Vitamin D

Volume 1: Biochemistry, Physiology and Diagnostics
 
 
Academic Press
  • 4. Auflage
  • |
  • erschienen am 14. Dezember 2017
  • |
  • 1180 Seiten
 
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978-0-12-809966-7 (ISBN)
 

Vitamin D: Volume One: Biochemistry, Physiology and Diagnostics, Fourth Edition, presents the latest information from international experts in endocrinology, bone biology and human physiology, taking readers through the basic research of vitamin D.

This impressive reference presents a comprehensive review of the multifaceted vitamin D. Researchers from all areas will gain insight into how clinical observations and practices can feed back into the research cycle, thus allowing them to develop more targeted genomic and proteomic insights on the mechanisms of disease.

  • Offers a comprehensive reference, ranging from basic bone biology, to biochemistry, to the clinical diagnostic and management implications of vitamin D
  • Saves researchers and clinicians time in quickly accessing the very latest details on the diverse scientific and clinical aspects of Vitamin D, as opposed to searching through thousands of journal articles
  • Targets chemistry, metabolism and circulation, mechanisms of action, mineral and bone homeostasis, human physiology, diagnosis and management, nutrition, sunlight, genetics and vitamin D deficiency
  • Volume II of this collection presents a clinical focus on disorders, analogs, cancer; immunity, inflammation and disease and therapeutic applications
  • Englisch
  • Saint Louis
  • |
  • USA
Elsevier Science
  • 37,19 MB
978-0-12-809966-7 (9780128099667)
0128099666 (0128099666)
weitere Ausgaben werden ermittelt
  • Front Cover
  • VITAMIN D: VOLUME 1: BIOCHEMISTRY,PHYSIOLOGY AND DIAGNOSTICS
  • VITAMIN D: VOLUME 1: BIOCHEMISTRY,PHYSIOLOGY AND DIAGNOSTICS
  • Copyright
  • Contents
  • List of Contributors
  • IN MEMORIAM
  • Preface to the Fourth Edition
  • Abbreviations
  • RELEVANT LAB VALUES IN ADULTS AND CHILDREN
  • Recommendations for Adults
  • Recommendations for pediatrics
  • Approximate normal ranges for serum values in adultsa
  • Approximate normal ranges for serum values in childrena
  • Useful equivalencies of different units
  • I - HISTORY, CHEMISTRY METABOLISM,CIRCULATION & REGULATION
  • 1 - Historical Overview of Vitamin D
  • DISCOVERY OF THE VITAMINS
  • Early Nutritional Views
  • McCollum and Osborne and Mendel's Discovery of Vitamin A and B Complex
  • History of Rickets
  • Discovery of Vitamin D
  • Discovery That Vitamin D Is Not a Vitamin
  • Isolation and Identification of Nutritional Forms of Vitamin D
  • DISCOVERY OF THE PHYSIOLOGICAL FUNCTIONS OF VITAMIN D
  • Intestinal Calcium and Phosphorus Absorption
  • Mobilization of Calcium From Bone
  • Renal Reabsorption of Calcium and Phosphorus
  • Discovery of New Functions of Vitamin D
  • DISCOVERY OF THE HORMONAL FORM OF VITAMIN D
  • Early Work of Kodicek
  • Radiolabeled Vitamin D Experiments
  • Isolation and Identification of the Active Form of Vitamin D
  • Proof That 1,25(OH)2D3 Is the Active Form of Vitamin D
  • Discovery of the Vitamin D Endocrine System
  • Other Metabolites of Vitamin D
  • Discovery of the Vitamin D Receptor
  • Acknowledgment
  • References
  • 2 - Evolutionary Biology: Mysteries of Vitamin D in Fish
  • BIOLOGICAL DISTRIBUTION OF VITAMIN D
  • EVOLUTIONARY ORIGINS OF VITAMIN D
  • EVOLUTION OF VITAMIN D FUNCTION
  • ORIGIN OF VITAMIN D IN FISH
  • FUNCTIONAL METABOLISM OF VITAMIN D IN FISH
  • A POSSIBLE ROLE FOR SUNLIGHT IN THE ORIGIN OF VITAMIN D IN FISH
  • VITAMIN D FUNCTION IN FISH
  • TRANSPORT OF VITAMIN D AND ITS METABOLITES
  • VITAMIN D TOXICITY FROM ORAL INGESTION
  • References
  • 3 - Evolution of Human Skin Color and Vitamin D
  • INTRODUCTION
  • THE SOLAR CONTEXT OF HUMAN SKIN COLOR EVOLUTION
  • THE NATURE OF THE SELECTIVE FACTORS LEADING TO THE EVOLUTION OF SKIN PIGMENTATION IN EARLY HOMO
  • FOLATE CONSERVATION AND THE EVOLUTION OF PERMANENT PROTECTIVE PIGMENTATION
  • EARLY HOMININ DISPERSAL OUT OF THE TROPICS AND VITAMIN D PRODUCTION
  • THE EVOLUTION OF SKIN PIGMENTATION IN HOMO SAPIENS
  • THE EFFECTS OF CULTURAL BUFFERING, RAPID MIGRATIONS, AND MODERN LIFESTYLES ON SKIN COLOR AND VITAMIN D
  • References
  • Further Reading
  • 4 - Photobiology of Vitamin D
  • INTRODUCTION
  • HISTORICAL PERSPECTIVE
  • PHOTOBIOLOGY OF VITAMIN D
  • Photosynthesis of Vitamin D3
  • Regulation of Vitamin D Synthesis by Sunlight
  • Influence of Latitude, Season, and Time of Day on Vitamin D Synthesis
  • Influence of Sunscreen Use, Melanin, Clothing, Glass, and Plastics on Vitamin D Synthesis
  • Optimizing Sunscreen Formulation to Enhance Vitamin D Production With Minimal Erythemal Risk
  • ROLE OF SUNLIGHT AND DIETARY VITAMIN D IN BONE HEALTH, OVERALL HEALTH, AND WELL-BEING
  • Ultraviolet Devices for Producing Vitamin D
  • SUNLIGHT, VITAMIN D, AND SKIN CANCER
  • CONCLUSIONS
  • References
  • Further Reading
  • 5 - The Activating Enzymes of Vitamin D Metabolism (25- and 1a-Hydroxylases)
  • INTRODUCTION
  • GENERAL INFORMATION REGARDING VITAMIN D HYDROXYLASES
  • VITAMIN D3-25-HYDROXYLASES
  • CYP2R1
  • CYP27A1
  • Other Cytochrome P450s
  • 25-HYDROXYVITAMIN D-1?-HYDROXYLASE
  • ADDITIONAL TOPICS
  • Crystal Structures and Homology Models of Vitamin D-Related Cytochrome P450s
  • Inhibitors of Vitamin D-Related Cytochrome P450 Enzymes
  • Future Directions
  • References
  • 6 - CYP24A1: Structure, Function, and Physiological Role
  • INTRODUCTION
  • CYP24A1-CATALYZED PATHWAYS
  • C24-OXIDATION PATHWAY
  • C23-HYDROXYLATION PATHWAY
  • CYP24A1, A MULTIFUNCTIONAL ENZYME
  • BIOLOGICAL RELEVANCE OF THE C24-OXIDATION PATHWAY
  • STRUCTURE-FUNCTION RELATIONSHIPS
  • MUTATIONS OF CYP24A1 AND IDIOPATHIC INFANTILE HYPERCALCEMIA
  • PRECLINICAL MODELS OF IDIOPATHIC INFANTILE HYPERCALCEMIA
  • PUTATIVE CYP24A1 INVOLVEMENT IN OTHER SYSTEMS
  • CYP24A1 IN CHRONIC KIDNEY DISEASE
  • ROLE OF 24,25(OH)2D IN CHONDROCYTE MATURATION
  • 24,25(OH)2D AND FRACTURE REPAIR
  • PERSPECTIVES
  • Idiopathic Infantile Hypercalcemia Diagnosis and?Treatment
  • 24,25(OH)2D Supplementation for Fracture Repair
  • CYP24A1 Inhibitors
  • References
  • 7 - The Vitamin D-Binding Protein
  • SUMMARY
  • INTRODUCTION
  • VITAMIN D-BINDING PROTEIN: GENE AND PROTEIN STRUCTURE
  • Gene
  • Protein Structure
  • Polymorphism of Vitamin D-Binding Protein
  • Posttranslational Modifications
  • Vitamin D-Binding Protein: Synthesis and Turnover
  • FUNCTIONS OF VITAMIN D-BINDING PROTEIN
  • Vitamin D Transport
  • Measurement of Vitamin D-Binding Protein in Serum
  • Vitamin D-Binding Protein-Null Mice
  • Megalin- and Megalin-Related Proteins-Null Mice
  • THE VITAMIN D-BINDING PROTEIN-ACTIN COMPLEX
  • Role of Vitamin D-Binding Protein in the Actin-Scavenger System
  • General Features of the Vitamin D-Binding Protein-Actin Structure
  • Implications for the Actin-Scavenger System
  • The Role of Vitamin D-Binding Protein in Inflammatory Processes and in the Immune System
  • CONCLUSIONS AND PERSPECTIVES
  • References
  • 8 - Regulation of Renal and Extrarenal 1a-Hydroxylase
  • INTRODUCTION
  • RENAL 1?-HYDROXYLASE
  • 1a-Hydroxylase and the CYP27B1 Gene
  • Expression of 1a-Hydroxylase in the Kidney
  • Regulation of Renal 1a-Hydroxylase
  • Vitamin D Binding Protein, Megalin, and 25-Hydroxyvitamin D Bioavailability
  • Calcium, Parathyroid Hormone, and Phosphate
  • Fibroblast Growth Factor 23
  • Thyroid Hormone
  • EXTRARENAL EXPRESSION OF 1?-HYDROXYLASE
  • Dysregulated Synthesis of 1,25-Dihydroxyvitamin D and Human Disease
  • Subcellular Localization, Substrate Selectivity, and Kinetics of the Macrophage 1a-Hydroxylase
  • Macrophages Lack the 1a-Hydroxylase Regulatory Pathways Associated With Renal Synthesis of 1,25-Dihydroxyvitamin D
  • Vitamin D Binding Protein and Macrophage Availaibility of Substrate 25-Hydroxyvitamin D
  • Vitamin D Catabolism and Macrophage 1,25-Dihydroxyvitamin D Production
  • Macrophage 1a-Hydroxylase Exhibits Responsiveness to Immune Cell Regulators
  • Cytokines
  • Pathogen-Associated Molecular Patterns
  • Nitric Oxide
  • Fibroblast Growth Factor 23
  • Regulation of 1a-Hydroxylase in Cells Other Than Macrophages
  • 1a-Hydroxylase in the Placenta
  • CONCLUSIONS AND FUTURE PROSPECTS
  • References
  • II - MECHANISM OF ACTION
  • 9 - Genome-Wide Perspectives on Vitamin D Receptor-Mediated Control of Gene Expression in Target Cells
  • INTRODUCTION
  • THE BIOLOGY OF VITAMIN D
  • THE METABOLIC ACTIVATION OF VITAMIN D
  • OVERVIEW OF THE VITAMIN D RECEPTOR: THE PROTEIN, ITS STRUCTURE, AND FUNCTION
  • The Vitamin D Receptor
  • General Features of Vitamin D Receptor Action
  • Sites of DNA Binding
  • Heterodimer Formation With Retinoid X Receptors
  • The Vitamin D Receptor Functions to Recruit Coregulatory Complexes That Mediate Gene Regulation
  • The Role of 1,25(OH)2D3 in Activation of Gene Expression Through Vitamin D Receptor
  • RECENT ADVANCES IN THE MECHANISMS OF ACTION OF VITAMIN D
  • New Methodological Approaches Provide Genome-Wide Opportunities and Revitalize Transcription Research
  • New Genome-Scale Concepts of Vitamin D Action
  • Overarching Principles of Vitamin D Receptor Interaction at Target Cell Genomes
  • Genome-Wide Coregulatory Recruitment to Target Genes via the Vitamin D Receptor
  • Identifying Functional Outcomes in Response to VDR/RXR Binding
  • The Dynamic Effect of Cellular Differentiation and Disease on the Vitamin D Receptor Cistrome
  • Linking Vitamin D Receptor Binding to the Expression of Specific Genes
  • The Problem
  • Solutions
  • Characterizing the Regulatory Elements of the CYP24A1 Gene
  • Characterizing the Regulatory Elements of the Tnfsf11 (RANKL) Gene
  • Genome-Editing Approaches to Understanding Enhancer Function In Vivo
  • Using CRISPR/Cas9 to Evaluate the Roles of Enhancers
  • CRISPR/Cas9-Mediated Deletion of the 1,25(OH)2D3-Inducible Mmp13 Enhancer In Vivo
  • ADVANCES IN UNDERSTANDING THE REGULATION OF THE VITAMIN D RECEPTOR GENE
  • Important Features of the Vitamin D Receptor Gene
  • Organization of the VDR Gene
  • Distribution and Regulation of VDR Gene Expression
  • Establishing the VDR Gene Locus and Its Regulatory Boundaries
  • Exploring VDR Gene BAC Clone Activity in Bone Cells
  • Examining the Expression and Regulation of Mouse and Human VDR BAC Transgenes in Mice In Vivo
  • Mouse and Human VDR Transgenes Rescue the Aberrant Phenotype of the VDR-Null Mouse
  • EXPLOITING HUMANIZED VDR TRANSGENIC MICE TO UNDERSTAND EXPRESSION, REGULATION, AND VDR PROTEIN FUNCTION IN VIVO
  • Vitamin D Receptor Expression Levels In Vivo Are Weak Determinants of Biological Response
  • Evaluating the Role of Vitamin D Receptor Phosphorylation as a Determinant of Biological Response to 1,25(OH)2D3
  • ESTABLISHING A HUMANIZED MOUSE MODEL FOR THE STUDY OF HUMAN DISEASE
  • SUMMARY AND CONCLUSIONS
  • Acknowledgments
  • References
  • 10 - Diverse Mechanisms of Transcriptional Regulation by the Vitamin D Receptor
  • INTRODUCTION
  • INTERPLAY BETWEEN TRANSFORMING GROWTH FACTOR ? AND VITAMIN D RECEPTOR SIGNALING
  • THE VITAMIN D RECEPTOR AND TRANSCRIPTION FACTOR ACTIVATOR PROTEIN-1
  • INTERPLAY BETWEEN VDR AND JAK/STAT SIGNALING IN IMMUNITY
  • REGULATION OF WNT SIGNALING BY THE VITAMIN D RECEPTOR: A MOLECULAR BASIS FOR CANCER PREVENTION
  • CONTROL OF FOXO PROTEIN FUNCTION BY THE VITAMIN D RECEPTOR
  • REGULATION OF THE C-MYC/MXD1 NETWORK BY THE HORMONE-BOUND VITAMIN D RECEPTOR
  • MULTIPLE MECHANISMS OF REGULATION OF NF-?B SIGNALING BY THE HORMONE-BOUND VITAMIN D RECEPTOR
  • INSIGHTS INTO TRANSCRIPTIONAL REGULATION BY THE VITAMIN D RECEPTOR FROM GENOMICS STUDIES
  • CONCLUSIONS
  • References
  • 11 - Structural Basis for Ligand Activity in Vitamin D Receptor
  • INTRODUCTION
  • 1?,25-DIHYDROXYVITAMIN D3 RECOGNITION BY VITAMIN D RECEPTOR
  • Crystal Structure of Human Vitamin D Receptor Ligand-Binding Domain in Complex With 1a,25-Dihydroxyvitamin D3
  • Rat and Zebrafish Vitamin D Receptor Ligand-Binding Domain-1a,25-Dihydroxyvitamin D3 Complexes
  • Insights Into the apo Vitamin D Receptor Ligand-Binding Domain Structure
  • Structure of the Full Human Retinoid X Receptor-Vitamin D Receptor Complex
  • NATURAL METABOLITES
  • OTHER VITAMIN D RECEPTOR NATURAL LIGANDS
  • Crystal Structures of Vitamin D Receptor Ligand-Binding Domain With Lithocholic Acid
  • An Alternative Lithocholic Acid-Binding Site Revealed by the Zebrafish Vitamin D Receptor Ligand-Binding Domain-Lithocholic Acid...
  • SECOSTEROIDAL ANALOGS OF 1?,25-DIHYDROXYVITAMIN D3
  • A-Ring Modified Analogs
  • Analogs With Modifications in C/D Rings
  • Side Chain Modifications
  • STRUCTURES OF VITAMIN D RECEPTOR WITH ANALOGS THAT INDUCE STRUCTURAL REARRANGEMENTS
  • Gemini Analogs
  • 22-Alkyl Derivatives
  • Adamantyl-Containing Compounds
  • SYNTHETIC MIMICS OF 1?,25-DIHYDROXYVITAMIN D3
  • Derivatives of LG190178
  • Bis- and Tris-Aromatic Compounds
  • Compounds With p-Carborane Core
  • CONCLUSIONS AND PERSPECTIVES
  • Acknowledgments
  • References
  • 12 - Ligand-Independent Actions of Vitamin D Receptor
  • THE VITAMIN D RECEPTOR
  • SKELETAL DEFECTS INDUCED BY IMPAIRED VITAMIN D RECEPTOR SIGNALING
  • LIGAND-INDEPENDENT ROLE OF VITAMIN D RECEPTOR IN HAIR CYCLE
  • UNLIGANDED VITAMIN D RECEPTOR REPRESSIVE ACTIVITIES INDUCE SEVERE SKELETAL DEFECTS
  • TOWARD IMPROVED DIAGNOSIS AND TREATMENTS OF HEREDITARY VITAMIN D RESISTANT RICKETS PATIENTS
  • CONCLUSION AND PERSPECTIVES
  • Acknowledgments
  • References
  • 13 - Vitamin D and Chromatin
  • INTRODUCTION
  • THE NUCLEAR RECEPTOR SUPERFAMILY MEMBER VITAMIN D RECEPTOR
  • GENOME-WIDE LOCATION OF VITAMIN D RECEPTOR-BINDING SITES
  • CTCF AS ORGANIZER OF VITAMIN D-DEPENDENT CHROMATIN DOMAINS
  • THE IMPACT OF EPIGENOMICS
  • VITAMIN D-TRIGGERED EPIGENOME CHANGES
  • A CHROMATIN MODEL OF VITAMIN D SIGNALING EMERGES
  • VITAMIN D SIGNALING IN VIVO
  • CONCLUSION
  • Acknowledgments
  • References
  • 14 - Mesenchymal Differentiation, Epigenetic Dynamics, and Interactions With VDR
  • GENETIC CONTROL OF MESENCHYMAL LINEAGE CELLS
  • Mesenchymal Differentiation Determinants
  • Vitamin D Receptor Expression and Cistrome
  • Vitamin D Receptor Cistromic Changes Throughout Differentiation
  • EPIGENETIC FATE DETERMINATION
  • Histone Modifications as Genomic Signatures
  • Impact of Epigenetics on Mesenchymal Stem Cells Biology
  • Epigenetics and Vitamin D
  • OSTEOBLAST ENHANCER COMPLEX: CONSOLIDATED AND DISPERSED
  • Consolidated Versus Dispersed Enhancers
  • Dynamics of Mmp13 Regulation
  • DYNAMICS OF TRANSDIFFERENTIATION
  • Default Epigenetic Patterns
  • Epigenetic Plasticity and Transdifferentiation
  • CONCLUSIONS
  • Acknowledgments
  • Conflict of Interest
  • References
  • 15 - Vitamin D and MicroRNAs
  • INTRODUCTION
  • MICRORNAS: THE POSTTRANSCRIPTIONAL AGE
  • COMPLEXITY OF MICRORNA REGULATION, BIOGENESIS, AND POSTTRANSCRIPTIONAL REGULATORY ACTIONS
  • NUCLEAR RECEPTORS AND MICRORNAS
  • DUALITY AMONG MICRORNAS AND THE VITAMIN D SYNTHESIS, METABOLISM, AND SIGNALING SYSTEMS
  • INTERPLAY BETWEEN VITAMIN D AND MICRORNAS IN BIOLOGICAL SYSTEMS
  • Cancer
  • Bone
  • Circulating Vitamin D Levels and MicroRNAs
  • Translational Aspects of MicroRNAs
  • STRATEGIES FOR MICRORNA AND TARGET IDENTIFICATION FOR VITAMIN D RESEARCH
  • CONCLUDING REMARKS
  • Acknowledgments
  • References
  • 16 - Vitamin D Sterol/Vitamin D Receptor Conformational Dynamics and Nongenomic Actions
  • INTRODUCTION
  • 1?,25(OH)2 VITAMIN D3 REGULATION OF GENOMIC VERSUS NONGENOMIC SIGNALING
  • Differentiating the Signals
  • VITAMIN D3 STEROL CHEMISTRY
  • The Conformational Dynamics of the Vitamin D3 Sterol Seco-B-ring and A-rings
  • The Vitamin D3 Sterol Side-Chain Conformational Dynamics: Dot Maps
  • The Vitamin D3 Sterol Conformational Ensemble
  • Nongenomic Agonist Structural Features and Molecular Dynamics
  • Nongenomic Antagonist Structural Features and Molecular Dynamics
  • 1,25(OH)2D3-MEDIATED RAPID, NONGENOMIC RESPONSES
  • Potentiation of Voltage-Gated Ion Channels
  • Control of Phosphatase, Kinase, and Phospholipase?Activity
  • Cross-Talk
  • THE PLASMA MEMBRANE VITAMIN D RECEPTOR
  • Structural/Scaffolding Proteins (e.g., Caveolins)
  • Other Signaling Factor/Scaffolding Proteins (e.g., PP1c and Src)
  • Covalent Modification (e.g., Palmitoylation)
  • Membrane Binding (e.g., PIP2/3)
  • THE VITAMIN D RECEPTOR CONFORMATIONAL ENSEMBLE MODEL
  • The Overlapping Two-Pocket Model
  • Experimental Support for the Vitamin D Receptor Alternative Ligand-Binding Pocket
  • Understanding the Nongenomic Agonist/Antagonist Affinity/Function Conundrum
  • VITAMIN D RECEPTOR LIGAND SPECIFICITY: DOES AN UNLIGANDED VITAMIN D RECEPTOR EVER EXIST IN VIVO?
  • References
  • III - MINERAL AND BONE HOMEOSTASIS
  • 17 - Vitamin D Regulation of Osteoblast Function
  • INTRODUCTION
  • PROPERTIES OF MATURE OSTEOBLASTS AND OSTEOCYTES
  • MAJOR REGULATORY FUNCTIONS OF OSTEOBLASTS AND OSTEOCYTES AND CONTROL BY THE VITAMIN D ENDOCRINE SYSTEM
  • Bone Remodeling
  • Regulation of Phosphate Homeostasis
  • Response of Bone to Mechanical Loads
  • EFFECTS OF 1,25(OH)2D3 ON OSTEOBLAST DIFFERENTIATION
  • In Vitro Effects of 1,25(OH)2D3 on Osteoblasts in Cell Culture
  • Direct Actions of 1,25(OH)2D3 on Osteoblast/Osteocyte Differentiation In Vivo
  • REGULATION OF INTRACELLULAR SIGNALING PATHWAYS BY 1,25(OH)2D3
  • Mitogen-Activated Protein Kinases Signaling Pathways
  • The Wnt Pathway and Control of Osteoblast Versus Adipocyte Lineages
  • SUMMARY AND CONCLUSIONS
  • References
  • 18 - Osteoclastogenesis and Vitamin D
  • INTRODUCTION
  • REGULATION OF MINERAL METABOLISM BY VITAMIN D, PARATHYROID HORMONE, AND FIBROBLAST GROWTH FACTOR 23
  • PHENOTYPES OF VITAMIN D RECEPTOR KNOCKOUT MICE
  • REGULATION OF OSTEOCLASTOGENESIS BY THE RECEPTOR ACTIVATOR OF NUCLEAR FACTOR-?B LIGAND/RECEPTOR ACTIVATOR OF NUCLEAR FACTOR-?B/O...
  • IN VITRO REGULATION OF OSTEOCLASTOGENESIS BY VITAMIN D
  • Proresorptive Activities
  • Antiresorptive Activities
  • IN VIVO REGULATION OF OSTEOCLASTOGENESIS BY VITAMIN D COMPOUNDS
  • Proresorptive Activities
  • Antiresorptive Activities
  • Effects on Osteoclast Precursors
  • In Vivo Effects on Osteoblastic Cells
  • Contradictory Actions of Vitamin D
  • CONCLUSION
  • References
  • 19 - Vitamin D Activities in Osteocytes
  • INTRODUCTION
  • CELL BIOLOGY OF OSTEOCYTES
  • Mineral Handling
  • Mechanosensation
  • Bone Matrix Repair
  • Endocrine Activities
  • Other Actions
  • DIRECT ACTIONS OF 1,25-DIHYDROXYVITAMIN D ON OSTEOCYTE MATURATION AND ACTIVITIES
  • RECEPTOR ACTIVATOR OF NUCLEAR FACTOR ? B LIGAND
  • Sclerostin
  • Fibroblast Growth Factor-23
  • ENPP1/ANK
  • Alkaline Phosphatase
  • VITAMIN D METABOLISM WITHIN OSTEOCYTES
  • THE ROLE OF OSTEOCYTES AND VITAMIN D IN BONE TURNOVER
  • THE ROLE OF VITAMIN D AND OSTEOCYTES IN ENDOCRINE FEEDBACK
  • CONCLUSIONS
  • References
  • 20 - Regulation of Intestinal Calcium and Phosphate Absorption
  • AN OVERVIEW OF INTESTINAL CALCIUM ABSORPTION
  • Habitual Dietary Calcium Intake Is a Major Physiologic Regulator of Intestinal Calcium Absorption Efficiency
  • Role of Vitamin D Status and Vitamin D Signaling in Intestinal Calcium Absorption
  • Critical Role of Vitamin D Receptor in Control of Intestinal Ca Absorption
  • Can High Vitamin D Status Increase Intestinal Calcium Absorption?
  • Molecular Models of Ca Absorption
  • Facilitated Diffusion
  • Vesicular Transport
  • Transcaltachia
  • Regulated Paracellular Movement Through Tight Junctions
  • Conclusions Regarding the Role of Vitamin D on Intestinal Calcium Absorption
  • AN OVERVIEW OF INTESTINAL PHOSPHATE ABSORPTION
  • Intestinal Pi Absorption Is Sodium Dependent and Is Mediated Through the NaPi IIb Transporter
  • Prior Dietary Phosphate Intake Is the Major Physiologic Regulator of Intestinal Phosphate Absorption
  • Role of Vitamin D Status and Vitamin D Signaling in Intestinal Phosphate Absorption
  • The Role of Vitamin D Receptor and Phosphatonins in Phosphate Absorption
  • Conclusion Regarding the Role of Vitamin D on Phosphate Absorption
  • References
  • 21 - Calbindin-D28K and Calbindin-D9K and the Epithelial Calcium Channels TRPV5 and TRPV6
  • INTRODUCTION AND GENERAL CONSIDERATIONS, THE CALBINDINS
  • LOCALIZATION AND PROPOSED FUNCTIONAL SIGNIFICANCE OF THE CALBINDINS
  • Intestine
  • Kidney
  • Bone
  • Pancreas
  • Reproductive Tissues
  • Nervous Tissue
  • Calbindin-D28K and Apoptosis
  • REGULATION OF CALBINDIN GENE EXPRESSION
  • Calbindin-D28K
  • Genomic Organization of the Calbindin-D28K Gene
  • Regulation by 1,25-Dihydroxyvitamin D3
  • Regulation by Other Steroids and Factors
  • Calbindin-D9K
  • Genomic Organization of the Calbindin-D9K Gene
  • Regulation of Calbindin-D9K by 1,25-Dihydroxyvitamin D3
  • Regulation of Calbindin-D9K by Other Steroids and Factors
  • EPITHELIAL CALCIUM CHANNELS
  • Transient Receptor Potential Vanilloid 5
  • General Considerations and Genomic Organization of the TRPV5 Gene
  • Regulation of Transient Receptor Potential?Vanilloid 5
  • Proposed Functional Significance
  • Transient Receptor Potential Vanilloid 6
  • General Considerations and Genomic Organization of the TRPV6 Gene
  • Regulation of TRPV6 by 1,25(OH)2D3 and Functional Significance
  • CONCLUSION
  • References
  • 22 - Calcium Homeostasis and Eggshell Biomineralization in Female Chicken
  • INTRODUCTION
  • MINERALIZATION ASSOCIATED WITH LAYING HEN REPRODUCTION
  • Medullary Bone
  • Eggshell Formation
  • TRANSEPITHELIAL TRANSFER OF CALCIUM
  • Mechanisms of Ionic Transfer in the Hen Intestine
  • Mechanisms of Calcium Transfer in the Uterus
  • REGULATION OF CALCIUM METABOLISM IN HENS
  • Regulation of Vitamin D Metabolites in Hens
  • Control of Intestinal Absorption by Vitamin D
  • Regulation of Uterine Calcium Transfer
  • Regulation of Eggshell Matrix Proteins Synthesis and Secretion
  • Regulation of Medullary Bone During the Laying Cycle
  • Induction and Maintenance of Medullary Bone by Sex Steroid Hormones
  • Role of Parathyroid Hormone in Daily Mobilization of Medullary Bone
  • Putative Role of Fibroblast Growth Factor 23 in Bone and Phosphorus Metabolism in Hens
  • Acknowledgments
  • References
  • 23 - Mineralization in Mammals
  • INTRODUCTION
  • Definitions
  • DIRECT AND INDIRECT EFFECTS OF VITAMIN D AND VITAMIN D METABOLITES ON MINERALIZATION
  • Physical Chemistry of Mineralization
  • The Nature of Vertebrate Mineral
  • Mineralization Mechanisms in Bone, Cartilage, Dentin, and Pulp
  • METHODS FOR QUANTIFYING TISSUE MINERALIZATION
  • Where Is the Tissue Mineralized?
  • How Much Mineral Is Present?
  • Is the Mineral Characteristic of Physiologic Mineral (Is It a Poorly Crystalline Apatite)?
  • Methods for Studying In Vitro Mineralization
  • MECHANISM OF EFFECTS OF VITAMIN D ON MINERALIZATION
  • Physicochemical Effects
  • Effects of Vitamin D on Cells and Matrix Molecules
  • The Influence of Vitamin D on Bone Matrix Proteins
  • Collagen
  • Noncollagenous Proteins
  • Growth Factors
  • MINERALIZATION AND MINERAL PROPERTIES IN SYSTEMS WITH VITAMIN D ALTERATIONS
  • Vitamin D Deficiency
  • Vitamin D Receptor Alterations
  • Vitamin D-Binding Protein Knockout
  • 1a-Hydroxylase Knockout
  • Osteoporosis and Osteomalacia in Humans
  • CONCLUSIONS
  • Acknowledgments
  • References
  • Further Reading
  • 24 - Cartilage
  • PROPERTIES OF CARTILAGE TISSUES
  • REGULATION BY VITAMIN D
  • Separate Roles for 24R,25-dihydroxyvitamin D3 and 1a,25-dihydroxyvitamin D3 in Cartilage
  • RAPID ACTIONS OF VITAMIN D AND NONGENOMIC?MECHANISMS
  • Definitions and Models for Studying Rapid Actions
  • Membrane Signaling by 1a,25-dihydroxyvitamin D3
  • Membrane Signaling by 24R,25-dihydroxyvitamin D3
  • Physiologic Relevance of Nongenomic Regulation of Matrix Vesicles
  • SUMMARY
  • References
  • 25 - Vitamin D and Bone: An Integrated Approach
  • LINK BETWEEN BONE METABOLISM, CALCIUM HOMEOSTASIS, AND 1,25(OH)2D3 ACTIVITY
  • 1,25(OH)2D3 AND BONE METABOLISM DURING A POSITIVE CALCIUM BALANCE
  • Intestinal Calcium Absorption
  • Pathways and Transporters Mediating Intestinal Calcium Absorption
  • Regulation of Intestinal Calcium Absorption by 1,25(OH)2D3
  • Indirect Versus Direct Effects of 1,25(OH)2D3 on Bone During a Positive Calcium Balance
  • Indirect Effects: Importance of Intestinal Calcium Absorption
  • Indirect Effects: Serum Calcium Levels and Matrix Mineralization
  • Direct Effects of 1,25(OH)2D on Bone Cell Function
  • Conclusion
  • NEGATIVE CALCIUM BALANCE RESULTING FROM INSUFFICIENT VITAMIN D ACTION
  • Hormonal and Mineral Changes
  • Renal Adaptations
  • Bone Phenotype
  • Conclusion
  • NEGATIVE CALCIUM BALANCE WITH SUFFICIENT VITAMIN D
  • Hormonal and Mineral Changes
  • Bone Phenotype
  • Conclusion
  • VITAMIN D AND FIBROBLAST GROWTH FACTOR 23
  • CONCLUSION
  • References
  • IV - EXTRA-SKELETAL TARGETS
  • 26 - Vitamin D and the Kidney
  • INTRODUCTION
  • Calcium Handling by the Kidney
  • Phosphate Handling by the Kidney
  • ROLE OF THE KIDNEY IN THE METABOLISM OF 25-HYDROXYVITAMIN D
  • Formation of 1a,25-Dihydroxyvitamin D3
  • 24-Hydroxylase Activity in the Kidney
  • EFFECTS OF VITAMIN D, 25(OH)D3 AND 1?,25(OH)2D3 ON THE RENAL HANDLING OF CALCIUM AND PHOSPHORUS
  • DISTRIBUTION AND REGULATION OF VITAMIN D-DEPENDENT PROTEINS IN THE KIDNEY
  • 1a,25-Dihydroxyvitamin D3 Receptor (Vitamin D Receptor) in the Kidney
  • Calbindins-D
  • The Plasma Membrane Calcium Pump
  • The Epithelial Calcium Channel, Vanilloid-Receptor Related Transient Receptor Potential Channels 5 and 6
  • The 25-Hydroxyvitamin D3- and 1a,25-Dihydroxyvitamin D3-24-Hydroxylase
  • CONCLUSION
  • References
  • 27 - Vitamin D and the Parathyroids
  • INTRODUCTION
  • PARATHYROID HORMONE BIOSYNTHESIS
  • THE PARATHYROID HORMONE GENE
  • The Parathyroid Hormone Gene and Messenger RNA
  • Promoter Sequences
  • DEVELOPMENT OF THE PARATHYROID AND TISSUE-SPECIFIC EXPRESSION OF THE PARATHYROID HORMONE GENE
  • REGULATION OF PARATHYROID HORMONE GENE EXPRESSION
  • 1,25-Dihydroxyvitamin D
  • Calreticulin and the Action of 1,25-Dihydroxyvitamin D on the Parathyroid Hormone Gene
  • Calcium Receptor and Vitamin D Receptor Interactions in the Parathyroid
  • 1,25-Dihydroxyvitamin D3 Analogs
  • Mice With Vitamin D Receptor Gene Deletion
  • Calcium
  • Phosphate Regulates the Parathyroid Independently of Calcium and 1,25-Dihydroxyvitamin D3
  • Fibroblast Growth Factor 23 and the Parathyroid
  • Fibroblast Growth Factor 23 Decreases Parathyroid Hormone Expression
  • Resistance of the Parathyroid to Fibroblast Growth Factor 23 in Chronic Kidney Disease
  • Protein-PTH mRNA Interactions Determine the Regulation of PTH Gene Expression by Serum Calcium and Phosphate
  • The PTH mRNA 3´-UTR Binding Proteins That Determine PTH mRNA Stability
  • AU-Rich Binding Factor
  • K-homology Splicing Regulator Protein
  • A Conserved Sequence in the PTH mRNA 3´-UTR Binds Parathyroid Cytosolic Proteins and Determines mRNA Stability in Response to Ch...
  • The Peptidyl-Prolyl Isomerase Pin1 Determines Parathyroid Hormone mRNA Levels and Stability in Secondary Hyperparathyroidism
  • microRNAs in the Parathyroid
  • Parathyroid-Specific Deletion of Dicer-Dependent microRNAs Abrogates the Response of the Parathyroid to Acute and Chronic Hypoca...
  • Mammalian Target of Rapamycin in Parathyroid Cell Proliferation
  • Phosphorylation of Ribosomal Protein S6 Mediates mTOR Induced Parathyroid Cell Proliferation in Secondary Hyperparathyroidism
  • SUMMARY
  • References
  • 28 - The Calcium-Sensing Receptor and Vitamin D
  • INTRODUCTION
  • THE CALCIUM-SENSING RECEPTOR
  • CASR Gene
  • CaSR Protein
  • Calcium-Sensing Receptor Activation
  • CaSR Ligands
  • Calcium-Sensing Receptor and Signaling Pathways
  • Altered Calcium-Sensing Receptor Expression
  • CaSR Allosteric Modulators: PAMs and NAMs
  • OVERVIEW OF EXTRACELLULAR CA2+ HOMEOSTASIS: ROLES OF CALCIUM-SENSING RECEPTOR AND VITAMIN D RECEPTOR
  • CALCIUM-SENSING RECEPTOR AND VITAMIN D RECEPTOR IN TISSUES INVOLVED IN CA2+ HOMEOSTASIS
  • Calcium-Sensing Receptor and Vitamin D Receptor in the Parathyroid
  • Calcium-Sensing Receptor and Vitamin D Receptor in the Thyroid C-cell
  • Calcium-Sensing Receptor and Vitamin D Receptor in the Kidney
  • Calcium-Sensing Receptor and Vitamin D Receptor in the Skeleton
  • Cartilage
  • Bone
  • Calcium-Sensing Receptor and Vitamin D Receptor in the Intestine
  • Calcium-Sensing Receptor and Vitamin D Receptor in the Placenta
  • Calcium-Sensing Receptor and Vitamin D Receptor in the Breast
  • CALCIUM-SENSING RECEPTOR AND VITAMIN D RECEPTOR IN TISSUES UNINVOLVED IN EXTRACELLULAR CA2+ HOMEOSTASIS
  • Calcium-Sensing Receptor, Vitamin D Receptor, and Renin Secretion
  • CaSR and VDR in the Growth and Differentiation of Normal and Neoplastic Tissues
  • Calcium-Sensing Receptor and Vitamin D Receptor in Keratinocytes
  • Calcium-Sensing Receptor and Vitamin D Receptor in Colon Cancer
  • MOUSE MODELS OF CALCIUM-SENSING RECEPTOR DELETION RELATIVE TO PRESENTATION IN HUMANS
  • CONCLUSIONS
  • References
  • 29 - Vitamin D in Dentoalveolar and Oral Health
  • INTRODUCTION
  • A BRIEF PRIMER ON DENTOALVEOLAR CELLS AND TISSUES
  • VITAMIN D METABOLISM AND MECHANISMS OF ACTION ON DENTAL CELLS
  • VITAMIN D, RICKETS, AND THE ORAL TISSUES
  • History of Vitamin D and Oral Tissues
  • Nutritional Rickets and the Dentoalveolar Complex
  • Hypervitaminosis D and Teeth
  • HEREDITARY VITAMIN D-RELATED DISEASES AND DENTOALVEOLAR TISSUES
  • Vitamin D-Dependent Rickets
  • Vitamin D-Resistant Rickets
  • Experimental Models of Vitamin D-Dependent Rickets and Vitamin D-Resistant Rickets
  • Other Genetic Considerations for Diagnosing Dental Rickets
  • VITAMIN D AND ORAL HEALTH
  • Vitamin D Supplementation and Incidence of Dental Caries
  • Vitamin D Intake and Other Dental and Craniofacial Consequences
  • CONCLUSIONS
  • Acknowledgments
  • References
  • 30 - The Role of Vitamin D and Its Receptor in Hair Follicle Biology
  • INTRODUCTION
  • HAIR CYCLE
  • KERATINOCYTE STEM CELLS
  • PATHWAYS IMPORTANT FOR KERATINOCYTE STEM CELL FUNCTION
  • THE VITAMIN D RECEPTOR SUPPRESSES PPARG SIGNALING IN KERATINOCYTE STEM CELLS
  • CONCLUSIONS
  • References
  • 31 - Vitamin D, Calcium, and the Epidermis
  • INTRODUCTION
  • CUTANEOUS PRODUCTION OF VITAMIN D AND ITS BIOLOGICALLY ACTIVE METABOLITES
  • Vitamin D Production
  • Hormonal Regulation of CYP27B1 in Keratinocytes
  • Regulation by Cytokines
  • Clinical Implications
  • REGULATION OF KERATINOCYTE DIFFERENTIATION
  • Microanatomy of the Epidermis (Fig. 31.1)
  • Calcium Regulated Differentiation
  • Changes Induced by the Calcium Switch
  • Phosphoinositide Metabolism
  • The E-Cadherin/Catenin (CDH1/CTNN) Complex (Fig. 31.2)
  • The Calcium-Sensing Receptor (Fig. 31.3)
  • Interactions Between l,25(OH)2D and Calcium in the Regulation of Proliferation and Differentiation
  • Vitamin D Signaling
  • Role of Coregulators
  • Interactions With Calcium (Fig. 31.4)
  • ROLE OF VITAMIN D SIGNALING IN SKIN CANCER
  • Response of Squamous Cell Carcinoma With Normal Vitamin D Receptor Levels to 1,25(OH)2D and Calcium
  • Tumor Suppressor Role of Vitamin D Receptor
  • DNA Damage Repair
  • Regulation of the Hedgehog Pathway
  • CTNNB1 Signaling in Epidermal Tumor Formation
  • Long Noncoding RNAs (LncRNA) in Epidermal Tumor Formation
  • ROLE OF VITAMIN D SIGNALING IN EPIDERMAL WOUND REPAIR
  • References
  • 32 - Vitamin D and the Cardiovascular System
  • INTRODUCTION
  • VASCULAR PHYSIOLOGY
  • IDENTIFICATION OF THE VITAMIN D RECEPTOR IN THE VASCULAR SYSTEM
  • VASCULAR RELAXATION
  • STRUCTURAL VASCULAR CHANGES
  • VASCULAR INFLAMMATION
  • ANGIOGENESIS
  • BLOOD COAGULATION AND FIBRINOLYSIS
  • ANIMAL MODELS
  • Hypertension
  • Atherosclerosis
  • CLINICAL STUDIES IN CARDIOVASCULAR DISEASE
  • Surrogate Markers of Cardiovascular Disease
  • Peripheral Vascular Disease
  • Clinical Cardiovascular Disease
  • CONCLUSION
  • Acknowledgments
  • References
  • 33 - Vitamin D Brain Development and Function
  • INTRODUCTION
  • VITAMIN D SIGNALING IN THE BRAIN
  • Vitamin D Metabolites in the Brain
  • Local Activation and Catabolism of Vitamin D in the Brain
  • Is the Vitamin D Receptor in Brain?
  • Distribution of Vitamin D Receptor in the Brain
  • Vitamin D Receptor and Nonneuronal Cells
  • Vitamin D Receptor in the Embryonic and Neonatal Brain
  • DIETARY VITAMIN D DEFICIENCY, EFFECT ON BRAIN DEVELOPMENT AND FUNCTION
  • Developmental Dietary Restriction: Impact on Cellular Differentiation and Anatomy of the Developing Brain
  • Developmental Dietary Restriction: Persistent Impact on Anatomy of the Adult Brain
  • Developmental Dietary Restriction: Impact on Dopamine Neurons in the Developing Brain
  • Developmental Dietary Restriction: Persistent Impact on Adult Brain Neurotransmitters
  • Developmental Dietary Restriction: Impact on Gene and Protein Expression in the Developing Brain
  • Developmental Dietary Restriction: Persistent Impact on Gene and Protein Expression in the Adult Brain
  • The Impact of Developmental Vitamin D Deficiency on Adult Behavior
  • Behaviour in Developmental Vitamin D-Deficient Rats
  • Behaviour of Developmental Vitamin D-Deficient Mice
  • Genetically Modifying Vitamin D Signaling Affect on Brain Development and Function
  • THE EFFECTS OF EXCESS VITAMIN D ON BRAIN DEVELOPMENT AND FUNCTION
  • VITAMIN D REGULATES ESSENTIAL PROCESSES IN NORMAL BRAIN DEVELOPMENT
  • Vitamin D and Axonal Growth
  • Vitamin D and Neurotrophic Factors
  • Vitamin D as a Regulator of Dopamine in Development
  • POSSIBLE NEUROPROTECTIVE MECHANISMS OF VITAMIN D IN THE DEVELOPING BRAIN
  • Regulation of Calcium
  • Regulation of Reactive Oxygen Species and Nitric Oxide
  • Regulation of Glucocorticoids
  • DEVELOPMENTAL VITAMIN D DEFICIENCY AND NEUROPSYCHIATRIC DISORDERS
  • Schizophrenia
  • Autism Spectrum Disorders
  • Other Neurodevelopmental Psychiatric Disorders
  • CONCLUSIONS
  • References
  • 34 - Vitamin D, Vitamin D Receptor, and Adipose Tissue: Focus on Cellular Mechanisms
  • ADIPOSE TISSUE: STORAGE DEPOT AND TARGET FOR?VITAMIN D
  • Overview
  • Storage of Vitamin D Metabolites in Adipose Tissue
  • EFFECT OF VITAMIN D ON ADIPOGENESIS AT THE CELLULAR LEVEL
  • Model Systems for the Study of Adipogenesis
  • Effects of 1,25(OH)2D Treatment and Vitamin D Receptor on Differentiation in 3T3-L1 Cells
  • Effects of 1,25(OH)2D on Additional Established Rodent Cell Line Models of Adipogenesis
  • Vitamin D Signaling in Primary Cultures of Mesenchymal Cells
  • Role of the Vitamin D Receptor in Control of?Adipogenesis
  • Effect of 1,25(OH)2D on Differentiation of Human Mesenchymal Precursors
  • IMPACT OF VITAMIN D SIGNALING ON ADIPOSITY IN MOUSE MODELS
  • Genetically Engineered Mouse Models
  • Effect of Vitamin D Deficiency and Supplementation on Adiposity and Metabolism in Animal Models
  • TRANSLATIONAL CONSIDERATIONS
  • Vitamin D Status and Body Weight: Insight Into Clinical Trials
  • CONCLUSIONS AND FUTURE DIRECTIONS
  • References
  • 35 - Vitamin D and Skeletal Muscle
  • SKELETAL MUSCLE PHYSIOLOGY
  • VITAMIN D RECEPTOR IN MUSCLE
  • Conclusion
  • VITAMIN D AND CALCIUM SIGNALING IN MUSCLE
  • Conclusion
  • VITAMIN D AND PHOSPHATE SIGNALING IN MUSCLE
  • VITAMIN D AND INSULIN SIGNALING IN MUSCLE
  • Conclusion
  • VITAMIN D, MUSCLE CONTRACTION, AND STRENGTH
  • Conclusion
  • VITAMIN D, MUSCLE DEVELOPMENT, AND MASS
  • Conclusions
  • VITAMIN D, MUSCLE INJURY, AND REPAIR
  • Conclusion
  • VITAMIN D AND AGE-RELATED CHANGES IN MUSCLE
  • Conclusions
  • VITAMIN D AND BONE MUSCLE CROSS-TALK
  • CONCLUSIONS AND FUTURE DIRECTIONS
  • References
  • 36 - Understanding Vitamin D From Mouse Knockout Models
  • VITAMIN D METABOLISM
  • 1,25 DIHYDROXYVITAMIN D/VITAMIN D RECEPTOR SYSTEM AND MINERAL AND SKELETAL HOMEOSTASIS
  • Introduction
  • 1,25 Dihydroxyvitamin D/Vitamin D Receptor System and Mineral Homeostasis
  • 1,25 Dihydroxyvitamin D/Vitamin D Receptor Action and Calcium Transport in Intestine and Kidney
  • Intestinal Calcium Absorption
  • Renal Calcium Reabsorption
  • 1,25 Dihydroxyvitamin D/Vitamin D Receptor Action and Phosphate Transport in Intestine and Kidney
  • Interaction of Active Vitamin D With Hormones Regulating Calcium and Phosphorus
  • Regulation of Parathyroid Gland Function
  • Interaction of Parathyroid Hormone and 1,25 dihydroxyvitamin D on Calcium and Phosphate Homeostasis
  • Regulation of Fibroblast Growth Factor 23 Production
  • 1,25 Dihydroxyvitamin D/Vitamin D Receptor System and Skeletal Homeostasis
  • Anabolic Effects of Vitamin D on the Skeleton
  • Role of Vitamin D Receptor or 1a-hydroxylase in Chondrocytes
  • Effects on Mineralization
  • Effects on Bone
  • Effects on Bone Resorption
  • EXTRASKELETAL ACTIONS OF 1,25 DIHYDROXYVITAMIN D
  • The 1,25 Dihydroxyvitamin D/Vitamin D Receptor System and Ectopic Calcification
  • The 1,25 Dihydroxyvitamin D/Vitamin D Receptor System and Cancer
  • The 1,25 Dihydroxyvitamin D/Vitamin D Receptor System and Skin
  • Vitamin D Receptor is Essential for Hair Cycling
  • 1a-hydroxylase Is Required for Optimal Epidermal Differentiation
  • The 1,25 Dihydroxyvitamin D/Vitamin D Receptor System and the Immune System
  • CONCLUSION
  • References
  • Further Reading
  • V - HUMAN PHYSIOLOGY
  • 37 - Pharmacology and Pharmacokinetics
  • OVERVIEW
  • VITAMIN D ABSORPTION
  • Absorption Kinetics and Net Absorption
  • Mechanisms of Absorption
  • Possible Effect of Age
  • Absorption From Foods and Matrix Effects
  • 25(OH)D Response to Bolus Vitamin D
  • KINETICS OF CUTANEOUS SYNTHESIS
  • TISSUE DISTRIBUTION
  • Muscle and Adipose Tissue
  • Distribution of Vitamin D During Pregnancy and Lactation
  • Body Pool of Vitamin D and 25(OH)D
  • METABOLISM AND DETERMINANTS OF METABOLIC FATE OF VITAMIN D
  • HALF-LIVES OF VITAMIN D METABOLITES
  • Methodological Consideration of Half-Life Studies
  • Plasma Half-Lives of Vitamin D Metabolites
  • FACTORS INFLUENCING VITAMIN D HALF-LIFE
  • Disease
  • Drugs
  • Vitamin D Status
  • Calcium, Phosphate, Parathyroid Hormone
  • Age and Sex
  • Pregnancy and Lactation
  • THE PHARMACOKINETICS OF BOUND AND FREE VITAMIN D METABOLITES
  • INFLUENCE OF VITAMIN D-BINDING PROTEIN GENOTYPE AND CONCENTRATION ON VITAMIN D METABOLISM AND 25(OH)D HALF-LIFE
  • DOSE-RESPONSE TO VITAMIN D SUPPLEMENTATION
  • Dose-Ranging Studies and Metaregression Analyses of the Response to Vitamin D Supplementation
  • Factors Influencing the Dose-Response: Time Lag in Response, Dose, Frequency of Administration, and Form of Vitamin D
  • Time Lag Between the Start of Supplementation and Equilibrium in Plasma 25(OH)D
  • Dose and Frequency of Administration
  • Form of Vitamin D
  • Study Design and Methodological Considerations
  • Assay Aspects
  • Total Vitamin D Intake and Supplemental Intake
  • Consideration of Cutaneous Vitamin D Supply in Metaregression Analyses
  • Statistical Methodology
  • Biological Factors Influencing the Dose-Response
  • Age
  • Gender
  • Race or Ethnicity
  • Body Mass Index, Weight, Lean, and Fat Mass
  • The Influence of Baseline 25(OH)D
  • Other Potential Influencing Factors
  • THE 3-EPIMER OF 25(OH)D AND 1,25(OH)2D
  • CATABOLISM AND EXCRETION
  • VITAMIN D TOXICITY
  • Acknowledgments
  • References
  • 38 - Vitamin D Role in the Calcium and Phosphorus Economies
  • INTRODUCTION
  • OVERVIEW OF THE CALCIUM ECONOMY
  • Body Calcium Compartments
  • Regulation of Extracellular Fluid [Ca2+]
  • Driving Transfers
  • Mineralization of Bone
  • Obligatory Loss
  • Response of the System to Demand
  • Parathyroid Hormone Mediation of Response
  • Vitamin D Deficiency
  • Feast and Famine
  • Independence of Parathyroid Hormone Effector Mechanisms
  • OVERVIEW OF THE PHOSPHORUS ECONOMY
  • Body Phosphorus Compartments
  • ECF [Pi] and Its Regulation
  • Bone Mineralization
  • Regulation of Extracellular Fluid [Pi] Concentration
  • CALCIUM AND PHOSPHORUS ABSORPTIVE INPUTS
  • Location and Timing of Calcium Absorption in the Gut
  • Calcium Absorption as a Function of Intake
  • Partition of Calcium Absorption Between Active and Passive Mechanisms
  • Phosphorus Absorption
  • PHYSIOLOGICAL SOURCES OF VITAMIN D ACTIVITY
  • OPTIMAL VITAMIN D STATUS
  • SUMMARY AND CONCLUSIONS
  • References
  • 39 - Fetus, Neonate, and Infant
  • OVERVIEW OF CALCIUM METABOLISM IN THE FETUS
  • ANIMAL DATA RELEVANT TO VITAMIN D AND THE FETUS
  • HUMAN DATA RELEVANT TO VITAMIN D AND THE FETUS
  • Observational Studies, Case Reports, and Case Series
  • Intervention Studies
  • Associational Studies
  • OVERVIEW OF CALCIUM METABOLISM IN THE NEONATE AND INFANT
  • ANIMAL DATA RELEVANT TO VITAMIN D AND THE NEONATE AND INFANT
  • HUMAN DATA RELEVANT TO VITAMIN D AND THE NEONATE AND INFANT
  • Observational Studies, Case Reports, and Case Series
  • Intervention Studies
  • Associational Studies
  • CONCLUSIONS
  • References
  • 40 - Consequences of Perinatal Vitamin D Deficiency on Later Bone Health
  • INTRODUCTION
  • VITAMIN D PHYSIOLOGY AND EPIDEMIOLOGY IN PREGNANCY
  • THE LIFECOURSE DETERMINANTS OF OSTEOPOROSIS
  • Development of Peak Bone Mass: The Importance of the Early Environment
  • Evolutionary Biology
  • Gene-Environment Interaction in the Determination of Later Disease
  • Intrauterine Vitamin D Exposure, Epigenetic Marks, and Later Bone Health
  • Growth and Skeletal Development
  • Historical Perspective
  • Prospective Assessments of Early Growth and Postnatal Bone Size, Mineralization, and Geometry
  • Critical Growth Periods for Later Bone Development
  • Early Growth and Risk of Adult Hip Fracture
  • MATERNAL VITAMIN D SUPPLEMENTATION DURING PREGNANCY AND OFFSPRING BONE HEALTH
  • MATERNAL VITAMIN D SUPPLEMENTATION DURING PREGNANCY AND OFFSPRING BONE HEALTH: THE MAVIDOS TRIAL
  • CONCLUSION
  • Acknowledgment
  • References
  • 41 - Adolescence and Acquisition of Peak Bone Mass
  • INTRODUCTION
  • PUBERTAL BONE ACQUISITION
  • SEX AND RACE DIFFERENCES
  • Calcium Metabolism
  • Skeletal Accretion
  • SERUM 25(OH)D IN CHILDREN AND ADOLESCENTS
  • Latitude and Season
  • Race and Income
  • Age and Pubertal Maturation
  • Sex
  • Obesity
  • VITAMIN D AND INTERMEDIATE ENDPOINTS OF VITAMIN D AND BONE METABOLISM
  • 25(OH)D
  • 1,25(OH)2D
  • Intact Parathyroid Hormone
  • Fractional Calcium Absorption
  • Biochemical Markers of Bone Turnover
  • VITAMIN D AND OTHER PREDICTORS OF CALCIUM RETENTION
  • VITAMIN D AND BONE
  • VITAMIN D AND MUSCLE
  • VITAMIN D REQUIREMENTS IN CHILDREN AND ADOLESCENTS
  • SUMMARY AND CONCLUSIONS
  • References
  • 42 - Pregnancy, Lactation, and Postweaning Recovery
  • INTRODUCTION
  • OVERVIEW OF MINERAL PHYSIOLOGY DURING PREGNANCY
  • Minerals and Calciotropic Hormones
  • Intestinal Absorption of Calcium
  • Renal Handling of Calcium
  • Skeletal Metabolism
  • ANIMAL DATA RELEVANT TO VITAMIN D AND PREGNANCY
  • HUMAN DATA RELEVANT TO VITAMIN D AND PREGNANCY
  • Randomized Interventions of Vitamin D Supplementation
  • Genetic Disorders of Vitamin D Physiology
  • Studies of Associations Between Obstetrical Outcomes and Vitamin D Status
  • OVERVIEW OF MINERAL PHYSIOLOGY DURING LACTATION AND POSTWEANING RECOVERY
  • Minerals and Calciotropic Hormones
  • Intestinal Absorption of Calcium
  • Renal Handling of Calcium
  • Calcium Pumping in the Breast and Milk Formation
  • Skeletal Metabolism During Lactation
  • Skeletal Metabolism During Postweaning
  • ANIMAL DATA RELEVANT TO VITAMIN D, LACTATION, AND POSTWEANING RECOVERY
  • HUMAN DATA RELEVANT TO VITAMIN D, LACTATION, AND POSTWEANING RECOVERY
  • CONCLUSIONS
  • References
  • 43 - Role in Reproductive Biology and Reproductive Dysfunction in Women
  • INTRODUCTION
  • PROCREATIVE RELEVANCE OF VITAMIN D-ANIMAL MODELS
  • THERAPEUTIC RELEVANCE OF VITAMIN D-DATA FROM EXPERIMENTAL ANIMAL MODELS OF HUMAN GYNECOLOGICAL DISORDERS
  • Endometriosis
  • Uterine Fibroids
  • VITAMIN D-RELEVANCE IN HUMAN FEMALE REPRODUCTIVE PHYSIOLOGY
  • Menarche
  • Ovarian Physiology and Menstrual Cycles
  • Ovarian Reserve
  • VITAMIN D-RELEVANCE IN FEMALE REPRODUCTIVE DISORDERS
  • POLYCYSTIC OVARY SYNDROME
  • PREMENSTRUAL SYNDROME
  • MENSTRUAL PAIN (DYSMENORRHEA)
  • ENDOMETRIOSIS
  • UTERINE LEIOMYOMAS (FIBROIDS)
  • VITAMIN D AND FEMALE INFERTILITY
  • Vitamin D, Ovulatory Infertility, and Ovulation?Induction
  • Vitamin D and In Vitro Fertilization
  • CONCLUDING REMARKS
  • References
  • 44 - Vitamin D, Reproductive Biology, and Dysfunction in Men
  • INTRODUCTION
  • Vitamin D Physiology
  • Testicular Function
  • VITAMIN D AND LEYDIG CELL FUNCTION
  • VITAMIN D AND SEX STEROIDS
  • VITAMIN D AND SERTOLI CELL FUNCTION
  • VITAMIN D AND GERM CELL FUNCTION
  • VDR, ACTIVATION AND INACTIVATION OF VITAMIN D?IN HUMAN SPERM
  • VITAMIN D AND SPERM FUNCTION
  • VITAMIN D, EPIDIDYMIS, PROSTATE, AND SEMINAL VESICLE
  • VITAMIN D AND REPRODUCTIVE HORMONES
  • VITAMIN D, SEMEN QUALITY, AND FERTILITY: FUNCTIONAL MODELS
  • VITAMIN D, SEMEN QUALITY, AND FERTILITY: HUMAN?STUDIES
  • TESTICULAR GERM CELL TUMORS
  • CONCLUDING REMARKS AND FUTURE PERSPECTIVES
  • References
  • 45 - Vitamin D and the Renin-Angiotensin System
  • INTRODUCTION
  • THE RENIN-ANGIOTENSIN SYSTEM
  • The Renin-Angiotensin Cascade and Its Biological Functions
  • Control of Renin Production and Secretion
  • Angiotensin II-Dependent and Angiotensin II-Independent Activities of Prorenin
  • Transcriptional Regulation of Renin Gene Expression
  • Pharmacological Inhibition of the Renin-Angiotensin System
  • VITAMIN D REGULATION OF THE RENIN-ANGIOTENSIN SYSTEM
  • Vitamin D Hormone as a Negative Endocrine Regulator of the Renin-Angiotensin System
  • Molecular Mechanism for Vitamin D Repression of Renin Expression
  • Vitamin D Analogs as Renin Inhibitors
  • Regulation of Angiotensinogen
  • Pathophysiological Implications
  • VITAMIN D AND THE RENIN-ANGIOTENSIN SYSTEM IN DISEASE
  • Cardiovascular System
  • Vitamin D Deficiency and Cardiovascular Diseases
  • Therapeutic Effects of Vitamin D on Cardiovascular Diseases
  • Correlation of Vitamin D With the Renin-Angiotensin System in Cardiovascular Diseases
  • Kidney
  • Vitamin D Deficiency in Chronic Kidney Disease
  • Renoprotective Action of Vitamin D: Targeting the Local Renin-Angiotensin System
  • Vitamin D Therapy of Chronic Kidney Disease
  • Brain
  • Immune System
  • Pancreas
  • Lung
  • Gastrointestinal Track
  • CONCLUSION
  • References
  • 46 - Parathyroid Hormone, Parathyroid Hormone-Related Protein, and Calcitonin
  • PARATHYROID HORMONE
  • Introduction
  • The PTH Gene
  • PTH Secretion
  • PTH Receptors
  • PTH Functions
  • Kidney
  • The Skeleton
  • Pathophysiology
  • Clinical Applications
  • PARATHYROID HORMONE-RELATED PROTEIN
  • Introduction
  • The PTHrP Gene
  • PTHrP Protein
  • PTHrP Receptors
  • Nuclear PTHrP
  • PTHrP Functions
  • The Skeleton
  • Mammary Gland
  • Placenta
  • Smooth Muscle and the Cardiovascular System
  • Teeth
  • Pathophysiology
  • Hypercalcemia of Malignancy
  • Bone Metastases
  • Skeletal Dysplasias
  • Clinical Applications
  • CALCITONIN
  • Introduction
  • Gene and Protein
  • Calcitonin Receptor
  • Regulation of Calcitonin Secretion
  • Calcitonin Functions
  • Pathophysiology
  • Clinical Applications
  • References
  • 47 - FGF-23 Counter-Regulatory Hormone for Vitamin D Actions on Mineral Metabolism, Hemodynamics, and Innate Immunity
  • INTRODUCTION
  • PARATHYROID HORMONE-VITAMIN D AXIS: KEY REGULATOR OF CALCIUM HOMEOSTASIS
  • FIBROBLAST GROWTH FACTOR-23/?-KLOTHO
  • FIBROBLAST GROWTH FACTOR-23 ENDOCRINE NETWORKS
  • Fibroblast Growth Factor-23 Coordinates Bone Mineralization With Renal Phosphate Handling
  • Questionable Role of Serum Phosphate in Fibroblast Growth Factor-23 Regulation
  • Fibroblast Growth Factor-23 Counteracts Multiple Functions of 1,25-Dihydroxyvitamin D
  • Counter-Regulatory Hormone for 1,25-Dihydroxyvitamin D Effects on Mineral Homeostasis
  • FGF-23 Counters the Effects of Vitamin D on Inflammation and Innate Immune Responses
  • FGF-23 Counteracts the Hemodynamic and Cardiovascular Effects of 1,25(OH)2D
  • NONCANONICAL ?-KLOTHO AND FIBROBLAST GROWTH FACTOR-23 SIGNALING
  • a-Klotho Effects That Are Independent of Fibroblast Growth Factor-23
  • Fibroblast Growth Factor-23 Effects That Are Independent of a-Kl
  • Interactions Between Fibroblast Growth Factor-23 and Parathyroid Hormone Homeostasis
  • Unexpected Endocrine Networks
  • Translational Relevance of Fibroblast Growth Factor-23 Regulation and Function
  • CONCLUSIONS
  • References
  • VI - DIAGNOSIS AND MANAGEMENT
  • 48 - Approach to the Patient With Metabolic Bone Disease
  • INTRODUCTION
  • DIAGNOSTIC EVALUATION
  • Medical History
  • Chief Complaint
  • History of Present Illness
  • Past Medical History
  • Social History
  • Family History
  • Review of Systems
  • Physical Examination
  • Laboratory Testing
  • Radiological Examination
  • X-ray Images
  • Bone Scintigraphy
  • Bone Densitometry
  • Other Radiological Procedures
  • BIOCHEMICAL INVESTIGATION
  • HISTOPATHOLOGICAL ASSESSMENT
  • TREATMENT
  • CONCLUSIONS
  • Acknowledgments
  • References
  • 49 - Detection of 1,25-Dihydroxyvitamin D in Human Serum Using Receptor Assisted Chemiluminescent Hormone Assay Technology
  • INTRODUCTION
  • METHODOLOGY
  • Development of the Monoclonal Antibody Specific to Ligand Binding Domain-1,25-Dihydroxyvitamin D Complex
  • IDENTIFICATION OF THE DNA CONSENSUS SEQUENCE OF THE IMMUNOGLOBULIN G VH AND VL GENE, EXPRESSED BY HYBRIDOMA CLONE 11B4
  • PREPARATION OF THE ASSAY REAGENTS
  • ASSAY FORMAT AND PERFORMANCE
  • DISCUSSION
  • References
  • 50 - Mass Spectrometry Assays of Vitamin D Metabolites
  • INTRODUCTION
  • APPROACHES AND UTILITY OF VITAMIN D METABOLITE MEASUREMENTS IN THE CLINICAL LABORATORY SETTING
  • OVERVIEW OF METHODOLOGY FOR ANALYSIS OF CIRCULATING VITAMIN D METABOLITES BY LC-MS/MS
  • Sample Extraction
  • Sample Derivatization
  • Sample Separation
  • Mass Spectrometry
  • APPLICATION OF LC-MS/MS TO THE STUDY OF VITAMIN D METABOLISM IN ANIMAL MODELS
  • FUTURE DIRECTIONS
  • References
  • 51 - Free Vitamin D: Concepts, Assays, Outcomes, and Prospects
  • INTRODUCTION
  • METABOLISM
  • TRANSPORTATION AND INTERNALIZATION: FREE HORMONE HYPOTHESIS AND BIOAVAILABLE LIGAND
  • VITAMIN D-BINDING PROTEIN GENOTYPE
  • FREE VITAMIN D: MATHEMATICAL ESTIMATION
  • FREE VITAMIN D: DIRECT PHYSICAL MEASUREMENT
  • POTENTIAL UTILITY OF FREE 25(OH)D FOR CLINICAL- AND POPULATION-BASED DETECTION OF VITAMIN D DEFICIENCY
  • Correlations Between Free and Total 25(OH)D
  • African Ancestry and Vitamin D-Binding Protein Concentration
  • Pregnancy and Estrogen Therapy as Determinant of Free 25(OH)D
  • Obesity
  • Cirrhotic Patients
  • Associations With Health Outcomes
  • Parathyroid Hormone, Bone Mineral Density, and Markers of Bone Turnover
  • Colorectal Cancer
  • Response to Vitamin D Supplementation
  • CONCLUSIONS AND KNOWLEDGE GAPS
  • References
  • 52 - 25-Hydroxyvitamin D Assays: Standardization Guidelines, Problems, and Interpretation
  • INTRODUCTION
  • VITAMIN D STANDARDIZATION PROGRAM OBJECTIVES
  • STANDARDIZATION AND TRACEABILITY
  • VITAMIN D STANDARDIZATION PROGRAM STANDARDIZATION PROTOCOLS
  • Steps in Standardization (Prospective)
  • Protocol for Retrospective Standardization
  • PERFORMANCE TESTING/QUALITY ASSESSMENT OF ASSAYS FOR VITAMIN D METABOLITES
  • Overview
  • Beyond Standardization
  • Preanalytical
  • Sample Stability
  • Blood Collection Containers
  • Analytical
  • Postanalytical
  • Units
  • Reference Ranges
  • VITAMIN D STANDARDIZATION PROGRAM EFFORTS GOING INTO THE FUTURE
  • SUMMARY AND CONCLUSIONS
  • References
  • 53 - Bone Histomorphometry
  • INTRODUCTION
  • BONE BIOPSY
  • Procedure
  • Adverse Effects
  • Indications for Bone Biopsy
  • HISTOMORPHOMETRY
  • Theoretical Considerations
  • Methodology
  • Terminology
  • Limitations of Bone Histomorphometry
  • ASSESSMENT OF MINERALIZATION
  • In Vivo Tetracycline Labeling
  • Measurement of Osteoid
  • Dynamic Indices of Mineralization
  • Mineral Apposition Rate
  • Adjusted Apposition Rate
  • Mineralization Lag Time and Osteoid Maturation Time
  • HISTOLOGICAL DIAGNOSIS OF OSTEOMALACIA
  • Generalized Osteomalacia
  • Focal Osteomalacia
  • ASSESSMENT OF BONE TURNOVER
  • Mineralizing Perimeter
  • Bone Formation Rates
  • Bone Resorption Rates
  • Remodeling Periods
  • Activation Frequency
  • ASSESSMENT OF REMODELING BALANCE
  • Bone Formation
  • Bone Resorption
  • ASSESSMENT OF BONE STRUCTURE
  • Structural Determinants of Bone Strength
  • INFLUENCE OF VITAMIN D STATUS ON BONE HISTOMORPHOMETRY
  • FUTURE DEVELOPMENTS
  • References
  • 54 - Radiology of Rickets and Osteomalacia
  • INTRODUCTION AND HISTORICAL ASPECTS
  • VITAMIN D DEFICIENCY
  • Rickets
  • Osteomalacia
  • Secondary Hyperparathyroidism
  • RENAL OSTEODYSTROPHY
  • Hyperparathyroidism
  • Subperiosteal Erosions
  • Intracortical Bone Resorption
  • Osteosclerosis
  • Brown "Tumors"
  • Osteoporosis
  • Periosteal Reaction
  • Ectopic Calcification
  • Aluminum Toxicity
  • RENAL TUBULAR DEFECTS AND HYPOPHOSPHATEMIA
  • X-Linked Hypophosphatemia
  • Rickets in X-Linked Hypophosphatemia
  • Osteomalacia in X-Linked Hypophosphatemia
  • Osteosclerosis in X-Linked Hypophosphatemia
  • Abnormalities of Bone Modeling
  • Extraskeletal Ossification
  • Osteoarthritis in X-Linked Hypophosphatemia
  • Tumor-Induced ("Oncogenic") Rickets/Osteomalacia
  • Acidemia
  • DIFFERENTIAL DIAGNOSES
  • Hypophosphatasia
  • Other Differential Diagnoses
  • VITAMIN D INTOXICATION
  • Technical Aspects of Imaging
  • Radiographs
  • Nuclear Medicine
  • Other Imaging Techniques
  • Venous Hormone Sampling
  • Bone Mineral Densitometry
  • CONCLUSIONS
  • References
  • 55 - High-Resolution Imaging Techniques for Bone Quality Assessment
  • INTRODUCTION
  • X-RAY COMPUTED TOMOGRAPHY
  • Multidetector Computed Tomography
  • Image Acquisition
  • Image Analysis
  • Densitometric Analysis
  • Morphometric Analysis
  • Biomechanical Analysis
  • Applications
  • Microcomputed Tomography
  • Image Acquisition
  • Conventional Microcomputed Tomography
  • Synchrotron Radiation Microcomputed Tomography
  • Image Analysis
  • Quantitative Microcomputed Tomography
  • Morphometric Analysis
  • Biomechanical Analysis
  • Applications
  • Basic and Preclinical Studies
  • Clinical Studies
  • High-Resolution Peripheral Quantitative Computed Tomography
  • Image Acquisition
  • Hardware
  • Positioning
  • Tomography
  • Image Analysis
  • Densitometric Analysis
  • Morphometric Analysis
  • Biomechanical Analysis
  • Longitudinal Analysis
  • Applications
  • Cross-Sectional Studies
  • Longitudinal Studies
  • Vitamin D and Related Disorders
  • MAGNETIC RESONANCE IMAGING
  • Trabecular Bone Magnetic Resonance Imaging
  • Image Acquisition
  • Signal to Noise Considerations
  • Spatial Resolution
  • Pulse Sequences
  • Image Analysis
  • Coil Sensitivity Correction
  • Grayscale Versus Binarization
  • Trabecular Bone Analysis
  • Finite Element Analysis
  • Image Registration
  • Applications
  • Cortical Bone Magnetic Resonance Imaging
  • Image Acquisition
  • Morphological Assessment
  • Cortical Porosity and Bone Water Quantification
  • Standard Pulse Sequences
  • Advanced Pulse Sequences
  • Image Analysis
  • Applications
  • References
  • 56 - The Role of Vitamin D in Orthopedic Surgery
  • INTRODUCTION
  • IMPACT ON ORTHOPEDIC TRAUMA
  • Fragility Fracture
  • Fracture Healing
  • Fracture Fixation
  • Nonunion
  • Stress and Insufficiency Fractures
  • IMPACT ON PEDIATRIC ORTHOPEDICS
  • Rickets
  • Slipped Capital Femoral Epiphysis
  • IMPACT ON TOTAL JOINT ARTHROPLASTY
  • Osteoarthritis
  • Periprosthetic Fracture
  • Thigh Pain
  • Impact on Muscle Strength and Rehabilitation
  • Vitamin D and Falls
  • Prevention and Treatment in Orthopedic Patients
  • References
  • Introduction to Chapters 57A and 57B
  • References
  • 57A - The IOM-Endocrine Society Controversy on Recommended Vitamin D Targets: In Support of the IOM Position
  • INTRODUCTION
  • Vitamin D Supplementation to Prevent Rickets
  • VITAMIN D STATUS AND BONE HEALTH IN ADULTS AND THE ELDERLY
  • Vitamin D Status and Serum 1,25-Dihydroxyvitamin D3
  • Vitamin D Status and Parathyroid Function
  • Vitamin D Status and Intestinal Calcium Absorption
  • Vitamin D Status and Bone Mineral Density
  • Vitamin D Status and Fracture Risk
  • Vitamin D Status and Bone Health: Conclusions
  • VITAMIN D AND EXTRASKELETAL HEALTH
  • Skin Diseases
  • Cancer
  • Immune System and Vitamin D Status
  • Cardiovascular and Metabolic Risks/Diseases and Vitamin D Status
  • Diabetes, Metabolic Syndrome, and Vitamin D Status
  • Muscle Function and Vitamin D Status
  • Vitamin D in Pregnancy and the Perinatal Period
  • Mortality
  • Conclusions: Extraskeletal Effects of Vitamin D
  • LESSONS FROM RECENTLY UPDATED GUIDELINES ON?VITAMIN D SUPPLEMENTATION
  • VITAMIN D AND HUMAN HEALTH: WHAT IS THE OPTIMAL VITAMIN D STATUS
  • SUMMARY OF RECOMMENDATIONS
  • HIGHLIGHTS
  • References
  • 57B - The IOM-Endocrine Society Controversy on Recommended Vitamin D Targets: In Support of the Endocrine Society Position
  • SECTION I. DEFINING THE DISAGREEMENT BETWEEN IOM AND ENDOCRINE SOCIETY
  • SECTION II. SCIENTIFIC BASIS FOR WHY IOM VERSUS ENDOCRINE SOCIETY VALUES DIFFER IN TERMS OF BONE HEALTH
  • II-A. The Minimum Desirable Serum 25(OH)D Threshold for Bone Density and Bone Mineralization
  • II-B. The Minimum Desirable Serum 25(OH)D Concentration for Risk of Osteomalacia
  • II-C. The Daily Vitamin D Intake Needed So That Serum 25(OH)D Is at Least 50nmol/L in 97.5% of the Population
  • SECTION III. TOXICITY AND PERCEPTIONS OF RISK OF HIGHER VITAMIN D INTAKES: HIGHER-DOSE CLINICAL TRIALS AND EPIDEMIOLOGY U-SHAPED...
  • III-A. Reverse Causality Contributes to Cross-Sectional Data Suggestive of U- or J-Shaped Risk Curves
  • III-B. Adverse Effects of Seasonality on Musculoskeletal Health Relate to Seasonal Drops in Serum 25(OH)D Concentrations
  • III-C. Declining 25(OH)D Levels After a Pulsatile Large Vitamin D Dose Cause a Paradoxical Vitamin D Deficiency at the Cellular ...
  • III-D. Mass Action Drives 1,25(OH)2D Production Within Cells
  • III-E. High and Stable Serum 25(OH)D Levels are Normal
  • III-F. Effects of Seasonal Sunshine Exposure on Health Outcomes
  • SECTION IV. EXTRASKELETAL EFFECTS OF VITAMIN D
  • SECTION V. EXTRASKELETAL EFFECTS: CROSS-SECTIONAL OBSERVATIONS VERSUS THE FINDINGS OF DOUBLE-BLIND, RANDOMIZED CLINICAL TRIALS
  • SECTION VI. EMERGING BENEFITS OF HIGHER VITAMIN D: LIFE EXPECTANCY
  • SECTION VII. NEW EVIDENCE THAT VITAMIN D LOWERS RISK OF PRETERM BIRTH
  • SECTION VIII. CONCLUSION
  • References
  • Index for Volume 1
  • #
  • A
  • B
  • C
  • D
  • E
  • F
  • G
  • H
  • I
  • J
  • K
  • L
  • M
  • N
  • O
  • P
  • Q
  • R
  • S
  • T
  • U
  • V
  • W
  • X
  • Y
  • Z
  • Back Cover

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