Vitamin D

Vitamin D

Two-Volume Set

3rd Edition - May 12, 2011

Write a review

  • Editors: David Feldman, J. Wesley Pike, John Adams
  • eBook ISBN: 9780123819796

Purchase options

Purchase options
DRM-free (Mobi, EPub, PDF)
Sales tax will be calculated at check-out

Institutional Subscription

Free Global Shipping
No minimum order

Description

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, pediatrics, nephrology, dermatology, immunology, and genetics. This 3e includes over 100 chapters covering everything from chemistry and metabolism to mechanisms of action, diagnosis and management, new analogs, and emerging therapies. This complete reference works is a must-have resource for anyone working in endocrinology, osteology, bone biology, or cancer research.

Readership

Bone specialists, endocrinologists, basic scientists and researchers interested in vitamin D and osteoporosis prevention.

Table of Contents

  • 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

Product details

  • No. of pages: 2144
  • Language: English
  • Copyright: © Academic Press 2011
  • Published: May 12, 2011
  • Imprint: Academic Press
  • eBook ISBN: 9780123819796

About the Editors

David Feldman

David Feldman, MD, is Emeritus Professor of Medicine (Active) at Stanford University School of Medicine where he has been on the faculty since 1974. He has been a full professor since 1984 and was chief of the Endocrinology Division for 10 years. His laboratory studies the role of steroid hormone receptors, particularly the vitamin D receptor, and its mechanism of action. His current major research focus is hormone-dependent cancer including breast cancer and prostate cancer and the pathways by which vitamin D inhibits cancer growth. Professor Feldman is actively involved in both basic science approaches to the anti-cancer actions of vitamin D as well as to clinical trials studying the use of vitamin D in breast and prostate cancer. Professor Feldman was recently honored with an award for a Career of Outstanding Contributions to Vitamin D Research. He has authored over 290 medical research articles, reviews, editorials, and book chapters. In addition to being a co-editor of all four editions of OSTEOPOROSIS, he is the editor-in-chief of Vitamin D, just published in its third edition.

Affiliations and Expertise

Emeritus Professor of Medicine, Stanford University School of Medicine, Stanford, California, USA

J. Wesley Pike

Dr. Pike’s laboratory is focused on the molecular mechanisms whereby vitamin D, the sex steroids, and other systemic hormones regulate the production as well as cellular activity of bone-forming osteoblasts and bone-resorbing osteoclasts. A long-term area of interest has been in the actions of vitamin D. His laboratory has shown that these actions are mediated by a specific receptor that is localized to the nucleus of target cells and which functions as a transcription factor following activation by its hormonal vitamin D ligand. This research led to the molecular cloning of this factor and elucidation of its regulation and mechanism of action.

Affiliations and Expertise

Professor, Department of Biochemistry, University of Wisconsin, Madison, USA

John Adams

Affiliations and Expertise

Vice Chair for Research, UCLA-Orthopaedic Hospital Department of Orthopaedic Surgery Director, Orthopaedic Hospital Research Center, University of California, Los Angeles

Ratings and Reviews

Write a review

There are currently no reviews for "Vitamin D"