The Osteoporosis Primer Edited by Janet E

Cambridge University Press 0521644461 - The Osteoporosis Primer Edited by Janet E. Henderson and David Goltzman Frontmatter More information

The Osteoporosis Primer

Osteoporosis is one of the leading causes of morbidity and mortality amongst the elderly. The rationale for The Osteoporosis Primer is to provide an introductory text that relates the clinical presentation of osteoporosis to its molecular biochemical basis. The text has been organized into four sections that deal with the molecular/cellular components of bone, the development of peak bone mass, the pathophysiology of aging bone and, ﬁnally, how all of these relate to the prevention, diagnosis and treatment of osteoporosis. The international team of authors includes many leading clinicians and scientists. They have provided the reader with a concise, yet comprehen- sive synopsis of bone development and skeletal homeostasis. This will be an essential introduction for individuals working on osteoporosis, including students and doctors considering a career related to metabolic bone disease, physicians in general practice, geriatricians, rheumatologists, and endocrinologists.

Janet E. Henderson is Assistant Professor of Medicine at McGill University and a Project Director at the Lady Davis Institute for Medical Research, which is aﬃliated to the Sir Mortimer B. Davis–Jewish General Hospital in Montreal.

David Goltzman is Professor and Chair of the Department of Medicine of McGill University and Physician-in-Chief at the McGill University Health Centre (MUHC).

The Osteoporosis Primer

Edited by Janet E. Henderson McGill University and Lady David Institute for Medical Research Montreal, Quebec, Canada and David Goltzman McGill University and Royal Victoria Hospital Montreal, Quebec, Canada

          The Pitt Building, Trumpington Street, Cambridge, United Kingdom    The Edinburgh Building, Cambridge CB2 2RU, UK http://www.cup.cam.ac.uk 40 West 20th Street, New York, NY 10011–4211, USA http://www.cup.org 10 Stamford Road, Oakleigh, Melbourne 3166, Australia Ruiz de Alarcón 13, 28014 Madrid, Spain

This book is in copyright. Subject to statutory exception and to the provisions of relevant collective licensing agreements, no reproduction of any part may take place without the written permission of Cambridge University Press.

First published 2000

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A catalogue record for this book is available from the British Library

ISBN 0 521 64446 1 paperback

Every eﬀort has been made in preparing this book to provide accurate and up-to-date information which is in accord with accepted standards and practice at the time of publication. Nevertheless, the authors, editors and publisher can make no warranties that the information contained herein is totally free from error, not least because clinical standards are constantly changing through research and regulation. The authors, editors and publisher therefore disclaim all liability for direct or consequential damages resulting from the use of material contained in this book. Readers are strongly advised to pay careful attention to information provided by the manufacturer of any drugs or equipment that they plan to use

Contents

List of contributors viii Preface xiii

Part 1 Molecular and cellular environment of bone 1 Endochondral bone formation and development in the 3 axial and appendicular skeleton A. Robin Poole, Sheila Laverty and Fackson Mwale

2 The role of osteoblasts 18 Jane E. Aubin

3 Osteoclasts: characteristics and regulation of formation and activity 36 Johan N. M. Heersche and Morris F. Manolson

4 Bone matrix proteins 46 Marc D. McKee and Jaro Sodek

5 Local regulators of bone turnover 64 Lawrence J. Fraher and Patricia H. Watson

6 The PTH/PTHrP system and calcium homeostasis 73 Geoffrey N. Hendy

7 Vitamin D metabolism 88 Marielle Gascon-Barré

8 Sodium-dependent phosphate transport in kidney, bone and intestine 102 Harriet S. Tenenhouse

9 Molecular genetic analysis of growth factor signaling in bone 114 Janet E. Henderson and David Goltzman

vi Contents

Part 2 Determinants of peak bone mass 10 Genetic determinants of osteoporosis 131 Millan S. Patel, Laurence A. Rubin and David E. C. Cole

11 Non-genetic determinants of peak bone mass 147 Velimir Matkovic and John D. Landoll

12 Bone mineral acquisition during childhood and adolescence: physical exercise as a preventative measure 170 Heather A. McKay and Karim M. Khan

13 Osteoporosis in children 186 Frank Rauch and Francis H. Glorieux

Part 3 Pathophysiology of the aging skeleton 14 Consequences of alterations in bone remodeling 199 Karen M. Prestwood and Lawrence G. Raisz

15 The role of parathyroid hormone and hyperparathyroidism in osteoporosis 211 Pierre D’Amour

16 Senile osteoporosis 225 Patrick M. Doran and Sundeep Khosla

Part 4Clinical aspects of osteoporosis 17 Biochemical markers of bone turnover 239 David A. Hanley

18 Radiologic assessment of osteoporosis 253 Jacqueline C. Hodge

19 Bone mineral density measurements 262 Paul D. Miller and Carol Zapalowski

20 Hormone replacement therapy 277 Jonathan D. Adachi and Alexandra Papaioannou

21 Selective estrogen receptor modulators 291 Felicia Cosman and Robert Lindsay

vii Contents

22 Bisphosphonate therapy of osteoporosis 304 Frederick R. Singer and Payam Minoofar

23 The action of ﬂuoride on bone 318 Marc D. Grynpas, Debbie Chachra and Hardy Limeback

24 PTH peptides as anabolic agents in bone 331 Anthony B. Hodsman

25 Vitamin D and vitamin D analogs as therapeutic agents 347 Richard Kremer

Index 364

Contributors

Jonathan D. Adachi Pierre D’Amour Department of Medicine, Department of Medicine, Université de Montréal, St Joseph’s Hospital Centre de Recherche Clinique, Hôpital St Luc, 501–25 Charlton Avenue East 264 Rene-Levesque Boulevard East, Montréal, Hamilton, Ontario L8N 1Y2, Canada Québec H2X 1P1, Canada

Jane E. Aubin Patrick M. Doran Department of Anatomy and Cell Biology, c/o Endocrine Research Unit, Division of University of Toronto, Faculty of Medicine, Endocrinology and Metabolism, 6th Floor, Medical Sciences Building Mayo Clinic and Mayo Foundation 1 King’s College Circle, Toronto, 200 First Street, SW, Rochester, MN 55905, USA Ontario M5S 1A8, Canada Lawrence J. Fraher Debbie Chachra Division of Medicine and Biochemistry, Samuel Lunenfeld Research Institute of Mount Research Institute, Room 4–514, Sinai Hospital, University of Toronto, St Joseph’s Health Centre, 268 Grosvenor Street, 600 University Avenue, Room 984B, London, Ontario N6A 4V2, Canada Toronto, Ontario M5G 1X5, Canada Marielle Gascon-Barré David E. C. Cole Department of Pharmacology, Université de Department of Medicine and Genetics, Montréal University of Toronto, Room 402, Banting Institute, Centre de Recherche Clinique, Hôpital St Luc, 100 College Street,Toronto, Ontario M5G 1L5, 264 Rene-Levesque Boulevard East, Montréal, Canada Québec H2X 1P1, Canada

Felicia Cosman Francis H. Glorieux Regional Bone Center, Helen Hayes Hospital, Department of Medicine, McGill University, Route 9 West, West Haverstraw, NY 10993, USA Genetics Unit, Shriner’s Hospital for Children, 1529 Cedar Avenue, Montréal, Québec H3G 1A6, Canada

viii

ix List of contributors

David Goltzman Jacqueline C. Hodge Department of Medicine, McGill University, Department of Diagnostic Radiology, Calcium Research Laboratory, Royal Victoria Royal Victoria Hospital, Hospital, 687 Pine Avenue West, 687 Pine Avenue West, Room H4.67 Montréal, Québec H3A 1A1, Canada Montréal, Québec H3A 1A1, Canada Anthony B. Hodsman Marc D. Grynpas Osteoporosis Program, Department of Medicine, Samuel Lunenfeld Research Institute, St Joseph’s Health Centre, 268 Grosvenor Street, Mount Sinai Hospital, London, Ontario N6A 4V2, Canada 600 University Avenue, Room 984B, Toronto, Ontario M5G 1X5, Canada Karim M. Khan School of Human Kinetics, David A. Hanley University of British Columbia, Division of Endocrinology and Metabolism 210 War Memorial Gym, Department of Medicine, University of Calgary, 6081 University Boulevard, Vancouver BC V6T Health Sciences Centre, 1Z1, Canada 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada Sundeep Khosla Endocrine Research Unit, Division of Johan N. M. Heersche Endocrinology and Metabolism, Faculty of Dentistry Research Institute, Mayo Clinic and Mayo Foundation, Department of Dentistry, University of Toronto, 200 First Street SW, Rochester, MN 55905, USA 124 Edward Street, Toronto, Ontario M5G 1G6, Canada Richard Kremer Department of Medicine, McGill University, Janet E. Henderson Division of Biochemistry, Royal Victoria Hospital, Department of Medicine, 687 Pine Avenue West, Room H4.67 Lady Davis Institute for Medical Research, Montréal, Québec H3A 1A1, Canada 3999 Cote Ste Catherine Road, Room 602, Montréal, Québec H3T 1E2, Canada John D. Landoll Bone and Mineral Metabolism Laboratory Geoffrey N. Hendy Davis Medical Research Center, Department of Medicine, McGill University, The Ohio State University, Calcium Research Laboratory, Royal Victoria 480 West 9th Avenue, Columbus, Hospital, OH 43210–1290, USA 687 Pine Ave West, Room H4.67 Montréal, Québec H3A 1A1, Canada Sheila Laverty Faculty of Veterinary Medicine, University of Montreal, 3200 rue Sicotte, Ste Hyacinthe, Québec J2S 7C6, Canada

x List of contributors

Hardy Limeback Payam Minoofar Division of Preventive Dentistry, Faculty of Department of Endocrinology/Bone Disease Dentistry, Program, University of Toronto, 124 Edward Street, John Wayne Cancer Institute, Toronto, Ontario M5G 1G6, Canada 2200 Santa Monica Boulevard, Santa Monica, CA 90404, USA Robert Lindsay Columbia University College of Physicians and Fackson Mwale Surgeons c/o Joint Diseases Laboratory, Chief Internal Medicine, Helen Hayes Hospital, Shriner’s Hospital for Children, Route 9 West, 1529 Cedar Avenue, Montreal, Québec H3G 1A6, West Haverstraw, NY 10993, USA Canada

Heather A. McKay Alexandra Papaioannou School of Human Kinetics, Auditorium Annex Hamilton Health Sciences Corporation, Chedoke 155, Site, 1924 West Mall, University of British Columbia, Box 2000, Hamilton, Ontario L8N 3Z5, Canada Vancouver, BC V6T 1Z2, Canada Millan S. Patel Marc D. McKee c/o Department of Medicine and Genetics, Faculty of Dentistry, University of Toronto, Banting Institute, McGill University 100 College Street,Toronto, Ontario M5G 1L5, Strathcona Building, Room M43, Canada 3640 University Street Montréal, Québec, H3A 2B2, Canada A. Robin Poole Joint Diseases Laboratory, Shriner’s Hospital for Morris F. Manolson Children Faculty of Dentistry Research Institute, 1529 Cedar Avenue, Montréal, Québec H3G 1A6, Department of Dentistry, University of Toronto, Canada 124 Edward Street, Toronto, Ontario M5G 1G6, Canada Karen M. Prestwood University of Connecticut Center on Aging Velimir Matkovic MC-5215, Bone and Mineral Metabolism Laboratory, University of Connecticut Health Center, Davis Medical Research Center, Farmington, CT 06030–5215, USA Ohio State University, 480 West 9th Avenue, Columbus, OH 43210–1290, USA Lawrence G. Raisz University of Connecticut Center on Aging Paul D. Miller MC-5215, Colorado Center for Bone Research, University of Connecticut Health Center, 3190 South Wadsworth Boulevard, Suite 250 Farmington, CT 06030–5215, USA Lakewood, CO 80227, USA

xi List of contributors

Frank Rauch Harriet S. Tenenhouse c/o Genetics Unit, Shriner’s Hospital for Children, MRC Genetics Group, Montreal Children’s 1529 Cedar Avenue, Montréal, Québec H3G 1A6, Hospital, Canada 2300 Tupper Street, Montréal, Québec H3H 1P3, Canada Laurence A. Rubin Faculty of Medicine, University of Toronto and Patricia H. Watson Division of Rheumatology and Multidisciplinary Department of Medicine, University of Western Osteoporosis Program, Ontario, Sunnybrook and Women’s College Health Science Rm G444 Lawson Research Institute, Center St Joseph’s Health Center, 60 Grosvenor Street, Suite 416, 268 Grosvenor Street, London, Ontario N6A 4V2, Toronto, Ontario M5S 1B6, Canada Canada

Frederick R. Singer Carol Zapalowski Department of Endocrinology/Bone Disease Colorado Center for Bone Research Program, 3190 South Wadsworth Boulevard, Suite 250, John Wayne Cancer Institute, Lakewood, CO 80227, USA 2200 Santa Monica Boulevard, Santa Monica, CA 90404, USA

Jaro Sodek MRC Group, Peridontal Physiology University of Toronto, Fitzgerald Building Room 239, 150 College Street, Toronto, Ontario M5S 3E2, Canada

Preface

Osteoporosis is one of the leading causes of morbidity and mortality amongst the elderly. With the prediction that the number of people who are 60 years or more will increase from ~300 million to greater than 700 million in the next 25 years, it can be appreciated that osteoporosis will rapidly reach epidemic proportions. This will not only represent a huge health care cost but also compromise the physical well-being and quality of life of a substantial segment of the world’s population. Osteoporosis has been deﬁned as ‘. . . a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a conse- quent increase in bone fragility and susceptibility to fracture.’ By World Health Organization standards, the term osteoporosis is used to designate bone mass values of 2.5 standard deviations below the young adult mean. Using this criter- ion, based on bone mass alone, 18 million North Americans have established osteoporosis and 10 million have osteopenia, which is a major risk factor for osteoporosis. As a consequence of these alarming predictions there has been a steady increase in the attention focused on the physiology and pathophysiology of bone. Many excellent texts are now available, which deal in depth with topics related to the clinical presentation and management of osteoporosis. Likewise, specialized volumes on bone cell biology and the molecular biochemical mechanisms that regulate bone development and skeletal homeostasis are now available. While acting as compre- hensive reference texts for physicians and scientists actively working in bone development and metabolism, they are less attractive to those who require a more general approach to the subject. The rationale for the Osteoporosis Primer is to provide an introductory text that relates the clinical presentation of osteoporosis to its molecular biochemical basis. It is aimed primarily at individuals who require an introduction to the domain of metabolic bone disease. This would include students considering a career related to metabolic bone disease, physicians in general practice, geriatricians, rheumatologists, and others. The text of this volume has been organized into four sections that deal with the molecular/cellular components of bone, the development of peak bone mass, the pathophysiology of aging bone and, ﬁnally, how all of these relate to the prevention, xiii

xiv Preface

diagnosis and treatment of osteoporosis. The authors who have contributed to this volume enjoy an international reputation for excellence in their area of expertise. They represent clinicians and scientists who are dedicated to the pursuit of improving our understanding of the etiology and pathogenesis of disorders of bone and mineral metabolism. As such, they have provided the reader with a concise, yet com- prehensive, synopsis of bone development and skeletal homeostasis. The reader is first introduced to endochondral bone formation, which is the process by which the vast majority of bones in the mammalian skeleton are formed. The recruitment and activity of cells that perform anabolic and catabolic functions in bone are described in relationship to the systemic hormones and locally derived factors which regulate these activities. The genetic and non-genetic determinants of peak bone mass are then outlined before describing age-related changes in the cellular and hormonal environment of bone that lead to a decline in bone mass. The final section deals with the epidemiology, laboratory diagnosis and treatment of osteoporosis. It includes discussion of the potential of antiresorptive agents, such as estrogen and bisphosphonates, anabolic agents, such as fluoride and PTH and nutritional therapy with calcium and vitamin D for the treatment and prevention of osteoporosis. These topics are related throughout the text to current research ini- tiatives, using in vitro and in vivo models, which are aimed at improving the diagnosis and treatment of osteopenic disorders. It is hoped that the blend of clinical and basic science brings the reader to a more complete understanding of the complexity of the problem and an appreciation of the research efforts still required before prevention of osteoporosis is a reality.

Janet E. Henderson PhD David Goltzman MD