Fundamentals of Osteoporosis (eBook)

Front Cover 1
Fundamentals of Osteoporosis 4
Copyright Page 5
Contents 6
Contributors 10
Preface 12
Chapter 1 The Bone Organ System: Form and Function 14
I. Introduction 14
II. Composition and Organization of Bone 14
III. Cellular Components of Bone 22
IV. Bone Homeostasis 25
V. Bone Mechanics 28
VI. Summary 33
Chapter 2 The Nature of Osteoporosis 38
I. Defining Osteoporosis 38
II. Material and Structural Basis of Skeletal Fragility 39
III. Conclusions 44
Chapter 3 Skeletal Heterogeneity and the Purposes of Bone Remodeling: Implications for the Understanding of Osteoporosis 48
I. Introduction 48
II. Skeletal Heterogeneity 49
III. The Purposes of Bone Remodeling 51
IV. Implications for Understanding Osteoporosis 56
Chapter 4 Osteoblast Biology 68
I. Overview 68
II. Embryonic Development of the Osteoblast Phenotype: Lessons for Bone Formation in the Postnatal Skeleton 68
III. Developmental Sequence of Osteoblast Phenotype Development 75
IV. Phenotypic Properties of Osteogenic Lineage Cells 81
V. Molecular Mechanisms Mediating Progression of Osteoblast Growth and Differentiation 91
VI. Conclusion 103
Chapter 5 Osteoclast Biology 126
I. Introduction 126
II. Key Osteoclast Differentiation Pathways 126
III. The Fully Differentiated Osteoclast: Mechanisms of Bone Degradation 129
IV. Bone Resorption Coordinated by Intermediate Proteins 132
V. Osteoclast Death 133
VI. Mechanistic Approaches to Modification of Osteoclastic Activity In Vivo 133
VII. Regulation of Osteoclastic Differentiation and Activity In Vivo 135
VIII. Interaction of Hormonal and Local Signals with Osteoclast Activity 136
IX. Diseases with Altered Bone Resorption 137
Chapter 6 Osteocytes 144
I. Introduction 144
II. Osteocyte Ontogeny 144
III. Osteoid-Osteocytes 145
IV. Osteocyte Selective Genes/Proteins and their Potential Functions 146
V. Morphology of Osteocytes: Lacunocanalicular System and Dendrite Formation 147
VI. Osteocyte Cell Models 149
VII. Mechanisms and Response of Osteocytes to Mechanical Forces 149
VIII. Osteocyte Signals for Bone Formation 152
IX. Osteocyte Signals for Bone Resorption 153
X. Osteocyte Apoptosis 154
XI. Osteocyte Modification of Its Microenvironment 154
XII. Osteocyte Density 155
XIII. Role of Gap Junctions and Hemichannels in Osteocyte Communication 155
XIV. Osteocytes in the Embryonic and the Adult Skeleton 156
XV. The Implications of Osteocyte Biology for Bone Disease 157
XVI. Conclusions 158
Chapter 7 The Regulatory Role of Matrix Proteins in Mineralization of Bone 166
I. Introduction 166
II. Collagenous Proteins 168
III. Intermediate Cartilage Matrix 170
IV. Bone-Enriched Matrix Proteins 176
V. The Mineralization of Bone Matrix 194
Chapter 8 Development of the Skeleton 216
I. Introduction 216
II. Patterning the Skeleton 216
III. Endochondral Bone Formation 225
IV. Intramembranous Bone Formation 236
Chapter 9 Mouse Genetics as a Tool to Study Bone Development and Physiology 246
I. Introduction: Historical Perspective and Significance 246
II. Introduction To Mouse Skeletal Physiology 247
III. Inbred Strains of Mice 248
IV. Recombinant Inbred strains 250
V. Congenic Strains 251
VI. Recombinant Congenic Strains 254
VII. Summary 255
Chapter 10 Parathyroid Hormone and Parathyroid Hormone-Related Protein 258
I. Introduction 258
II. Secretion of Parathyroid Hormone 258
III. Metabolism of Parathyroid Hormone 259
IV. Bone Resorbing Action of Parathyroid Hormone 260
V. Effects of Parathyroid Hormone on Bone Formation 261
VI. Renal Actions of Parathyroid Hormone 263
VII. Parathyroid Hormone-Related Protein as a Mediator of Malignancy-Associated Hypercalcemia 264
VIII. Physiological Roles of Parathyroid Hormone-Related Protein 264
IX. Mechanism of Action of Parathyroid Hormone and Parathyroid Hormone-Related Protein 269
Chapter 11 Vitamin D: Biology, Action, and Clinical Implications 292
I. Introduction 292
II. Vitamin D Synthesis and Metabolism 293
III. Pathways of Activation and Inactivation of Vitamin D 301
IV. Mechanism of 1,25(OH)2D Action 306
V. Nongenomic Actions of Vitamin D 316
VI. Physiology: Regulation of Serum Calcium 317
VII. Genetic Disorders 319
VIII. 1,25(OH)2D3 Analogs with Decreased Calcemic Activity 321
IX. Actions of Vitamin D in Classical Target Organs to Regulate Mineral Homeostasis 323
X. Actions of 1,25(OH)2D in Nonclassical Target Organs 329
XI. Vitamin D and Osteoporosis 335
Chapter 12 Regulation of Bone Cell Function by Estrogens 358
I. Introduction 358
II. What is an Estrogen? 358
III. Estrogen Receptors 358
IV. ERa and ERß Knockout Mice (ERKO and ßERKO) 367
V. Estrogens and Bone 367
VI. Estrogen Receptors in Bone Cells 368
VII. Estrogenic Responses in Bone Cells 373
VIII. Estrogen-Related Receptor-a and Osteopontin Gene Expression 385
IX. Nongenomic Actions of Estrogens in Bone Cells 385
X. Conclusion 386
Chapter 13 Androgens and Skeletal Biology: Basic Mechanisms 400
I. Introduction 400
II. Androgens and the Role of Androgen Metabolism 400
III. Cellular Biology of the Androgen Receptor in the Skeleton 403
IV. The Consequences of Androgen Action in Bone Cells 408
V. The Skeletal Effects of Androgen: Animal Studies 412
VI. Animal Models of Altered Androgen Responsiveness 415
VII. Effects on the Periosteum: The Role of Androgen Receptor versus Aromatization of Testosterone 416
VIII. Summary 417
Chapter 14 Phosphatonins 426
I. Introduction 426
II. Phosphorus Homeostasis 426
III. Phosphatonins 429
IV. Fibroblast Growth Factor 23 429
V. Secreted Frizzled-Related Protein 4 435
VI. Matrix Extracellular Phosphoglycoprotein 435
VII. Fibroblast Growth Factor 7 436
VIII. Summary 437
Chapter 15 Wnt Signaling in Bone 442
I. Wnts 442
II. The Wnt/ß-Catenin Signaling Pathway 443
III. Other Wnt Pathways 448
IV. Mutations in Wnt Pathway Components and Altered Bone Mass 450
V. Wnt Signaling and Bone Cell Function 452
VI. Wnt Signaling and the Bone Response to Mechanical Loading 455
VII. Conclusions and Future Directions 456
Chapter 16 Cytokines and Bone Remodeling 466
I. Introduction 466
II. Evidence for a Role of Cytokines in Osteoclastic Bone Resorption 467
III. The Osteoclast as a Cell Source of Cytokines Involved in Osteoclastic Resorption 468
IV. The Osteoblast as a Cell Source of Cytokines Involved in Osteoclastic Resorption 468
V. Rank Ligand and Its Signaling Receptor, RANK 469
VI. Osteoprotegerin 472
VII. Macrophage–Colony-Stimulating Factor and Its Receptor, C-fms 473
VIII. Vascular Endothelial Growth Factor 475
IX. Tumor Necrosis Factor 475
X. Interleukin-6 (IL-6) 476
XI. Interleukin-15 (IL-15), Interleukin-17 (IL-17), and Interleukin-18 (IL-18) 477
XII. Bone Morphogenetic Proteins 478
XIII. Hedgehog (Hh) Signaling Molecules 484
XIV. Sclerostin 486
XV. Parathyroid Hormone-Related Peptide (Pthrp) 486
XVI. Neuronal Regulation of Bone Remodeling 487
XVII. Conclusion 490
Chapter 17 Skeletal Growth Factors 504
I. Introduction 504
II. Platelet-Derived Growth Factor 504
III. Vascular Endothelial Growth Factor 506
IV. Fibroblast Growth Factor 507
V. Transforming Growth Factor Beta 508
VI. Bone Morphogenetic Protein 509
VII. Insulin-Like Growth Factor 510
VIII. Insulin-Like Growth Factor Binding Proteins 512
IX. Hepatocyte Growth Factor 513
Chapter 18 Intercellular Communication during Bone Remodeling 522
I. Introduction 522
II. Sequence of Cellular Events in Bone Remodeling 523
III. Cell Interactions Early in Remodeling 523
IV. Interaction of Osteoblast Lineage Cells with Osteoclasts 524
V. Factors Proposed to Mediate the Coupling of Bone Formation to Resorption 525
VI. Osteoclast Products in the Coupling Process 527
VII. Similarities between Bone Remodeling and Inflammation 528
VIII. Bone Mass Homeostasis 529
IX. The Role of Mechanical Function (Strain) in the Coupling of Bone Resorption to Bone Formation 529
X. Integrated View of the Coupling of Bone Resorption and Bone Formation 530
Index 536