Osteoporosis in Clinical Practice

237 Pages·2023·11.869 MB·English

by  Reiner Bartl

Osteoporosis in
Clinical Practice
Reiner Bartl
123
Osteoporosis in Clinical Practice
Reiner Bartl
Osteoporosis in Clinical
Practice
Reiner Bartl
Osteoporosis and Bone Center Munich
München, Germany
ISBN 978-3-031-14651-0 ISBN 978-3-031-14652-7 (eBook)
https://doi.org/10.1007/978-3-031-14652-7
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Illustrations: Harald Konopatzki, Heidelberg and Reinhold Henkel, Heidelberg
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Preface
With the dawn of the twenty-first century has come the realisation that bone and
joint diseases are a major cause of pain and physical disability worldwide. The
number of people suffering from osteoporosis—already many millions in the devel-
oped and underdeveloped countries of the world—is expected to double within the
next 20 years. In many countries, this increase will be even greater due to the longer
survival and consequently larger numbers of older people in the population. It is
therefore inevitable that the already astronomical costs of health care will rise pro-
portionally (Fig. 1).
On the positive side, the enormous amount of work, research and study of bone
disorders over the past 30 years or so has contributed greatly to our understanding
of the causes, diagnosis, prevention and treatment of osteoporosis. Most impor-
tantly, perhaps, the skeleton is now regarded in a new light: as a dynamic organ
undergoing constant renewal throughout life from start to finish, “from the cradle to
the grave”, and what is more: it is now abundantly clear that the skeleton
Fig. 1 Osteoporosis—a silent thief! Osteoporosis slowly but surely nibbles away at the bones,
possibly unnoticed for years until finally it is exposed by the occurrence of a fracture almost with-
out cause! (Illustration by H. Henkel. Reproduced with permission from Bartl, R., Frisch,
B. (2009). Epidemiology of Osteoporosis. In: Osteoporosis. Springer, Berlin, Heidelberg. https://
doi.org/10.1007/978-3-540-79527-8_1)
v
vi Preface
participates, usually not to its advantage, in almost every condition that may affect
the organs and tissues in our body!
This applies especially to osteoporosis, which is now preventable, treatable and
even curable at an early stage! How did this come about?
• Because of the elucidation of many of the factors involved in osseous remodelling.
• Because of the development of simple, fast, reliable and non-invasive methods
for measurement of bone density, and for testing other factors such as mineral-
ization, trabecular architecture, cortical thickness and the bone cells themselves.
• Because of the identification of general and individual risk factors so that appro-
priate measures can be taken to prevent development of osteoporosis and/or its
progression, if and when fractures have already occurred.
• And finally, because new and effective drugs for prevention and therapy are now
readily available worldwide.
The efficacy of the classes of compounds known as the bisphosphonates, as well
as the RANKL-antibody denosumab, the anabolic parathyroid hormones and more
recently the sclerostin-antibody romosozumab, has now been unequivocally estab-
lished by numerous large multicentre trials involving literally millions of patients.
In addition, simple methods such as a healthy lifestyle, adequate nutrition, sufficient
physical activity, vitamin D and calcium supplements, as required, can be recom-
mended and adopted on a large scale (Fig. 2). Introduction and acceptance of these
methods requires public awareness and support and the realisation that every indi-
vidual is the guardian and caretaker of his/her own bones and responsible for their
structural and functional integrity.
Fig. 2 Be active and be optimistic! The five main steps to preserve strong bones are: (1) Don’t
smoke, (2) Be active, (3) Eat well, (4) Think positive, and (5) Take vitamin D! (Illustration by
H. Henkel. Reproduced with permission from Bartl, R., Frisch, B. (2009). Prevention of
Osteoporosis. In: Osteoporosis. Springer, Berlin, Heidelberg. https://doi.
org/10.1007/978-3-540-79527-8_9)
Preface vii
Well-diagnostic techniques and effective therapies—both antiresorptive and
osteoanabolic—are now available for prevention, diagnosis and treatment of osteo-
porosis. It should be emphasized that the treatments recommended in this text are
all founded on “Evidence-based Medicine” (unless otherwise stated) for which the
appropriate references are given at the end of the text in “Literature”.
The aim of this book is to demonstrate that “Bone is EveryBody’s Business”
and especially every doctor’s, and to provide evidence-based guidelines for diagno-
sis, therapy and prevention of osteoporosis in a concise form that practitioners can
use to make judgements about the latest tests and treatments. This book will con-
tinue to raise awareness and to provide information to anyone seeking it and espe-
cially to doctors across disciplines concerning this preventable and now treatable
disease. Consequently, we have adhered stringently to simplicity, comprehensive-
ness, and to our own goal of keeping this text as “user-friendly” as possible so that
any doctor seeking information on a particular topic in osteoporosis has uncompli-
cated and time-saving access to it.
We wish all our readers success in their endeavours to help patients and to reduce
suffering on this strife-ridden, beautiful planet of ours.
Osteoporosis—a pandemic whose time has come!
I would like to thank Harald Konopatzki who made significant contribution to
this book with numerous high-quality illustrations. Also, I wish to acknowledge
H. Henkel for the preparation of the drawings included in this preface.
München, Germany Reiner Bartl
Contents
1 Architecture, Remodelling and Regulators of the Skeleton . . . . . . . . . 1
1.1 Function of the Skeleton . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
1.2 Architecture of Bone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
1.3 Blood Vessels and Nerves of Bone and Marrow . . . . . . . . . . . . . . . . 7
1.4 Modelling and Remodelling of Bone . . . . . . . . . . . . . . . . . . . . . . . . . 8
1.5 Bone Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
1.6 Bone Remodelling Units . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
1.7 Regulators of Bone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
1.7.1 RANK/RANKL/Osteoprotegerin System . . . . . . . . . . . . . . . 14
1.7.2 Sclerostin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
1.7.3 Leptin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
1.7.4 Systemic Hormones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
1.7.5 Local Cytokines and Signals . . . . . . . . . . . . . . . . . . . . . . . . . 16
1.7.6 Transcriptional Regulation and Genes . . . . . . . . . . . . . . . . . . 16
1.7.7 Vitamins and Minerals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
1.7.8 Mechanical Loading. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
1.8 Growth and Ageing of Bone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
2 Definition and Pathogenesis of Osteoporosis . . . . . . . . . . . . . . . . . . . . . 19
2.1 The Global Scope of the Problem . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
2.2 Definition of Osteoporosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
2.3 Pathogenesis of Osteoporosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
3 Risk Factors and Prevention of Osteoporosis . . . . . . . . . . . . . . . . . . . . . 29
3.1 Risk Factors for Osteoporosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
3.1.1 R isk Factors Which Cannot (Yet) be Influenced . . . . . . . . . . 30
3.1.2 R isk Factors Which Can be Influenced . . . . . . . . . . . . . . . . . 32
3.2 A Step-by-Step Programme for Healthy Bones . . . . . . . . . . . . . . . . . 36
4 Clinical Aspects and Diagnosis of Osteoporosis . . . . . . . . . . . . . . . . . . . 37
4.1 Indicative Symptoms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
4.2 Role of Conventional X-Rays in Osteoporosis . . . . . . . . . . . . . . . . . 41
4.3 Other Useful Imaging Techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . 42
4.4 Recommended Laboratory Tests . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
4.5 Significance of Bone Turnover Markers (BTMs) . . . . . . . . . . . . . . . 46
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x Contents
4.6 Bone and Bone Marrow Biopsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
4.6.1 I ndications for Taking a Bone Biopsy . . . . . . . . . . . . . . . . . . 48
4.6.2 B iopsy Needles and Biopsy Sites . . . . . . . . . . . . . . . . . . . . . 49
5 Dual-Energy X-Ray Absorptiometry (DXA) and Other Technologies . 51
5.1 Methods for Measurement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
5.1.1 Dual-Energy X-Ray Absorptiometry (DEXA, DXA) . . . . . . 52
5.2 Skeletal Sites of Measurement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
5.3 TBS (Trabecular Bone Score): A Bone Analysis Assessing Bone
Microarchitecture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
5.4 The FRAX® Risk Calculation Tool . . . . . . . . . . . . . . . . . . . . . . . . . . 60
5.5 Indications for Bone Density Measurement (DXA) . . . . . . . . . . . . . 60
6 Treatment Strategies and Drugs in Osteoporosis . . . . . . . . . . . . . . . . . . 63
6.1 Evidence-Based Strategies for Therapy of Osteoporosis . . . . . . . . . . 63
6.2 Comprehensive Approach to Therapy of Osteoporosis . . . . . . . . . . . 65
6.3 Indication for Treatment: Combining BMD with Clinical Factors . . 67
6.4 The Osteoporosis Treatment Gap . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68
7 Management of Pain in Osteoporosis . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
7.1 Acute Phase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72
7.2 Chronic Phase: Short Term . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73
7.3 Chronic Phase: Long Term . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74
7.4 Mechanical Loading and Electromagnetic Fields on Bone . . . . . . . . 74
7.5 Hydrotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
8 Calcium and Vitamin D Deficiency and Osteomalacia . . . . . . . . . . . . . 77
8.1 Calcium and Osteoporosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
8.2 Vitamin D and Osteoporosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80
8.2.1 F unctions, Sources and Deficiency of Vitamin D . . . . . . . . . 81
8.2.2 Rickets, Osteomalacia and Osteoporomalacia . . . . . . . . . . . . 83
8.2.3 R ecommended Vitamin D and Calcium Intake . . . . . . . . . . . 88
8.2.4 A ctive Vitamin D Metabolites in Chronic Renal
and Hepatic Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89
8.2.5 O ther Vitamins and Elements Involved in Skeletal Health . . 90
9 Hormone Replacement Therapy (HRT) and SERMs . . . . . . . . . . . . . . 91
9.1 Oestrogen and Progesterone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91
9.1.1 W hich Oestrogens and Progestins and How to
Take Them? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
9.1.2 Which Women to Treat? . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
9.1.3 How Long to Treat? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
9.1.4 How to Monitor HRT? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
9.1.5 W hat Are the Risks and Adverse Events of HRT? . . . . . . . . . 94
9.1.6 What Are the Main Contraindications? . . . . . . . . . . . . . . . . . 95
9.2 Natural Oestrogens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
9.3 Testosterone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
9.4 Anabolic Steroids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
9.5 Selective Oestrogen Receptor Modulators (SERMs) . . . . . . . . . . . . . 97
Contents xi
10 Bisphosphonates (BP) and Denosumab . . . . . . . . . . . . . . . . . . . . . . . . . 99
10.1 Bisphosphonates (BP) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
10.1.1 A Brief Survey of BP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
10.1.2 Pharmacokinetics of BP . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
10.1.3 Side Effects, Toxicity and Contraindications of BP . . . . . . 103
10.1.4 BP Currently Used in Osteoporosis . . . . . . . . . . . . . . . . . . 107
10.2 Denosumab . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108
10.2.1 Pharmacokinetics of Denosumab . . . . . . . . . . . . . . . . . . . . 108
10.2.2 Clinical Use of Denosumab . . . . . . . . . . . . . . . . . . . . . . . . 109
10.2.3 Bone Loss After Discontinuation of Denosumab . . . . . . . 111
10.2.4 Side Effects and Contraindications of Denosumab . . . . . . 111
11 Parathyroid Hormone (PTH) and Romosozumab . . . . . . . . . . . . . . . . . 113
11.1 Peptides of the Parathyroid Hormone Family . . . . . . . . . . . . . . . . . 113
11.2 Parathyroid Hormone (PTH) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113
11.3 Teriparatide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114
11.4 Abaloparatide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115
11.5 Romosozumab . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116
12 Monitoring of Patients on Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . 121
12.1 Adherence to Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121
12.2 Monitoring of Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122
12.3 Monitoring of Antiresorptive Therapy . . . . . . . . . . . . . . . . . . . . . . . 123
12.3.1 “Drug Holiday” in Patients on Treatment with BP . . . . . . 124
12.4 Monitoring of Osteoanabolic Therapy . . . . . . . . . . . . . . . . . . . . . . . 125
13 Risk Factors and Healing of Osteoporotic Fractures . . . . . . . . . . . . . . 127
13.1 Epidemiology and Cost of Osteoporotic Fractures . . . . . . . . . . . . . 127
13.2 Risk Factors of Osteoporotic Fractures . . . . . . . . . . . . . . . . . . . . . . 128
13.3 Fracture Risk Assessment (FRAX® Tool) . . . . . . . . . . . . . . . . . . . . 130
13.4 Sequence of Events in Fracture Healing . . . . . . . . . . . . . . . . . . . . . 131
13.5 Effects of Drugs and Ultrasound on Fracture Healing . . . . . . . . . . . 133
14 Localisation and Management of Osteoporotic Fractures . . . . . . . . . . 135
14.1 General Guidelines for the Management of Osteoporotic
Fractures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135
14.2 Hip Fractures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136
14.3 Atypical Femoral Fracture (AFF) . . . . . . . . . . . . . . . . . . . . . . . . . . 138
14.4 Vertebral Compression Fractures (VCFs) . . . . . . . . . . . . . . . . . . . . 140
14.5 Distal Radius Fractures (DRFs) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143
14.6 Proximal Humerus Fractures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143
14.7 Other Fractures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144
14.8 Peri-Implant Bone Loss . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144
14.8.1 Pathogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145
14.8.2 Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 146
14.8.3 Treatment Strategies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 146
14.9 Prevention of Further Fragility Fractures . . . . . . . . . . . . . . . . . . . . . 147