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Other companion titles in the Rheumatology series:
Ankylosing Spondylitis and the Spondyloarthropathies Osteoporosis and the Osteoporosis of Rheumatic Diseases Psoriatic and Reactive Arthritis Systemic Lupus Erythematosus
1600 John F. Kennedy Blvd. Ste 1800 Philadelphia, PA 19103-2899
OSTEOARTHRITIS: A COMPANION TO RHEUMATOLOGY Copyright © 2007 by Mosby, Inc., an affiliate of Elsevier Inc.
ISBN 13: 978-0-323-03929-1
All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Permissions may be sought directly from Elsevier’s Health Sciences Rights Department in Philadelphia, PA, USA: phone: (+1) 215 239 3804, fax: (+1) 215 239 3805, e-mail:
[email protected]. You may also complete your request on-line via the Elsevier homepage (http://www.elsevier.com), by selecting ‘Customer Support’ and then ‘Obtaining Permissions’.
Notice Knowledge and best practice in this field are constantly changing. As new research and experience broaden our knowledge, changes in practice, treatment and drug therapy may become necessary or appropriate. Readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and contraindications. It is the responsibility of the practitioner, relying on their own experience and knowledge of the patient, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions. To the fullest extent of the law, neither the Publisher nor the Authors assumes any liability for any injury and/or damage to persons or property arising out or related to any use of the material contained in this book. The Publisher
Library of Congress Cataloging-in-Publication Data Osteoarthritis : a companion to Rheumatology / [edited by] Leena Sharma, Francis Berenbaum. -- 1st ed. p. ; cm. Companion v. to: Rheumatology / edited by Marc C. Hochberg . . . [et al.]. 3rd ed. 2003. Includes bibliographical references and index. ISBN 978-0-323-03929-1 1. Osteoarthritis. 2. Rheumatology. I. Sharma, Leena. II. Berenbaum, Francis. III. Rheumatology . [DNLM: 1. Osteoarthritis. WE 348 08465 2007] RC931.0670868 2007 616.7′223--dc22 2006037786
Publishing Director: Kim Murphy Developmental Editor: Denise LeMelledo Project Manager: Bryan Hayward
Printed in the United States of America.
Last digit is the print number: 9 8 7 6 5 4 3 2 1
(From Leena Sharma:) I would like to dedicate this book to Sol, Ben, Becca and Oreo Aronson.
Contributors
Kim Bennell, BAppSci, PhD Professor Centre for Health, Exercise, and Sports Medicine School of Physiotherapy University of Melbourne Melbourne, Victoria, Australia Francis Berenbaum, MD, PhD Faculty of Medicine Pierre & Marie Curie—Paris VI Head of the Department of Rheumatology Saint-Antoine Hospital Paris, France Lan X. Chen, MD Clinical Assistant Professor Department of Medicine University of Pennsylvania; Attending Physician, Penn Presbyterian Medical Center Philadelphia, Pennsylvania Maxime Dougados, MD Faculty of Medicine University Paris-Descartes; Attending Physician, Hospital Cochin Paris, France Patrick Garnero, PhD, DSc Senior Scientist INSERM Research Unit 664; Vice President and Scientific Director Molecular Markers Synarc Lyon, France
Mary B. Goldring, PhD Associate Professor of Medicine Harvard Medical School; Associate Professor of Medicine, Beth Israel Deaconess Medical Center; Senior Scientist New England Baptist Bone and Joint Institute New England Baptist Hospital Boston, Massachusetts Nicola J. Goodson, MB, ChB, PhD Senior Lecturer in Rheumatology University of Liverpool; Honorary Consultant Rheumatologist University Hospital Aintree Liverpool, Merseyside, United Kingdom Rana S. Hinman, BPhysio, PhD Lecturer Center for Health Exercise and Sports Medicine The University of Melbourne Melbourne, Victoria, Australia Daniel Lajeunesse, PhD Professor Department of Medicine University of Montreal; Senior Researcher Department of Rheumatology Hospital Norte-Dame Montreal, Quebec, Canada Marie-Pierre Hellio Le Graverand, MD, DSc, PhD Senior Director Clinical Research and Development, Inflammation Pfizer Global Research and Development Ann Arbor, Michigan
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CONTRIBUTORS
Grace H. Lo, MD, MSc Assistant Professor Department of Medicine Division of Rheumatology Tufts University; Assistant Professor Department of Medicine Division of Rheumatology New England Medical Center Boston, Massachusetts Richard F. Loeser, Jr., MD Professor Department of Internal Medicine Division of Molecular Medicine Wake Forest University School of Medicine Winston-Salem, North Carolina L. Stefan Lohmander, MD, PhD Department of Orthopaedics Lund University Hospital Lund, Sweden Didier Mainard, MD, PhD Professor Laboratory of Pharmacology Faculty of Medicine; Head of Department of Orthopaedic and Trauma Surgery Centre Hospitalo-Universitaire Nancy, France Lisa A. Mandl, MD, MPH Assistant Professor of Medicine Department of Public Health Weill Medical College of Cornell University; Assistant Attending Physician Division of Rheumatology Hospital for Special Surgery New York, New York Jean-Pierre Martel-Pelletier, MD Professor Department of Medicine University of Montreal; Director, Osteoarthritis Research Unit Research Centre, University of Montreal Hospital Centre Notre-Dame Hospital Montreal, Quebec, Canada
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Johanne Martel-Pelletier, PhD Professor Department of Medicine University of Montreal; Director, Osteoarthritis Research Unit Research Centre, University of Montreal Hospital Centre Notre-Dame Hospital Montreal, Quebec, Canada Timothy E. McAlindon, MD, MPH Associate Professor of Medicine Division of Rheumatology Tufts University; Chief, Division of Rheumatology New England Medical Center Boston, Massachusetts Timothy J. Mosher, MD Associate Professor of Radiology Penn State University College of Medicine; Chief, Musculoskeletal Imaging, and Magnetic Resonance Imaging Department of Radiology Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania Patrick Netter, MD, PhD Professor Laboratory of Pharmacology, Faculty of Medicine University of Nancy Vandoeuvre les Nancy, France George Nuki, MB, FRCP Emeritus Professor of Rheumatology The Queen’s Medical Research Institute University of Edinburgh; Honorary Consultant Rheumatologist Western General Hospital Edinburgh, Scotland, United Kingdom Pascale Pottie, PhD Professor Laboratory of Pharmacology, Faculty of Medicine University of Nancy Vandoeuvre les Nancy, France Nathalie Presle, PhD Professor Laboratory of Pharmacology, Faculty of Medicine University of Nancy Vandoeuvre les Nancy, France
Donald M. Salter, BSc, MD, FRCPath, FRCPE Professor of Osteoarticular Pathology University of Edinburgh; Consultant Pathologist Edinburgh Royal Infirmary Edinburgh, Scotland, United Kingdom Leena Sharma, MD Professor of Medicine Feinberg School of Medicine Northwestern University Chicago, llinois Daniel H. Solomon, MD, MPH Associate Professor of Medicine Division of Rheumatology Division of Pharmacoepidemiology Harvard Medical School; Associate Physician Brigham and Women’s Hospital Boston, Massachusetts
Amanda M. Tiffany, MD, MPhil Johns Hopkins University House Staff Johns Hopkins Bayview Medical Center Baltimore, Maryland
CONTRIBUTORS
Pascale Reboul, PhD Assistant Professor of Medicine University of Montreal Montreal, Quebec, Canada
Eric Vignon, MD Professor Department of Rheumatology Claude Bernard University; Head of Rheumatology Centre Hospitalier Lyon Sud Lyon, France Frank A. Wollheim, MD, PhD, FRCP Department of Rheumatology Lund University Hospital Lund, Sweden Tim V. Wrigley, BSc, MSc Director, Movement Research Laboratories Centre for Health, Exercise and Sports Medicine School of Physiotherapy University of Melbourne Melbourne, Victoria, Australia
Bernard Terlain, PharmaD Professor Laboratory of Pharmacology, Faculty of Medicine University of Nancy Vandoeuvre les Nancy, France
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Preface
The most common type of arthritis that humans acquire is osteoarthritis (OA). The World Health Organization estimates that OA is a cause of disability in at least 10% of the world population over age 60 years. In 2006, we have at best a rudimentary understanding of how to modify its course or how to prevent function loss and disability in those who have it. There are at least three major reasons for our current level of understanding. First, OA is a difficult disease to study and is heterogeneous in its presentation, style and rate of progression, and manifestations. Second, the field of investigators dedicated to the study of osteoarthritis has been small. Third, although there is much discussion in the literature about the need for multidisciplinary teams to study osteoarthritis most studies reflect a perspective dominated by one discipline.
This book consists of chapters written by authors who are leaders in their fields, who are innovative thinkers, and who come from several disciplines relevant to OA. Their words speak for themselves. This is an important time—a time ripe for a substantial increase in knowledge concerning OA. In presenting this book, we have several goals and hopes: that this book serve as a source of information and ideas for those already involved in OA investigation and patient care (as well as for a new generation of clinicians and researchers), that it stimulate patient care approaches and research that arise from equal engagement of the key disciplines, and that it and others like it synergize with the landmark public data release known as the Osteoarthritis Initiative to accelerate the pace of travel toward more meaningful and effective prevention and treatment strategies for OA.
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Acknowledgements
We would like to acknowledge the wonderful work and contributions of the authors and the masterful editorial assistance of Faith Brody.
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EPIDEMIOLOGY
1
Epidemiology of Osteoarthritis Lisa A. Mandl
BACKGROUND Osteoarthritis (OA) is the most common joint disease in the world, with an age-associated increase in both incidence and prevalence.1 In the United States, “arthritis and rheumatism” (largely OA) is the single largest reason for disability among those over 18. This is more than double the number of people disabled by cardiac disease.2 OA affects predominantly older adults, and by the year 2020 the population 65 and over in developed countries is projected to increase by 71%.3 Already a major public health and economic problem costing the United States at least $15.5 billion per year,4 this demographic shift will cause the prevalence of OA to skyrocket over the next decade. It is estimated that the population burden of disease due to OA will be greater than either human immunodeficiency virus (HIV) or chronic obstructive pulmonary disease (COPD).3 It will, therefore, become increasingly important to define and study OA to better understand risk factors for disease, find the best treatment for symptoms, and discover new therapies to slow down or even prevent disease progression.
DEFINITIONS OF OSTEOARTHRITIS
Anatomic/Etiologic Definition OA can be broadly divided into primary, or idiopathic disease, and OA secondary to another condition. Primary OA may be localized to one joint, or in a generalized form to several joints. Definitions of generalized OA vary in the literature and commonly include small joint involvement of the hands coupled to involvement of one or more large joints (Table 1.1).
Radiographic/Functional Definitions Determining population rates of OA is not a straightforward endeavor, because the incidence and prevalence of OA vary dramatically depending on how one defines disease. The inconsistent relationship between clinical symptoms and X-ray findings can make identifying cases difficult. For example, it is estimated that
people aged 63 to 93 years have a 33% prevalence of radiographic knee OA, but only 9.5% are symptomatic.5 The converse is also true: patients can have debilitating OA pain with minimal or no radiographic findings. The most commonly used method for evaluating and defining radiographic OA is the Kellgren and Lawrence system (Table 1.2).6 This grading system is applied to specific joints by comparing a patient’s radiograph with that of a standard radiographic atlas. A Kellgren–Lawrence grade of 2 or greater is the most commonly used definition of radiographic OA.7 However, using radiographs alone to define OA will capture many individuals who have minimal or no symptoms of disability. Therefore, most functional definitions rely on a combination of clinical and radiographic findings. The most common epidemiologic definition is radiographic evidence of OA and pain on most days of a month within the past year. The American College of Rheumatology (ACR) has developed consensus criteria to define clinically relevant OA of the hand, knee, and hip (Table 1.3). These widely used criteria allow the identification of similar groups of patients for randomized controlled trials and other studies. The ACR criteria were derived from actual OA patients, and are the most suitable criteria for identifying OA patients in clinical practice. The uncoupling of symptomatology and imaging (at least early in the disease process) may be partially a function of technology.8 Radiographs, which cannot image soft tissues, are unable to identify early pathologic changes in the joint and thus provide only a gross estimate of joint disease. Although joint space narrowing, an important measure of OA progression, can be reliably measured by X-rays,9 it is important to realize that this technique depends not just on cartilage volume but on the integrity of associated ligaments, tendons, synovial tissue, and menisci.10 In contrast, magnetic resonance imaging (MRI) not only images bone but can provide important information on cartilage and other soft tissues. Specifically, MRI can identify very subtle changes in soft tissues that occur early
1
EPIDEMIOLOGY OF OSTEOARTHRITIS
TABLE 1.1 DEFINITIONS OF OSTEOARTHRITIS Primary OA
Grade
Radiographic Description
Idiopathic: ● Localized ● Generalized (three or more joints)
0
Normal
1
Possible osteophyte
Secondary OA
2
Definite osteophytes, possible joint space narrowing
3
Moderate osteophytes, definite narrowing, some sclerosis, possible attrition
4
Large osteophytes, marked narrowing, severe sclerosis, definite attrition
Examples include: 1. Developmental ● Congenital hip dislocation ● Legg-Calves-Perthes disease ● Congenital hip dislocation ● Epiphyseal dysplasias 2. Mechanical ● Hypermobility syndromes (Ehlers-Danlos, hyperlaxity syndromes) ● Leg length discrepancy ● Mal-alignment 3. Trauma (acute or chronic) ● Accidental ● Sports injury ● Occupational ● Iatrogenic (post-surgical) 4. Metabolic ● Hemachromatosis ● Wilson’s disease ● Mucopolysaccharidoses ● Amyloidosis ● Ochronosis ● Gout ● Pseudogout ● Calcium crystal deposition 5. Endocrine ● Acromegaly ● Hyperparathyroidism ● Hypothyroidism 6. Inflammatory ● Any systemic rheumatic disease ● Septic arthritis 7. Miscellaneous ● Hemophilias ● Paget’s disease ● Osteonecrosis ● Neuropathic arthropathy
2
TABLE 1.2 KELLGREN–LAWRENCE RADIOGRAPHIC GRADING SYSTEM FOR OSTEOARTHRITIS
in the disease process and which radiographs alone are not sensitive enough to discern.11 These two techniques can provide very different information. Cross-sectional data show that MRI identifies cartilage changes that are unable to be seen on plain radiographs.12 MRI has also been shown to be a more sensitive method of measuring cartilage changes over time compared with radiographs.13,14 In one study that followed OA patients for two years there was no
correlation between loss of cartilage volume, as measured by MRI, and joint space narrowing.15 As more work is done using MRI to study the development and evolution of OA, it is likely that future definitions of OA will incorporate MRI features.
INCIDENCE AND PREVALENCE OF OSTEOARTHRITIS
Prevalence of Pathologic Osteoarthritis Some damage to joint cartilage is probably unavoidable in later life. A 1926 series of 1,000 autopsies found evidence of OA in almost all people over 65.16 Autopsy studies show that knee OA is almost universally present after age 60, and is associated with increasing age.17 Postmortem studies show that up to 50% of postmenopausal Caucasian women have almost complete obliteration of the carpometacarpal (CMC) joint, and an additional 25% have severe damage to the cartilage.18 However, the link between such pathology and clinical symptoms is still poorly understood. Another autopsy study found that although 48% of knees had moderate to severe histologic OA medical record review revealed that only 10% of these patients had any clinical manifestation of knee OA.19 Future studies should evaluate the relationship between specific anatomic areas of cartilage destruction, the integrity of joint-associated soft tissues, the anatomic alignment of joint components, and clinical symptoms.
Prevalence of Radiographic Osteoarthritis Population-based studies consistently show high prevalence rates of radiographic OA in older adults. However, there may be significant geographic and ethnic differences in rates of radiographic OA, although it is difficult to make absolute comparisons due to differences in case ascertainment and radiographic assessment. To identify real differences among populations, future studies will need to be able to control for important potential
ACR Classification Criteria for Osteoarthritis of the Handa Hand, pain, aching, or stiffness and three or four of the following features. ●
Hard tissue enlargement of two or more of ten selected joints*
●
Hard tissue enlargement of two or more DIP joints
●
Fewer than three swollen MCP joints
●
Deformity of at least one of ten selected joints*
*Second and third DIPs, PIPs, and first CMC joints bilaterally 94% sensitive 87% specific ACR Combined Clinical and Radiographic Classification for Criteria for Osteoarthritis of the Hipb Hip pain and at least two of the following three features. ●
ESR 50 years
●
Age >50 years
●
Age >50 years
●
Stiffness
