Dynamics of Bone and Cartilage Metabolism: Principles and Clinical Applications, 2nd edition

Contents......Page 7
I. INTRODUCTION......Page 25
II. THE COLLAGEN FAMILIES......Page 27
III. BONE COLLAGENS......Page 29
IV. CARTILAGE COLLAGENS......Page 31
V. COLLAGEN BIOSYNTHESIS......Page 36
VI. COLLAGEN GENES AND TRANSCRIPTIONAL REGULATION......Page 39
VII. FACTORS REGULATING COLLAGEN BIOSYNTHESIS......Page 43
VIII. CONCLUSIONS......Page 47
I. INTRODUCTION......Page 63
II. FIBRILLOGENESIS......Page 64
III. CROSS-LINKING......Page 66
IV. CONCLUDING REMARKS......Page 72
II. INTRODUCTION......Page 77
III. OSTEOCALCIN......Page 78
IV. MATRIX Gla PROTEIN......Page 81
V. Gas6......Page 85
VI. VITAMIN K/WARFARIN......Page 86
I. INTRODUCTION......Page 93
II. CARTILAGE EXTRACELLULAR MATRIX......Page 94
III. BONE, EXTRACELLULAR MATRIX......Page 99
IV. CONCLUDING REMARKS......Page 101
I. INTRODUCTION......Page 107
II. GLYCOSAMINOGLYCANS......Page 108
III. PROTEOGLYCANS IN CARTILAGE......Page 109
IV. AGGRECAN......Page 110
V. LEUCINE-RICH PROTEOGLYCANS IN CARTILAGE AND BONE......Page 115
VI. PERLECAN IN CARTILAGE......Page 118
II. INSULIN-LIKE GROWTH FACTORS......Page 121
III. THE TRANSFORMING GROWTH FACTOR-BETA/BONE MORPHOGENETIC PROTEIN SUPERFAMILY......Page 122
IV. FIBROBLAST GROWTH FACTORS......Page 125
V. Wnts......Page 126
VI. ADDITIONAL GROWTH FACTORS......Page 127
VII. SUMMARY......Page 128
II. PROSTAGLANDINS......Page 137
III. THE ROLE THAT CYTOKINES HAVE IN OSTEOCLAST FORMATION AND FUNCTION......Page 139
IV. THE ROLE THAT PROINFLAMMATORY CYTOKINES HAVE IN BONE AND CARTILAGE METABOLISM......Page 140
II. INTRODUCTION......Page 151
III. MOLECULAR STRUCTURE OF ADHESION MOLECULES......Page 152
IV. ADHESION MOLECULES IN CELLS OF THE OSTEOBLAST LINEAGE......Page 156
V. ADHESION MOLECULES IN OSTEOCLASTS......Page 161
VI. ADHESION MOLECULES IN CHONDROCYTES......Page 164
VII. CONCLUSION......Page 166
II. STRUCTURE AND REGULATION OF THE TNAP GENE......Page 175
III. PROTEIN STRUCTURE......Page 177
IV. FUNCTION OF TNAP......Page 179
V. CLINICAL USE......Page 182
I. ACID PHOSPHATASES......Page 187
II. TARTRATE-RESISTANT ACID PHOSPHATASE (TRACP)......Page 188
III. PROSTATIC ACID PHOSPHATASE (PAP)......Page 195
II. ASPARTIC PROTEINASES......Page 203
III. CYSTEINE PROTEINASES......Page 204
IV. SERINE PROTEINASES......Page 206
V. METALLOPROTEINASES......Page 208
II. THE STRUCTURE AND FUNCTION OF BONE......Page 223
III. BONE MINERALIZATION......Page 226
IV. BONE MODELING AND REMODELING......Page 231
II. GRAVITY AND THE NEED FOR STIFFNESS, FLEXIBILITY, LIGHTNESS AND SPEED......Page 235
III. THE MATERIAL COMPOSITION AND STRUCTURAL DESIGN OF BONE......Page 236
IV. BONE MODELING AND REMODELING - THE MECHANISM OF BONE'S CONSTRUCTION DURING GROWTH AND DECAY WITH ADVANCING AGE......Page 238
V. STRENGTH MAINTENANCE......Page 239
VI. CONCLUSION......Page 241
II. INTRODUCTION......Page 243
III. DEVELOPMENTAL SIGNALS FOR CARTILAGE AND BONE TISSUE FORMATION......Page 244
IV. OSTEOGENIC LINEAGE CELLS......Page 249
V. THE OSTEOCLAST: A FUNCTIONALLY UNIQUE CELL FOR PHYSIOLOGICALLY REGULATED RESORPTION OF BONE MINERAL......Page 258
VI. PERSPECTIVES......Page 264
II. INTRODUCTION......Page 281
III. THE CONTROL OF OSTEOCLASTS......Page 282
VI. HORMONE AND CYTOKINE INFLUENCES ON THE CONTACT DEPENDENT REGULATION OF OSTEOCLASTS......Page 283
VII. DISCOVERY OF THE PHYSIOLOGICAL SIGNALING MECHANISMS IN OSTEOCLAST CONTROL......Page 284
VIII. RANK SIGNALING......Page 285
IX. COUPLING OF BONE FORMATION TO RESORPTION - RELEASE OF GROWTH FACTORS FROM BONE MATRIX......Page 286
XI. COUPLING OF BONE FORMATION TO RESORPTION - ARE OSTEOCLASTS A SOURCE OF COUPLING ACTIVITY?......Page 288
II. STRUCTURE OF THE PTH GENE......Page 295
III. CHROMOSOME LOCATION......Page 296
IV. CONTROL OF GENE EXPRESSION......Page 297
VI. METABOLISM OF PARATHYROID HORMONE......Page 300
VIII. STRUCTURE OF THE PTH/PTHrP (PTH1R) RECEPTOR......Page 301
IX. ACTIVATION OF THE CYCLIC ADENOSINE MONOPHOSPHATE SECOND-MESSENGER SYSTEM BY PARATHYROID HORMONE......Page 303
XI. PHYSIOLOGICAL ACTIONS OF PTH......Page 304
XII. CELL-TO-CELL COMMUNICATION: OSTEOBLASTS AND OSTEOCLASTS......Page 306
XIII. PREFERENTIAL ACTIONS OF PTH AT SELECTED SKELETAL SITES......Page 307
II. INTRODUCTION......Page 315
III. MOLECULAR BIOLOGY AND MECHANISM OF ACTION......Page 316
IV. THE SKELETAL ACTIONS OF PTHrP......Page 320
V. SUMMARY......Page 323
I. INTRODUCTION......Page 329
II. METABOLISM OF VITAMIN D......Page 330
III. NUCLEAR VITAMIN D RECEPTOR......Page 331
IV. VITAMIN D AND BONE CELLS......Page 334
V. PATHOLOGY AND THERAPY RELATED TO VITAMIN D AVAILABILITY, METABOLISM, AND FUNCTION......Page 336
VI. CONCLUSIONS......Page 341
II. INTRODUCTION......Page 349
III. MOLECULAR STRUCTURES, SYNTHESIS, MECHANISM OF ACTION OF MAJOR SEX STEROIDS, AND TRANSCRIPTIONAL COREGULATOR FUNCTION......Page 350
IV. EFFECTS OF SEX STEROIDS ON BONE CELLS AND BONE TURNOVER......Page 353
V. EFFECTS OF ESTROGENS AND ANDROGENS ON BONE METABOLISM IN MEN VERSUS WOMEN......Page 357
VI. EFFECTS OF SEX STEROIDS ON EXTRASKELETAL CALCIUM HOMEOSTASIS......Page 358
VII. SUMMARY......Page 359
II. INTRODUCTION......Page 367
IV. DETERMINANTS OF EXTRACELLULAR CALCIUM CONCENTRATION......Page 368
VI. HOMEOSTATIC RESPONSES TO HYPOCALCEMIA......Page 371
VII. CALCIUM AND BONE GROWTH......Page 374
IX. DETERMINANTS OF EXTRACELLULAR PHOSPHATE CONCENTRATION......Page 375
X. HOMEOSTATIC RESPONSES TO CHANGES IN PHOSPHATE SUPPLY OR DEMAND......Page 378
XI. CONCLUSIONS......Page 379
I. INTRODUCTION......Page 383
II. ACTIONS OF LEPTIN......Page 384
III. SYMPATHETIC NERVOUS SYSTEM......Page 387
IV. NEUROPEPTIDE Y AND THE Y RECEPTORS......Page 391
V. INTERACTION BETWEEN LEPTIN AND Y2-REGULATED BONE ANTIOSTEOGENIC PATHWAYS......Page 393
VI. CONCLUDING REMARKS......Page 395
II. AN OVERVIEW OF THE REMODELING CYCLE......Page 399
III. FUNCTIONS OF BONE REMODELING......Page 402
IV. THE ROLE OF APOPTOSIS IN REGULATING BONE BALANCE......Page 403
V. POSSIBLE MECHANISMS WHEREBY A REDUCTION IN ACTIVATION FREQUENCY MAY PROTECT AGAINST FRACTURE......Page 405
I. INTRODUCTION......Page 413
II. PRODUCTS OF BONE COLLAGEN SYNTHESIS, THE PROCOLLAGEN PROPEPTIDES......Page 414
III. DEGRADATION PRODUCTS OF TYPE I COLLAGEN......Page 419
IV. CLOSING REMARKS......Page 424
II. INTRODUCTION......Page 429
III. LIGHT AND ELECTRON MICROGRAPHY......Page 430
IV. BIOCHEMISTRY OF CARTILAGE......Page 431
VI. STRUCTURE OF FIBRIL FRAGMENTS OBTAINED BY MECHANICAL DISRUPTION OF TISSUE......Page 433
VIII. RECONSTITUTION OF AGGREGATES FROM SOLUBLE COLLAGENS AND OTHER MACROMOLECULES......Page 434
IX. STUDIES OF TRANSGENIC MICE AND OF HUMAN GENETIC MATRIX DISEASES......Page 436
X. CORRELATING STRUCTURE WITH THE BIOMECHANICAL ROLE OF ARTICULAR CARTILAGE......Page 437
XI. MODELS OF CARTILAGE FIBRIL STRUCTURE......Page 438
XII. FUTURE PERSPECTIVES......Page 439
I. INTRODUCTION......Page 443
II. THE CHONDROCYTE AND ITS EXTRACELLULAR MATRIX......Page 444
III. PRODUCTS OF COLLAGEN METABOLISM......Page 446
IV. PRODUCTS OF AGGRECAN METABOLISM......Page 451
V. PRODUCTS OF THE METABOLISM OF OTHER PROTEOGLYCANS......Page 456
VI. PRODUCTS OF THE METABOLISM OF LINK PROTEIN AND HYALURONAN......Page 457
VII. OTHER PRODUCTS OF CHONDROCYTE METABOLISM......Page 459
VIII. CONCLUDING STATEMENT......Page 460
II. INTERPRETATION OF MARKER DATA AND STRATEGIES FOR DEALING WITH THEM......Page 473
III. CONCLUSION......Page 478
II. GENERATION OF MOUSE MODELS......Page 479
III. TRANSGENIC MODELS IN BONE BIOLOGY......Page 482
IV. PERSPECTIVES AND FUTURE DIRECTIONS......Page 487
II. OSTEOPOROSIS HAS GENETIC INFLUENCES......Page 493
III. GENOME-WIDE APPROACHES TO FIND THE GENES......Page 495
IV. ASSOCIATION ANALYSIS OF CANDIDATE GENE POLYMORPHISMS......Page 498
V. HAPLOTYPES......Page 500
VI. META-ANALYSES......Page 502
VII. OSTEOPOROSIS CANDIDATE GENES: COLLAGEN TYPE Ia1 AND THE VITAMIN D RECEPTOR......Page 504
VIII. SUMMARY......Page 505
I. MEASUREMENT OF CALCIUM......Page 509
II. MEASUREMENT OF PHOSPHATE......Page 517
III. MEASUREMENT OF MAGNESIUM......Page 521
II. BACKGROUND......Page 529
III. DIFFERENT IMMUNOMETRIC ASSAYS FOR THE DETECTION OF PTH......Page 531
VI. PSEUDOHYPOPARATHYROIDISM ( PHP)......Page 532
VII. CONCLUSION......Page 533
II. MEASUREMENT OF 25- HYDROXYVITAMIN D......Page 535
III. MEASUREMENT OF 1,25-DIHYDROXYVITAMIN D......Page 546
II. INTRODUCTION......Page 551
III. PROPEPTIDES OF TYPE I PROCOLLAGEN......Page 552
V. BONE ALKALINE PHOSPHATASE......Page 555
VI. OSTEOCALCIN......Page 557
VII. DISCUSSION......Page 559
I. INTRODUCTION......Page 563
II. COLLAGEN RELATED MARKERS......Page 565
III. NON-COLLAGENOUS PROTEINS OF THE BONE MATRIX......Page 575
IV. OSTECLAST ENZYMES......Page 577
I. INTRODUCTION......Page 587
II. SOURCES OF PRE-ANALYTICAL VARIABILITY IN THE MEASUREMENT OF BIOCHEMICAL MARKERS OF BONE TURNOVER......Page 588
III. STATISTICAL CONSIDERATION OF VARIABILITY......Page 593
IV. SUMMARY......Page 599
I. INTRODUCTION......Page 605
II. VALIDATION OF BIOCHEMICAL MARKERS BY CALCIUM KINETICS......Page 606
III. VALIDATION OF BIOCHEMICAL MARKERS BY BONE HISTOMORPHOMETRY......Page 610
IV. CONCLUSIONS......Page 614
II. ANKYLOSING SPONDYLITIS......Page 617
III. REACTIVE ARTHRITIS......Page 619
IV. RHEUMATOID ARTHRITIS......Page 620
V. JUVENILE RHEUMATOID ARTHRITIS......Page 627
VI. CONCLUSION......Page 628
I. INTRODUCTION......Page 633
II. POSTMENOPAUSAL BONE LOSS......Page 634
III. MANAGEMENT OF POSTMENOPAUSAL OSTEOPOROSIS......Page 638
IV. CONCLUSION......Page 646
I. INTRODUCTION......Page 651
II. CELLULAR AND REGULATORY MECHANISMS OF THE ANABOLIC ACTIONS OF PARATHYROID HORMONE......Page 652
III. PHARMACOKINETICS OF TERIPARATIDE IN HUMAN SUBJECTS......Page 653
IV. ACTIONS OF PARATHYROID HORMONE TO IMPROVE BONE QUALITY......Page 654
V. CONCLUSIONS......Page 664
I. INTRODUCTION......Page 671
II. EFFECTS OF PRETREATMENT BONE TURNOVER AND MINERAL DENSITY ON THERAPEUTIC OUTCOMES......Page 672
III. THE ROLE OF MARKERS OF BONE TURNOVER IN MONITORING ANTIRESORPTIVE OSTEOPOROSIS THERAPY......Page 673
IV. INTERPRETATION OF CHANGES IN BONE TURNOVER MARKERS......Page 683
I. INTRODUCTION......Page 693
II. EPIDEMIOLOGY AND PATHOGENESIS OF AGE-RELATED OSTEOPOROSIS-RELATIONSHIP TO BONE TURNOVER......Page 694
III. MARKERS OF BONE TURNOVER AND AGE-RELATED OSTEOPOROSIS-CLINICAL IMPLICATIONS......Page 701
IV. SUMMARY......Page 705
III. EPIDEMIOLOGY......Page 711
IV. PATHOGENESIS......Page 712
V. EFFECTS OF GLUCOCORTICOIDS ON HISTOLOGICAL INDICES OF BONE TURNOVER......Page 713
VI. EFFECT OF GLUCOCORTICOIDS ON MARKERS OF BONE TURNOVER......Page 714
VIII. TREATMENT AND FOLLOW-UP......Page 716
I. INTRODUCTION......Page 723
II. KIDNEY TRANSPLANTATION......Page 724
III. CARDIAC TRANSPLANTATION......Page 727
V. LUNG TRANSPLANTATION......Page 728
VII. MECHANISMS OF BONE LOSS AFTER TRANSPLANTATION......Page 729
VIII. PREVENTION AND MANAGEMENT OF TRANSPLANTATION OSTEOPOROSIS......Page 731
IX. CONCLUSIONS......Page 733
II. HYPERTHYROIDISM AND OSTEOPOROSIS......Page 739
III. OSTEOPOROSIS SECONDARY TO HYPOGONADISM......Page 746
IV. ANTICONVULSANT DRUGS AND OSTEOPOROSIS......Page 752
I. DEFINITION......Page 761
II. ETIOLOGY......Page 763
III. INCIDENCE AND EPIDEMIOLOGY......Page 764
IV. CALCIOPENIC RICKETS AND OSTEOMALACIA......Page 765
V. PHOSPHOPENIC RICKETS AND OSTEOMALACIA......Page 769
VI. NORMAL MINERAL RICKETS AND OSTEOMALACIA......Page 772
I. INTRODUCTION......Page 777
II. BIOCHEMICAL ASSESSMENT OF RENAL OSTEODYSTROPHY......Page 779
III. SKELETAL IMAGING IN RENAL OSTEODYSTROPHY......Page 783
IV. SUMMARY......Page 784
II. ETIOLOGY......Page 789
III. CLINICAL PRESENTATION......Page 790
IV. BONE MARKERS IN PRIMARY HYPERPARATHYROIDISM......Page 792
VI. TREATMENT OF PRIMARY HYPERPARATHYROIDISM......Page 794
VII. SUMMARY......Page 797
II. ETIOLOGY AND PATHOGENESIS......Page 801
III. TREATMENT......Page 806
I. ABSTRACT......Page 815
II. INTRODUCTION......Page 816
III. USE OF MARKERS OF BONE TURNOVER FOR THE DIAGNOSIS OF BONE METASTASES......Page 818
IV. USE OF MARKERS OF BONE TURNOVER FOR THE MONITORING OF TUMOR BONE DISEASE......Page 824
V. PREDICTION OF THE DEVELOPMENT OF BONE METASTASES......Page 828
I. INTRODUCTION......Page 833
II. OSTEOPENIA......Page 834
III. OSTEOSCLEROSIS AND HYPEROSTOSIS......Page 839
IV. ECTOPIC CALCIFICATION......Page 845
V. OTHER DISORDERS......Page 847
I. INTRODUCTION......Page 853
II. CLASSIFICATION......Page 854
III. DIAGNOSIS......Page 855
V. PATHOGENESIS......Page 856
VI. BISPHOSPHONATE THERAPY IN OI......Page 857
VII. MEDICAL THERAPIES OTHER THAN BISPHOSPHONATES......Page 860
IX. CONCLUSIONS......Page 861
II. INTRODUCTION......Page 865
III. EFFECTS OF JOINT INFLAMMATION ON SKELETAL REMODELING......Page 866
IV. EFFECTS OF JOINT INFLAMMATION ON CARTILAGE REMODELING......Page 874
V. CONCLUSION......Page 880
I. INTRODUCTION......Page 893
III. ETIOLOGY......Page 894
VI. BIOCHEMICAL ASPECTS OF OSTEOARTHRITIS......Page 895
VII. MARKERS OF BONE TURNOVER......Page 896
VIII. MARKERS OF CARTILAGE METABOLISM......Page 900
IX. SPINE DEGENERATION AND MARKERS......Page 904
X. SUMMARY......Page 905
XI. CONCLUSIONS......Page 906
Index......Page 911