Osteoporosis: Diagnosis, Prevention, Therapy

313 Pages·2009·8.282 MB·English

by  Prof. Dr. Reiner Bartl, Prof. Dr. Bertha Frisch (auth.)

Osteoporosis
Reiner Bartl • Bertha Frisch
Osteoporosis
Diagnosis, Prevention, Therapy
Second Revised Edition
In Collaboration with Christoph Bartl
1 3
Prof. Dr. Reiner Bartl Prof. Dr. Bertha Frisch
Bavarian Center of Osteoporosis Professor of Hematology
University of Munich Departments of Pathology and Hematology
Marchioninistraße 15 Sourasky Medical Center
81377 Munich University of Tel-Aviv
Germany 6 Weizmann Street
[email protected] 64233 Tel-Aviv
Israel
Christoph Bartl, MD
[email protected]
Department of Orthopaedic and Trauma Surgery
University of Ulm
Steinhövelstraße 9
89075 Ulm
Germany
ISBN: 978-3-540-79526-1 e-ISBN: 978-3-540-79527-8
DOI: 10.1007/ 978-3-540-79527-8
Library of Congress Control Number: 2009922223
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Preface

fracture is projected to increase by 240% in women
and 310% in men by 2050, unless appropriate preven-
tive measures are taken on suf(cid:191) ciently large national
and international scales, for which, hopefully, this
book will provide a stimulus!
On the positive side, the enormous amount of
With the dawn of the 21th century has come the re- work, research and study of bone disorders over the
alization that bone and joint diseases are the major past 10–20 years or so has contributed greatly to our
cause of pain and physical disability worldwide. More- understanding of the causes, treatment and prevention
over, according to the WHO Scienti(cid:191) c Group, there of osteoporosis and other disorders. Most importantly
are more than 150 musculoskeletal diseases and syn- perhaps, the skeleton is now regarded in a new light,
dromes, all of which are usually associated with pain as a dynamic organ undergoing constant renewal
and loss of function. It is undoubtedly these insights throughout life from start to (cid:191) nish, from the cradle
that prompted the WHO to declare the (cid:191) rst 10 years to the grave. And what is more: it is now abundantly
of the new century as “The Bone and Joint Decade clear that the skeleton participates, usually not to its
2000–2010”. This declaration obviously made a highly advantage, in almost every condition that may affect
signi(cid:191) cant impact on international, national and medi- the organs and tissues in the body! This applies es-
cal authorities, as well as on physicians, scientists and pecially to osteoporosis, which is now under control!
citizens worldwide as evidenced by an overwhelm- How did this come about?
ing (cid:192) ood (a regular tsunami) of articles, studies and (cid:404)Because of the elucidation of many of the factors
books on the subject in the last few years alone! That involved in osseous remodelling.
is not to mention the coverage in newspapers and (cid:404)Because of the development of simple, fast, reli-
journals, on the radio and television and of course able and non-invasive methods for measuring bone
all the up-to-date information freely available on the density and for testing other factors such as miner-
Internet. The number of people suffering from these alization, trabecular architecture, cortical thickness
diseases – already many millions in the developed and and the bone cells themselves.
underdeveloped countries of the world is expected to (cid:404)Because of the identi(cid:191) cation of general and indi-
double within the next 20 years. In many countries vidual risk factors, such that appropriate measures
this increase will be even greater due to the longer can be taken to prevent development of osteoporosis
survival and consequently larger numbers of older and/or its progression, if and when fractures have
people in the population. It is therefore inevitable that already occurred.
the already astronomical costs of health care will rise (cid:404)And (cid:191) nally, because effective medication for pre-
proportionally. According to the National Osteoporo- vention and therapy is now readily available world-
sis Foundation (NOF), the worldwide incidence of hip wide.
v
vi Preface
The ef(cid:191) cacy of the classes of compounds known as attention. However, statistics published some years
‘bisphosphonates’ as well as of selective oestrogen ago estimated that 40% of osteoporoses in women
receptor modulators (SERMs) and, more recently, of and 50% in men are secondary. Most probably with
the anabolic parathyroid hormones has now been un- the increase in survival and therefore the number of
equivocally established by numerous large multicen- older people in many populations, these proportions
tre trials involving literally millions of patients. In have also increased. In addition, the increase in sur-
addition, simple methods such as a healthy lifestyle, vival of patients with co-morbidities due to improved
adequate nutrition, suf(cid:191) cient physical activity and vi- therapeutic and management strategies must also be
tamin D and calcium supplements, as required, can be taken into account. Therefore, in this edition, more at-
recommended and adopted on a large scale, beginning tention has been paid to the recognition of metabolic
with the responsible authorities and reaching to the interactions, risk factors, diagnosis, therapy and man-
individual citizens. Introduction and acceptance of agement of secondary osteoporoses.
these methods requires public awareness and sup- Novel directions in classi(cid:191) cations and inter-re-
port and the realization that every individual is the lationships of major diseases and their subtypes, in-
guardian and caretaker of his/her own bones and re- cluding osteoporosis, as well as in the application of
sponsible for their structural and functional integrity. the particular up-to-date criteria required by systems
Fortunately, some progress has been made, as shown biology and by the relatively novel (cid:191) elds of genomics,
by the numerous articles recently published from the metabolomics and pharmacogenomics, among others,
“four corners of the globe” which unequivocally es- are brie(cid:192) y mentioned but not actually utilized in this
tablish the epidemic proportions of the problem. Well- text. All of the above have been developed, con(cid:191) rmed
founded diagnostic techniques and effective therapies and published and many have gained recognition and
– both antiresorptive and osteo-anabolic – are now approval, although widespread acceptance and utili-
available for the prevention, diagnosis and treatment zation is only just beginning. Consequently, we have
of osteoporosis. It should be emphasized that the treat- adhered stringently to simplicity, comprehensiveness,
ments recommended in this text are all founded on and practicality of approach to examinations, methods
“evidence-based medicine” (unless otherwise stated) and implementation of up-to-date testing, prevention
for which the appropriate references are given at the strategies, diagnosis criteria, and presentation of ther-
end of the text. apeutic possibilities, as well as to our own particular
The aim of this book is to demonstrate that “bone is goal which is to keep this text as “user-friendly” as
everybody’s business” and especially every patient’s possible, so that any doctor seeking information on
and doctor’s, and to provide guidelines for the diag- a particular topic in osteoporosis and associated and
nosis, therapy and prevention of osteoporosis – from secondary osteopathies has uncomplicated and time-
paediatrics to geriatrics. It is hoped and anticipated saving access to such information. We wish all our
that this book will raise awareness and provide infor- readers success in their endeavours to help patients
mation to anyone seeking it, and especially to doctors and to reduce suffering in this strife-ridden, beautiful
across all disciplines concerned with this preventable planet of ours. God bless you all!
and treatable disease.
The main subjects of the (cid:191) rst edition of this book Munich, Tel-Aviv and Ulm Reiner Bartl
were primary and involutional osteoporoses, while Bertha Frisch
the secondary osteoporoses only received ‘secondary’ Christoph Bartl
Contents

1 Epidemiology of Osteoporosis ............ 1 3.4 Osteoporosis – Also a Question
1.1 Osteoporosis: A Silent Thief! ........ 1 of Quality! ................................. 32
1.2 Osteoporosis: The Global Scope 3.5 De(cid:191) nition of “Fracture” ............... 34
of the Problem ............................ 2 3.6 Vertebral (Spinal) Fractures .......... 34
3.7 Hip Fractures ............................. 36
2 Biology of Bone ................................. 7
3.8 Wrist Fractures ........................... 37
2.1 Bone: An Architectural Masterpiece 7
3.9 Other Fractures .......................... 37
2.2 Bone: A Permanent Building
and Rebuilding Site ..................... 10 4 Subgroups of Osteoporosis ................. 39
2.3 Remodelling Units ...................... 15 4.1 According to Spread .................... 39
2.4 Some Biological Perspectives on the 4.2 According to Age and Sex ............ 40
Mechanisms Involved in the Control 4.3 According to Extent .................... 42
and Regulation of Bone Remodelling 17 4.4 According to Histology ................ 43
2.5 Minimodelling ........................... 18
5 Risk Factors for Fractures ....................... 45
2.6 Stimuli, Triggers and Mechanisms of
5.1 Risk Factors Which Cannot (Yet) be
Activation of Bone Remodelling ......... 19
In(cid:192) uenced ................................. 46
2.7 Control of Bone Remodelling:
5.2 Risk Factors Which Can be
A Network of Complex Mechanisms 20
In(cid:192) uenced ................................. 48
2.8 Osteoimmunology: A Representative
of Systems Biology ............................. 23 6 Clinical Evaluation of Osteoporosis .... 55
2.9 The RANK/RANKL/ 6.1 Indicative Symptoms ................... 55
Osteoprotegerin System ............... 23 6.2 Osteoporosis and Teeth, Skin and
2.10 Leptin: Role of the Central Nervous Hair – What are the Connections? ....... 57
System in Regulation of Bone ....... 25 6.3 Role of Conventional X-Rays in
2.11 Growth of the Embryo in the Uterus ... 26 Osteoporosis .............................. 57
2.12 Peak Bone Mass: An Investment 6.4 Other Useful Imaging Techniques .... 60
for a Healthier Life ...................... 27
7 Bone Density in Osteoporosis ............. 63
3 Pathogenesis of Osteoporosis .............. 29 7.1 Why Measure Bone Mineral
3.1 Factors in the Development Density? .................................... 63
of Osteoporosis ........................... 29 7.2 Which Instruments to Use? ........... 63
3.2 De(cid:191) nition of Osteoporosis ............ 30 7.3 Which Bones to Measure? ............ 70
3.3 Osteoporosis – Which Bones are 7.4 Who is Due or Overdue for a BMD
Vulnerable? ............................... 31 Test? ......................................... 70
vii
viii Contents
7.5 Bone Densitometry in Children 11 Treatment Strategies in Osteoporosis ..... 99
– Now Readily Available! ............. 72 11.1 Evidence-Based Strategies
7.6 BMD Measurement – Not a Scary for the Therapy of Osteoporosis ... 99
Procedure, Nothing to be Afraid of! 73 11.2 Comprehensive Approach
to the Therapy of Osteoporosis .... 103
8 Laboratory Evaluation of Osteoporosis .. 75
11.3 Indication for Treatment –
8.1 Recommended Tests .................... 75
Combining BMD with Clinical
8.2 Signi(cid:191) cance of Markers of Bone
Factors .................................... 104
Turnover ................................... 75
8.3 Recommendations for Practical Use 12 Management of Pain
of Bone Markers ......................... 79 in Osteoporosis ................................. 107
8.4 Potential of Bone Biopsy in Clinical 12.1 Start with the Patient, not the
Practice ..................................... 79 Disease! .................................. 107
8.5 When is a Bone Biopsy Indicated? .... 80 12.2 Acute Phase ............................. 107
8.6 Up-to-Date Methods .................... 81 12.3 Chronic Phase – Short Term ........ 108
12.4 Chronic Phase – Long Term ........ 109
9 Prevention of Osteoporosis ................. 83
12.5 Electric Potentials in Bone .......... 109
9.1 Step 1: First of all a Calcium-Rich
Diet! ......................................... 83 13 Calcium and Vitamin D . . . . . . . . . . . . . . 111
9.2 Step 2: Ensure an Adequate Supply 13.1 Calcium: A Lifelong Companion ..... 111
of Vitamins! ............................... 85 13.2 The Concept of Vitamin D
9.3 Step 3: Protect the Spine in in the 21th Century ..................... 113
Everyday Life! ............................ 86 13.3 Vitamin D: Don’t Rely
9.4 Step 4: Regular Physical Activity – on Sunshine, Take Supplements .... 114
for the Preservation of Strong 13.4 Rickets ..................................... 115
Bones! ...................................... 87 13.5 Other Vitamins Involved
9.5 Step 5: No Smoking, Please! ......... 90 in Skeletal Health ....................... 117
9.6 Step 6: Reduce Nutritional “Bone
14 Hormones for Replacement
Robbers”! .................................. 90
Therapy ............................................. 119
9.7 Step 7: Strive for an Ideal Body
14.1 Hormone Replacement Therapy
Weight! ..................................... 91
for Women – Now Recommended
9.8 Step 8: Identify Drugs that Cause
for Symptoms Only! ................... 119
Osteoporosis and Take Appropriate
14.2 Which Oestrogens and Progestins,
Steps to Counteract Them When
and How to Take Them? ............. 120
Possible and Necessary! ............... 92
14.3 Which Women to Treat? ............. 121
9.9 Step 9: Recognize Diseases Which
14.4 How Long to Treat? ................... 121
Damage Bones! .......................... 92
14.5 How to Monitor HRT? ............... 121
9.10 Step 10: Management of Patients
14.6 What are the Risks and Adverse
Who Have Already Sustained
Events of HRT? ........................ 122
a Fracture .................................. 93
14.7 What are the Main
10 Physical Activity and Exercise Contraindications? .................... 122
Programs ......................................... 95 14.8 Natural Oestrogens –
10.1 Strong Muscles Make and Maintain How Effective are They? ............ 122
Strong Bones! ............................ 95 14.9 Dehydroepiandrosterone
10.2 The Muscle–Bone Unit and (DHEA) – Is it Useful for the
Sarcopenia ................................. 96 Prevention of Bone Loss? ........... 124
10.3 Excercise Programs – Preventive 14.10 Testosterone – Good for Bones
and Restorative ........................... 97 and Well-Being in Men! ............. 124
10.4 Implementation of a Training 14.11 Anabolic Steroids – Strong
Program .................................... 97 Muscles for Healthy Bones! ........ 124
Contents ix
15 Bisphosphonates ............................... 127 22.1 Adherence to Treatment .............. 161
15.1 A Brief Survey of 22.2 Monitoring Treatment ................. 161
Bisphosphonates .............................. 128 23.3 Monitoring Antiresorptive
15.2 Pharmacokinetics ....................... 131 Therapy ................................... 163
15.3 Toxicity and Contraindications .... 132 24.4 Monitoring Osteo-anabolic
15.4 Osteomyelitis/Osteonecrosis Therapy ................................... 164
of the Jaw (ONJ) ....................... 133
23 Osteoporotic Fractures ...................... 165
15.5 Contraindications ...................... 135
23.1 Fragility Fractures ..................... 165
15.6 Oral Bisphosphonates Currently
23.2 Fractures and the Healing
Used in Osteoporosis ................. 135
Process ................................... 166
15.7 Alendronate ............................. 135
23.3 Effects of Drugs and Lifestyle on
15.8 Risedronate .............................. 136
Fracture Healing ...................... 167
15.9 Etidronate ................................ 137
23.4 Risk Factors for Osteoporotic
15.10 Ibandronate ............................. 137
Fractures ................................. 168
15.11 Intravenous Bisphosphonates for
23.5 Management of Osteoporotic
the Treatment of Osteoporosis ..... 138
Fractures .................................. 171
15.12 Ibandronate ............................. 138
23.6 Prevention of Further Fragility
15.13 Zoledronate ............................. 138
Fractures with Speci(cid:191) c Drugs ...... 171
15.14 Clodronate and Pamidronate ....... 139
23.7 Fracture Sites and Their Clinical
15.15 Recommendations for Intravenous
Signi(cid:191) cance .............................. 171
Therapy ................................... 139
15.16 Duration of Therapy with 24 Pregnancy and Lactation .................... 179
Bisphosphonates and Long-Term
25 Osteoporosis in Men .......................... 183
Studies ..................................... 139
25.1 Clinical Evaluation of
15.17 A Summary of Results Achieved
Osteoporosis in Men .................. 183
to Date .................................... 140
25.2 Special Features in Men ............. 186
15.18 Meta-analyses of Antiresorptive
25.3 Prevention and Treatment in
Substances ............................... 142
Men .................................................... 186
16 Selective Oestrogen-Receptor 25.4 Therapy of Osteoporosis in Men ... 187
Modulators ....................................... 145
26 Osteoporosis in Children ................... 189
16.1 A Brief Overview of SERMs – New
26.1 First Clari(cid:191) cation – Hereditary or
Selective Antiresorptive Agents ..... 145
Acquired? ........................................ 189
16.2 Raloxifene – Utilization of
26.2 Idiopathic Juvenile Osteoporosis,
Physiological Effects on Bone ...... 145
Idiopathic Juvenile Arthritis, and
17 Peptides of the Parathyroid Other Conditions ...................... 194
Hormone Family ............................... 149 26.3 Osteogenesis Imperfecta Must Not
17.1 Osteoanabolic Action of PTH – Be Overlooked! ........................ 195
Paradoxical Effects Depend on 26.4 Turner Syndrome and Charge
Type of Administration .............. 149 Syndrome ................................ 197
26.5 X-Linked Hypophosphatemic
18 Strontium Ranelate ........................... 153
Rickets .................................... 197
19 Calcitonin and Fluoride ..................... 155 26.6 Gaucher’s Disease ..................... 197
20 Combination and Sequential 27 Immobilization Osteoporosis ............. 199
Therapies ........................................... 157 27.1 Examples of Bone Loss .............. 199
27.2 Space Travel and the Force
21 Future Directions .............................. 159
of Gravity ................................ 200
22 Adherence and Monitoring of 27.3 Therapy of Immobilization
Osteoporosis Therapy .......................... 161 Osteoporosis ............................ 200
x Contents
28 Osteoporosis in Medical Disciplines ..... 203 32.2 Transient Osteoporosis and the
28.1 Assessment of Secondary Bone Marrow Oedema Syndrome
Osteoporoses ............................ 203 (BMOS) .................................. 235
28.2 Cardiology ............................... 203 32.3 Vanishing Bone Disease
28.3 Dermatology ............................ 205 (Gorham-Stout Syndrome) .......... 239
28.4 Endocrinology .......................... 205 32.4 Fibrous Dysplasia ...................... 241
28.5 Gastroenterology ...................... 207 32.5 Paget’s Disease of Bone ............. 242
28.6 Genetics .................................. 207
33 Periprosthetic Osteoporosis and
28.7 Haematology and Storage
Aseptic Loosening of Prostheses ......... 247
Disorders ................................. 208
33.1 Pathogenesis ............................ 247
28.8 Infectious Disorders ................... 210
33.2 Diagnosis ................................ 249
28.9 Nephrology ............................... 211
33.3 Treatment Strategies .................. 249
28.10 Neurology and Psychiatry ........... 212
33.4 Bisphosphonates ....................... 249
28.11 Oncology ................................. 212
28.12 Pulmonology ............................. 213 34 Oral Bone Loss, Periodontitis
28.13 Rheumatology and Immunology ... 213 and Osteoporosis .............................. 251
34.1 Oral Bone Loss and Systemic
29 Osteoporosis and Drugs ...................... 215
Osteoporosis ............................ 251
29.1 Corticosteroid-Induced
34.2 Pathogenesis of Periodontitis ....... 251
Osteoporosis ............................. 215
34.3 Clinical Findings ...................... 251
29.2 Transplantation Osteoporosis ....... 217
34.4 Treatment Strategies .................. 252
29.3 Tumour Therapy-Induced
34.5 Bisphosphonates ....................... 252
Osteoporosis ............................. 219
29.4 Drug-Induced Osteoporomalacia ... 222 35 Disorders of Bone Due to Tumours ...... 253
29.5 Antiepileptic Drug-Related 35.1 Links Between Osteoporosis and
Osteopathy, a Pressing Need Cancer .................................... 253
for Better Understanding ............ 222 35.2 Tumour-Induced Hypercalcaemia
(TIH) ...................................... 253
30 AIDS Osteopathy .............................. 225
35.3 Tumour-Induced Bone Pain (TIBP) 254
30.1 Manifestations of AIDS
35.4 Skeletal Manifestations in Multiple
Osteopathy .............................. 226
Myeloma (MM) ........................ 256
30.2 Diagnosis ................................ 227
35.5 Skeletal Metastases – The
30.3 Treatment Strategies .................. 228
Fundamental Problem in Clinical
Oncology ................................. 257
31 Renal Osteopathy .............................. 229
35.6 Skeletal Metastases of Breast and
31.1 De(cid:191) nition ................................ 229
Prostate Cancer ........................ 259
31.2 Pathophysiology ....................... 229
31.3 Symptoms ............................... 230 36 The Metabolic Syndrome – A Major
31.4 Biochemical Investigation ........... 230 Cause of Osteoporosis in the World
31.5 Radiological Investigation .......... 230 Today .............................................. 265
31.6 Treatment Strategies .................. 231
Bibliography ........................................... 271
32 Localized Osteopathies ...................... 233
Selected Articles in Journals ..................... 273
32.1 Complex Regional Pain Syndrome
(CRPS) ................................... 233 Subject Index ........................................... 313