Osteoporosis: Pathophysiology and Clinical Management

Front Cover......Page 1
Preface......Page 6
Contents......Page 8
Contributors......Page 10
STUDIES IN HUMANS......Page 13
STUDIES IN ANIMALS......Page 25
THE APPLICATION AND RESEARCH FINDINGS IN CLINICAL SITUATIONS......Page 32
REFERENCES......Page 35
INTRODUCTION......Page 45
WHY STUDY THE GENETICS OF OSTEOPOROSIS......Page 46
PROBLEMS IN DEFINING THE PHENOTYPE......Page 47
GROWTH, PEAK BONE SIZE, AND PEAK VOLUMETRIC BMD......Page 53
AGING AND CHANGES IN BONE SIZE AND VOLUMETRIC BMD......Page 60
SUMMARY AND CONCLUSION......Page 66
REFERENCES......Page 67
CHARACTERISTICS OF PEAK BONE MASS ACQUISITION......Page 73
CALCIUM-PHOSPHATE METABOLISM DURING GROWTH......Page 76
DETERMINANTS OF BONE MASS GAIN......Page 78
CONDITIONS IMPAIRING PEAK BONE MASS ATTAINMENT......Page 84
REFERENCES......Page 86
INTRODUCTION......Page 95
PROJECTIONAL ABSORPTIOMETRY......Page 96
DUAL X-RAY ABSORPTIOMETRY (DXA)......Page 99
X-RAY COMPUTED TOMOGRAPHY......Page 105
PHYSICAL SIGNIFICANCE OF QCT MEASUREMENTS......Page 107
COMMERCIALLY-AVAILABLE EQUIPMENT FOR SPINAL QCT MEASUREMENTS......Page 109
MEASUREMENT OF BMD USING VOLUMETRIC CT IMAGES OF THE SPINE AND HIP......Page 110
REFERENCES......Page 113
INTRODUCTION......Page 117
PRESENTATION OF BMD......Page 118
INTERPRETATION OF BMD RESULTS......Page 120
APPLICATION OF BMD MEASUREMENTS......Page 122
WHICH SITE TO MEASURE......Page 124
TREATMENT CONSIDERATIONS......Page 125
REFERENCES......Page 129
INTRODUCTION AND OVERVIEW OF QUANTITATIVE ULTRASOUND (QUS) IN BONE DENSITOMETRY......Page 133
BASIC PRINCIPLES OF ULTRASOUND......Page 134
PRINCIPLES OF ULTRASOUND APPLIED TO BONE......Page 138
DESCRIPTION OF CLINICAL QUS SYSTEMS......Page 142
WHAT DOES QUS MEASURE? CLUES FROM IN VITRO STUDIES......Page 145
TECHNICAL CHALLENGES FOR SKELETAL ASSESSMENT USING QUS......Page 150
REFERENCES......Page 155
QUANTITATIVE ULTRASOUND AS AN INDICATOR OF OSTEOPOROSIS......Page 161
QUANTITATIVE ULTRASOUND AS AN INDICATOR OF FRACTURE RISK......Page 164
QUANTITATIVE ULTRASOUND UTILITY TO MONITOR CHANGES IN BONE MASS......Page 165
QUANTITATIVE ULTRASOUND USE IN CLINICAL SITUATIONS THAT MAY AFFECT BONE METABOLISM......Page 166
FUTURE DIRECTIONS IN THE USE OF ULTRASOUND CLINICALLY......Page 167
REFERENCES......Page 168
INTRODUCTION......Page 175
MARKERS OF BONE FORMATION......Page 176
MARKERS OF BONE RESORPTION......Page 181
PREANALYTICAL VARIABILITY OF BONE TURNOVER MARKER......Page 186
REFERENCES......Page 191
BONE TURNOVER MARKERS......Page 197
SOURCES OF VARIABILITY IN BONE TURNOVER MARKERS......Page 198
DIAGNOSIS OF PRIMARY AND SECONDARY OSTEOPOROSIS......Page 199
MONITORING OF TREATMENT RESPONSE......Page 200
HOW TO INTERPRET RESULTS/ASSESSING CHANGE IN MARKER LEVELS......Page 203
PRACTICAL IMPLEMENTATION......Page 204
REFERENCES......Page 207
EXERCISE INFLUENCES ON BONE MORPHOLOGY IN CLINICAL SETTINGS......Page 211
BONE’S MECHANICAL ENVIRONMENT......Page 214
WHAT MECHANICAL PARAMETERS INFLUENCE BONE ADAPTATION?......Page 218
EXAMPLE FOR A SAFE CLINICAL APPLICATION OF BIOPHYSICAL STIMULI......Page 227
SUMMARY AND OUTLOOK......Page 228
REFERENCES......Page 229
INTRODUCTION......Page 233
EXERCISE STUDY DESIGN......Page 234
THE EFFECTS OF EXERCISE ON BONE MASS......Page 235
EXERCISE STUDIES ACROSS THE LIFESPAN......Page 237
CALCIUM AND EXERCISE......Page 245
CONCLUSIONS......Page 246
HORMONE RESPONSE TO INTENSE EXERCISE......Page 247
EXERCISE, FALLING, AND FRACTURE......Page 248
CONCLUSIONS AND RECOMMENDATIONS......Page 250
REFERENCES......Page 252
INTRODUCTION......Page 259
THE ROLE OF THE KIDNEY IN EXTRACELLULAR CALCIUM BALANCE......Page 263
THE ROLE OF THE INTESTINE IN EXTRACELLULAR CALCIUM BALANCE......Page 264
THE ROLE OF BONE IN EXTRACELLULAR CALCIUM BALANCE......Page 266
SIMILARITIES OF CALCIUM TRANSPORT MECHANISMS EMPLOYED BY CALCIUM TRANSPORTING EPITHELIA AND BONE MESENCHYMAL CELLS......Page 268
REFERENCES......Page 271
CALCIUM AND THE ORIGINS OF LIFE ON EARTH......Page 277
CALCIUM IN THE HUMAN BODY......Page 278
THE CALCIUM ECONOMY OF THE HUMAN ORGANISM: INPUTS, OUTPUTS, AND THEIR CONTROLS......Page 281
THE CALCIUM REQUIREMENT......Page 292
CALCIUM SOURCES......Page 294
REFERENCES......Page 301
INTRODUCTION......Page 305
TREATMENT OF VITAMIN D DEFICIENCY......Page 306
CALCITRIOL IN POSTMENOPAUSAL OSTEOPOROSIS......Page 308
ALFACALCIDOL IN POSTMENOPAUSAL OSTEOPOROSIS......Page 310
MALE OSTEOPOROSIS......Page 314
CONCLUSIONS......Page 315
REFERENCES......Page 316
INTRODUCTION......Page 321
ESTROGEN AND PEAK BONE MASS......Page 323
ESTROGEN AND REGULATION OF BONE REMODELING......Page 324
ANIMAL MODELS FOR POSTMENOPAUSAL OSTEOPOROSIS......Page 326
ESTROGEN AS A FAMILY OF BONE ACTIVE COMPOUNDS WITH DISTINCT ACTIVITIES......Page 328
MECHANISMS OF ACTION OF ESTROGEN ON BONE......Page 333
SUMMARY......Page 335
REFERENCES......Page 336
ESTROGEN AND OSTEOPOROSIS......Page 343
RANDOMIZED CONTROLLED CLINICAL TRIALS: THE POSTMENOPAUSAL ESTROGEN/ PROGESTIN INVERVENTIONS TRIAL (PEPI)......Page 344
HRT AND FRACTURE PREVENTION......Page 346
HRT AND COMPLIANCE......Page 347
ESTROGEN THERAPY IN OLDER WOMEN......Page 348
“ULTRA”-LOW-DOSE ESTROGEN THERAPY......Page 352
FIRST GENERATION SERMS: TAMOXIFEN......Page 353
THE EFFECTS OF RALOXIFENE ON BONE METABOLISM......Page 354
REFERENCES......Page 357
INTRODUCTION......Page 361
MOLECULAR MECHANISMS OF ANDROGEN ACTION IN BONE CELLS: THE ANDROGEN RECEPTOR......Page 362
THE ANDROGEN RECEPTOR SIGNALING PATHWAY......Page 363
LOCALIZATION OF ANDROGEN RECEPTOR EXPRESSION......Page 365
EFFECTS OF ANDROGENS ON THE PROLIFERATION AND APOPTOSIS OF OSTEOBLASTIC CELLS......Page 367
EFFECTS OF ANDROGENS ON THE DIFFERENTIATION OF OSTEOBLASTIC CELLS......Page 370
INTERACTION WITH OTHER FACTORS TO MODULATE BONE FORMATION AND RESORPTION......Page 371
METABOLISM OF ANDROGENS IN BONE-AROMATASE AND 5α- REDUCTASE ACTIVITIES......Page 373
GENDER-SPECIFICITY IN THE ACTIONS OF SEX STEROIDS......Page 378
REFERENCES......Page 379
INTRODUCTION......Page 387
ANDROGEN ACTION IN ANIMAL MODEL SYSTEMS......Page 389
REFERENCES......Page 399
INTRODUCTION......Page 405
EFFECTS OF GONADAL STEROIDS ON BONE METABOLISM IN NORMAL MEN......Page 406
GONADAL STEROIDS AND BONE TURNOVER......Page 409
BONE DENSITY IN MEN WITH DISORDERS OF ANDROGEN METABOLISM OR ACTION......Page 410
THE EFFECTS OF ANDROGEN THERAPY ON BONE DENSITY IN MEN......Page 415
ESTROGEN AND BONE METABOLISM IN MEN......Page 416
REFERENCES......Page 419
ENDOGENOUS CALCITONIN......Page 425
CALCITONIN AS A DRUG......Page 434
REFERENCES......Page 442
INTRODUCTION......Page 449
PREVIOUS CLINICAL TRIALS WITH SALMON CALCITONIN......Page 450
DOES NASAL SPRAY SALMON CALCITONIN PREVENT FRACTURE? THE PROOF STUDY......Page 451
QUANTITY VS QUALITY: THE MECHANISM OF ACTION OF NS-SCT, THE QUEST STUDY......Page 453
CLINICAL USAGE OF SALMON CALCITONIN......Page 454
REFERENCES......Page 456
BISPHOSPHONATE PHARMACOKINETICS (PK)......Page 459
MICROSCOPIC LOCALIZATION OF BPS IN BONE......Page 460
CELLULAR EFFECTS OF BISPHOSPHONATES......Page 461
MOLECULAR MECHANISMS OF BISPHOSPHONATE ACTION......Page 462
REFERENCES......Page 465
INTRODUCTION......Page 471
ETIDRONATE......Page 472
TILUDRONATE......Page 473
ALENDRONATE......Page 474
RISEDRONATE......Page 477
COMPARING AGENTS, JUDGING EFFICACY......Page 478
REMAINING QUESTIONS, UNRESOLVED ISSUES......Page 479
REFERENCES......Page 480
CELL AND MOLECULAR ACTIONS......Page 487
PRECLINICAL STUDIES......Page 493
REFERENCES......Page 498
ENDOGENOUS PARATHYROID HORMONE......Page 505
PRIMARY HYPERPARATHYROIDISM AND CANCELLOUS BONE......Page 506
RATIONALE FOR ANABOLIC AGENTS IN OSTEOPOROSIS......Page 507
OBSERVATIONAL STUDIES OF PARATHYROID HORMONE (TABLE 1)......Page 511
CONTROLLED CLINICAL TRIALS (TABLE 2)......Page 515
PTH ADMINISTERED ALONE......Page 519
PTH IN COMBINATION WITH ANOTHER AGENT......Page 522
CONCLUSIONS......Page 528
REFERENCES......Page 529
GLUCOCORTICOIDS......Page 535
CYCLOSPORIN......Page 539
TACROLIMUS (FK506)......Page 540
OTHER IMMUNOSUPPRESSANTS......Page 541
CONCLUSION......Page 542
REFERENCES......Page 543
SKELETAL EFFECTS OF IMMUNOSUPPRESSIVE DRUGS......Page 549
EFFECT OF TRANSPLANTATION ON BONE AND MINERAL METABOLISM......Page 554
EVALUATION AND MANAGEMENT OF CANDIDATES FOR TRANSPLANTATION......Page 564
PREVENTION OF TRANSPLANTATION OSTEOPOROSIS......Page 566
SUMMARY AND CONCLUSIONS......Page 571
REFERENCES......Page 572
INTRODUCTION......Page 581
ESTABLISHED THERAPIES......Page 583
POTENTIAL TARGETS FOR INHIBITION OF BONE RESORPTION......Page 590
NEW STRATEGIES FOR STIMULATION OF BONE FORMATION......Page 594
EXPERIMENTAL STRATEGIES......Page 598
REFERENCES......Page 599
A......Page 607
B......Page 608
C......Page 611
D......Page 613
E......Page 614
F......Page 615
H......Page 616
I......Page 617
M......Page 618
O......Page 619
P......Page 620
Q......Page 622
S......Page 623
T......Page 624
V......Page 625
W–Z......Page 626
About the Editors......Page 627
Back Cover......Page 628