Cover -- Title page -- Copyright page -- Contents -- Contributors -- Primer Corporate Sponsors -- Preface to the Eighth Edition of the Primer -- About ASBMR -- President's Preface -- About the Companion Website -- Section I: Molecular Cellular and Genetic Determinants of Bone Structure and Formation -- 1: Skeletal Morphogenesis and Embryonic Development -- Early Skeletal Patterning -- Craniofacial patterning -- Axial patterning -- Limb patterning -- Embryonic Cartilage and Bone Formation -- Chondrocyte Proliferation and Differentiation in The Developing Cartilage -- Regulation of Chondrocyte Survival -- Conclusions -- References -- 2: Signal Transduction Cascades Controlling Osteoblast Differentiation -- Introduction -- Runx2 and Osterix Transcription Factors -- BMP Signaling -- TGF-β Signaling -- WNT Signaling -- Hedgehog Signaling -- PTH Signaling -- IGF-1 Signaling -- FGF Signaling -- Notch Signaling -- Concluding Remarks -- Acknowledgments -- References -- 3: Osteoclast Biology and Bone Resorption -- Cell Biology of The Osteoclast -- Integrin Signaling -- Small GTPases -- Factors Regulating Osteoclast Formation And/Or Function -- Proteins -- Small molecules -- Cell-Cell Interactions in Bone Marrow -- Intracellular Signaling Pathways -- Human Genetics -- References -- 4: Osteocytes -- Introduction -- Osteocyte Ontogeny -- Osteocytes as Orchestrators of Bone (Re)Modeling -- Osteocyte Cell Death and Apoptosis -- Osteocyte Modification of Their Microenvironment -- Mechanosensation and Transduction -- Role of Gap Junctions and Hemichannels in Osteocyte Communication -- The Potential Role of Osteocytes in Bone Disease -- Acknowledgment -- References -- 5: Connective Tissue Pathways That Regulate Growth Factors -- Introduction -- The Fibrillinopathies -- Fibrillin Microfibrils -- Regulation of Growth Factors by Fibrillin Microfibrils.

Molecular Mechanisms Orchestrated on a Microfibril Scaffold -- Summary -- Abbreviations -- References -- 6: The Composition of Bone -- Introduction -- The Composite -- The mineral -- Collagen -- Noncollagenous Proteins -- Serum-derived proteins -- Proteoglycans -- Glycosylated proteins -- Small integrin-binding ligand, N-glycosylated protein, and other glycoproteins with cell attachment activity -- Gla-containing proteins -- Other Components -- References -- 7: Assessment of Bone Mass and Microarchitecture in Rodents -- Introduction -- Radiographs -- Peripheral Dual-Energy X-Ray Absorptiometry -- Peripheral Quantitative Computed Tomography -- Magnetic Resonance Imaging -- Microcomputed Tomography -- Nanocomputed Tomography -- Imaging Considerations -- Voxel size and image resolution -- Segmentation -- Skeletal site and volume of interest -- Calibration -- Other considerations -- Conclusions -- References -- 8: Animal Models: Genetic Manipulation -- Introduction -- Overexpression of Target Genes -- Chondrocytes -- Osteoblasts -- Tendon and ligament -- Osteoclasts -- Advantages and disadvantages of overexpression approaches -- Gene Targeting -- Advantages and disadvantages of gene targeting -- Tissue-Specific and Inducible Knockout and Overexpression -- Uncondensed mesenchyme, mesenchymal condensations, and neural crest -- Cartilage -- Osteoblasts -- Osteoclasts -- Considerations when using inducible knockouts -- Lineage Tracing and Activity Reporters -- Functional Genomics -- General Considerations -- Acknowledgments -- References -- 9: Animal Models: Allelic Determinants for BMD -- Introduction -- Phenotypes -- Themes of Existing Data -- Future Directions -- Acknowledgments -- References -- 10: Neuronal Regulation of Bone Remodeling -- Introduction -- An Adipocyte-Driven Central Control of Bone Mass.

Anatomical, Cellular, and Molecular Bases of The Central Control of Bone Mass -- Brainstem-Derived Serotonin Controls Bone Formation -- The Sympathetic Nervous System Is a Peripheral Mediator of Leptin Signaling in the Brain -- Cart Is a Mediator of Leptin Regulation of Bone Mass -- Both Arms of the Autonomic Nervous System Control Bone Remodeling -- The Growing List of Skeletogenic Neuropeptides -- What about Sensory Nerves? -- Looking Forward -- References -- 11: Skeletal Healing -- The Process of Skeletal Healing -- Conditions that Impair Fracture Healing and Therapeutic Modalities -- Molecular Therapies to Enhance Bone Healing -- References -- 12: Biomechanics of Fracture Healing -- Introduction -- Biomechanical Assessment of Fracture Healing -- Biomechanical Stages of Fracture Healing -- Noninvasive Assessment of Fracture Healing -- Mechanobiology of Fracture Healing -- Summary -- References -- 13: Human Genome-Wide Association (GWA) Studies -- References -- 14: Circulating Osteogenic Cells -- Introduction -- Parabiosis Experiments -- Bone Marrow Transplantation Experiments -- Ectopic Bone Formation Experiments -- COP Cells in Human Diseases -- MSC Mobilization Studies Using Pharmacological Agents -- Approaches for Isolation and Characterization of COP Cells -- Plastic adherence -- Plastic-nonadherent cells -- COP cells isolated from vascular lineage cells -- Isolation of COP cells from fibrocytes, monocytes, and other cells from the hematopoietic lineage -- What Are the Possible Physiologic and Pathologic Functions of COP Cells? -- COP Cells: A Synthesis -- Concluding Remarks -- Acknowledgments -- References -- Section II: Skeletal Physiology -- 15: Human Fetal and Neonatal Bone Development -- Introduction -- Physiology of Fetal and Neonatal Bone Development -- Inherited Fetal/Neonatal Bone Disorders -- Defects in bone matrix production.

Defects in mineral homeostasis -- Defects in mineral deposition -- Defects in osteoclastic function -- Defects in cranial suture closure and osteogenesis -- References -- 16: Skeletal Growth and Peak Bone Strength -- Introduction -- Modeling and Remodeling and Bone's External Size, Shape, and Internal Architecture -- Sex Differences in Bone Morphology -- Growth of Metaphyses and Fractures in Childhood -- Effect of Illnesses on Bone Morphology Is Maturational Stage-Specific -- Summary -- References -- 17: Ethnic Differences in Bone Acquisition -- Ethnic Differences in Bone and Mineral Metabolism -- Ethnic Differences in Bone Acquisition, Mass, and Geometry -- Ethnic Differences in Dietary Calcium and Bone Mass -- South Africa: A Case Study -- Summary -- References -- 18: Calcium and Other Nutrients During Growth -- Introduction -- Calcium -- Vitamin D -- Fruit and Vegetables -- Diet in Pregnancy -- Breastfeeding -- Salt -- Soft Drinks and Milk Avoidance -- Acknowledgments -- References -- 19: Growing a Healthy Skeleton: The Importance of Mechanical Loading -- Introduction -- What Is the Window of Opportunity? -- Characteristics of an Effective Loading Prescription -- Peak Bone Mass or Peak Bone Strength? -- Persistence of Childhood Bone Adaptation -- Conclusions -- References -- 20: Pregnancy and Lactation -- Pregnancy -- Mineral ions and calcitropic hormones -- Intestinal absorption of calcium -- Renal handling of calcium -- Skeletal calcium metabolism -- Osteoporosis in pregnancy -- Primary hyperparathyroidism -- Familial hypocalciuric hypercalcemia -- Hypoparathyroidism and pseudohypoparathyroidism -- Vitamin D deficiency and insufficiency -- Low calcium intake -- Lactation -- Mineral ions and calciotropic hormones -- Intestinal absorption of calcium -- Renal handling of calcium -- Skeletal calcium metabolism -- Osteoporosis of lactation.

Hypoparathyroidism and pseudohypoparathyroidism -- Vitamin D deficiency and insufficiency -- Low calcium intake -- Adolescent Pregnancy and Lactation -- Implications -- References -- 21: Menopause -- Introduction -- Effects on Bone -- Effects on Calcium Metabolism -- Summary -- References -- Section III: Mineral Homeostasis -- 22: Regulation of Calcium and Magnesium -- Calcium (Ca) -- Distribution -- Mineral homeostasis -- PTH and 1,25(OH)2D3 actions on target tissues -- Regulation of hormone production and actions on calcium homeostasis -- Magnesium -- References -- 23: Fetal Calcium Metabolism -- Mineral Ions and Calciotropic Hormones -- Fetal Parathyroids -- Calcium Sensing Receptor (Casr) -- Fetal Kidneys and Amniotic Fluid -- Placental Mineral Ion Transport -- Fetal Skeleton -- Fetal Response to Maternal Hyperparathyroidism -- Fetal Response to Maternal Hypoparathyroidism -- Fetal Response to Maternal Vitamin D Deficiency -- Integrated Fetal Calcium Homeostasis -- Calcium sources -- Blood calcium regulation -- Placental calcium transfer -- Skeletal mineralization -- References -- 24: Fibroblast Growth Factor-23 (FGF23) -- Introduction -- The FGF23 Gene and Protein -- FGF23 Activity -- Regulation of FGF23 In Vivo -- FGF23 Receptors -- Serum Assays -- FGF23-Associated Syndromes -- Disorders associated with increased FGF23 bioactivity -- Disorders associated with reduced FGF23 bioactivity -- References -- 25: Gonadal Steroids -- Introduction -- Hormone Biosynthesis -- Receptors and Molecular Mechanisms of Action -- Effects of Sex Steroids on Skeletal Growth -- Effects on linear growth -- Effects on periosteal expansion -- Effects of Sex Steroids on Skeletal Maintenance -- Effects on osteoclasts -- Effects on osteoblasts -- Effects on osteocytes -- Loss of Sex Steroids and Aging.

Reactive oxygen species (ROS) influence the birth and death of bone cells.