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THE YEAR IN
OSTEOPOROSIS VOLUME 2
EDITED BY
K R I S T I N A Å K E S S O N , J O N AT H A N D A D A C H I ANTHONY D WOOLF
CLINICAL PUBLISHING OX F O R D
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Clinical Publishing an imprint of Atlas Medical Publishing Ltd Oxford Centre for Innovation Mill Street, Oxford OX2 0JX, UK Tel:
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[email protected] © Atlas Medical Publishing Ltd 2006 First published 2006 All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, without the prior permission in writing of Clinical Publishing or Atlas Medical Publishing Ltd Although every effort has been made to ensure that all owners of copyright material have been acknowledged in this publication, we would be glad to acknowledge in subsequent reprints or editions any omissions brought to our attention A catalogue record for this book is available from the British Library ISBN 1 904392 62 8 ISSN 1742-3090 Electronic ISBN 978 1 84692 561 0 The publisher makes no representation, express or implied, that the dosages in this book are correct. Readers must therefore always check the product information and clinical procedures with the most up-to-date published product information and data sheets provided by the manufacturers and the most recent codes of conduct and safety regulations. The authors and the publisher do not accept any liability for any errors in the text or for the misuse or misapplication of material in this work Project Manager: Rosemary Osmond, Helimetrics Ltd, Chipping Norton, Oxon, UK Typeset by Hope Services (Abingdon) Ltd, Abingdon, Oxon, UK Printed by T G Hostench SA, Barcelona, Spain
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Contents Editors and contributors vii Preface xi
Part I
Epidemiology and pathophysiology 1.
Impact of the condition 3 L Joseph Melton III
2.
Risk factors for osteoporosis and fracture 23 Dipak Roy, Terence O’Neill
3.
Pathophysiology of osteoporosis 43 Östen Ljunggren
4.
Genetics of osteoporosis 53 Bente Langdahl
5.
Glucocorticoid-induced osteoporosis 69 Jeffrey Curtis, Kenneth Saag
6.
Secondary osteoporosis 91 M Susan Burke, Solomon Epstein
Part II
Bone mass and measurement 7.
Quantitative ultrasound measurements and fracture risk: a review 119 Claire Wang, Nguyen Nguyen, Tuan Nguyen
8.
Update on the role of biochemical markers in the management of osteoporosis 133 Peter Ebeling
9. Bone quality Juliet Compston
153
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VI
CONTENTS
Part III
Management and prevention 10.
Falls: epidemiological aspects and prevention 171 Paul Gerdhem
11.
Diet and osteoporosis with specific reference to calcium and vitamin D 191 Susan Lanham-New
12.
Physical activity and osteoporosis 209 Magnus Karlsson, Henrik Ahlborg
13.
Management of osteoporosis: HRT; SERMs 225 Cecilia Bottomley, Janice Rymer
14.
Management of osteoporosis: bisphosphonates 257 Socrates Papapoulos
15.
Strontium and parathyroid hormone 281 Jonathan Adachi, Alexandra Papaioannou
Part IV
Therapeutic issues 16.
How to identify new therapeutic targets—from the bench to the bedside 299 Jonathan Tobias
17.
Preventing fractures in the very elderly 321 Steven Boonen, Walter Pelemans, Patrick Haentjens, Dirk Vanderschueren
Acronyms/abbreviations 339 Index of papers reviewed 343 General index 355
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Editors Jonathan D Adachi, MD, FRCP(C) Professor, Department of Medicine, St. Joseph’s Healthcare, McMaster University, Hamilton, Ontario, Canada Kristina Åkesson, MD, PHD Associate Professor, Department of Orthopaedics, Malmö University Hospital, Lund University, Malmö, Sweden Anthony D Woolf, BSC, MBBS, FRCP Professor, Institute of Health and Social Care, Peninsula Medical School, Department of Rheumatology, Royal Cornwall Hospital, Truro, Cornwall, UK
Contributors Jonathan D Adachi, MD, FRCP(C) Professor, Department of Medicine, St. Joseph’s Healthcare, McMaster University, Hamilton, Ontario, Canada Henrik G Ahlborg, MD PHD Orthopaedic Surgeon, Consultant, Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences, Lund University; Department of Orthopaedics, Malmö University Hospital, Malmö, Sweden Steven Boonen, MD, PHD Professor of Medicine, Leuven University Centre for Metabolic Bone Diseases and Division of Geriatric Medicine, Katholieke Universiteit Leuven, Universitaire Ziekenhuizen KULeuven, Leuven, Belgium Cecilia Bottomley, MA, MRCOG Clinical Research Fellow in Gynaecology, St George’s Hospital, London, UK M Susan Burke, MD, FACP Clinical Assistant Professor, Thomas Jefferson University; Director, Internal Medicine Clinical Care Center, Lankenau Hospital, Wynnewood, Pennsylvania, USA
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CONTRIBUTORS
Juliet Compston, FMEDSCI Professor of Bone Medicine, University of Cambridge School of Clinical Medicine; Department of Medicine, Addenbrooke’s Hospital, Cambridge, UK Jeffrey R Curtis, MD, MPH Assistant Professor of Medicine, Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama, USA Peter R Ebeling, MD, FRACP Professor of Medicine, Departments of Medicine, The University of Melbourne, Western Hospital, Footscray, Victoria, Australia Solomon Epstein, MD, FRCP, FACP Professor of Medicine, Mount Sinai Bone Program, Department of Medicine, Mount Sinai School of Medicine, New York, New York; Doylestown Hospital, Doylestown, Pennsylvania, USA Paul Gerdhem, MD, PHD Associate Professor, Department of Orthopaedics, Malmö University Hospital, Lund University, Malmö, Sweden Patrick Haentjens, MD, PHD Professor, Department of Orthopaedics and Traumatology, A-Z VUB, Vrije Universiteit Brussels, Brussels, Belgium Magnus K Karlsson, MD, PHD Professor of Orthopaedics, Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences, Lund University; Department of Orthopaedics, Malmö University Hospital, Malmö, Sweden Jean-Marc Kaufman, MD, PHD Professor, Department of Endocrinology, University Hospital Ghent, Ghent, Belgium Bente L Langdahl, MD, PHD, DMSC Consultant Associate Professor, Department of Endocrinology and Metabolism, Aarhus University Hospital, Aarhus, Denmark Susan A Lanham-New, BA, MSC, PHD, RPHNUTR Reader in Nutrition, Centre for Nutrition and Food Safety, School of Biomedical and Molecular Sciences, University of Surrey, Guildford, Surrey, UK Östen Ljunggren, MD, PHD Professor, Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden
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CONTRIBUTORS
IX
L Joseph Melton III, MD Michael M Eisenberg Professor, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota, USA Nguyen D Nguyen, MD Postgraduate Research Scholar, Bone and Mineral Research Program, Garvan Institute of Medical Research, Sydney, New South Wales, Australia Tuan V Nguyen, PHD Senior Research Fellow and Associate Professor, Bone and Mineral Research Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia Terence W O’Neill, MD, FRCP Senior Lecturer, ARC Epidemiology Unit, University of Manchester, Manchester, UK Alexandra Papaioannou, MD, FRCP(C) Associate Professor, Department of Medicine, Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada Socrates E Papapoulos, MD, PHD Professor of Medicine, Consultant Physician and Director, Bone and Mineral Research, Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands Walter Pelemans, MD, PHD Professor, Division of Geriatric Medicine, Katholieke Universiteit Leuven, Universitaire Ziekenhuizen KULeuven, Leuven, Belgium Dipak K Roy, PHD, MRCP Clinical Research Fellow, ARC Epidemiology Unit, University of Manchester, Manchester, UK Janice Rymer, MD, MRCOG, FRANZCOG, ILTM Professor of Obstetrics and Gynaecology, King’s College School of Medicine, Guy’s and St Thomas’ Hospital, London, UK Kenneth G Saag, MD, MSC Associate Professor and Director, Center for Education and Research on Therapeutics of Musculoskeletal Disorders, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama, USA
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CONTRIBUTORS
Jonathan H Tobias, MBBS, MD, PHD, FRCP Consultant and Reader in Rheumatology, Rheumatology Unit, Department of Clinical Science at South Bristol, University of Bristol, Bristol Royal Infirmary, Bristol, UK Dirk Vanderschueren, MD, PHD Professor, Department of Endocrinology, Katholieke Universiteit Leuven, Leuven, Belgium Claire Y Wang, BSC(HONS) Postgraduate Research Scholar, Bone and Mineral Program, Garvan Institute of Medical Research, Sydney, Australia
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Preface KRISTINA ÅKESSON, RICK ADACHI, ANTHONY WOOLF
There continue to be enormous advances in the knowledge and understanding of the scientific and clinical aspects of osteoporosis over the last years, with increasing numbers of publications appearing in a wide spectrum of journals both in the clinical (internal medicine, primary care, rheumatology, orthopaedics, endocrinology, gynaecology, gerontology) and the many areas of basic science (genetics, biophysics, materials, cell biology). The purpose of this book is to help those interested in osteoporosis remain up to date by experts in the field providing a critical appraisal of the most important recent publications that they have identified and by communicating the key messages. The literature from the past 18 months is reviewed, covering all aspects of osteoporosis that are relevant to the practitioner or researcher working within this area. Advances in our understanding of the epidemiology of osteoporosis are first considered, reviewing the impact and who is most at risk. The pathogenesis and the important role of genetics are considered as well as specific situations of glucocorticoid-induced and other secondary causes of osteoporosis. The use of ultrasound and bone markers for case-finding and monitoring response to treatment are reviewed. Other factors that influence bone quality are also considered. Prevention involves maximising bone strength through physical activity and nutrition, preventing falls and reducing the impact of falls. There is also new evidence for pharmacological treatment of osteoporosis and fracture prevention. How to apply this evidence to the population at highest risk – the very elderly – is considered. Finally, the development of new therapies based on a better understanding of the scientific background to osteoporosis is reviewed. This volume therefore provides a comprehensive update of recent advances in many aspects of osteoporosis that will help ensure best practice in its prevention and management on a background of a better understanding of the scientific basis.
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Part I Epidemiology and pathophysiology
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1 Impact of the condition L JOSEPH MELTON III
Introduction Adverse outcomes of osteoporosis relate mainly to osteoporotic fractures. Hip and spine fractures are associated with increased mortality, and fractures of all types may lead to disability and a reduced quality of life |1|. Moreover, expenditures for the care of these fractures are high. This chapter reviews recent reports on the burden of osteoporosis with respect to mortality, morbidity and cost.
Mortality from osteoporosis Mortality is increased in patients with low bone density even before fractures occur |2|, but death is most closely linked to fractures. The influence on survival varies with the type of fracture. Hip fractures are the most serious: the hazard of death is increased by more than 10-fold in the first weeks following fracture, then diminishes |3|. Mortality is also increased following vertebral fractures, and serious underlying medical conditions, which also increase the risk of osteoporosis, are presumed to be responsible |4|. By contrast, no excess mortality follows distal forearm fractures, although other limb fractures have been linked to greater death rates |5|. These observations have been extended by recent reports that better describe the risk of death associated with incident hip fractures and define the proportion of deaths that can be attributed directly or indirectly to vertebral fractures.
✍
Effect of hip fracture on mortality in elderly women: the EPIDOS Prospective Study Empana J-P, Dargent-Molina P, Bréart G, for the EPIDOS Group. J Am Geriatr Soc 2004; 52: 685–90
B A C K G R O U N D . Although mortality in the first year following hip fracture may be several times higher than corresponding death rates in the population at large, hip fractures tend to occur in persons with more clinical problems and functional deficits than others of similar age and sex. Consequently, the excess mortality attributable to
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I . E P I D E M I O L O G Y A N D PAT H O P H Y S I O L O G Y
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hip fracture is likely to be overestimated. To address this issue, 7512 ambulatory volunteers were recruited from women aged 75 years or older in Amiens, Lyon, Montpellier, Paris and Toulouse, France. After completing baseline functional and clinical examinations, these women were followed every 4 months for 4 years. A multivariate proportional hazards model assessed the association of hip fracture, as a time-dependent variable, with mortality after adjusting for age and baseline health status. I N T E R P R E T A T I O N . During a mean follow-up of 3.9 ± 0.9 years, 338 women had a first hip fracture and 60 of these died. Their age-adjusted post-fracture mortality rate was 112.4 per 1000 woman-years versus 27.3 per 1000 for the 6115 women who did not have a fracture of any type (P
