery of an amino bisphosphonate prevents the resorptive phase of alveolar bone following mucoperiosteal flap surgery in rats. Author(s): Yaffe A, Iztkovich M, Earon Y, Alt I, Lilov R, Binderman I. Source: J Periodontol. 1997 September; 68(9): 884-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9379334&dopt=Abstract

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Long-term prevention of bone loss. Author(s): Lesser GT. Source: Annals of Internal Medicine. 2000 July 4; 133(1): 72-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10877744&dopt=Abstract

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Nonclinical model for assessing gastric effects of bisphosphonates. Author(s): Blank MA, Ems BL, Gibson GW, Myers WR, Berman SK, Phipps RJ, Smith PN. Source: Digestive Diseases and Sciences. 1997 February; 42(2): 281-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9052507&dopt=Abstract

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On the absorption of alendronate in rats. Author(s): Lin JH, Chen IW, deLuna FA. Source: Journal of Pharmaceutical Sciences. 1994 December; 83(12): 1741-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7891304&dopt=Abstract

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Osteoporosis: diagnosis, prevention, and treatment of established disease. Author(s): Dunlop MB, Lane NE. Source: Bulletin on the Rheumatic Diseases. 1999; 48(6): 1-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10544524&dopt=Abstract

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Osteoporosis: evaluation and treatment. Author(s): Milott JL, Green SS, Schapira MM. Source: Compr Ther. 2000 Fall; 26(3): 183-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10984823&dopt=Abstract

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Osteoporosis: protecting bone mass with fundamentals and drug therapy. Author(s): Kleerekoper M. Source: Geriatrics. 1999 July; 54(7): 38-43; Quiz 44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10431598&dopt=Abstract

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Prevention and treatment of osteoporosis. Author(s): Prestwood KM, Raisz LG.


Source: Clinical Cornerstone. 2002; 4(6): 31-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12739329&dopt=Abstract •

Prevention of osteocyte and osteoblast apoptosis by bisphosphonates and calcitonin. Author(s): Plotkin LI, Weinstein RS, Parfitt AM, Roberson PK, Manolagas SC, Bellido T. Source: The Journal of Clinical Investigation. 1999 November; 104(10): 1363-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10562298&dopt=Abstract

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Response to alendronate in osteoporotic women previously treated with pamidronate. Author(s): Peretz A, Siderova V, Body JJ, Dumon JC, Rozenberg S, Fellemans C, Fuss M, Bergmann P; Interdisciplinary Group for the Study of Bone Diseases and Calcium metabolism (GIPOB). Source: Maturitas. 2003 February 25; 44(2): 111-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12590006&dopt=Abstract

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Sodium EDTA enhances intestinal absorption of two bisphosphonates. Author(s): Janner M, Muhlbauer RC, Fleisch H. Source: Calcified Tissue International. 1991 October; 49(4): 280-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1836974&dopt=Abstract

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The influence of alendronate on bone formation and resorption in a rat ectopic bone development model. Author(s): Yaffe A, Kollerman R, Bahar H, Binderman I. Source: J Periodontol. 2003 January; 74(1): 44-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12593595&dopt=Abstract

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Tissue inhibitor of metalloproteinase-2 protection of matrix metalloproteinase-2 from degradation by plasmin is reversed by divalent cation chelator EDTA and the bisphosphonate alendronate. Author(s): Farina AR, Tacconelli A, Teti A, Gulino A, Mackay AR. Source: Cancer Research. 1998 July 15; 58(14): 2957-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9679953&dopt=Abstract

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Use of alendronate in peri-implant defect regeneration. Author(s): Meraw SJ, Reeve CM, Wollan PC. Source: J Periodontol. 1999 February; 70(2): 151-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10102552&dopt=Abstract

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Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •

Alternative Medicine Foundation, Inc.: http://www.herbmed.org/

•


•

Chinese Medicine: http://www.newcenturynutrition.com/

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drkoop.com®: http://www.drkoop.com/InteractiveMedicine/IndexC.html

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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm

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Google: http://directory.google.com/Top/Health/Alternative/

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Healthnotes: http://www.healthnotes.com/

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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine

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Open Directory Project: http://dmoz.org/Health/Alternative/

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HealthGate: http://www.tnp.com/

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WebMD®Health: http://my.webmd.com/drugs_and_herbs

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/

The following is a specific Web list relating to Fosamax; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

General Overview Bone Loss Source: Integrative Medicine Communications; www.drkoop.com Hyperparathyroidism Source: Integrative Medicine Communications; www.drkoop.com Menopause Source: Integrative Medicine Communications; www.drkoop.com Osteoporosis Source: Healthnotes, Inc.; www.healthnotes.com Osteoporosis Source: Integrative Medicine Communications; www.drkoop.com Osteoporosis Source: Prima Communications, Inc.www.personalhealthzone.com


•

Herbs and Supplements Alendronate Source: Healthnotes, Inc.; www.healthnotes.com Bisphosphonate Derivatives Source: Integrative Medicine Communications; www.drkoop.com Bisphosphonates Source: Healthnotes, Inc.; www.healthnotes.com

General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.

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CHAPTER 4. CLINICAL TRIALS AND FOSAMAX Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning Fosamax.

Recent Trials on Fosamax The following is a list of recent trials dedicated to Fosamax.8 Further information on a trial is available at the Web site indicated. •

Alendronate to Treat Polyostotic Fibrous Dysplasia and McCune-Albright Syndrome Condition(s): Polyostotic Fibrous Dysplasia Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Dental and Craniofacial Research (NIDCR) Purpose - Excerpt: This study will evaluate the effectiveness of alendronate in treating the bone abnormality in polyostotic fibrous dysplasia and McCune-Albright syndrome. In these diseases, areas of normal bone are replaced with a fibrous growth similar to a scar. The weakened bone causes pain and increases patients' risk of bone fractures and bone deformities. Alendronate belongs to a class of drugs called "bisphosphonates," which are approved by the Food and Drug Administration to treat bone weakening, deformity and pain in other medical conditions. It is thought that bisphosphonates might work by slowing the activity of osteoclasts-cells that break down bone. Patients 12 years of age and older with polyostotic fibrous dysplasia or McCune-Albright syndrome may be eligible for this 3-year study. Candidates must also be enrolled in NIDCR's protocol 98-D-0145 (Screening and Natural History of Patients with Polyostotic Fibrous Dysplasia and McCune-Albright Syndrome). Participants will be randomly assigned to one of two treatment groups: they will take one capsule a day of either alendronate or placebo (a look-alike capsule that has no active ingredient). They will take the capsules for 6 months, stop for 6 months, then take them for another 6 months and then go off them for 6 months. They will then remain off the drug or placebo for an additional 12 months and complete the study with a final follow-up visit at 36 months. While taking

8

These are listed at www.ClinicalTrials.gov.

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alendronate or placebo, patients will also take calcium and vitamin D to prevent secondary hyperparathyroidism-a side effect of alendronate in which the bone does not release enough calcium. Patients will come to NIH for a physical examination and blood and urine tests every 6 months and for monitoring of their bone disease, vision, hearing, pain levels, functional evaluation, and photographs every 12 months. Many of the monitoring procedures, including imaging studies and biopsies, are performed for the screening protocol (98-D-0145) and will not be duplicated for this study. During the study periods when patients are taking alendronate or placebo, they will have blood samples drawn by their local physician once every 3 months and sent to NIH to check for secondary hyperparathyroidism. If at the end of the study alendronate is found to be effective, patients who were in the placebo treatment group will be offered alendronate for a 24-month period. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001728 •

Comparison of Study Drug With Alendronate on How it Effects GlucocorticoidInduced Osteoporosis Condition(s): Osteoporosis Study Status: This study is currently recruiting patients. Sponsor(s): Eli Lilly and Company Purpose - Excerpt: Osteoporosis is a condition in which the amount of bone is reduced, the bones are weak, and there is an increased risk for fractures. Glucocorticoids (a type of cortisone such as prednisone) are prescribed to treat a large number of conditions such as arthritis and asthma. When taken for several months or longer, glucocorticoids can cause bone loss and lead to a form of osteoporosis called "glucocorticoid-induced osteoporosis." This study will be comparing the effects of the study drug to an available drug called alendronate on glucocorticoid-induced osteoporosis. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00051558

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EVA: Evista Alendronate Comparison Condition(s): Osteoporosis Study Status: This study is currently recruiting patients. Sponsor(s): Eli Lilly and Company Purpose - Excerpt: The purpose of this study is to determine how treatment with raloxifene compares to treatment with alendronate in postmenopausal women with osteoporosis on the chance of experiencing fractures Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below

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Web Site: http://clinicaltrials.gov/ct/show/NCT00035971 •

Phase II Randomized Study of Alendronate Sodium for Osteopenia in Patients with Gaucher's Disease Condition(s): Gaucher's Disease; Osteopenia Study Status: This study is currently recruiting patients. Sponsor(s): FDA Office of Orphan Products Development; Children's Hospital Medical Center - Cincinnati Purpose - Excerpt: Objectives: I. Determine the efficacy of alendronate sodium in treating osteopenia (generalized bone density and focal bone lesions) in patients with Gaucher's disease. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004488

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Randomized Study of Alendronate in Adult Patients With Cystic Fibrosis Related Osteoporosis Condition(s): Osteoporosis; Cystic Fibrosis Study Status: This study is currently recruiting patients. Sponsor(s): FDA Office of Orphan Products Development; University of North Carolina Purpose - Excerpt: Objectives: I. Determine the bioavailability and biologic effect of alendronate on bone metabolism in patients with cystic fibrosis. II. Assess the safety and efficacy of this treatment regimen in improving osteoporosis in this patient population. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004489

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A Randomized Phase II Study of High Dose Ketoconazole Plus Alendronate Versus High Dose Ketoconazole in Patients with Androgen Independent Metastatic Prostate Cancer Condition(s): Neoplasm Metastasis; Prostatic Neoplasm Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: This is an open-label, randomized, phase II study of high-dose ketoconazole plus alendronate versus high dose ketoconazole in patients with androgen-independent metastatic prostate cancer. Following pharmacokinetic assessment, ketoconazole will be initiated at a dose of 400 mg three times per day, plus 30 mg of hydrocortisone (20 mg in the morning and 10 mg in the evening), plus or minus alendronate 40 mg orally every morning. Each patient will be evaluated every 4 weeks for the duration of the study. Radiographic studies will be repeated every 2 months. Phase(s): Phase II

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Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001802 •

Alendronate and/or Parathyroid Hormone for Osteoporosis Condition(s): Osteoporosis Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: This study looks at the effects of two medications, alendronate and parathyroid hormone, on bone mass and on bone formation and bone breakdown in women with osteoporosis. We will randomly select postmenopausal women who have osteoporosis to receive laboratory-produced human parathyroid hormone (hPTH), or alendronate, or both for 2.5 years. Study participants will return to the study center periodically to have their bone mass measured and to give blood and urine samples for tests of bone formation and breakdown and for other laboratory tests. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000400

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Low-Dose Hormone Replacement Therapy and Alendronate for Osteoporosis Condition(s): Osteopenia; Osteoporosis Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: Osteoporosis, a condition in which bones are fragile and break easily, is a major health problem for postmenopausal women. Research studies have shown that both estrogen/progestin replacement therapy (hormone replacement therapy, or HRT) and alendronate are effective in preventing and treating osteoporosis. However, because these drugs work in somewhat different ways, a combination of the two drugs might protect women from osteoporosis better than either drug alone. In this study we will test whether HRT and alendronate given together for 3.5 years to postmenopausal women with low bone mass will have a greater effect on bone than either HRT or alendronate given alone. We will also give every participant in this study calcium and vitamin D supplements. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000430

•

Parathyroid Hormone (PTH) with Alendronate for Osteoporosis Condition(s): Osteoporosis

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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: This study investigates the effectiveness of parathyroid hormone (PTH) in combination with alendronate, a standard treatment for osteoporosis that blocks or reduces bone loss. We are using alendronate because it may help protect patients against any possible harmful effects of PTH in cortical bone such as the long bones or hip. We are testing two different treatment schedules of PTH-one in which we give PTH daily and one in which we give PTH for 3 out of every 6 months in a cyclical fashion. The entire study is 21 months long; the active treatment period is 18 months with a 6-month followup period. The main effects we will look for in this study are changes in body chemicals that are signs of bone formation or bone breakdown, and changes in bone density throughout the skeleton. We will randomly assign all study participants, who are women aged 50 and over, to either stay on alendronate alone, receive daily continuous PTH plus alendronate, or receive daily PTH for 3 months out of every 6 for a total of three separate 3-month cycles of PTH plus daily alendronate. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005006 •

PaTH Study: Parathyroid Hormone and Alendronate for Osteoporosis Condition(s): Osteoporosis Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: This 2-year study will test the effectiveness of combining parathyroid hormone (PTH) and alendronate for treating osteoporosis in postmenopausal women. Alendronate is a drug used to treat osteoporosis and primarily prevents bone loss, whereas PTH increases bone formation. We will treat the study participants either with PTH and alendronate, alendronate alone, or PTH alone. We will determine the effects of these treatments by looking for changes in bone mineral density in the hip and spine. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005005

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Phase II Study of Alendronate Sodium in Children With High-Turnover Idiopathic Juvenile Osteoporosis Condition(s): Osteoporosis Study Status: This study is not yet open for patient recruitment. Sponsor(s): FDA Office of Orphan Products Development; Medical University of South Carolina

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Purpose - Excerpt: Objectives: I. Determine the effects of alendronate sodium on skeletal remodeling and bone mineral density of the hip and spine in children with highturnover idiopathic juvenile osteoporosis. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00010439 •

The Effect of Alendronate, Calcium, and Vitamin D on Bone Mineral Density in HIV Infected Patients Condition(s): HIV Infections Study Status: This study is not yet open for patient recruitment. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: Alendronate is a drug that has been shown to be effective in treating osteoporosis. The purpose of this study is to examine if alendronate in combination with calcium and vitamin D is safe and effective for treating bone loss in people with HIV. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00061256

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Treatment of Childhood Osteoporosis with Alendronate (Fosamax) Condition(s): Osteoporosis Study Status: This study is completed. Sponsor(s): National Institute of Child Health and Human Development (NICHD) Purpose - Excerpt: Bones grow and stay strong through a continuous process of formation (building) and resorption (break down). When more bone is formed than resorbed, the density (level of calcium) in bone increases and the bones become stronger. However, if more bone is resorbed than formed the density of bone decreases and the bones become weak. This condition is called osteoporosis. Osteoporosis is a rare but serious condition in children. Childhood osteoporosis can occur without a known cause (idiopathic juvenile osteoporosis). Children with osteoporosis suffer from pain, inability to stay active, and increased amounts of broken bones, including fractures of the spine. Even mild childhood osteoporosis may have long-term consequences since individuals who achieve a less than normal bone composition (peak bone mass) during the first 2030 years of life may be at an increased risk for osteoporosis as adults. Alendronate (Fosamax) is a drug that works by stopping bone resorption (break down). It has been used to treat post-menopausal osteoporosis, male osteoporosis and adults with osteoporosis due to long-term steroid therapy. The goal of this study is to determine the effectiveness of alendronate in children with idiopathic juvenile osteoporosis. Researchers believe that children treated with alendronate will improve bone strength and decrease the amount of fractures caused by osteoporosis. Phase(s): Phase II Study Type: Interventional

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Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001720

Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. 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 the Web site at http://www.clinicaltrials.gov/ and search by “Fosamax” (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 cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/

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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm

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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm

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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm

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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp

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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm

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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/

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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

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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm

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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm

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•

For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm

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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm

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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials

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CHAPTER 5. PATENTS ON FOSAMAX Overview 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.9 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 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. 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. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “Fosamax” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on Fosamax, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Fosamax By performing a patent search focusing on Fosamax, 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

9Adapted

from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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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 Fosamax: •

Alendronate therapy to prevent loosening of, or pain associated with, orthopedic implant devices Inventor(s): Yates; Ashley J. (Westfield, NJ) Assignee(s): Merck & Co., Inc. (Rahway, NJ) Patent Number: 5,646,134 Date filed: April 21, 1994 Abstract: Disclosed is a therapy for treating and for preventing periprosthetic bone loss by the administration of a bisphosphonate bone resorption inhibitor, e.g., alendronate, in patients who have an orthopedic implant device. Excerpt(s): The instant invention relates generally to the use of alendronate to prevent periprosthetic bone loss in patients having an orthopedic implant device. A major problem with patients who have orthopedic implant devices or joint prosthesis, such as hip replacements, is that many of these begin to fail after five years or so from the time that they are inserted. The failure rate increases exponentially with time so that many patients with an aging hip prosthesis (10 to 15 years), experience pain at the site of the implant and eventually require revision to the original procedure. Although initially this was considered to be a result of fragmentation of the cement substances utilized in older hip prostheses, the problem continues to be observed even in the newer devices which do not rely on the use of cement. A hallmark of these patients is that at the time they develop pain and loosening of the joint they have markedly increased bone turnover, especially bone resorption, in the bone immediately adjacent to the implant. Evidence for this bone turnover can be seen from the fact that bone scanning agents, which are bisphosphonates tagged with technetium, are often taken up at very high concentrations in these areas indicating that there may well be significant targeting of bisphosphonates to the periprosthetic bone. There is a need in the art for localized controlled/extended release dosage forms of bone growth promotant since in the United States, there are approximately 5 million fractures and 265,000 prosthetic implants per year. Of this population, there is about a 20-30% failure rate within five years of the operation, requiring a repeat surgery and device implant. Web site: http://www.delphion.com/details?pn=US05646134__

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Anhydrous alendronate monosodium salt formulations Inventor(s): Brenner; Gerald S. (Norristown, PA), Oberholtzer, Jr.; Earl R. (Hatfield, PA), Ostovic; Drazen (Lansdale, PA), Thies; J. Eric (Scotch Plains, NJ) Assignee(s): Merck & Co., Inc. (Rahway, NJ) Patent Number: 5,849,726 Date filed: December 3, 1997 Abstract: Disclosed is a method for treating and preventing bone loss in patients by administering a formulation of anhydrous alendronate sodium. Also described is a pharmaceutical dosage form of said anhydrous alendronate sodium, being anhydrous 4-amino-1-hydroxy-butylidene-1,1-bisphosphonic acid, monosodium salt, in a pharmaceutically acceptable excipient.

Patents 45

Excerpt(s): The instant invention relates to the use of the anhydrous crystal form of alendronate sodium, i.e., 4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid monosodium, hereinafter referred to as "anhydrous alendronate sodium" or "AAS", to inhibit bone resorption in human patients. Normal bones are living tissues undergoing constant resorption and redeposition of calcium, with the net effect of maintenance of a constant mineral balance. The dual process is commonly called "bone turnover". In normal growing bones, the mineral deposition is in equilibrium with the mineral resorption, whereas in certain pathological conditions, bone resorption exceeds bone deposition, for instance due to malignancy or primary hyperparathyroidism, or in osteoporosis. In other pathological conditions the calcium deposition may take place in undesirable amounts and areas leading to e.g., heterotopic calcification, osteoarthritis, kidney or bladder stones, atherosclerosis, and Paget's disease which is a combination of an abnormal high bone resorption followed by an abnormal calcium deposition. U.S. Pat. No. 4,621,077 to Istituto Gentili discloses a method of treating urolithiasis and inhibiting bone reabsorption by the use of 4-amino-1-hydroxybutylidene-1,1bisphosphonic acid (also named 4-amino-1-hydroxybutane-1,1-bisphosphonic acid) and its salts with an alkali metal, an organic base or a basic amino acid. The compound 4amino-1-hydroxybutylidene-1,1-bisphosphonic acid is described as being between 100 and 300 times more active than dichloromethane-biphosphonic acid in inhibiting bone reabsorption. Web site: http://www.delphion.com/details?pn=US05849726__ •

Effervescent alendronate formulation Inventor(s): Gardner; Colin R. (Blue Bell, PA), Katdare; Ashok V. (Norristown, PA), Kramer; Kenneth A. (Green Lane, PA) Assignee(s): Merck & Co. Inc. (Rahway, NJ) Patent Number: 5,853,759 Date filed: May 8, 1997 Abstract: An effervescent formulation of alendronate contains an acid source, a carbonate source, a binder, a lubricant and optionally, flavoring agents, colorants and sweeteners. Excerpt(s): The present application claims priority to U.S. provisional application Ser. No. 60/017,881, filed May 17, 1996, now abandoned. This invention relates to pharmaceutical effervescent formulations of bisphosphonates, especially alendronate, and in particular, tablets and powders which effervesce when added to water. zoledronate--›1-hydroxy-2-(1H-imidazol-1-yl)ethylidene!bis-phosphonate. Web site: http://www.delphion.com/details?pn=US05853759__

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Hydrate forms of alendronate sodium, processes for manufacture thereof, and pharmaceutical compositions thereof Inventor(s): Aronhime; Judith (Rehovot, IL), Finkelstein; Nina (Herzliya, IL), LidorHadas; Ramy (Kfar Saba, IL) Assignee(s): Teva Pharmaceutical Industries Ltd. (Petah Tiqva, IL) Patent Number: 6,281,381 Date filed: August 27, 1999 Abstract: New hydrate forms of alendronate sodium, having water content of between about one and about twelve percent, and processes for their manufacture, are disclosed. New crystalline forms of alendronate sodium B, D, E, F, G and H, and processes for manufacturing them, are also disclosed. These new forms of alendronate sodium are suitable for incorporation into pharmaceutical compositions for combating bone resorption in bone diseases. Excerpt(s): This invention relates to new hydrate and crystalline forms of alendronate sodium, processes for the manufacture thereof, and pharmaceutical compositions thereof. It is an agent for combating bone resorption in bone diseases including osteoporosis and Paget's disease. Various methods for preparing alendronic acid are known in the art and have been disclosed in M. I. Kabachnik et al., Synthesis and Acid-Base and Complexing Properties of Amino-Substituted.alpha.-Hydroxyalkylidenediphosphonic Acids, Izv. Akad. Nauk USSR, Ser. Khim, 2,433 (1978) and in U.S. Pat. Nos. 4,407,761, 4,621,077, 4,705,651, 5,039,819 and 5,159,108. Web site: http://www.delphion.com/details?pn=US06281381__

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Prevention of tooth loss by the administration of alendronate or its salts Inventor(s): Karpf; David B. (Edison, NJ), Yates; Ashley John (Westfield, NJ) Assignee(s): Merck & Co., Inc. (Rahway, NJ) Patent Number: 5,914,099 Date filed: November 4, 1997 Abstract: Alendronate, a bisphosphonate can prevent tooth loss not necessarily associated with periodontal disease. Preferably, alendronate (or a pharmaceutically acceptable salt thereof) is given daily for an extended period of time. Excerpt(s): This invention relates to a method of preventing tooth loss by the administration of alendronate or a pharmaceutically acceptable salt thereof. Alendronate, 4-amino-1-hydroxybutylidene- 1,1-bisphosphonic acid, and its pharmaceutically acceptable salts are known to be useful in the treatment of osteoporosis. See, for example U.S. Patent 4,621,077. It has also been used experimentally to treat alveolar bone loss associated with periodontitis and periodontal disease, as set forth in U.S. Pat. No. 5,270,365. Alveolar bone of the mandible and maxilla serves as the primary foundation for tooth support. While alveolar bone is generally subject to metabolic and other systemic diseases of the skeleton, there has been relatively little work on the occurrence, progression, or impact of systemic osteoporosis on alveolar bone, although such a relationship may exist. Mandibular bone loss has been correlated with systemic bone loss, and it has been reported that tooth loss is exacerbated by osteoporosis.

Patents 47

Web site: http://www.delphion.com/details?pn=US05914099__ •

Process for removing waste pox, alendronate and its by products Inventor(s): Forman; Andrew L. (Rahway, NJ), Magliette, Jr.; Ralph J. (Piscataway, NJ), McKinney; Donald (Freehold, NJ), Venkataramani; Edamanal S. (Berkeley Heights, NJ) Assignee(s): Merck & Co., Inc. (Rahway, NJ) Patent Number: 5,449,819 Date filed: June 6, 1994 Abstract: Disclosed is a process for removing by-product phosphorus-containing (PO.sub.x) materials, alendronate and alendronate byproducts from crude mother liquors in an omega amino-1-hydroxy-C.sub.2 -C.sub.6 alkylidene-1,1-bisphosphonic acid synthesis process, e.g. alendronate sodium. Calcium chloride is added first to the crude mother liquors, then calcium oxide to precipitate the PO.sub.x materials, then neutralized to about pH 7 to complete precipitation. Substantially all of the alendronate sodium active ingredient is removed from the precipitate. Following filtration, the PO.sub.x filtercake can then be disposed of by incineration, landfilling or reclamation of usable phosphorus as fertilizer. The remaining filtrate can then be further treated in an environmentally acceptable manner by wastewater treatment or recycling to the process. Excerpt(s): This invention relates to a process for removing phosphorus-containing materials, POx, alendronate and alendronate byproducts from crude process mother liquors in a bisphosphonate synthesis using a CaCl.sub.2 /CaO precipitation/neutralization and filtration procedure. Alendronate sodium, 4-amino-1hydroxybutylidene-1-bisphosphonic acid monosodium trihydrate, is a promising new agent for combatting bone resorption in bone diseases including osteoporosis, particularly in post-menopausal women. The compound, utility and method of preparation are described in U.S. Pat. Nos. 4,922,007 and 5,019,651, both assigned to Merck & Co., Inc. Large scale processes as described in the above patents for producing alendronate sodium generate large volumes of soluble phosphorus-containing materials (PO.sub.x) including sodium salts of phosphates, phosphites and pyrophosphates as waste. Web site: http://www.delphion.com/details?pn=US05449819__

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Sodium alendronate preparation for local administration Inventor(s): Dohi; Masahiko (Tokyo, JP), Hujii; Takao (Tokyo, JP), Makino; Yuji (Tokyo, JP) Assignee(s): Merck & Co., Inc. (Rahway, NJ) Patent Number: 5,958,908 Date filed: April 13, 1998 Abstract: The present invention provides a method local administration of an effective amount of sodium alendronate to permit selective delivery to the bone site where bone resorption is accentuated. Excerpt(s): A preparation for local administration which comprises an effective amount of sodium alendronate and a medium such as water, propylene glycol or a pharmaceutically acceptable buffer. The preparation is suitable for administering

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percutaneously by iontophoresis. The present invention relates to drug therapy by sodium alendronate. Further the present invention relates to a sodium alendronate preparation to provide selective and safe delivery of an effective amount of sodium alendronate to the bone site in a body which needs sodium alendronate and in which bone resorption is accentuated by local and percutaneous administration. Preparations for sodium alendronate are being developed as therapeutic agents for parenteral and oral administration. In the case of such diseases as osteoporosis, it is difficult to predict the affected site in the bone structure of the body. Such diseases requires systemic administration by parenteral or oral administration. However, systemic administration of sodium alendronate is not required in cases where local accentuation of bone resorption is observed in diseases such as osteoarthritis (OA) and chronic articular rheumatism, and cases where accentuation of bone resorption is locally observed in the cartilaginous tissue in contact with the artificial joint having been installed. Local delivery to the site where bone resorption is accentuated provides an effective administration which reduces the adverse affects. Web site: http://www.delphion.com/details?pn=US05958908__ •

Sodium alendronate preparation for local administration Inventor(s): Dohi; Masahiko (Tokyo, JP), Hujii; Takao (Tokyo, JP), Makino; Yuji (Tokyo, JP) Assignee(s): Merck & Co., Inc. (Rahway, NJ) Patent Number: 6,008,206 Date filed: May 28, 1998 Abstract: The object of the present invention is to provide a preparation for local administration to permit selective delivery of an effective amount of sodium alendronate to the bone site where bone resorption is accentuated. Excerpt(s): A preparation for local administration which comprises an effective amount of sodium alendronate and a medium such as water, propylene glycol or a pharmaceutically acceptable buffer. The preparation is suitable for administering percutaneously by iontophoresis. The present invention relates to drug therapy by sodium alendronate. Further the present invention relates to a sodium alendronate preparation to provide selective and safe delivery of an effective amount of sodium alendronate to the bone site in a body which needs sodium alendronate and in which bone resorption is accentuated by local and percutaneous administration. Sodium alendronate inhibits bone resorption by osteoclast, in vivo, and can be used as therapeutic agent for hypercalcemia, Paget's disease and osteoporosis (History of Medical Science, 165(9), pp. 674-678, 1993). In recent years, there have been note worthy cases where local accentuation of bone resorption is observed in such diseases as osteoarthritis (OA) and chronic articular rheumatism. Sodium alendronate is expected to provide an effective therapeutic agent for these diseases. Web site: http://www.delphion.com/details?pn=US06008206__

Patents 49

Patent Applications on Fosamax As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to Fosamax: •

Composition and dosage form for delayed gastric release of alendronate and/or other bis-phosphonates Inventor(s): Dahan, Mazal; (Jerusalem, IL), Flashner-Barak, Moshe; (Petach Tikva, IL), Lerner, Yitzhak; (Petach Tikva, IL), Rosenberger, Vered; (Jerusalem, IL) Correspondence: Kenyon & Kenyon; One Broadway; New York; NY; 10004; US Patent Application Number: 20030203878 Date filed: April 22, 2003 Abstract: The present invention provides a compacted pharmaceutical composition for oral administration to a patient which expands upon contact with gastric fluid to retain a dosage form in the patient's stomach for an extended period of time, the formulation comprising a non-hydrated hydrogel, a superdisintegrant and tannic acid. The present invention further provides a pharmaceutical dosage form containing an active ingredient, and the compacted pharmaceutical composition. The invention further provides a dosage form suitable for delivering a therapeutic bis-phosphonate such as alendronate to the stomach of a patient over and extended period Excerpt(s): This application is a continuation of U.S. patent application Ser. No. 10/246,502, filed Sep. 16, 2002, which is a continuation of U.S. patent application Ser. No. 09/770,898, filed Jan. 26, 2001, now U.S. Pat. No. 6,476,006, and claims the benefit under 35 U.S.C.sctn.119(e) of U.S. provisional applications Serial No. 60/213,832, filed Jun. 23, 2000 and Serial No. 60/260,438, filed Jan. 9, 2001, the contents of all of which are incorporated herein by reference. The present invention relates to gastric retention systems and to pharmaceutical dosage forms that use them to release a drug in a patient's stomach or duodenum. More particularly, the invention relates to gastric retention systems suitable for use with bis-phosphonates such as alendronic acid and its pharmaceutically acceptable salts and hydrates thereof to release these drugs in a controlled manner. After discovery of a new drug for treatment of a human disease further investigation must be undertaken to determine whether it is most effective to administer the drug to a patient intravenously, transdermally, subcutaneously or orally. Orally administered drugs are easy to administer and therefore are often favored whenever an oral route is feasible. However, compliance problems sometimes occur with orally administered drugs when the dosage form is inconvenient to take or must be taken frequently or at inconvenient times. Orally administered drugs are often presented to a patient in such dosage forms as tablets, pills, lozenges and capsules. Most orally administered drugs are absorbed into the bloodstream from the patient's gastrointestinal tract, excepting inhalants which are absorbed by the lungs and sinuses. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

10

This has been a common practice outside the United States prior to December 2000.

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•

Novel hydrate forms of alendronate sodium, processes for manufacture thereof, and pharmaceutical compositions thereof Inventor(s): Aronhime, Judith; (Rehovot, IL), Finkelstein, Nina; (Herzliya, IL), LidorHadas, Ramy; (Kfar Saba, IL) Correspondence: Kenyon & Kenyon; One Broadway; New York; NY; 10004; US Patent Application Number: 20030065214 Date filed: July 3, 2001 Abstract: New hydrate forms of alendronate sodium, having water content of between about one and about twelve percent, and processes for their manufacture, are disclosed. New crystalline forms of alendronate sodium B, D, E, F, G and H, and processes for manufacturing them, are also disclosed. These new forms of alendronate sodium are suitable for incorporation into pharmaceutical compositions for combating bone resorption in bone diseases. Excerpt(s): This invention relates to new hydrate and crystalline forms of alendronate sodium, processes for the manufacture thereof, and pharmaceutical compositions thereof. It is an agent for combating bone resorption in bone diseases including osteoporosis and Paget's disease. Various methods for preparing alendronic acid are known in the art and have been disclosed in M. I. Kabachnik et al., Synthesis and AcidBase and Complexing Properties of Amino-Substituted.alpha.-Hydroxyalkylidenediphosphonic Acids, Izv. Akad. Nauk USSR, Ser. Khim, 2,433 (1978) and in U.S. Pat. Nos. 4,407,761, 4,621,077, 4,705,651, 5,039,819 and 5,159,108. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Use of alendronate for the prevention of osteoporosis Inventor(s): Yates, Ashley J.; (Westfield, NJ) Correspondence: Merck & CO., INC.; Patent Department; P.O. Box 2000- Ry60-30; Rahway; NJ; 07065-0907; US Patent Application Number: 20010046977 Date filed: February 27, 2001 Abstract: Alendronate, an aminobisphosphonate, can prevent osteoporosis in early post menopausal women. Excerpt(s): This invention relates to the use of alendronate, an amino-bisphosphonate, for the prevention of osteoporosis in early post-menopausal women. Alendronate, 4amino-1-hydroxybutylidene-1,1-bisphosphonic acid, and its pharmaceutically acceptable salts has been found to be useful in the treatment of osteoporosis. Alendronate is a specific inhibitor of bone resorption. It has a high affinity for bone mineral and is taken up into the bone selectively where it inhibits osteoclast activity. While alendronate has been shown to be useful in restoring lost bone, there has been no indication that it can prevent the loss of bone in otherwise healthy individuals. Peak bone mass in women is achieved at around 30-35 years of age, after which bone mass is lost progressively throughout life. The rate of loss is accelerated during the early post menopausal period, especially at sites with a high component of trabecular bone. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Patents 51

Keeping Current In order to stay informed about patents and patent applications dealing with Fosamax, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “Fosamax” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on Fosamax. You can also use this procedure to view pending patent applications concerning Fosamax. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 6. BOOKS ON FOSAMAX Overview This chapter provides bibliographic book references relating to Fosamax. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on Fosamax include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “Fosamax” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 •

Alendronate for prevention of postmenopausal osteoporosis. Author: ECRI (Organization).; Year: 1999; Plymouth Meeting, PA: ECRI, 1999

•

Alendronate for treatment of postmenopausal osteoporosis Author: ECRI (Organization). Health Technology Assessment Information Service.; Year: 1999; Plymouth Meeting, PA: ECRI, 1999

11

In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.

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Chapters on Fosamax In order to find chapters that specifically relate to Fosamax, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and Fosamax using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use 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 format option “Book Chapter.” Type “Fosamax” (or synonyms) into the “For these words:” box.

55

CHAPTER 7. PERIODICALS AND NEWS ON FOSAMAX Overview In this chapter, we suggest a number of news sources and present various periodicals that cover Fosamax.

News Services and Press Releases One of the simplest ways of tracking press releases on Fosamax is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “Fosamax” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to Fosamax. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “Fosamax” (or synonyms). The following was recently listed in this archive for Fosamax: •

Merck says it will explore options to defend Fosamax patent in UK Source: Reuters Industry Breifing Date: November 07, 2003

•

US court panel says Teva generic Fosamax infringes Source: Reuters Industry Breifing Date: October 31, 2003

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•

Merck pits Fosamax osteoporosis drug head-to-head with rival Actonel Source: Reuters Industry Breifing Date: February 05, 2003

•

UK rules two Merck Fosamax patents invalid Source: Reuters Industry Breifing Date: January 21, 2003

•

Ivax gets tentative FDA approval for generic Fosamax Source: Reuters Industry Breifing Date: July 25, 2002

•

Barr gets tentative FDA approval for generic Fosamax Source: Reuters Industry Breifing Date: April 24, 2002

•

Merck sues Barr in ongoing battle over Fosamax patents Source: Reuters Industry Breifing Date: December 17, 2001

•

Merck's once weekly Fosamax for osteoporosis extended to men Source: Reuters Industry Breifing Date: February 02, 2001

•

Merck receives approval for weekly Fosamax regimen Source: Reuters Industry Breifing Date: October 23, 2000

•

FDA approves use of Fosamax in men Source: Reuters Health eLine Date: October 02, 2000

•

FDA Approves Merck's Fosamax For Postmenopausal Osteoporosis Source: Reuters Medical News Date: April 29, 1997

•

FDA Panel Unanimous -- Fosamax Okay for Osteoporosis Prevention Source: Reuters Medical News Date: February 21, 1997 The NIH

Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name.

Periodicals and News

57

Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “Fosamax” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “Fosamax” (or synonyms). If you know the name of a company that is relevant to Fosamax, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “Fosamax” (or synonyms).

Academic Periodicals covering Fosamax Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to Fosamax. In addition to these sources, you can search for articles covering Fosamax that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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CHAPTER 8. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for Fosamax. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI® Advice for the Patient® can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with Fosamax. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The

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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to Fosamax: Alendronate •

Systemic - U.S. Brands: Fosamax http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202794.html

Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.

Mosby’s Drug Consult™ Mosby’s Drug Consult™ database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

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APPENDICES

63

APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute12: •

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

•

National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

•

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

•

National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

•

National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

•

National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

•

National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

•

National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

12

These publications are typically written by one or more of the various NIH Institutes.

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•

National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

•

National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

•

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

•

National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

•

National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

•

National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

•

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

•

National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

•

National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

•

National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

•

National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

•

National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

•

National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

•

Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

•

National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

•

National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

•

Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

•

Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

Physician Resources

65

NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.13 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:14 •

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

•

HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

•

NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

•

Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

•

Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html

•

Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

•

Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

•

Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

•

Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

•

Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

•

MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

13

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 14 See http://www.nlm.nih.gov/databases/databases.html.

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•

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

•

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html

The NLM Gateway15 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.16 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “Fosamax” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total

Items Found 893 4 949 15 0 1861

HSTAT17 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.18 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.19 Simply search by “Fosamax” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

15

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

16

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 17 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 18 19

The HSTAT URL is http://hstat.nlm.nih.gov/.

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.

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Coffee Break: Tutorials for Biologists20 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.21 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.22 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

•

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

20 Adapted 21

from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 22 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. 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. Since new guidelines on Fosamax 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.

Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to Fosamax. 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. The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below. Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to Fosamax. 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 when searched for “Fosamax”:

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•

Other guides Hormone Replacement Therapy http://www.nlm.nih.gov/medlineplus/hormonereplacementtherapy.html Menopause http://www.nlm.nih.gov/medlineplus/menopause.html Osteogenesis Imperfecta http://www.nlm.nih.gov/medlineplus/osteogenesisimperfecta.html Osteoporosis http://www.nlm.nih.gov/medlineplus/osteoporosis.html Paget's Disease of Bone http://www.nlm.nih.gov/medlineplus/pagetsdiseaseofbone.html

You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are 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 NIH Search Utility The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. 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 Fosamax. 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 are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •


•

Family Village: http://www.familyvillage.wisc.edu/specific.htm

•

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/

Patient Resources

•

71

WebMD®Health: http://my.webmd.com/health_topics

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to Fosamax. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with Fosamax. 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 Fosamax. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “Fosamax” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. 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 “Fosamax”. 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.” Type “Fosamax” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months.

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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 health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “Fosamax” (or a synonym) into the search box, and click “Submit Query.”

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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.23

Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of

23

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)24: •

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

•

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)

•

Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

•

California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html

•

California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html

•

California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

•

California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

•

California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

•

California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

•

California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

•

California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

•

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

•

California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

•

Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

•

Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

•

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

24

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

Finding Medical Libraries

75

•

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

•

Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

•

Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

•

Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

•

Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

•

Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

•

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

•

Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

•

Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

•

Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

•

Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

•

Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

•

Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

•

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

•

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

•

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

•

Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

•

Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

•

Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

•

Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

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Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

•

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

•

Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

•

Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

•

Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

•

Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

•

Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

•

Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

•

Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

•

Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

•

Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

•

Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

•

Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

•

Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

•

Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

•

Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

•

National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

•

National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

•

National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

Finding Medical Libraries

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•

Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

•

New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

•

New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

•

New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

•

New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

•

New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

•

New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

•

New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

•

New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

•

Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

•

Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

•

Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

•

Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

•

Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

•

Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

•

Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

•

Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

•

Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

•

Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

•

Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

•

Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

•

Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

•

Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

•

MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

•

Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

•

Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

•

On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

•

Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

•

Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a).

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

•

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

•

Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

•

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

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FOSAMAX DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Activities of Daily Living: The performance of the basic activities of self care, such as dressing, ambulation, eating, etc., in rehabilitation. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Alendronate: A nonhormonal medication for the treatment of postmenopausal osteoporosis in women. This drug builds healthy bone, restoring some of the bone loss as a result of osteoporosis. [NIH] Alendronate Sodium: A drug that affects bone metabolism. It is used in treating osteoporosis and Paget's disease, and is being studied in the treatment of hypercalcemia (abnormally high levels of calcium in the blood) and in treating and reducing the risk of bone pain caused by cancer. Alendronate sodium belongs to the family of drugs called bisphosphonates. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaline Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1. [NIH]

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Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Alveolar Bone Loss: The resorption of bone in the supporting structures of the maxilla or mandible as a result of periodontal disease. [NIH] Alveolar Process: The thickest and spongiest part of the maxilla and mandible hollowed out into deep cavities for the teeth. [NIH] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Androgen-Binding Protein: Carrier proteins produced in the Sertoli cells of the testis, secreted into the seminiferous tubules, and transported via the efferent ducts to the epididymis. They participate in the transport of androgens. Androgen-binding protein has the same amino acid sequence as sex hormone binding-globulin. They differ by their sites of synthesis and post-translational oligosacaccharide modifications. [NIH] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Aqueous: Having to do with water. [NIH]

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Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arthroplasty: Surgical reconstruction of a joint to relieve pain or restore motion. [NIH] Articular: Of or pertaining to a joint. [EU] Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Asymptomatic: Having no signs or symptoms of disease. [NIH] Autodigestion: Autolysis; a condition found in disease of the stomach: the stomach wall is digested by the gastric juice. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Tract: The gallbladder and its ducts. [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] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bladder: The organ that stores urine. [NIH] Bloating: Fullness or swelling in the abdomen that often occurs after meals. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH]

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Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Bone Cements: Adhesives used to fix prosthetic devices to bones and to cement bone to bone in difficult fractures. Synthetic resins are commonly used as cements. A mixture of monocalcium phosphate, monohydrate, alpha-tricalcium phosphate, and calcium carbonate with a sodium phosphate solution is also a useful bone paste. [NIH] Bone Density: The amount of mineral per square centimeter of bone. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is most frequently measured by photon absorptiometry or x-ray computed tomography. [NIH] Bone Development: Gross development of bones from fetus to adult. It includes osteogenesis, which is restricted to formation and development of bone from the undifferentiated cells of the germ layers of the embryo. It does not include osseointegration. [NIH]

Bone metastases: Cancer that has spread from the original (primary) tumor to the bone. [NIH]

Bone Remodeling: The continuous turnover of bone matrix and mineral that involves first, an increase in resorption (osteoclastic activity) and later, reactive bone formation (osteoblastic activity). The process of bone remodeling takes place in the adult skeleton at discrete foci. The process ensures the mechanical integrity of the skeleton throughout life and plays an important role in calcium homeostasis. An imbalance in the regulation of bone remodeling's two contrasting events, bone resorption and bone formation, results in many of the metabolic bone diseases, such as osteoporosis. [NIH] Bone Resorption: Bone loss due to osteoclastic activity. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH]

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Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardiac: Having to do with the heart. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] 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] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clodronate: A drug used as treatment for hypercalcemia (abnormally high levels of calcium in the blood) and for cancer that has spread to the bone (bone metastases). It may decrease pain, the risk of fractures, and the development of new bone metastases. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Clot Retraction: Retraction of a clot resulting from contraction of platelet pseudopods attached to fibrin strands that is dependent on the contractile protein thrombosthenin. Used as a measure of platelet function. [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collagen disease: A term previously used to describe chronic diseases of the connective tissue (e.g., rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis), but now is thought to be more appropriate for diseases associated with defects in collagen, which is a component of the connective tissue. [NIH] 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] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH]

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Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine.

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Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] Connective Tissue Diseases: A heterogeneous group of disorders, some hereditary, others acquired, characterized by abnormal structure or function of one or more of the elements of connective tissue, i.e., collagen, elastin, or the mucopolysaccharides. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]

Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cytokines: Non-antibody proteins secreted by inflammatory leukocytes and some non-

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leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dermal: Pertaining to or coming from the skin. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Diverticulum: A pathological condition manifested as a pouch or sac opening from a tubular or sacular organ. [NIH] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect. They include capsules, liniments, ointments, pharmaceutical solutions, powders, tablets, etc. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH]

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Duodenum: The first part of the small intestine. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Ectopic: Pertaining to or characterized by ectopia. [EU] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Endoscopy: Endoscopic examination, therapy or surgery performed on interior parts of the body. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophageal Perforation: A dilated vessel in the lower end of the esophagus that result from portal hypertension. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH] Estrogen: One of the two female sex hormones. [NIH] Estrogen receptor: ER. Protein found on some cancer cells to which estrogen will attach.

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[NIH]

Etidronate: A drug that belongs to the family of drugs called bisphosphonates. Bisphosphonates are used as treatment for hypercalcemia (abnormally high levels of calcium in the blood) and for cancer that has spread to the bone (bone metastases). [NIH] Excipient: Any more or less inert substance added to a prescription in order to confer a suitable consistency or form to the drug; a vehicle. [EU] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Flavoring Agents: Substances added to foods and medicine to improve the quality of taste. [NIH]

Flexor: Muscles which flex a joint. [NIH] Fosamax: A Merck's osteoporosis drug. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes

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are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Germ Layers: The three layers of cells comprising the early embryo. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Gonadal: Pertaining to a gonad. [EU] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Hip Prosthesis: Replacement for a hip joint. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone Replacement Therapy: Therapeutic use of hormones to alleviate the effects of hormone deficiency. [NIH] Hormone therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH] Hydrocortisone: The main glucocorticoid secreted by the adrenal cortex. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation,

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allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions. [NIH] Hydrogel: A network of cross-linked hydrophilic macromolecules used in biomedical applications. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hypercalcemia: Abnormally high level of calcium in the blood. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incineration: High temperature destruction of waste by burning with subsequent reduction to ashes or conversion to an inert mass. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

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Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Ingestion: Taking into the body by mouth [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Intestinal: Having to do with the intestines. [NIH] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Ion Exchange: Reversible chemical reaction between a solid, often an ION exchange resin, and a fluid whereby ions may be exchanged from one substance to another. This technique is used in water purification, in research, and in industry. [NIH] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Iontophoresis: Therapeutic introduction of ions of soluble salts into tissues by means of electric current. In medical literature it is commonly used to indicate the process of increasing the penetration of drugs into surface tissues by the application of electric current. It has nothing to do with ion exchange, air ionization nor phonophoresis, none of which requires current. [NIH] Irritable Bowel Syndrome: A disorder that comes and goes. Nerves that control the muscles in the GI tract are too active. The GI tract becomes sensitive to food, stool, gas, and stress. Causes abdominal pain, bloating, and constipation or diarrhea. Also called spastic colon or mucous colitis. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Ketoconazole: Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Lesion: An area of abnormal tissue change. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Lichen Planus: An inflammatory, pruritic disease of the skin and mucous membranes,

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which can be either generalized or localized. It is characterized by distinctive purplish, flattopped papules having a predilection for the trunk and flexor surfaces. The lesions may be discrete or coalesce to form plaques. Histologically, there is a "saw-tooth" pattern of epidermal hyperplasia and vacuolar alteration of the basal layer of the epidermis along with an intense upper dermal inflammatory infiltrate composed predominantly of T-cells. Etiology is unknown. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [NIH] Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Mammary: Pertaining to the mamma, or breast. [EU] Mammogram: An x-ray of the breast. [NIH] Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Melanin: The substance that gives the skin its color. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in

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the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microcalcifications: Tiny deposits of calcium in the breast that cannot be felt but can be detected on a mammogram. A cluster of these very small specks of calcium may indicate that cancer is present. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Milliliter: A measure of volume for a liquid. A milliliter is approximately 950-times smaller than a quart and 30-times smaller than a fluid ounce. A milliliter of liquid and a cubic centimeter (cc) of liquid are the same. [NIH] Mineralization: The action of mineralizing; the state of being mineralized. [EU] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]

Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training,

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health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Neutralization: An act or process of neutralizing. [EU] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Observational study: An epidemiologic study that does not involve any intervention, experimental or otherwise. Such a study may be one in which nature is allowed to take its course, with changes in one characteristic being studied in relation to changes in other characteristics. Analytical epidemiologic methods, such as case-control and cohort study designs, are properly called observational epidemiology because the investigator is observing without intervention other than to record, classify, count, and statistically analyze results. [NIH] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Osseointegration: The growth action of bone tissue, as it assimilates surgically implanted devices or prostheses to be used as either replacement parts (e.g., hip) or as anchors (e.g., endosseous dental implants). [NIH] Ossification: The formation of bone or of a bony substance; the conversion of fibrous tissue or of cartilage into bone or a bony substance. [EU] Osteoarthritis: Degeneration of articular cartilage. Primary osteoarthritis is very common in older persons, especially affecting weight-bearing joints. Articular cartilage becomes soft, frayed and thinned. [NIH] Osteoblasts: Bone-forming cells which secrete an extracellular matrix. Hydroxyapatite crystals are then deposited into the matrix to form bone. [NIH] Osteocalcin: Vitamin K-dependent calcium-binding protein synthesized by osteoblasts and found primarily in bone. Serum osteocalcin measurements provide a noninvasive specific marker of bone metabolism. The protein contains three residues of the amino acid gammacarboxyglutamic acid (GLA), which, in the presence of calcium, promotes binding to hydroxyapatite and subsequent accumulation in bone matrix. [NIH] Osteoclasts: A large multinuclear cell associated with the absorption and removal of bone. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in cementum resorption. [NIH] Osteogenesis: The histogenesis of bone including ossification. It occurs continuously but particularly in the embryo and child and during fracture repair. [NIH]

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Osteogenesis Imperfecta: A collagen disorder resulting from defective biosynthesis of type I collagen and characterized by brittle, osteoporotic, and easily fractured bones. It may also present with blue sclerae, loose joints, and imperfect dentin formation. There are four major types, I-IV. [NIH] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pamidronate: A drug that belongs to the family of drugs called bisphosphonates. Pamidronate is used as treatment for abnormally high levels of calcium in the blood. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Parathyroid: 1. Situated beside the thyroid gland. 2. One of the parathyroid glands. 3. A sterile preparation of the water-soluble principle(s) of the parathyroid glands, ad-ministered parenterally as an antihypocalcaemic, especially in the treatment of acute hypoparathyroidism with tetany. [EU] Parathyroid Glands: Two small paired endocrine glands in the region of the thyroid gland. They secrete parathyroid hormone and are concerned with the metabolism of calcium and phosphorus. [NIH] Parathyroid hormone: A substance made by the parathyroid gland that helps the body store and use calcium. Also called parathormone, parathyrin, or PTH. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pelvic: Pertaining to the pelvis. [EU] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Perimenopausal: The time of a woman's life when menstrual periods become irregular. Refers to the time near menopause. [NIH]

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Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Periodontitis: Inflammation of the periodontal membrane; also called periodontitis simplex. [NIH]

PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use, they do not fall into another group of products. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phonophoresis: Use of ultrasound to increase the percutaneous adsorption of drugs. [NIH] Phosphates: Inorganic salts of phosphoric acid. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen: Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] Plasminogen Activators: A heterogeneous group of proteolytic enzymes that convert

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plasminogen to plasmin. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation. EC 3.4.21.-. [NIH] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polyostotic Fibrous Dysplasia: Abnormal tissue development or growth occurring subsequent to the appearance of the primordial cells. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Porosity: Condition of having pores or open spaces. This often refers to bones, bone implants, or bone cements, but can refer to the porous state of any solid substance. [NIH] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Post-translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precipitation: The act or process of precipitating. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Propylene Glycol: A clear, colorless, viscous organic solvent and diluent used in pharmaceutical preparations. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the

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lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Prosthesis: An artificial replacement of a part of the body. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Protein-Tyrosine Kinase: An enzyme that catalyzes the phosphorylation of tyrosine residues in proteins with ATP or other nucleotides as phosphate donors. EC 2.7.1.112. [NIH] Protein-Tyrosine-Phosphatase: An enzyme group that specifically dephosphorylates phosphotyrosyl residues in selected proteins. Together with protein-tyrosine kinase, it regulates tyrosine phosphorylation and dephosphorylation in cellular signal transduction and may play a role in cell growth control and carcinogenesis. EC 3.1.3.48. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Pruritic: Pertaining to or characterized by pruritus. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radioactive: Giving off radiation. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH]

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Raloxifene: A second generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women. It has estrogen agonist effects on bone and cholesterol metabolism but behaves as a complete estrogen antagonist on mammary gland and uterine tissue. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Reabsorption: 1. The act or process of absorbing again, as the selective absorption by the kidneys of substances (glucose, proteins, sodium, etc.) already secreted into the renal tubules, and their return to the circulating blood. 2. Resorption. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] 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] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Rheumatic Diseases: Disorders of connective tissue, especially the joints and related structures, characterized by inflammation, degeneration, or metabolic derangement. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH]

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Sclera: The tough white outer coat of the eyeball, covering approximately the posterior fivesixths of its surface, and continuous anteriorly with the cornea and posteriorly with the external sheath of the optic nerve. [EU] Sclerae: A circular furrow between the sclerocorneal junction and the iris. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Selective estrogen receptor modulator: SERM. A drug that acts like estrogen on some tissues, but blocks the effect of estrogen on other tissues. Tamoxifen and raloxifene are SERMs. [NIH] Self Care: Performance of activities or tasks traditionally performed by professional health care providers. The concept includes care of oneself or one's family and friends. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sex Hormone-Binding Globulin: A glycoprotein migrating as a beta-globulin. Its molecular weight, 52,000 or 95,000-115,000, indicates that it exists as a dimer. The protein binds testosterone, dihydrotestosterone, and estradiol in the plasma. Sex hormone-binding protein has the same amino acid sequence as androgen-binding protein. They differ by their sites of synthesis and post-translational oligosacaccharide modifications. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH]

Dictionary 103

Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Spastic: 1. Of the nature of or characterized by spasms. 2. Hypertonic, so that the muscles are stiff and the movements awkward. 3. A person exhibiting spasticity, such as occurs in spastic paralysis or in cerebral palsy. [EU] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Sterile: Unable to produce children. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Steroid therapy: Treatment with corticosteroid drugs to reduce swelling, pain, and other

104 Fosamax

symptoms of inflammation. [NIH] 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] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Subcutaneous: Beneath the skin. [NIH] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH] Technetium: The first artificially produced element and a radioactive fission product of uranium. The stablest isotope has a mass number 99 and is used diagnostically as a radioactive imaging agent. Technetium has the atomic symbol Tc, atomic number 43, and atomic weight 98.91. [NIH] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetany: 1. Hyperexcitability of nerves and muscles due to decrease in concentration of extracellular ionized calcium, which may be associated with such conditions as parathyroid hypofunction, vitamin D deficiency, and alkalosis or result from ingestion of alkaline salts; it is characterized by carpopedal spasm, muscular twitching and cramps, laryngospasm with inspiratory stridor, hyperreflexia and choreiform movements. 2. Tetanus. [EU] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH]

Dictionary 105

Tooth Loss: The failure to retain teeth as a result of disease or injury. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ultrasonography: The visualization of deep structures of the body by recording the reflections of echoes of pulses of ultrasonic waves directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1.6 to 10 megahertz. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uraemia: 1. An excess in the blood of urea, creatinine, and other nitrogenous end products of protein and amino acids metabolism; more correctly referred to as azotemia. 2. In current usage the entire constellation of signs and symptoms of chronic renal failure, including nausea, vomiting anorexia, a metallic taste in the mouth, a uraemic odour of the breath, pruritus, uraemic frost on the skin, neuromuscular disorders, pain and twitching in the muscles, hypertension, edema, mental confusion, and acid-base and electrolyte imbalances. [EU]

Uranium: A radioactive element of the actinide series of metals. It has an atomic symbol U, atomic number 92, and atomic weight 238.03. U-235 is used as the fissionable fuel in nuclear weapons and as fuel in nuclear power reactors. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urolithiasis: Stones in the urinary system. [NIH] Uvea: The middle coat of the eyeball, consisting of the choroid in the back of the eye and the ciliary body and iris in the front of the eye. [NIH] Uveitis: An inflammation of part or all of the uvea, the middle (vascular) tunic of the eye, and commonly involving the other tunics (the sclera and cornea, and the retina). [EU]

106 Fosamax

Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasculitis: Inflammation of a blood vessel. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vertebral: Of or pertaining to a vertebra. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Weight-Bearing: The physical state of supporting an applied load. This often refers to the weight-bearing bones or joints that support the body's weight, especially those in the spine, hip, knee, and foot. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Zoledronate: A drug that belongs to the family of drugs called bisphosphonates. It is used to prevent bone fractures and reduce bone pain in people who have cancer that has spread to the bone. [NIH]

107

INDEX A Abdominal, 81, 93, 97 Abdominal Pain, 81, 93 Activities of Daily Living, 5, 81 Adenosine, 81, 98 Adrenal Cortex, 81, 87, 89, 91, 99 Adverse Effect, 81, 102 Affinity, 50, 81, 103 Agonist, 81, 101 Alendronate Sodium, 13, 20, 37, 39, 40, 44, 45, 46, 47, 50, 81 Algorithms, 81, 83 Alimentary, 81, 93, 97 Alkaline, 3, 5, 13, 81, 84, 104 Alkaline Phosphatase, 3, 5, 13, 81 Alternative medicine, 57, 82 Alveolar Bone Loss, 20, 29, 46, 82 Alveolar Process, 82, 101 Amino Acid Sequence, 82, 102 Anal, 82, 94 Androgen-Binding Protein, 82, 102 Angiogenesis, 82, 94 Antibiotic, 82, 103, 104 Antibody, 81, 82, 86, 87, 91, 92, 103 Antifungal, 82, 93 Antigen, 81, 82, 86, 92 Anti-inflammatory, 82, 87, 91, 99 Apoptosis, 31, 82 Aqueous, 82, 83, 88 Arterial, 83, 92, 100 Arteries, 83, 84, 87, 95 Arthroplasty, 14, 83 Articular, 48, 83, 96 Ascorbic Acid, 83, 92 Assay, 7, 83 Asymptomatic, 83, 97 Autodigestion, 83, 97 B Base, 45, 46, 50, 83, 88, 93, 105 Bile, 83, 90, 94, 103 Biliary, 83, 97 Biliary Tract, 83, 97 Bioavailability, 37, 83 Biochemical, 6, 8, 28, 83 Biopsy, 83, 97 Biosynthesis, 83, 97 Biotechnology, 6, 53, 57, 65, 83 Bladder, 45, 83, 99, 105

Bloating, 83, 93 Blood Coagulation, 83, 84 Blood pressure, 83, 92, 95, 103 Blood vessel, 82, 83, 84, 103, 104, 106 Body Fluids, 84, 103 Bone Cements, 84, 99 Bone Density, 8, 9, 10, 14, 29, 37, 39, 84 Bone Development, 31, 84 Bone metastases, 29, 84, 85, 90 Bone Remodeling, 5, 8, 84 Bone Resorption, 3, 5, 6, 40, 44, 45, 46, 47, 48, 50, 84 Bone scan, 8, 44, 84 Bowel, 12, 82, 84, 88, 104 Bowel Movement, 84, 88, 104 Branch, 77, 84, 97, 100, 103, 104 Breakdown, 38, 39, 84, 88, 90 C Calcification, 18, 45, 84 Calcium, 7, 15, 18, 24, 25, 27, 28, 31, 36, 38, 40, 45, 47, 81, 84, 85, 86, 90, 92, 94, 95, 96, 97, 102, 104 Capsules, 35, 49, 84, 88 Carcinogenesis, 84, 100 Carcinogenic, 85, 103 Carcinoma, 28, 85 Cardiac, 85, 89, 95, 103 Case report, 9, 22, 85 Cell, 29, 81, 82, 83, 85, 86, 88, 90, 94, 95, 96, 99, 100, 101, 102 Cell Death, 82, 85, 96 Cholesterol, 83, 85, 101, 103 Chromatin, 82, 85 Chronic, 4, 5, 9, 17, 48, 85, 92, 94, 97, 105 Clinical trial, 3, 4, 20, 35, 41, 65, 85, 87, 95, 100, 101 Clodronate, 4, 85 Cloning, 83, 85 Clot Retraction, 85, 98 Cofactor, 85, 100 Colitis, 85, 93 Collagen, 5, 85, 87, 90, 92, 94, 97, 99 Collagen disease, 85, 92 Collapse, 84, 85 Combination Therapy, 19, 85 Complement, 86 Complementary and alternative medicine, 27, 33, 86

108 Fosamax

Complementary medicine, 27, 86 Complete remission, 86, 101 Computational Biology, 65, 86 Computed tomography, 84, 86, 87 Computerized axial tomography, 86, 87 Computerized tomography, 5, 86 Conduction, 22, 87 Congestion, 87, 89 Connective Tissue, 15, 83, 85, 87, 90, 101 Connective Tissue Cells, 87 Connective Tissue Diseases, 15, 87 Constipation, 87, 93 Consumption, 4, 87, 101 Contraindications, ii, 87 Controlled study, 20, 21, 87 Cornea, 87, 102, 105 Coronary, 18, 87, 95 Coronary Thrombosis, 87, 95 Cortex, 87 Cortical, 5, 10, 39, 87 Corticosteroid, 87, 99, 103 Cortisone, 36, 87, 99 Curative, 87, 104 Cutaneous, 19, 87 Cytokines, 20, 87 Cytoplasm, 82, 88 D Databases, Bibliographic, 65, 88 Deletion, 82, 88 Density, 4, 8, 10, 12, 13, 14, 16, 17, 22, 27, 39, 40, 84, 88, 96, 103 Dermal, 88, 94 Diagnostic procedure, 43, 57, 88 Diarrhea, 88, 93 Digestion, 81, 83, 84, 88, 94, 104 Digestive system, 41, 88 Dihydrotestosterone, 88, 102 Direct, iii, 4, 59, 88, 101 Discrimination, 3, 88 Dissociation, 81, 88, 93 Diverticulum, 18, 88 Dosage Forms, 44, 49, 88 Drug Interactions, 60, 88 Duodenum, 49, 83, 89, 104 Dysplasia, 35, 89 E Ectopic, 31, 89 Efficacy, 11, 15, 19, 37, 89 Elastin, 85, 87, 89, 90 Electrolyte, 87, 89, 103, 105 Electrons, 83, 89, 93 Embryo, 84, 89, 91, 96

Endoscopy, 7, 21, 89 Environmental Health, 64, 66, 89 Enzymatic, 84, 86, 89 Enzyme, 81, 89, 98, 100, 102, 106 Epidermal, 89, 94 Epidermis, 89, 94 Epinephrine, 89, 105 Erythema, 19, 89 Esophageal, 18, 89 Esophageal Perforation, 18, 89 Esophagus, 88, 89, 104 Estradiol, 5, 89, 102 Estrogen, 4, 14, 15, 16, 19, 24, 38, 89, 101, 102 Estrogen receptor, 16, 89 Etidronate, 7, 8, 12, 13, 27, 90 Excipient, 44, 90 Extracellular, 87, 90, 94, 96, 103, 104 Extracellular Matrix, 87, 90, 94, 96 Extracellular Matrix Proteins, 90, 94 F Family Planning, 65, 90 Fat, 87, 90, 101, 103 Femur, 5, 90 Fetus, 84, 90, 98 Fibrin, 83, 85, 90, 98 Fibrosis, 37, 90 Filtration, 47, 90 Flavoring Agents, 45, 90 Flexor, 90, 94 G Gallbladder, 81, 83, 88, 90 Gas, 90, 92, 93, 104 Gastric, 15, 17, 30, 49, 83, 88, 90 Gastrin, 90, 91 Gastrointestinal, 8, 49, 89, 90 Gastrointestinal tract, 8, 49, 90 Gene, 5, 16, 53, 83, 90, 91 Gene Expression, 5, 91 Germ Layers, 84, 91 Gland, 81, 87, 91, 97, 99, 101, 104 Glucocorticoid, 12, 36, 91, 99 Glucose, 83, 91, 101 Glycoprotein, 91, 102 Gonadal, 91, 103 Governing Board, 91, 99 Growth, 7, 35, 44, 82, 85, 91, 94, 96, 99, 100, 104, 105 H Haptens, 81, 91 Hemorrhage, 91, 104 Hereditary, 87, 91

Index 109

Heredity, 90, 91 Heterogeneity, 81, 91 Hip Prosthesis, 44, 91 Homeostasis, 84, 91 Hormonal, 5, 87, 91 Hormone, 5, 7, 10, 13, 14, 15, 38, 39, 70, 82, 87, 89, 90, 91, 99, 102, 104 Hormone Replacement Therapy, 10, 38, 70, 91 Hormone therapy, 14, 15, 91 Hydrocortisone, 37, 91 Hydrogel, 49, 92 Hydrogen, 83, 90, 92, 95, 98 Hydrophilic, 92 Hydroxylysine, 85, 92 Hydroxyproline, 5, 85, 92 Hypercalcemia, 48, 81, 85, 90, 92 Hyperplasia, 92, 94 Hypertension, 89, 92, 105 I Id, 24, 32, 70, 76, 78, 92 Idiopathic, 14, 39, 40, 92 Immune response, 82, 87, 91, 92, 106 Immunodeficiency, 11, 92 Immunology, 81, 92 Immunosuppressive, 91, 92 Impairment, 92, 94 In vitro, 6, 92 In vivo, 4, 48, 92 Incineration, 47, 92 Infarction, 87, 92, 95 Infection, 92 Inflammation, 82, 85, 90, 91, 93, 97, 98, 101, 104, 105, 106 Ingestion, 4, 13, 93, 104 Intermittent, 93, 94 Intestinal, 31, 93 Intestines, 81, 90, 93 Intramuscular, 93, 97 Intravenous, 6, 16, 93, 97 Intrinsic, 81, 93 Ion Exchange, 93 Ionization, 93 Ions, 83, 88, 89, 92, 93 Iontophoresis, 48, 93 Irritable Bowel Syndrome, 15, 24, 93 J Joint, 44, 48, 83, 90, 91, 93, 104 K Kb, 64, 93 Ketoconazole, 37, 93

L Large Intestine, 88, 93, 101, 103 Lesion, 93, 105 Leukocytes, 87, 93 Library Services, 76, 93 Lichen Planus, 11, 93 Ligament, 94, 100 Liver, 81, 83, 88, 90, 94, 99 Localized, 44, 92, 94, 105 Longitudinal study, 15, 94 Long-Term Care, 8, 27, 94 M Malignancy, 45, 94 Malignant, 6, 94 Mammary, 94, 101 Mammogram, 84, 94, 95 Mandible, 46, 82, 94, 101 Matrix metalloproteinase, 31, 94 MEDLINE, 65, 94 Melanin, 94, 98, 105 Membrane, 86, 90, 94, 98, 99, 101, 102 Menopause, 32, 70, 94, 97, 99 Menstruation, 94 Mental Disorders, 42, 94 Mental Health, iv, 4, 42, 64, 66, 94, 100 Metastasis, 29, 37, 94, 95 Metastatic, 37, 95 MI, 22, 79, 95 Microbe, 95, 105 Microcalcifications, 84, 95 Migration, 10, 95 Milliliter, 84, 95 Mineralization, 10, 95 Mitochondrial Swelling, 95, 96 Mitosis, 82, 95 Mobility, 5, 95 Modeling, 4, 95 Modification, 95, 100 Molecular, 16, 65, 67, 83, 86, 95, 98, 102 Molecule, 82, 83, 86, 88, 95, 101, 102 Monitor, 22, 95, 96 Multicenter study, 17, 95 Myocardium, 95 N Nausea, 88, 95, 105 NCI, 1, 37, 41, 63, 95 Necrosis, 9, 19, 82, 92, 95, 96 Need, 3, 6, 8, 44, 54, 71, 94, 96 Neoplastic, 92, 96 Neutralization, 47, 96 Nuclear, 8, 89, 96, 105 Nucleus, 82, 85, 88, 96

110 Fosamax

O Observational study, 12, 96 Ointments, 88, 96 Opacity, 88, 96 Osseointegration, 84, 96 Ossification, 96 Osteoarthritis, 45, 48, 96 Osteoblasts, 8, 96 Osteocalcin, 5, 7, 96 Osteoclasts, 35, 96 Osteogenesis, 11, 70, 84, 96, 97 Osteogenesis Imperfecta, 11, 70, 97 Ovary, 89, 97 P Palliative, 97, 104 Pamidronate, 4, 5, 16, 18, 31, 97 Pancreas, 81, 88, 97 Pancreatic, 97 Pancreatitis, 11, 97 Parathyroid, 5, 10, 17, 20, 21, 38, 39, 97, 104 Parathyroid Glands, 97 Parathyroid hormone, 5, 10, 17, 20, 21, 38, 39, 97 Parenteral, 48, 97 Partial remission, 97, 101 Pathologic, 82, 83, 87, 97, 101 Pathologic Processes, 82, 97 Pelvic, 97, 99 Percutaneous, 48, 97, 98 Perimenopausal, 15, 24, 97 Periodontal disease, 46, 82, 98 Periodontitis, 20, 29, 46, 98 PH, 84, 98 Pharmaceutical Preparations, 98, 99 Pharmaceutical Solutions, 88, 98 Pharmacokinetic, 37, 98 Pharmacologic, 98, 105 Phenylalanine, 98, 105 Phonophoresis, 93, 98 Phosphates, 47, 98 Phosphorus, 47, 84, 97, 98 Phosphorylation, 98, 100 Physical Examination, 36, 98 Physiologic, 81, 83, 94, 98, 101 Placenta, 89, 98, 99 Plasma, 98, 102 Plasmin, 31, 98, 99 Plasminogen, 98 Plasminogen Activators, 98 Polymorphism, 16, 99 Polyostotic Fibrous Dysplasia, 35, 99

Polypeptide, 82, 85, 98, 99 Porosity, 10, 99 Post-translational, 82, 99, 102 Practice Guidelines, 66, 99 Precipitation, 47, 99 Precursor, 89, 98, 99, 105 Prednisolone, 99 Prednisone, 36, 99 Progesterone, 99, 103 Progression, 18, 46, 99 Progressive, 91, 96, 99 Proline, 85, 92, 99 Propylene Glycol, 47, 48, 99 Prospective study, 94, 99 Prostate, 10, 28, 37, 99 Prosthesis, 44, 100 Protease, 85, 100 Protein C, 82, 96, 100 Protein S, 53, 83, 96, 100, 104 Proteins, 82, 85, 86, 87, 90, 94, 95, 98, 100, 101, 102 Protein-Tyrosine Kinase, 100 Protein-Tyrosine-Phosphatase, 28, 100 Proteolytic, 86, 98, 100 Protocol, 5, 35, 100 Pruritic, 93, 100 Public Health, 4, 66, 100 Public Policy, 65, 100 Publishing, 6, 100 Pulse, 95, 100 Q Quality of Life, 4, 100 R Race, 3, 95, 100 Radioactive, 84, 92, 93, 96, 100, 104, 105 Radiological, 97, 100 Raloxifene, 8, 36, 101, 102 Randomized, 5, 7, 8, 10, 13, 14, 17, 19, 20, 21, 27, 37, 89, 101 Reabsorption, 45, 101 Receptor, 14, 82, 101, 102 Recombinant, 7, 101 Rectum, 84, 88, 90, 93, 100, 101 Refer, 1, 86, 99, 101 Regeneration, 31, 101 Regimen, 37, 56, 89, 101 Remission, 28, 101 Resorption, 3, 31, 40, 45, 48, 82, 84, 96, 101 Respiration, 95, 101 Retina, 101, 105 Retrospective, 12, 101 Rheumatic Diseases, 12, 30, 101

Index 111

Rheumatism, 12, 48, 101 S Salivary, 88, 101 Salivary glands, 88, 101 Saponins, 101, 103 Sclera, 102, 105 Sclerae, 97, 102 Screening, 35, 85, 102 Selective estrogen receptor modulator, 101, 102 Self Care, 81, 102 Semen, 99, 102 Senile, 97, 102 Serum, 5, 7, 86, 96, 102 Sex Characteristics, 102, 104 Sex Hormone-Binding Globulin, 15, 102 Shock, 92, 102, 105 Side effect, 4, 8, 36, 59, 81, 102, 105 Signal Transduction, 100, 102 Signs and Symptoms, 101, 102, 105 Skeletal, 4, 5, 40, 103 Skeleton, 4, 39, 46, 84, 90, 93, 103 Small intestine, 89, 91, 93, 103 Social Environment, 100, 103 Sodium, 31, 44, 45, 46, 47, 48, 50, 81, 84, 101, 103 Soft tissue, 103 Solvent, 98, 99, 103 Sound wave, 87, 103 Spastic, 93, 103 Specialist, 71, 103 Species, 89, 95, 100, 103, 105, 106 Specificity, 81, 103 Spectrum, 93, 103 Spinal cord, 9, 85, 103 Sterile, 97, 103 Steroid, 16, 40, 87, 101, 103 Steroid therapy, 40, 103 Stomach, 12, 24, 49, 81, 83, 88, 89, 90, 91, 93, 95, 103, 104 Stool, 93, 104 Stress, 93, 95, 104 Stroke, 42, 64, 104 Subcutaneous, 97, 104 Suction, 90, 104 Supplementation, 7, 27, 104 Symphysis, 100, 104 Symptomatic, 11, 97, 104 Systemic, 46, 48, 60, 83, 85, 89, 92, 99, 104 Systemic disease, 46, 104 T Technetium, 44, 104

Testis, 82, 89, 104 Testosterone, 5, 102, 104 Tetany, 97, 104 Tetracycline, 28, 104 Therapeutics, 17, 60, 104 Thrombosis, 100, 104 Thyroid, 97, 104, 105 Thyroid Gland, 97, 104 Tissue, 8, 14, 31, 48, 82, 83, 85, 87, 88, 90, 92, 93, 94, 95, 96, 97, 99, 101, 102, 103, 104, 106 Tomography, 104 Tooth Loss, 46, 105 Toxic, iv, 105 Toxicity, 8, 88, 105 Toxicology, 66, 105 Transfection, 83, 105 Trauma, 96, 97, 105 Tryptophan, 85, 105 Tuberculosis, 87, 105 Tyrosine, 6, 29, 100, 105 U Ulcer, 17, 105 Ultrasonography, 15, 105 Unconscious, 92, 105 Uraemia, 97, 105 Uranium, 104, 105 Urethra, 99, 105 Urinary, 5, 21, 105 Urine, 7, 13, 36, 38, 83, 105 Urolithiasis, 45, 105 Uvea, 105 Uveitis, 11, 16, 105 V Vaccine, 100, 106 Vascular, 92, 98, 99, 104, 105, 106 Vasculitis, 97, 106 Vein, 93, 96, 106 Venous, 100, 106 Vertebrae, 103, 106 Vertebral, 7, 20, 27, 29, 106 Veterinary Medicine, 65, 106 Virulence, 105, 106 Virus, 11, 106 Vitro, 106 Vivo, 106 W Weight-Bearing, 96, 106 Wound Healing, 94, 106 X X-ray, 84, 86, 94, 96, 106

112 Fosamax

Z

Zoledronate, 45, 106

Index 113

114 Fosamax

Index 115

116 Fosamax

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