Bone Disease of Organ Transplantation (eBook)

Cover 1
Copyright Page 5
Contents 6
Preface 18
Contributors 20
Part I: Basic Transplantation and Bone Biology 24
Chapter 1. Principles of Transplantation Immunology 26
I. Immunological Mechanisms 26
II. Immunosuppressants 31
III. Rejection Management 38
References 46
Chapter 2. Bone Biology: Bone Structure and Remodeling 54
I. Introduction 54
II. Bone Structure 54
III. Bone Remodeling 55
IV. Systemic Regulators of Bone Growth and Remodeling 59
V. Local Regulators of Bone Remodeling 62
VI. Conclusion 63
References 64
Chapter 3. Skeletal Effects of Glucocorticoids: Basic and Clinical Aspects 70
I. Introduction 70
II. Mechanisms of Glucocorticoid Action in Bone 70
III. Clinical Aspects of Glucocorticoid-Induced Osteoporosis 74
IV. Management of Glucocorticoid-Induced Osteoporosis 76
References 79
Chapter 4. Transplantation Bone Disease Induced by Non-Steroid Immunosuppressants 84
I. Introduction 84
II. Calcineurin Inhibitors 85
III. Mechanisms 85
IV. Therapeutic Considerations 88
V. Clinical Studies Supporting the Role of Calcineurin Inhibitors in Bone Loss after Transplantation 90
VI. Other Immune-Modifying Drugs 91
VII. Cancer Therapies and Hypogonadism 94
VIII. Conclusion 95
References 95
Chapter 5. Molecular Effects of Calcineurin Inhibitors 102
I. Introduction 102
II. Cyclosporin A 103
III. FK506 104
IV. Mechanism of Bone Loss with Calcineurin Inhibition 106
V. Rapamycin 108
VI. Summary 109
References 109
Chapter 6. Bone and the Immune System 114
I. Introduction 114
II. Cells and Cytokines That Regulate Osteoclast Formation 115
III. Mechanism of Action of Estrogen in Bone 117
IV. T Cell–Produced Cytokines and Bone Loss 118
V. Mechanisms of Estrogen Regulation of T-cell Production of TNF 120
VI. Estrogen Regulation of IFN. Production and in Vivo Effects of IFN. in Bone 123
VII. The Role of IL-7 in PTBD and Postmenopausal Bone Loss 124
VIII. Conclusions 125
References 126
Part II: Pathogenesis of Transplantation-Related Bone Disease 134
Chapter 7. Fracture Prevalence and Incidence in Solid Organ Transplant Recipients 136
I. Introduction 136
II. Liver Transplantation 138
III. Cardiac Transplantation 159
IV. Lung Transplantation 162
V. Kidney Transplantation 165
VI. Kidney–Pancreas Transplantation 172
VII. Summary and Conclusions 172
References 174
Chapter 8. Bone Histomorphometry and Its Application to Transplantation Bone Disease 182
I. Introduction 182
II. Pathophysiology of Bone Loss after Transplantation 183
III. Histomorphometric Assessment of Bone Remodelling and Structure 185
IV. Bone Histomorphometric Analysis of Transplantation Bone Disease 187
References 192
Chapter 9. The Role of Parathyroid Hormone in the Evolution of Bone Loss after Organ Transplantation 196
I. Introduction 196
II. Isolated Glucocorticoid Use and PTH 197
III. Isolated Calcineurin Inhibitor Use and PTH 200
IV. Transplant-Induced Osteoporosis and PTH: Dynamic Evidence 201
V. Transplant-Induced Osteoporosis and PTH: Densitometric Evidence 204
VI. Transplant-Induced Osteoporosis and PTH: Histomorphometric Evidence 205
VII. Bone Formation Recovery: Is There a Role for PTH? 207
VIII. Conclusion 208
References 209
Chapter 10. The Role of Hypogonadism in the Evolution of Bone Loss before and after Cardiac Transplantation 216
I. Introduction 216
II. The Role of Calcineurin-Phosphatase Inhibitors in Regulation of Gonadal Hormones 217
III. The Effects of Glucocorticoids on Gonadal Hormones 219
IV. The Effect of Antiproliferative Agents on Gonadal Hormones 220
V. Clinical Features of Hypogonadism after Cardiac Transplantation 221
VI. Clinical Features of Hypogonadism before Cardiac Transplantation 223
VII. Prevention and Management of Hypogonadism 224
References 226
Chapter 11. Pathogenesis of Transplantation Bone Disease: A Unifying Hypothesis 232
I. Introduction 232
II. A Proposed Model 232
III. Evidence for the Proposed Model 233
IV. Implications of the Model for Treatment 237
V. Summary 238
References 238
Part III: Clinical Features of Transplantation Bone Disease 242
Chapter 12. Bone Disease after Kidney Transplantation 244
I. Introduction 244
II. Terminology 244
III. Substrate:The Chronic Kidney Disease Patient at the Time of Transplantation 246
IV. Post-Transplant Bone Diseases 247
V. Management 252
References 260
Chapter 13. Histologic Abnormalities of Bone before and after Kidney Transplantation 266
I. Pretransplant Bone Disease 267
II. Post–Kidney Transplant Bone Disease 269
References 273
Chapter 14. Bone Disease Following Kidney–Pancreas and Pancreas Transplantation 278
I. Introduction 278
II. Fractures Following Transplantation 279
III. Bone Mineral Density 280
IV. Bone Biomarkers 281
V. Bone Histology 282
VI. Pathophysiology 282
VII. Evaluation for Post-Transplant Bone Disease 285
VIII. Management of Bone Disease 285
IX. Summary and Conclusions 287
References 288
Chapter 15. Bone Disease after Liver Transplantation 294
I. Introduction 294
II. Post-Transplantation Bone Loss 294
III. Fractures after Liver Transplantation 296
IV. Biochemical and Hormonal Parameters 296
V. Histomorphometric Data 298
VI. Risk Factors for Fractures and Bone Loss 299
VII. Pathogenesis of Bone Disease after Liver Transplantation 301
VIII. Treatment 302
References 305
Chapter 16. Bone Disease in Patients before and after Cardiac Transplantation 310
I. Introduction 310
II. Bone Disease prior to Cardiac Transplantation 310
III. Bone Disease after Cardiac Transplantation 312
IV. Management of Osteoporosis in Recipients of Cardiac 317
V. Conclusions 321
References 321
Chapter 17. Bone Loss in Patients before and after Lung Transplantation 326
I. Introduction 326
II. Bone Disease in Patients with End-Stage Pulmonary Disease 326
III. Osteoporosis in Patients after Lung Transplantation 330
IV. Prevention and Treatment of Osteoporosis in Patients with Chronic Lung Disease 332
V. Prevention and Treatment of Osteoporosis in Patients after Lung Transplantation 334
VI. Conclusions 338
References 339
Chapter 18. Transplantation for Cystic Fibrosis: Effect on the Skeleton 342
I. Introduction 342
II. Description and Pathophysiology of Bone Disease in Cystic Fibrosis 343
III. Clinical Manifestations of Low Bone Mineral Density in Cystic Fibrosis Patients 349
IV. Therapy for Low Bone Mineral Density in Cystic Fibrosis Patients before Lung Transplantation 350
V. Lung Transplantation for Cystic Fibrosis Patients 353
VI. Conclusions 356
References 357
Chapter 19 Bone Disease after Bone Marrow Transplantation 362
I. Introduction 362
II. Candidates for Bone Marrow Transplantation 362
III. Bone Loss after Bone Marrow Transplant 363
IV. Bone Marrow Transplantation 364
V. Prevention and Management of Osteoporosis after Bone Marrow Transplant 368
VI. Summary 371
References 371
Chapter 20. Osteonecrosis and Organ Transplantation 376
I. Introduction 376
II. Clinical Features of Osteonecrosis 376
III. Osteonecrosis and Organ Transplantation 377
IV. Pathophysiology of Osteonecrosis 380
V. Diagnosis of Osteonecrosis 382
VI. Natural History of Osteonecrosis 384
VII. Management of Osteonecrosis 386
VIII. Conclusion 389
References 389
Chapter 21. Pediatric Transplant Bone Disease 396
I. Introduction 396
II. Epidemiology of Solid–Organ Transplantation in Children 397
III. Impact of the Underlying Primary Disease on Bone 399
IV. Threats to Bone Health Following Transplantation 403
V. Assessment of Bone Status in Children and Adolescents 406
VI. Clinical Studies of Bone Health in Pediatric Transplant Recipients 409
VII. Potential Therapies for Bone Health in Transplant Recipients 413
VIII. Summary 416
References 417
Part IV: Management 426
Chapter 22. Management of Bone Disease in Candidates for Organ Transplant 428
I. Introduction 428
II. Assessment of Bone Health That Applies to All Transplant Candidates 429
III. General Measures to Improve Bone Strength 431
IV. Heart or Lung Transplant Candidates 440
V. Liver Transplant Candidates 442
VI. Renal Osteodystrophy 451
VII. Summary 457
References 457
Chapter 23. Management: Prevention of Bone Loss after Organ Transplantation 470
I. Introduction 470
II. Vitamin D 471
III. Bisphosphonates 474
IV. Combinations of Bisphosphonates and Vitamin D 478
V. Other Therapies and Approaches 479
VI. Summary 480
References 481
Chapter 24. Management: Established Osteoporosis in Organ Transplant Recipients 484
I. Introduction 484
II. Fracture Risk Assessment 486
III. Nonpharmacological Interventions 489
IV. Pharmacological Interventions 489
References 501
Index 506