LIMITED OFFER
Save 50% on book bundles
Immediately download your ebook while waiting for your print delivery. No promo code needed.
Vitamin D, a steroid hormone, has mainly been known for its effects on bone and osteoporosis. The current therapeutic practices expand into such markets as cancer research,… Read more
LIMITED OFFER
Immediately download your ebook while waiting for your print delivery. No promo code needed.
Preface to the 3rd Edition
Preface to the 2nd Edition
Preface to the 1st Edition
Contributors
Introduction
Abbreviations
Relevant Lab Values in Adults and Children
Criteria for Vitamin D Deficiency: 25(OH)D Serum Levels
Approximate normal ranges for serum values in adults
Approximate normal ranges for serum values in children
Useful equivalencies of different units
Volume I
Section I: Chemistry, Metabolism, Circulation
Chapter 1. Historical Overview of Vitamin D
Discovery of the Vitamins
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
Discovery of the Hormonal Form of Vitamin D
Acknowledgments
References
Chapter 2. Photobiology of Vitamin D
Introduction
Historical Perspective
Photobiology of Vitamin D
Role of Sunlight and Dietary Vitamin D in Bone Health, Overall Health, and Well-Being
Sunlight, Vitamin D, and Skin Cancer
Conclusion
Acknowledgment
References
Chapter 3. The Activating Enzymes of Vitamin D Metabolism (25- and 1α-Hydroxylases)
Introduction
General Information Regarding Vitamin D Hydroxylases
Vitamin D3-25-Hydroxylases
25-Hydroxyvitamin D-1α-Hydroxylase
Additional Topics
References
Chapter 4. CYP24A1: Structure, Function, and Physiological Role
Overview
CYP24A1-Catalyzed Pathways
Structure–Function Relationships
Putative CYP24A1 Involvement in Nonclassical Systems
Perspectives
References
Chapter 5. The Vitamin D Binding Protein DBP
Introduction
Vitamin D Binding Protein: Protein and Gene Structure
Functions of DBP
Conclusions and Perspectives
References
Chapter 6. Industrial Aspects of Vitamin D
History of Vitamin D Leading to Commercialization
Manufacture of the Provitamins
Irradiation of 7-Dehydrocholesterol and Ergosterol
Metabolite Manufacture
Analytical
Dietary Requirements
Economic Aspects
Storage and Shipping
References
Section II: Mechanisms of Action
Chapter 7. The Vitamin D Receptor: Biochemical, Molecular, Biological, and Genomic Era Investigations
Introduction
Vitamin D Biology
Discovery of the Vitamin D Receptor
VDR Research: The Biochemical Era
VDR Research: The Molecular Biological Era
VDR Research: The Genomic Era
VDR Chromosomal Gene: Structure and Molecular Regulation
Concluding Comments
Acknowledgment
References
Chapter 8. Nuclear Vitamin D Receptor: Natural Ligands, Molecular Structure–Function, and Transcriptional Control of Vital Genes
Ligands, Gene Targets, and Biological Actions of VDR
VDR as a Member of the Nuclear Receptor Superfamily
Molecular Structure–Function of VDR
Mechanisms of VDR-Mediated Control of Gene Expression
VDR-Mediated Control of Vital Genes in Healthful Aging and Disease Prevention
Conclusions and Perspectives
Acknowledgment
References
Chapter 9. Structural Basis for Ligand Activity in VDR
Introduction
Crystal Structure of hVDRΔ Bound to 1,25(OH)2D3
Crystal Structure of zVDR Wild-Type LBD Bound to 1,25(OH)2D3
Structure of VDR LBD Complexed to Superagonist Ligands
Structures of VDR Complexed to 2α-Substituted Analogs
Structures of VDR with Nonsteroidal Ligands
Structures of VDR With Analogs that Induce Structural Rearrangements
Structural Basis for Vitamin D Receptor Antagonism
Structure-Based Design of Novel Superagonist Analogs
Conclusion
References
Chapter 10. Coregulators of VDR-mediated Gene Expression
Introduction
Coactivators of VDR
Corepressors
Conclusion – Integrated Model of Coregulator Activity
References
Chapter 11. Target Genes of Vitamin D: Spatio-temporal Interaction of Chromatin, VDR, and Response Elements
Introduction
Transcriptional Regulation by 1,25(OH)2D3
Genomic VDR-Binding Sites
VDR Target Genes
VDR Target Gene Analysis
Transcriptional Cycling
Conclusion
Acknowledgments
References
Chapter 12. Epigenetic Modifications in Vitamin D Receptor-mediated Transrepression
Introduction
WINAC: a Novel VDR-Associating ATP-Dependent Chromatin Remodeling Complex
E-Box Motif Negative VDRE Mediates 1,25(OH)2D3-Induced Transrepression
Coregulator Switching at E-Box nVDREs in Ligand-Dependent Transrepression by VDR
WINAC Mediates Ligand-Induced Transrepression by VDR
1,25(OH)2D3-Dependent VDR Transrepression Involves CpG Site Methylation in the CYP27B1 Promoter
Cell-Cycle-Independent DNA Demethylation During CYP27B1 Transcriptional Derepression
MBD4 Mediates Active DNA Demethylation
MBD4 is a Downstream Mediator in PTH Signaling-Induced Transcriptional Derepression
Conclusion
References
Chapter 13. Vitamin D and Wnt/β-Catenin Signaling
Introduction
WNT Signaling
Antagonism of Wnt/β-Catenin Pathway by 1,25(OH)2D3 in Colon Cancer
Wnt and 1,25(OH)2D3 in the Bone
Wnt and 1,25(OH)2D3 in the Skin
Conclusions
References
Chapter 14. Vitamin D Response Element-binding Protein
Introduction
Current View of Steroid/Sterol Hormone Action
New World Primates
New World Primate-Like VItamin D Resistance in Man
Heterogeneous Nuclear Ribonucleoproteins (HNRNPS)
HNRNPS as Multi-Level, Multi-Site, cis-Binding Regulators of Gene Expression
The Estrogen Response Element Binding Protein (ERE-BP) and the Intracellular Estrogen Binding Protein (IEBP)
Compensation for the Dominant-Negative Acting, Response Element-Binding Proteins
Conclusion
References
Chapter 15. Vitamin D Sterol/VDR Conformational Dynamics and Nongenomic Actions
1α,25(OH)2-Vitamin D3 (1,25(OH)2D3) Regulation of Genomic Versus Nongenomic Signaling
Vitamin D3 Sterol (VDS) Chemistry
1,25(OH)2D3 Mediated Rapid, Nongenomic Responses
The Plasma Membrane Vitamin D Receptor
The VDR Conformational Ensemble Model
VDR Ligand Specificity: Does an Unliganded VDR Ever Exist in Vivo?
References
Section III: Mineral and Bone Homeostasis
Chapter 16. Genetic and Epigenetic Control of the Regulatory Machinery for Skeletal Development and Bone Formation: Contributions of Vitamin D3
Programs of Bone Formation
Nuclear Organization of the Regulatory Machinery for Bone Formation
Epigenetic Mechanism for Lineage Commitment
Gene Expression within the Three-Dimensional Context of Nuclear Architecture
Chromatin Remodeling Facilitates Bone-Specific and Vitamin-D-Mediated Promoter Accessibility and Integration of Regulatory Activities
Scaffolding of Regulatory Components for Combinatorial Control of Gene Expression
Closing Remarks
Acknowledgments
References
Chapter 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
Effects of 1,25(OH)2D3 on Osteoblast Differentiation
Regulation of Intracellular Signaling Pathways by 1,25(OH)2D3
Summary and Conclusions
Acknowledgments
References
Chapter 18. Osteoclasts
Introduction
References
Chapter 19. Molecular Mechanisms for Regulation of Intestinal Calcium and Phosphate Absorption by Vitamin D
An Overview of Intestinal Calcium Absorption
Critical Role of VDR in Control of Intestinal CA Absorption
Can High Vitamin D Status Increase Intestinal Calcium Absorption?
An Overview of Intestinal Phosphate Absorption
Acknowledgments
References
Chapter 20. The Calbindins: 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
Regulation of Calbindin Gene Expression
Epithelial Calcium Channels
Conclusion
References
Chapter 21. Mineralization
Introduction
Conclusions
References
Chapter 22. Vitamin D Regulation of Type I Collagen Expression in Bone
Introduction
Regulation of Bone Collagen Synthesis
Molecular Mechanisms of Regulation
Conclusions and Perspectives
References
Chapter 23. Target Genes: Bone Proteins
Vitamin D and Skeletal Homeostasis
Exogenous and Endogenous Sources of 1,25(OH)2D3
Direct Actions of Vitamin D in Bone
Concluding Remarks
References
Chapter 24. Vitamin D and the Calcium-Sensing Receptor
Introduction
What is the CASR?
Overview of Roles of CASR and VDR in Maintaining CA2+O Homeostasis
The CASR and VDR in Tissues Participating in CA2+O Homeostasis
The CASR and VDR in Tissues Uninvolved in CA2+O Homeostasis
Polymorphisms of the CASR and VDR and Calcium and Bone Homeostasis
Summary and Perspectives
References
Chapter 25. Effects of 1,25-Dihydroxyvitamin D3 on Voltage-Sensitive Calcium Channels in Osteoblast Differentiation and Morphology
Systemic and Intracellular Ca2+ Homeostasis
Voltage-Sensitive Calcium Channels
1,25-Dihydroxyvitamin D3 Actions on Voltage-Sensitive Ca2+ Channels
1,25-Dihydroxyvitamin D3-Regulated Osteoblast Differentiation
Influence of 1,25(OH)2D3 on Osteoblast Cell Survival
Acknowledgments
References
Section IV: Targets
Chapter 26. Vitamin D and the Kidney
Introduction
Role of the Kidney in the Metabolism of 25(OH)D
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
Conclusion
References
Chapter 27. Vitamin D and the Parathyroids
Introduction
Parathyroid Hormone Biosynthesis
The Parathyroid Hormone Gene
Development of the Parathyroid and Tissue-Specific Expression of The PTH Gene
Promoter Sequences
Regulation of PTH Gene Expression
Conclusion
References
Chapter 28. Cartilage
Chondrogenesis, Endochondral Ossification, and Vitamin D
Separate Roles for 24,25(OH)2D3 and 1,25(OH)2D3 in Cartilage
Rapid Actions of Vitamin D and Nongenomic Mechanisms
Physiologic Relevance of Nongenomic Regulation of Matrix Vesicles
Conclusion
References
Chapter 29. Vitamin D and Oral Health
Introduction: The Dento-Maxillofacial Skeleton
Dental Rare Diseases and Molecular Determinants of Dental Rickets
Experimental Analysis of Dental Pathway in Experimental Models of Vitamin D Bioactivation
Specificity of Oral Bone: Potential Vitamin D Impact in Development, Periodontal Disease, and JAW Osteonecrosis
Conclusions: Facts and Hypothesis
References
Chapter 30. The Role of Vitamin D and its Receptor in Skin and Hair Follicle Biology
Introduction
Keratinocyte Differentiation
Coactivators
Barrier Function
Hair Cycle
Keratinocyte Stem Cells
Pathways Important for Keratinocyte Stem Cell Function
Conclusions
References
Chapter 31. Vitamin D and the Cardiovascular System
Introduction
Vitamin D and the Vasculature
Vitamin D and the Heart
Clinical Epidemiological Considerations of Vitamin D Deficiency
Conclusion
Acknowledgments
References
Chapter 32. Vitamin D: A Neurosteroid Affecting Brain Development and Function; Implications for Neurological and Psychiatric Disorders
Introduction
Vitamin D Signaling in the Brain
Vitamin D Deficiency, Brain Development, and Function
Vitamin D and Neurological Disorders
Possible Neuroprotective Mechanisms of Vitamin D
Vitamin D and Neuropsychiatric Disorders
Conclusions
References
Chapter 33. Contributions of Genetically Modified Mouse Models to Understanding the Physiology and Pathophysiology of the 25-Hydroxyvitamin D-1-Alpha Hydroxylase Enzyme (1α(OH)ase) and the Vitamin D Receptor (VDR)
Introduction
Mouse Models
1,25(OH)2D/VDR System and Skeletal and Mineral Homeostasis
Extraskeletal Actions of 1,25(OH)2D
Conclusion
References
Section V: Human Physiology
Chapter 34. Vitamin D: Role in the Calcium and Phosphorus Economies
Introduction
Overview of the Calcium Economy
Overview of the Phosphorus Economy
Calcium and Phosphorus Absorptive Inputs
Physiological Sources of Vitamin D Activity
Optimal Vitamin D Status
Summary and Conclusions
References
Chapter 35. 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
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
Conclusions
References
Chapter 36. Vitamin D Deficiency and Calcium Absorption during Childhood
Introduction
Premature Infants
Full-Term Infants – Calcium
Vitamin D in Full-Term Infants
Toddlers and Prepubertal Children
Special Issues
References
Chapter 37. Adolescence and Acquisition of Peak Bone Mass
Introduction
Pubertal Bone Acquisition
Vitamin D in Children and Adolescents
Vitamin D and Intermediate Endpoints of Vitamin D and Bone Metabolism
Vitamin D and Other Predictors of Calcium Retention
Vitamin D and Bone
Vitamin D and Muscle
Sex and Racial Differences
Vitamin D and Diabetes
Vitamin D, Asthma, and Influenza
Vitamin D Requirements in Adolescents
Summary and Conclusions
References
Chapter 38. Vitamin D Metabolism in Pregnancy and Lactation
Introduction
Adaptations in Vitamin D and Calcium Metabolism
Changes in Bone Mineral Content and Density
Low Maternal Vitamin D During Pregnancy
Effect of Low Maternal Vitamin D During Lactation on the Infant
Potential Risk of High Maternal Vitamin D During Pregnancy
Conclusions
References
Chapter 39. Vitamin D: Relevance in Reproductive Biology and Pathophysiological Implications in Reproductive Dysfunction
Introduction
Procreative Relevance – Animal Models
Vitamin D – Relevance in Human Reproductive Physiology
References
Chapter 40. Vitamin D and the Renin-Angiotensin System
Introduction
The Renin-Angiotensin System
Vitamin D Regulation of the Renin-Angiotensin System
Vitamin D, Blood Pressure and Heart Disease
Vitamin D and Chronic Kidney Disease
Conclusion
References
Chapter 41. Parathyroid Hormone, Parathyroid Hormone-Related Protein, and Calcitonin
Parathyroid Hormone
Parathyroid-Hormone-Related Protein
Calcitonin
References
Chapter 42. FGF23/Klotho New Regulators of Vitamin D Metabolism
Introduction
Regulation of Vitamin D Metabolism
PTH–Vitamin D Axis: Key Regulator of Calcium Homeostasis
FGF23 Klotho Bone Kidney Axis: A Pathway Coordinating Phosphate and Vitamin D Homeostasis with Bone Mineralization
Relationship Beween FGF23 and PTH
Role of FGF23 in Phosphate Homeostasis
Hormonal Actions of klotho?
How Knowledge of FGF23 Regulation and Function Changes Concepts, Treatments, and Clinical Practice
Conclusion
References
Chapter 43. The Role of the Vitamin D Receptor in Bile Acid Homeostasis
Introduction
Bile Acids in Physiology and Disease
VDR as a Bile Acid Receptor
Regulation of Bile Acid Synthesis by VDR
Evolution of VDR: From Bile Acid Metabolism to Mineral Homeostasis
References
Chapter 44. Vitamin D and Fat
Introduction
Vitamin D Metabolism and Mechanism of Action
Vitamin D Deficiency and Adiposity
Vitamin D and Obesity: Clinical Implication
References
Chapter 45. Extrarenal 1α-Hydroxylase
Introduction
Vitamin D and Granuloma-Forming Disease: a Historical Perspective
Human Diseases With Extrarenal Overproduction of Active Vitamin D Metabolites
Extrarenal Synthesis of 1,25(OH)2D in Normal Physiology and Cancer
Mechanisms for the Regulation of Extrarenal 1α-Hydroxylase
Diagnosis, Prevention, and Treatment of the Patient with Endogenous Vitamin D Intoxication
Conclusions and Future Prospects
References
Section VI: Diagnosis and Management
Chapter 46. Approach to the Patient with Metabolic Bone Disease
Introduction
Diagnostic Evaluation
Treatment
Conclusion
Acknowledgments
References
Chapter 47. Detection of Vitamin D and Its Major Metabolites
Introduction
Detection of Vitamin D
Detection of 25(OH)D
Detection of 24,25(OH)2D
Detection of 1,25(OH)2D
Clinical Interpretation and Relevance of Antirachitic Sterol Measurements
Stability of 25(OH)D and 1,25(OH)2D in Serum or Plasma
Assessment of Assay Performance
References
Chapter 48. Bone Histomorphometry
Introduction
Bone Biopsy
Histomorphometry
Assessment of Mineralization
Histological Diagnosis of Osteomalacia
Assessment of Bone Turnover
Assessment of Remodeling Balance
Assessment of Bone Structure
Future Developments
References
Chapter 49. Radiology of Rickets and Osteomalacia
Introduction and Historical Aspects
Vitamin D Deficiency
Renal Osteodystrophy
Renal Tubular Defects and Hypophosphatemia
Acidemia
Differential Diagnoses
Vitamin D Intoxication
Technical Aspects of Imaging
Conclusions
References
Chapter 50. High-Resolution Imaging Techniques for Bone Quality Assessment
Introduction
X-ray Computed Tomography (CT)
Magnetic Resonance Imaging (MRI)
References
Chapter 51. The Role of Vitamin D in Orthopedic Surgery
Introduction
Impact on Orthopedic Trauma
Impact on Pediatric Orthopedics
Impact on Total Joint Arthroplasty
Impact on Muscle Strength and Rehabilitation
Prevention and Treatment in Orthopedic Patients
References
Section VII: Nutrition, Sunlight, Genetics and Vitamin D Deficiency
Chapter 52. Worldwide Vitamin D Status
Introduction
Vitamin D Status in North America (Including Canada and Mexico)
Vitamin D Status in South America
Vitamin D Status in Europe
Vitamin D Status in the Middle East
Vitamin D Status in Asia
Vitamin D Status in Africa
Vitamin D Status in Oceania
Multicenter and Global Studies using a Central Laboratory Facility
Ethnicity/Migration
Nutrition
Risk Groups
Implications
Conclusions
References
Chapter 53. Sunlight, Vitamin D and Prostate Cancer Epidemiology
Introduction
Types of Epidemiologic Studies
Subclinical Prostate Cancer is Prevalent and May Dilute Effects in Epidemiologic Studies
Prostate Cancer and the Vitamin D Hypothesis
1,25(OH)2D is Synthesized by Normal Prostate Epithelial Cells and its Synthesis is Reduced in Prostate Cancer Cells
Ecologic Studies of Sunlight and Prostate Cancer
Studies of Prostate Cancer and VDR Polymorphisms
Serological Studies of the Vitamin D Deficiency Hypothesis
Epidemiologic Studies of Sun Exposure and Prostate Cancer
Epidemiologic Studies of Calcium and Prostate Cancer
Conclusions
References
Chapter 54. Nutrition and Lifestyle Effects on Vitamin D Status
Introduction
Determinants of Vitamin D Status
Factors Influencing Skin Synthesis Supplying Vitamin D
Nutrient Intake as Determinant of Vitamin D Status
Lifestyle Strategies to Improve Vitamin D Status
References
Chapter 55. Bone Loss, Vitamin D and Bariatric Surgery: Nutrition and Obesity
Background
Epidemiology of Bariatric Surgery
Indications for Bariatric Surgery
Classification of Bariatric Surgery
Surgical Complications of Bariatric Surgery
Health Benefits of Bariatric Surgery
Medical Complications of Bariatric Surgery
Bone Loss After Gastric Bypass
Vitamin D Status
Calcium Malabsorption after Gastric Bypass Surgery
Evidence of Efficacy of Supplemental Vitamin D
Conclusion
Acknowledgment
References
Chapter 56. Genetics of the Vitamin D Endocrine System
Introduction
Genetic Studies
Candidate Genes
Genome-wide Association Studies
Future Developments
References
Chapter 57. The Pharmacology of Vitamin D
Introduction
Overview of the System of Vitamin D Metabolism and its Regulation
Placebo-Controlled Clinical-Trial Justification for an Optimal Serum 25(Oh)D Level
Dosage Considerations
Pharmacokinetic Principles, Volume of Distribution, Turnover and Half-Life as it Pertains to Vitamin D
Vitamin D Toxicity and Safety Issues
The Concept of a Loading Dose
Summary and Conclusions
References
Chapter 58. How to Define Optimal Vitamin D Status
Introduction
Vitamin D Status and Bone Health in Adults and The Elderly
Vitamin D and Extra-Skeletal Health
Vitamin D and Human Health: What is The Optimal Vitamin D Status
References
Volume II
Section VIII: Disorders
Chapter 59. The Hypocalcemic Disorders: Differential Diagnosis and Therapeutic Use of Vitamin D
Physiology
Differential Diagnosis of Hypocalcemia
Therapy for Hypocalcemia
Acknowledgments
References
Chapter 60. Vitamin D Deficiency and Nutritional Rickets in Children
Introduction
Historical Perspective
The Epidemiology of Vitamin D Deficiency and Nutritional Rickets
Clinical Presentation
Biochemical Abnormalities
Radiologic Changes
The Growth Plate in Rickets
Treatment and Prevention
Dietary Calcium Deficiency
The Pathogenetic Spectrum of Nutritional Rickets
Conclusions
References
Chapter 61. Vitamin D and Osteoporosis
Effects of Vitamin D on the Skeleton
The Role of Vitamin D Genetic Factors in Osteoporosis and Possible Interactions with Vitamin D Therapy
Primary Fracture Prevention with Vitamin D or Calcium and Vitamin D
Secondary Fracture Prevention with Vitamin D or Calcium and Vitamin D
Effects of Active Vitamin D Analogs on Fractures
Future Directions for Vitamin D in Osteoporosis
References
Chapter 62. Relevance of Vitamin D Deficiency in Adult Fracture and Fall Prevention
Muscle Effects of Vitamin D
Vitamin D Modulates Fracture Risk in Two Ways: By Increasing Bone Density and Decreasing Falls
Anti-fall and Fracture Efficacy of Vitamin D
Desirable 25(OH)D Status for Optimal Musculoskeletal Health
Dosing Interval of Vitamin D and Musculoskeletal Health
How to Achieve a Serum Concentration of at Least 75 nmol/l for Musculoskeletal Health
Summary
References
Chapter 63. Clinical Disorders of Phosphate Homeostasis
Introduction
Disorders of Phosphate Homeostasis
Disorders Related to an Altered Phosphate Load
Concluding remarks
References
Chapter 64. Pseudo-vitamin D Deficiency
Introduction
Clinical Manifestations
Biochemical Findings
Genetic and Molecular Studies
Treatment
Evolution of Pddr Under Treatment from Childhood to Adulthood
Conclusion
References
Chapter 65. Hereditary 1,25-Dihydroxyvitamin-D-Resistant Rickets
Introduction
The Clinical Features of HVDRR
Mechanism of 1,25(OH)2D Action
Cellular Basis of HVDRR
Molecular Basis for HVDRR
Therapy of HVDRR
Alopecia
Concluding Remarks
References
Chapter 66. Glucocorticoids and Vitamin D
Mechanisms of GlucocorticoId Osteoporosis
Steroid Receptors and Actions in Bone
Glucocorticoids, Vitamin D, and Inflammation
Effect of Glucocorticoids on Vitamin D Metabolism
Vitamin D as Treatment for Gio
Summary
References
Chapter 67. Drug and Hormone Effects on Vitamin D Metabolism
Introduction
Hormone Effects on Vitamin D Metabolism
Drug Effects on Vitamin D Metabolism
Conclusion
References
Chapter 68. Vitamin D and Organ Transplantation
Introduction
Effects of Vitamin D on Immunity and Graft Rejection
Vitamin D Deficiency Prior to Organ Transplant
Vitamin D Deficiency Following Organ Transplant
Treatment of Post-Transplant Bone Loss with Vitamin D and Analogs
Conclusions
References
Chapter 69. Vitamin D and Bone Mineral Metabolism in Hepatogastrointestinal Diseases
Physiologic Considerations
Gastrointestinal Diseases
Pancreatic Diseases
Hepatic Diseases
Total Parenteral Nutrition
References
Chapter 70. Vitamin D and Renal Disease
Introduction
Renal Maintenance of the Vitamin D Endocrine System
Contribution of the low 25(OH)D and 1,25(OH)2D Levels and Abnormal VDR Actions to Mineral and Skeletal Abnormalities, Renal, and Cardiovascular Damage
Safety and Efficacy of Vitamin D And 1,25(OH)2D Therapy to Improve Outcomes in Chronic Renal Failure
Adequacy of Current Recommendations to Correct Vitamin D Deficiency
Summary
Acknowledgments
References
Chapter 71. Idiopathic Hypercalciuria and Nephrolithiasis
Introduction
Idiopathic Hypercalciuria
Genetic Hypercalciuric Rats
Current View of Human Genetic Hypercalciuria
Therapeutics of Idiopathic Hypercalciuria and Effects on Calcium Metabolism
Risk of Stone Formation Using Vitamin D Analogs
Summary
References
Chapter 72. Hypercalcemia Due to Vitamin D Toxicity
Introduction
Forms of Exogenous Vitamin D Toxicity
Forms of Endogenous Vitamin D Toxicity
Mechanisms of Vitamin D Toxicity
Clinical Manifestations
Diagnosis of Vitamin D Toxicity
Treatment of Vitamin D Toxicity
Summary and Conclusions
References
Chapter 73. Vitamin D: Cardiovascular Effects and Vascular Calcification
Introduction
Vitamin D Signaling In Cardiovascular Remodeling And Myocardial Function
Vitamin D Actions In Atherosclerosis And Arteriosclerosis
Vitamin D and Human Cardiovascular Disease: Compelling Epidemiology and Physiology, Emerging but Less Compelling Evidence of Interventional Benefit in 2010
Vitamin D Intoxication and Cardiovascular Calcification: Pharmacological Considerations
The Impact of Calcium, Phosphate, and Vitamin D Excesses on Smooth Muscle Matrix Vesicle Physiology and Vascular Calcification
The FGF23/Klotho/Vitamin D Axis, Nephrocalcinosis, and Cardiovascular Calcification
Vitamin D, Vascular PTH Receptor Signaling and Arteriosclerotic Calcium Accrual: Lessons Learned from Preclinical Models and Patients with End-Stage Renal Disease
Defining Cardiovascular Toxicity Thresholds for Vitamin D: Critical Clues from the Clinical Literature
Vitamin D, The Calcium-Sensing Receptor (Casr), And Cardiovascular Disease
Summary, Conclusions, and Future Directions
Acknowledgment
References
Section IX: Analogs
Chapter 74. Alterations in 1,25-Dihydroxyvitamin D3 Structure that Produce Profound Changes in in Vivo Activity
Introduction
The Non-Calcemic Holy Grail of Vitamin D Analogs
Analogs Directed to Specific Structures
Summary
Acknowledgment
References
Chapter 75. Mechanisms for the Selective Actions of Vitamin D Analogs
Introduction
Identification of Selective Vitamin D Analogs
The In VIVO Selectivity of Vitamin D Analogs is Determined by Multiple Protein Interactions
Concluding Remarks
References
Chapter 76. Analogs of Calcitriol
Introduction
14-epi Analogs of 1,25(OH)2D3
Decalin Analogs
C- and D-ring Analogs
CF-ring Analogs
E-ring Analogs
Acyclic Analogs
Non-Secosteroidal Compounds
Conclusion
References
Chapter 77. Analogs for the Treatment of Osteoporosis
Introduction
Alfacalcidol
Eldecalcitol
Clinical Comparison Between Alfacalcidol and Eldecalcitol
Conclusion
Acknowledgments
References
Chapter 78. Non-secosteroidal Ligands and Modulators
Introduction
Diarylmethane Ligands
C/D-Ring Modified Ligands
Bis- and Tris-Aromatic Triols
Miscellaneous non-Secosteroids
Perspectives
References
Chapter 79. The Bile Acid Derivatives Lithocholic Acid Acetate and Lithocholic Acid Propionate are Functionally Selective Vitamin D Receptor Ligands
The Vitamin D Receptor is a Dual-Functional Receptor for Vitamin D and Bile Acids
Bile Acids and Nuclear Receptors
Development of Bile Acid Derivatives
X-Ray Crystal Structures of VDR in Complex with LCA Derivatives
Perspectives
References
Chapter 80. CYP24A1 Regulation in Health and Disease
Introduction
CYP24A1: Properties, Function and Expression
Regulation of CYP24A1 mRNA Expression and Stability
Dysregulation of CYP24A1 and Role in the Pathogenesis of Human Disease
CYP24A1 Inhibitors
Conclusion and Future Directions
References
Chapter 81. Calcitriol and Analogs in the Treatment of Chronic Kidney Disease
Introduction
Analogs of Vitamin D used in CKD
Analogs in Animal Models of Uremia
CKD Stages 3–4
ESRD
Cardiovascular Disease in CKD and Different Forms of Vitamin D
Conclusions
References
Section X: Cancer
Chapter 82. The Epidemiology of Vitamin D and Cancer Risk
Introduction
Overview of Epidemiologic Study Designs for the Study of Vitamin D and Cancer
Studies of 25(OH)D, Predicted 25(OH)D, Vitamin D intake and Cancer Risk by Cancer Site
Studies of Sun Exposure
Randomized Controlled Trials
Mortality/Survival
Summary and Synthesis of The Epidemiology of Vitamin D and Cancer
References
Chapter 83. Vitamin D: Cancer and Differentiation
Introduction
Vitamin D and Cancer
Vitamin D Effects on Tumor Cells
Combination Therapy
Resistance and Vitamin D Metabolism
Stimulation of Proliferation
Conclusions
References
Chapter 84. Vitamin D Effects on Differentiation and Cell Cycle
Introduction
Induction of Differentiation by 1,25(OH)2D3 and its Analogs
Cell Cycle Consequences of Vitamin-D-Induced Differentiation
Cell-Type Specificity of Inhibition of Cell Proliferation by Vitamin D and Analogs without Evidence of Differentiation
Conclusions
Acknowledgments
References
Chapter 85. Vitamin D Actions in Mammary Gland and Breast Cancer
Introduction
Vitamin D Actions on Breast Cancer Cells in Vitro
Determinants of Breast Cancer Sensitivity to Vitamin D
Vitamin D Metabolites and Analogs: Preclinical and Clinical Trials
Vitamin D and Prevention of Breast Cancer
Summary and Outstanding Research Questions
References
Chapter 86. Vitamin D and Prostate Cancer
Introduction
Prostate as a Target for Vitamin D
Vitamin D and Inhibition of Prostate Cancer Growth
Vitamin D Analogs and Prostate Cancer
Mechanisms of the Anti-Cancer Actions of Calcitriol
The Role of Calcitriol in Prostate Cancer Chemoprevention
Calcitriol in Combination with other Agents
Clinical Trials
Summary and Conclusions
References
Chapter 87. The Vitamin D System and Colorectal Cancer Prevention
Colorectal Cancer Epidemiology and Pathogenesis
Vitamin D and Colorectal Cancer Pathogenesis
Colonic Synthesis of 1,25(OH)2D3
Regulation of CYP27b1 and of CYP24a1 Expression by Nutrition
Acknowledgments
References
Chapter 88. Hematological Malignancy
Introduction
Overview of Hematopoiesis
Effects of Vitamin D Compounds on Normal Hematopoiesis
Effects of Vitamin D Compounds in Leukemic Cells
Vitamin D Analogs Activity Against Leukemic Cells
Conclusions
References
Chapter 89. Vitamin D and Skin Cancer
Two Sources of Vitamin D: Diet or Sunlight
Vitamin D and Indoor Tanning
UV Exposure Contributes to NMSC and Melanoma Development
Vitamin D and Visceral Cancer Risk and its Potential Role in Reducing Skin Cancer Risk
Role of Vitamin D in Keratinocytes
Role of Vitamin D in Squamous Cell Carcinomas (SCC)
Role of Vitamin D in Basal Cell Carcinomas (BCC)
Role of Vitamin D in Melanomas
Photoprotection and Vitamin D Levels
Conclusions
References
Chapter 90. The Anti-tumor Effects of Vitamin D in Other Cancers
Introduction
Thyroid Cancer
Bone and Soft Tissue Sarcomas
Melanoma
Gastro-Esophageal Cancers
Lung Cancers
Hepatocellular Carcinoma (HCC)
Bladder Cancer
Gliomas
Head and Neck
Renal Cell Carcinoma
Pancreatic Cancer
Conclusions
References
Section XI: Immunity, Inflammation, and Disease
Chapter 91. Vitamin D and Innate Immunity
Introduction and Historical Background
VDR Gene Polymorphisms and Infectious Diseases
Molecular Events Underlying Innate Immune Regulation by Vitamin D
Physiological and Pathophysiological Ramifications of 1,25(OH)2D3-Regulated Camp Expression
Conclusions and Future Directions
References
Chapter 92. Control of Adaptive Immunity by Vitamin D Receptor Agonists
Introduction
Vitamin D Receptor Agonists as Immunoregulatory Agents
Dendritic Cells as Targets for Immunoregulation by VDR Agonists
Induction of Tolerogenic Dendritic Cells by VDR Agonists
Modulation of T and B Lymphocytes by VDR Agonists
Vitamin D Deficiency in Autoimmune Diseases
Mechanisms for the Immunomodulatory Effects Of VDR Agonists in Autoimmune Diseases
References
Chapter 93. The Role of Vitamin D in Innate Immunity: Antimicrobial Activity, Oxidative Stress and Barrier Function
Innate Immunity
Immune Activity of 1,25-Dihydroxyvitamin D
Vitamin D Pathway and Tuberculosis
History of Vitamin D, Sunshine, and Tuberculosis
References
Chapter 94. Vitamin D and Diabetes
Introduction
Vitamin D and the Beta Cell
Vitamin D and the Immune System in Type 1 Diabetes
Vitamin D and Genetic Predisposition to Diabetes
Clinical Perspectives
References
Chapter 95. Vitamin D and Multiple Sclerosis
The Vitamin D–Multiple Sclerosis Hypothesis
Original Evidence Underlying the Vitamin D–Multiple Sclerosis Hypothesis
Multiple Sclerosis Etiology and the Association with Vitamin D
Genetic Evidence Linking Vitamin D and Multiple Sclerosis
Experimental Autoimmune Encephalomyelitis, A Multiple Sclerosis Model
Vitamin D and Prevention of EAE
Mechanisms of EAE Prevention
Vitamin D Amelioration of Established EAE
Mechanisms of EAE Amelioration
Multiple Sclerosis, Pregnancy, and Immune Tolerance
Vitamin D, Estrogen, EAE, and Multiple Sclerosis
Vitamin-D-Based Therapy of Multiple Sclerosis
Conclusions and Future Research Directions
Acknowledgments
References
Chapter 96. Vitamin D and Inflammatory Bowel Disease
Introduction
What is IBD?
Who Gets IBD?
The “Hygiene Hypothesis”
The “Vitamin D Hypothesis”
The Immune Response and IBD
Vitamin D Regulates T Cell Responsiveness
Experimental Models of IBD
Current Treatments for IBD
Vitamin D as a Treatment Option for IBD
References
Chapter 97. Psoriasis and Other Skin Diseases
Introduction/Historical Overview
Pathogenesis of Psoriasis
The Vitamin D System in Normal and Psoriatic Skin
Physiological and Pharmacological Actions of Vitamin D Analogs in Normal and Psoriatic Skin
Clinical use of Calcitriol in Psoriasis
Vitamin D Analog Therapy in Other Skin Diseases
Conclusion
References
Section XII: Therapeutic Applications and New Advances
Chapter 98. The Role of Vitamin D in Type 2 Diabetes and Hypertension
Epidemiology and Burden of Type 2 Diabetes and Hypertension
Biologic Plausibility of an Association Between Vitamin D and Type 2 Diabetes and Hypertension
Evidence from Human Studies for a Link Between Vitamin D and Type 2 Diabetes
Evidence from Human Studies for a Link Between Vitamin D and Hypertension
Summary of Evidence from Human Studies on Type 2 Diabetes and Hypertension and Limitations in the Study of Vitamin D
Optimal Intake of Vitamin D in Relation to Type 2 Diabetes and Hypertension
Conclusions
References
Chapter 99. Vitamin D Receptor Agonists in the Treatment of Benign Prostatic Hyperplasia
Benign Prostatic Hyperplasia: an Introduction
Pathogenesis of BPH
Medical Treatment for BPH
Vitamin D Receptor Agonists Control Prostate Cell Growth
Vitamin D Receptor Agonists and BPH-Related Luts
Vitamin D Receptor Agonists Inhibit Intraprostatic Inflammation
Vitamin D Receptor Agonists Modulate Prostatic Urethra Dysfunction
Concluding Remarks
References
Chapter 100. Sunlight Protection by Vitamin D Compounds
Introduction
UV-Induced DNA Damage and Repair
UV-Induced Immune Suppression
Photocarcinogenesis
Local Production of Vitamin D Metabolites in Skin
Vitamin D Compounds and Photoprotection
Mechanisms of Photoprotection
Perspectives on Future Use of Vitamin D Compounds for Sun Protection
References
Chapter 101. The Role of Vitamin D in Osteoarthritis and Rheumatic Disease
Osteoarthritis
Hyaline Cartilage in OA
Bone Health and OA
The Synovium
Vitamin D Receptor (VDR) Genotype and OA Progression
Vitamin D Status and OA Progression
Rheumatoid Arthritis
Systemic Lupus Erythematosus (SLE)
Psoriatic Arthritis (PsA)
Conclusions
References
Chapter 102. Vitamin D and Cardiovascular Disease
Introduction
Components of Direct Cardiovascular Effects
Components of Indirect Cardiovascular Effects
Cardio- and Cerebrovascular Mortality as Endpoint in Observational and Interventional Studies
Clinical Cardiovascular Outcomes in Observational and Randomized Interventional Studies
Situation in Patients With Chronic Kidney Disease or on Hemodialysis
Summary and Conclusions
References
Chapter 103. Vitamin D, Childhood Wheezing, Asthma, and Chronic Obstructive Pulmonary Disease
Introduction
Common Respiratory Disorders
Vitamin D and Respiratory Infection
Vitamin D and Asthma
Vitamin D and COPD
Potential Mechanisms
Future Research on Vitamin D and Respiratory/Allergic Disorders
Summary
Acknowledgments
References
Chapter 104. Vitamin D and Skeletal Muscle Function
Introduction
Myopathy
Physical Performance
Falls
Muscle Morphology
Molecular Mechanisms of Action
VDR Knockout Mouse Model
VDR Polymorphisms
PTH
Conclusion
References
Chapter 105. The VITamin D and OmegA-3 TriaL (VITAL): Rationale and Design of a Large-Scale Randomized Controlled Trial
Introduction
Biology of Vitamin D and Proposed Mechanisms for Lowering Cancer and CVD Risk
Current Evidence on Vitamin D and Risk of Cancer and CVD
Rationale for VITAL
Rationale for the Selected Vitamin D Dose in VITAL
Core Aspects of Trial Design
Trial Eligibility
Recruitment, Enrollment, Run-in and Randomization
Characteristics of Participants in VITAL
Detailed Assessment of Dietary and Supplement Intake in VITAL
Blood Collections in VITAL
Follow-up and Enpoint Determination Procedures
Monitoring of Compliance
Trial Monitoring and Safety
Statistical Power
Vital Value: Ancillary Studies and Establishment of a Clinical and Translational Science Center Sub-Cohort
Key Points
References
Color Plates
Color Plates
Index
DF
JP
JA