Osteoporosis in Men: The Effects of Gender on Skeletal Health, 2nd Edition

Copyright Page......Page 2
Contributors......Page 3
Foreword......Page 7
Preface to the Second Edition......Page 8
Bone Cells......Page 9
Skeletal Development......Page 10
The Mineral......Page 11
The Non-Collagenous Proteins: Gla Proteins......Page 12
Non-Collagenous Proteins: Siblings......Page 13
Non-Collagenous Proteins: Other......Page 14
How bones change with age......Page 15
References......Page 16
Resorption......Page 20
Reversal......Page 22
Formation......Page 23
Physiological functions of bone remodeling......Page 25
Variation in bone remodeling activity throughout the skeleton......Page 26
References......Page 27
Non-Collagenous Bone Proteins......Page 30
TRACP 5b......Page 31
Wnt signaling molecules......Page 32
Post-Translational Modifications of Bone Type I Collagen......Page 33
Factors influencing BTM levels in men......Page 34
Prediction of the Fragility Fractures by BTM in Elderly Men......Page 36
Testosterone Replacement Therapy (TRT)......Page 38
Anti-Resorptive Treatment......Page 39
Treatment with Bone Formation Stimulating Agents......Page 40
References......Page 41
Calcium......Page 46
Intestinal Absorption of Calcium......Page 47
Renal Transport of Calcium......Page 48
Phosphorus......Page 49
Magnesium......Page 50
Serum Mg......Page 51
Magnesium......Page 52
Calcium Balance......Page 53
Summary......Page 54
References......Page 55
The idea of hierarchy in bone mechanics......Page 56
Long Bone in Bending......Page 57
Stress, Strain, Toughness and Linear Isotropic Moduli......Page 58
Second Moment of Area......Page 59
The Final Calculations......Page 60
Cancellous Tissue in Simple Compression and Tension......Page 61
Cortical Tissue in Simple Compression and Tension: Asymmetry of Strength......Page 62
Experiment 2 Deproteinization (Ashing)......Page 63
Synthesis of the Experiments......Page 64
The Key Role of the Collagenous Bone Matrix......Page 65
Cancellous Microstructure......Page 66
Strain Rate......Page 67
Fatigue and Fatigue Damage......Page 68
References......Page 70
Introduction......Page 73
Hip Strength Analyses (HSA)......Page 74
Computed tomography (CT)......Page 75
Measurement of structure and BMD using volumetric CT images of the spine and hip......Page 76
Findings based on volumetric QCT analyses......Page 77
3D QCT of the vertebrae......Page 78
Finite element modeling (FEM)......Page 79
MicroCT methods......Page 80
Conclusion......Page 81
References......Page 82
Growth in stature......Page 86
Growth in bone structure......Page 87
Skeletal fragility has its origin early in life......Page 89
Bone growth and GH-IGF-I/sex hormones......Page 90
References......Page 91
Skeletal maturation......Page 95
Bone measurement techniques in children......Page 96
Bone Density......Page 98
Bone Size......Page 99
Conclusion......Page 100
References......Page 101
Longitudinal and radial bone growth......Page 104
Effects of Sex Steroids (Including their Interaction with the GH-IGF-I axis) on Longitudinal Bone Growth......Page 105
Bone mass acquisition during childhood and adolescence......Page 106
Changes in bone size by periosteal expansion during growth......Page 108
Mechanisms Regulating Periosteal and Endosteal Expansion During Growth......Page 109
‘Mechanostat’ Theory (The Utah Paradigm)......Page 110
‘Mechano-Hormonal’ Theory......Page 111
Genetic Factors (‘Sizostat’ Hypothesis)......Page 112
Relevant clinical observations on the sex steroids’ effect on bone growth......Page 113
References......Page 114
Assessing the role of nutrition in skeletal acquisition......Page 118
Relative role of nutrition in skeletal requisition......Page 119
Micronutrients and bone growth......Page 120
Magnesium and Phosphorus......Page 121
Enhancers and Inhibitors of Mineral Absorption......Page 123
Anorexia Nervosa......Page 124
Conclusions......Page 125
References......Page 126
Introduction......Page 129
How does bone adapt to physical activity?......Page 130
How does physical activity influence the normal pattern of bone accrual in boys?......Page 131
What have we learned from cross-sectional studies?......Page 132
Prospective observational studies......Page 133
What have we learned from exercise intervention studies?......Page 134
Do the benefits of physical activity persist?......Page 140
Summary and conclusion......Page 141
References......Page 142
Heritability of Peak Bone Mass......Page 145
Identification of Osteoporosis Susceptibility Genes......Page 146
Rare Monogenic Disorders Associated With Low Bone Mass......Page 147
Linkage Studies on Osteoporosis in Men......Page 148
Sex Hormones, Sex Hormone Receptors and Aromatase......Page 149
Vitamin D and Parathyroid Hormone (PTH) Receptor......Page 150
LRP5 Gene and the Wnt pathway......Page 151
Other Polymorphic Variants......Page 153
Sex-Specific Skeletal Traits and Genetics......Page 154
References......Page 156
The process and purpose of bone modeling and remodeling......Page 160
Abnormalities in bone remodeling during aging......Page 162
Bone loss during young adulthood, menopause and advanced age......Page 164
Reduced periosteal bone formation in adulthood......Page 166
Sex differences in trabecular and cortical bone loss and fracture rates......Page 167
Summary and Conclusion......Page 168
References......Page 169
Age-related changes in bone marker levels......Page 172
Bone markers, bone loss and fracture risk in aging men......Page 174
References......Page 175
Vitamin D......Page 178
Parathyroid Hormone......Page 180
Sex steroids......Page 181
Summary......Page 183
References......Page 184
Radial bone growth in children and adolescents......Page 186
Radial bone growth during aging......Page 187
Ethnic Factors......Page 188
Mechanical Load – Age Specificity and Site Specificity......Page 189
Sex Steroid Hormones – Testosterone......Page 190
Sex Steroid Hormones – 17-Estradiol and Estrogen Receptor Beta......Page 191
Bone Shape – Secular Trend and Age-Related Trend......Page 192
Mechanical Compensation of the Endosteal Bone Loss......Page 193
Neoteny......Page 194
Methodological limitations of the studies on the age-related changes in bone size......Page 195
References......Page 196
Defining Normal and Abnormal BMD in Men......Page 200
Screening Men for Important Bone Loss......Page 201
Age-Related Changes in QCT......Page 203
Bone Loss in Younger Men......Page 205
Ethnicity......Page 206
Vitamins......Page 208
Utilizing Economical and Convenient Screening......Page 209
References......Page 210
Biomechanical material properties of the skeleton......Page 213
Changes to biomechanical material properties with age......Page 215
Mineral effects in age-related material property alterations......Page 216
Collagen effects in age-related material property alterations......Page 218
Microdamage effects in age-related material property alterations......Page 219
Conclusions......Page 220
References......Page 221
Skeletal Resorption......Page 225
Calcium’s Threshold......Page 226
Bone Mineral Density in Men......Page 227
Calcium and fractures......Page 228
Children and calcium......Page 229
References......Page 230
Origin, metabolism, action and mode of action......Page 232
Intestinal Calcium Absorption......Page 233
Chondrocytes......Page 234
PTH level......Page 235
Hard endpoints......Page 236
Optimal vitamin D status versus present world reality......Page 238
References......Page 239
Dietary protein and bone growth......Page 243
Dairy products and bone growth......Page 244
Dietary protein and fracture risk......Page 245
Dietary protein and bone metabolism......Page 246
Effects of protein insufficiency correction......Page 248
References......Page 249
Introduction......Page 254
Effects on Osteoclastogenesis......Page 255
Interactions with BMP (Smad and Runx2) and TGF signaling......Page 256
Osteoblast Differentiation is Differentially Affected by Kinase-Initiated and Classical Nuclear Actions of the ER......Page 257
Pro-Survival Actions on Osteoblasts and Osteocytes......Page 258
Oxidative stress and the control of bone mass......Page 259
Osteoblasts, ER Level and Wnt Signaling......Page 260
T cells and the regulation of bone resorption......Page 261
References......Page 262
Estrogens and bone growth in males......Page 267
References......Page 269
Estrogen and bone growth in men......Page 272
Estrogen and bone maintenance in men......Page 273
Estrogen and fractures in men......Page 274
References......Page 275
DHT......Page 277
Aromatase......Page 278
Androgen Precursors and Metabolites......Page 279
Molecular mechanisms of androgen action in bone cells: The AR......Page 280
Localization of AR expression in osteoblastic populations......Page 281
Regulation of AR expression......Page 283
Effects of androgens on the proliferation and differentiation of osteoblastic cells......Page 285
Androgen effects on osteoclasts and other cells......Page 287
Effects on epiphyseal function during development......Page 288
Effects on bone mass in growing male animals: animal models of altered androgen responsiveness......Page 289
Effects on bone mass in adults: effects of castration in young and adult animals......Page 291
Effects of replacement sex steroids after castration......Page 293
References......Page 294
Androgens and Skeletal Changes at Puberty......Page 300
Relationship Between Androgens and Skeletal Parameters in Men......Page 302
Skeletal Health in Genetic Males with Androgen Insensitivity......Page 305
Skeletal Health in Men Taking 5-Reductase Inhibitors......Page 307
Effects of Androgen Replacement in Hypogonadal Men......Page 308
Effects of Dehydroepiandrosterone (DHEA) in Men......Page 309
Effects of Supraphysiological Androgen Administration in Normal Men......Page 310
References......Page 311
Epidemiological studies demonstrating the relationship of serum testosterone concentrations and muscle mass and physical function......Page 316
Testosterone dose-response relationships in young and older men......Page 317
Randomized clinical trials of testosterone in older men with low or low normal testosterone levels......Page 318
Effects of androgen replacement on body composition and muscle performance in men with chronic illness......Page 319
Possible Reasons for the Failure of the Previous Studies of Testosterone Replacement in Older Men and in Men With Chronic Illness to Demonstrate Significant Improvements in Physical Function......Page 320
Mechanisms of testosterone effects on skeletal muscle......Page 321
Achieving tissue selectivity of testosterone effects......Page 323
References......Page 324
Differences in fracture incidence patterns between men and women......Page 330
Osteoporotic fractures in men......Page 331
Hip Fractures......Page 332
Vertebral Fractures......Page 333
Other Fractures......Page 334
Bone density and fracture risk in men......Page 335
References......Page 336
Magnitude of the problem......Page 340
Distal Forearm Fractures......Page 341
Bone Mineral Density......Page 342
Other Risk Factors......Page 343
Prognosis......Page 344
References......Page 348
Physical Activity Assessment......Page 353
Physical Activity and Fall Risk Among Older Men: Observational Studies......Page 354
Physical Activity and Fracture Risk......Page 355
Assessment of Physical Function......Page 356
Upper Extremity Strength......Page 357
Relation of Decline in Muscle Strength to Decline in Muscle Mass......Page 358
Physical Performance and Fracture Risk in Older Men......Page 359
References......Page 360
Background......Page 363
Total Cost......Page 364
Attributable Cost......Page 365
North America......Page 366
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undefined......Page 368
Projected Costs......Page 369
References......Page 370
Radiographic Vertebral Fractures......Page 372
Hip Fracture......Page 373
Health-Related Quality Of Life......Page 374
Mortality After Hip Fracture......Page 375
References......Page 376
Diagnosis......Page 379
Fragility Fractures......Page 380
Exclusion of Secondary Causes......Page 381
Skeletal Phenotype......Page 382
Maturational Defect or Accelerated Bone Loss?......Page 383
Treatment......Page 384
References......Page 385
Pathophysiology......Page 388
Diagnosis......Page 390
Therapy......Page 391
References......Page 392
Androgen Secretion and Action......Page 395
Age-Related Changes in Gonadal Hormones......Page 396
Prepubertal Onset of Androgen Deficiency......Page 397
Post-Pubertal (Adult) Onset of Androgen Deficiency......Page 398
Effects of Androgen Replacement in Male Hypogonadism......Page 399
Partial Androgen Deficiency in Older Men......Page 400
References......Page 402
Epidemiology......Page 407
Alcohol impacts on bone and calcium homeostasis......Page 408
Bone mineral density (BMD)......Page 409
Alcohol, falls and fractures in men......Page 410
Issues confounding studies of alcohol use......Page 411
References......Page 412
Glucocorticoids......Page 415
Bone loss and fracture rate after kidney transplantation......Page 416
Bone loss and fracture rate after heart transplantation......Page 417
Mineral metabolism and bone turnover after liver transplantation......Page 418
Evaluation......Page 419
Bisphosphonates......Page 420
Summary and conclusions......Page 421
References......Page 422
Diagnosis of osteoporosis in stage 1–3 chronic kidney disease......Page 425
Biochemical markers of bone metabolism......Page 427
Quantitative bone histomorphometry......Page 428
Treatment of osteoporosis in CKD......Page 429
References......Page 433
Epidemiology......Page 436
Signs and symptoms......Page 438
Evaluation and diagnosis......Page 440
Parathyroid imaging......Page 441
Surgical treatment......Page 442
Clinical course after surgery......Page 444
Medical management......Page 445
References......Page 447
Clinical bone disease......Page 450
Serum 1,25D levels......Page 451
Relationship between urine Ca and bone loss......Page 452
Macroscopic Structure......Page 453
Intestinal Ca Transport......Page 454
Dietary factors......Page 455
Other Agents......Page 456
Salt Intake......Page 457
References......Page 458
Measurement of bone loading and bone mass......Page 461
Hormonal determinants of skeletal mass......Page 462
Growth Hormone and IGF-I......Page 463
Environmental and nutritional determinants of skeletal health in male athletes......Page 464
Calcium and Vitamin D Intake......Page 465
Comparison of male athletes to the female triad......Page 466
Bone mass and stress fractures in male athletes: A review of the literature......Page 467
Stress Fractures......Page 470
References......Page 471
Introduction......Page 474
Osteogenesis Imperfecta as a Cause of Male Osteoporosis......Page 475
Type I OI......Page 476
Type III OI......Page 477
OI Types VI, VII and VIII......Page 478
Ehlers–Danlos Syndromes and Osteoporosis......Page 479
Marfan syndrome and osteoporosis......Page 481
Hypophosphatasia in the adult male......Page 483
Fibrous dysplasia in adult males......Page 484
Occipital Horn Syndrome......Page 485
Hemochromatosis and osteoporosis in men......Page 486
Rett Syndrome in Males......Page 487
References......Page 488
Dual-energy X-ray (DXA) technology......Page 492
Understanding DXA results......Page 493
Pitfalls in DXA......Page 494
DXA Normative databases......Page 496
Utility of DXA for Diagnosis......Page 498
Utility of DXA for Fracture Risk Assessment......Page 501
Indications for DXA testing in men......Page 502
Vertebral fracture assessment......Page 503
Summary......Page 504
References......Page 505
Use of QUS to predict fracture in men......Page 508
Use of QUS to predict when to obtain DXA in men......Page 509
Conclusions......Page 510
References......Page 511
Introduction......Page 513
QCT and MDCT-based structural analyses in the diagnostics and monitoring of osteoporosis patients......Page 514
μCT imaging and individual trabeculae segmentation (its)-based morphological analysis......Page 517
High resolution peripheral quantitative ct (HR-pQCT)......Page 520
Magnetic resonance imaging (MRI)......Page 521
Image-based FEA......Page 524
Acknowledgments......Page 526
References......Page 527
Problems associated with identification of prevalent and incident VF......Page 531
Why are vertebral fractures relevant in men?......Page 532
VF Assessment (VFA) by Dual-Energy Absorptiometry (DXA)......Page 533
Quantitative Vertebral Morphometry (QM)......Page 535
Between Standard Radiography and VFA......Page 537
Indications for Imaging of t he Spine in the Context of Detecting VF......Page 538
References......Page 539
Age-dependent changes in bone properties in females......Page 542
Histomorphometry in male osteoporosis......Page 543
Corticosteroid-Induced Osteoporosis......Page 545
Alcoholism......Page 546
Hyper- and Hypothyroidism......Page 547
Osteopetrosis, Pycnodysostosis......Page 548
Conclusion......Page 549
References......Page 550
Which Men Should be Selected for Evaluation?......Page 554
Measures of Bone Mineral Density......Page 555
Choosing Among Forms of BMD Measures......Page 556
The Criteria for Determining Low BMD in Men......Page 557
Sex Steroid Measures......Page 558
Treatment considerations......Page 559
Thiazide Diuretics......Page 560
Testosterone Replacement in Andropause......Page 561
Calcium and Vitamin D......Page 562
References......Page 563
Diagnosis of osteoporosis......Page 567
Absolute Risk......Page 568
Normative reference ranges......Page 569
References......Page 572
Introduction......Page 574
Characteristics of good health economic modeling studies......Page 575
Review of cost-effectiveness studies in men......Page 576
Studies of Intervention for Elderly Men at High Risk of Fracture Based on Bone Mineral Density......Page 579
Studies of Intervention for Elderly Men at High Risk of Fracture Based on Absolute 10-Year Fracture Risk......Page 581
Cost-Effectiveness Modeling Studies for Prevention of Fractures Associated with Glucocorticoid Therapy......Page 582
How Well Do Available Fracture Prevention Strategies Work for Non-Vertebral Fracture?......Page 584
What is the Effect of Non-Compliance with Fracture Prevention Medication on the Cost-Effectiveness of Their Use?......Page 585
References......Page 586
Energy and Protein......Page 589
Calcium with Vitamin D......Page 590
Vitamin D and Fall Prevention......Page 591
References......Page 592
Goals of exercise in patients with osteoporosis......Page 594
The role of physics, anatomy and physiology for designing and assessing exercise interventions......Page 595
Bone strength and fall risk: two different goals, two different relationships to muscle......Page 597
The skeleton as tensegrity structure......Page 598
Relationships between muscle and bone: the muscle–bone unit......Page 599
Correlations of physical activity and locomotor performances with fractures, falls and onset of disability......Page 600
Sarcopenia and age-associated functional decline......Page 601
Osteoporosis-related fractures and falls......Page 602
Exercise interventions and bone strength......Page 603
Effect of exercise interventions on risk factors for falls, fractures and onset of disability......Page 604
Recommendations for designing and prescribing exercise programs for patients with osteoporosis......Page 605
Future developments and demands......Page 606
References......Page 607
Structure of calcitonin and its measurements......Page 612
Physiological role of calcitonin......Page 613
Clinical pharmacology......Page 615
Commercially available calcitonin preparations......Page 616
Secondary resistance......Page 617
Osteoporosis......Page 618
Hypercalcemia......Page 620
Analgesic Action of Calcitonin......Page 621
References......Page 622
Pharmacology of bisphosphonates......Page 626
Glucocorticoid-Induced Osteoporosis......Page 627
Alendronate......Page 629
Risedronate......Page 631
Androgen Deprivation Therapy......Page 634
Special issues related to treatment of male osteoporosis with bps......Page 635
References......Page 636
Anabolic actions of parathyroid hormone......Page 639
Indications for teriparatide use......Page 640
Teriparatide in male osteoporosis......Page 641
Combination or sequential therapy with PTH and an anti-resorptive agent......Page 642
Consequences of discontinuing PTH therapy......Page 643
Conclusions......Page 644
References......Page 645
Markers of fracture risk......Page 648
Effects of Testosterone On Muscle......Page 649
Interventional Trials of the Effect of Testosterone On Bone Outcomes......Page 650
Diagnosis of hypogonadism/androgen deficiency......Page 656
Intramuscular Testosterone......Page 658
Oral Testosterone......Page 659
Strategies to minimize risk of adverse effects......Page 660
Prostate......Page 661
Other Patient Populations......Page 662
References......Page 663
Strontium......Page 670
Bone Distribution of Strontium and Effects on Bone Morphology and Bone Material Properties......Page 671
Bone Remodeling, Histomorphometry and Micro-CT in Clinical Trials......Page 672
Tissue Specificity of SERMs......Page 673
Clinical Trials......Page 674
Selective androgen receptor modulators (SARMS)......Page 676
Propionamides......Page 677
Quinolinones......Page 678
Preclinical Studies......Page 679
Adverse Events......Page 681
Clinical Studies......Page 682
Calcium-Sensing Receptor (CaSR) Antagonists/Calcilytics......Page 683
Wnt--Catenin Signaling Pathway......Page 684
Acknowledgments......Page 685
References......Page 686
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