Pediatric Bone (eBook)

Front Cover 1
Pediatric Bone: Biology and Diseases 4
Copyright Page 5
Table of Contents 6
Contributors 12
Foreword 16
Preface 18
Chapter 1. Structure of Growth Plate and Bone Matrix 20
Introduction 20
Type I Collagen 20
Type V Collagen 25
Type II Collagen 27
Type IX Collagen 29
Type XI Collagen 30
Type X Collagen 33
Aggrecan 35
Cartilage Link Protein 1 35
Small, Leucine-Rich, Interstitial Proteoglycans 36
Perlecan 39
Matrilins 40
Thrombospondins 41
Osteonectin 42
Osteocalcin 43
Matrix Gla Protein 44
Bone Sialoprotein 44
Bone Acidic Glycoprotein-75 45
Dentin Matrix Acidic Phosphoprotein-1 45
Osteopontin 45
References 46
Chapter 2. Bone Cell Biology: Osteoblasts, Osteocytes, and Osteoclasts 62
Introduction 62
Ontogeny of Osteoblasts and Control of Osteoblast Development 63
Osteoprogenitor Cells and Regulation of Osteoblast Differentiation and Activity 69
Regulation of Osteoblast Differentiation and Activity 73
Osteocytes 77
Morphological Features of Osteoclasts 78
Mechanisms of Osteoclastic Bone Resorption 79
Origin of Osteoclasts 80
Regulation of Ostoclast Activity and Differentiation 80
Osteoclast Size: Multinucleation and Function 82
Stem Cell, Osteoblast, and Osteoclast Changes in Disease 82
Tissue Engineering and Stem Cell Therapy for Skeletal Diseases 83
References 84
Chapter 3. Prenatal Bone Development: Ontogeny and Regulation 96
Introduction 96
Skeletogenesis 97
Skeletal Organization and Embryonic Origin of Bones 101
Molecular Regulation of Bone Formation 115
References 123
Chapter 4. Postnatal Bone Growth: Growth Plate Biology, Modeling, and Remodeling 138
Endochondral and Intramembranous Bone Formation 138
Growth Hormone and Insulin-Like Growth Factor- 1 140
Fibroblast Growth Factors 141
Thyroid Hormone 143
Estrogen and Androgen 143
Osteoblasts and Bone Growth 143
Endocrine Regulation of Bone Formation 145
References 149
Chapter 5. Parathyroid Hormone and Calcium Homeostasis 154
Cellular and Extracellular Calcium Homeostasis 154
Parathyroids and Secretion and Metabolism of Parathyroid Hormone 159
Assay of PTH 166
Parathyroid Hormone Action 167
References 179
Chapter 6. Phosphate Homeostasis Regulatory Mechanisms 192
Introduction 192
Physiological Aspects 192
Cellular and Molecular Aspects 197
Pathophysiological Aspects 200
References 206
Chapter 7. Vitamin D Biology 212
Metabolic Activation of Vitamin D 212
Mechanism of Action 217
Role of Vitamin D in Calcium Homeostasis 220
Summary and Perspectives 227
References 228
Chapter 8. Other Factors Controlling Bone Growth and Development: Calcitonin, CGRP, Osteostatin, Amylin, and Adrenomedullin 236
Introduction 236
Calcitonin 236
Calcitonin Gene-Related Peptide 239
Parathyroid Hormone-Related Protein 242
Amylin 244
Adrenomedullin 247
References 248
Chapter 9. Peak Bone Mass and Its Regulation 254
Definition and Importance of Peak Bone Mass 254
Characteristics of Peak Bone Mass Acquisition 254
Calcium-Phosphate Metabolism During Growth 255
Determinants of Bone Mass Gain 257
Conclusions 261
References 262
Chapter 10. Pregnancy and Lactation 268
Introduction 268
Mineral Fluxes from Mother to Offspring 268
Pregnancy 269
Lactation 274
Summary 283
References 283
Chapter 11. Fetal Mineral Homeostasis 290
Fetal Adaptive Goals 290
Placental Calcium Transport 299
Placental Transport of Magnesium and Phosphate 307
Fetal Parathyroids 307
Calcium-Sensing Receptor 308
Thymus 309
Fetal Kidneys and Amniotic Fluid 309
Fetal Skeleton 310
Maternal Skeleton 311
Fetal Response to Maternal Hypoparathyroidism 312
Fetal Response to Maternal Hypoparathyroidism 312
Integrated Fetal Calcium Homeostasis 312
References 315
Chapter 12. Noninvasive Techniques for Bone Mass Measurement 322
Indications for Bone Mass Measurements 322
Challenges to Interpreting Bone Mass Measurements in Childhood and Adolescence 322
Noninvasive Measurement Techniques 323
Data Interpretation 335
References 338
Chapter 13. Assessment of Maturation: Bone Age and Pubertal Assessment 344
Background 344
Initial Considerations 344
Methods of Assessment 348
Reliability 352
Comparability of the Atlas and Bone-Specific Methods 352
Secondary Sexual Development 353
References 356
Chapter 14. Biochemical Markers o f Bone Metabolism 358
Introduction 358
Markers of Bone Formation 360
Markers of Bone Resorption 361
Bone Markers During Normal Development 363
Puberty 365
Bone and Collagen Markers in Metabolic Bone Diseases 365
Clinical and Research Value of Biochemical Markers of Bone Metabolism 371
References 372
Chapter 15. Bone Histomorphometry 378
Introduction 378
Methodology 378
Pediatric Bone Histomorphometry in Health and Disease 385
Indications for Bone Biopsy and Histomorphometry in Pediatric Bone Diseases 391
References 392
Chapter 16. A Diagnostic Approach to Skeletal Dysplasias 394
Introduction 394
Background 394
History and Physical Examination 395
Diagnostic Imaging 408
Biochemical Investigations 412
Cartilage Histology 414
Molecular Basis 415
Prenatal Detection of Suspected Skeletal Dysplasia 416
Conclusion 417
References 417
Chapter 17. The Spectrum of Pediatric Osteoporosis 420
Abstract 420
Introduction 420
Definition and Diagnosis of Osteopenia/Osteoporosis in Pediatric Patients 420
The Role of the Mechanostat in the Pathogenesis of Pediatric Osteoporosis 422
The Scope of the Problem 424
Approach to Prevention and Intervention 445
Differentiating Child Abuse from Bone Fragility Conditions 447
Summary and Future Directions 449
References 450
Chapter 18. Osteogenesis Imperfecta 462
Introduction 462
Classification 463
Types of OI 464
Differential Diagnosis 468
General Clinical Findings 469
Pathophysiology 472
Therapy 476
References 482
Chapter 19. Sclerosing Bony Dysplasia 492
Introduction 492
Defects in Osteoclastic Bone Resorption 492
Skeletal Abnormalities Related to Overproduction of Bone: Involvement of Transforming Growth Factors 497
Summary 499
References 500
Chapter 20. Parathyroid Disorders 504
Introduction 504
PTH Gene Structure and Function 504
Hypocalcemic Disorders 507
Hypercalcemic Diseases 515
Conclusion 520
References 521
Chapter 21. Fibrous Dysplasia 528
Introduction 528
Clinical Features 529
Molecular Genetics 535
Determinants of Phenotypic Variability 537
Pathology 539
Pathogenesis 545
Management and Treatment 549
References 552
Chapter 22. Nutritional Rickets 560
Introduction 560
Definition of Rickets 560
Classification of Rickets 561
Nutritional Rickets 561
References 579
Chapter 23. Metabolic Bone Disease of Prematurity 586
Introduction 586
In Utero Mineral Accretion and Bone Growth 586
Physiological Changes in Mineral Homeostasis at Birth 587
Metabolic Bone Disease 588
Skeletal Health in Preterm Infants 591
Suggested Guidelines for the Prevention of Metabolic Bone Disease in Preterm Infants 597
Conclusions 598
References 598
Chapter 24. Rickets Due to Hereditary Abnormalities of Vitamin D Synthesis or Action 602
Introduction 602
Biosynthesis of Vitamin D 602
Vitamin D Biosynthetic Enzymes 603
Vitamin D 25-Hydroxylase and 24-Hydroxylase 603
Vitamin D laL-Hydroxylase 603
Rickets Due to Abnormalities of Vitamin D Metabolism 604
Rickets Due to Abnormalities of Vitamin D Action 611
References 617
Chapter 25. Familial Hypophosphatemia and Related Disorders 622
Introduction 622
Clinical Description of Disease Entities 622
Treatment 632
Family/Genetic Studies 635
Molecules, Pathophysiology, and Lessons from Animal Models 636
Current Problems and Unresolved Questions 642
References 643
Chapter 26. Rickets Due to Renal Tubular Abnormalities 652
Introduction 652
Fanconi Syndrome 652
Renal Magnesium Wasting 659
Hypercalciuria 661
Renal Tubular Acidosis 663
Conclusion 666
References 666
Chapter 27 . Hypophosphatasia 670
Biology of Alkaline Phosphatase 670
Clinical Hypophosphatasia 680
References 691
Chapter 28. Renal Osteodystrophy: Pathogenesis , Diagnosis, and Treatment 698
Introduction 698
The Spectrum of Renal Osteodystrophy 698
Pathogenesis of Renal Osteodystrophy 701
Clinical Manifestations 704
Biochemical Determinations 705
Histologic Manifestations 706
Radiographic Features of Renal Osteodystrophy 708
Long-Term Consequences 709
Treatment 710
References 714
Chapter 29. Bone Tumors in Children 722
Introduction 722
General Principles of Treatement 722
Diagnosis 723
Classification and Nomenclature 725
Back Pain and Spinal Neoplasms in Children 726
Fibrous Tumors of Bone 728
Cartilage-Forming Tumors 732
Bone-Forming Tumors 741
Hematopoietic 749
Vascular 750
Neurogenic 752
Adipose 753
Mixed 753
Notochord 754
Tumor-Like 754
Conclusion 759
References 759
Index 764
Color Plate Section 780