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Vitamin D: Two-Volume Set
Автор: Academic Press
Активность, связанная с книгой
Начать чтениеДлина: 7,221 стр.76 ч
- Издатель:
- Academic Press
- Издано:
- May 12, 2011
- ISBN:
- 9780123819796
- Формат:
- Книге
Описание
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.
*Most comprehensive, up-to-date two-volume set on Vitamin D
*Initial chapters cover the chemistry and metabolism of vitamin D, role in mineralization, other target organs, and general physiological effects
*Second volume is more clinically oriented addressing deficiency problems (including diagnosis, interactions in the endocrine system, and involvement in malignancies)
*Further sections on emerging uses for treatments of auto-immune diseases and diabetes
*New chapters on squamous cell cancer, brain cancer, thyroid cancer and many more
*Over 600 illustrations and figures available on CD
*Most comprehensive, up-to-date two-volume set on Vitamin D
*Initial chapters cover the chemistry and metabolism of vitamin D, role in mineralization, other target organs, and general physiological effects
*Second volume is more clinically oriented addressing deficiency problems (including diagnosis, interactions in the endocrine system, and involvement in malignancies)
*Further sections on emerging uses for treatments of auto-immune diseases and diabetes
*New chapters on squamous cell cancer, brain cancer, thyroid cancer and many more
*Over 600 illustrations and figures available on CD
Активность, связанная с книгой
Начать чтениеСведения о книге
Vitamin D: Two-Volume Set
Автор: Academic Press
Длина: 7,221 стр.76 ч
Описание
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.
*Most comprehensive, up-to-date two-volume set on Vitamin D
*Initial chapters cover the chemistry and metabolism of vitamin D, role in mineralization, other target organs, and general physiological effects
*Second volume is more clinically oriented addressing deficiency problems (including diagnosis, interactions in the endocrine system, and involvement in malignancies)
*Further sections on emerging uses for treatments of auto-immune diseases and diabetes
*New chapters on squamous cell cancer, brain cancer, thyroid cancer and many more
*Over 600 illustrations and figures available on CD
*Most comprehensive, up-to-date two-volume set on Vitamin D
*Initial chapters cover the chemistry and metabolism of vitamin D, role in mineralization, other target organs, and general physiological effects
*Second volume is more clinically oriented addressing deficiency problems (including diagnosis, interactions in the endocrine system, and involvement in malignancies)
*Further sections on emerging uses for treatments of auto-immune diseases and diabetes
*New chapters on squamous cell cancer, brain cancer, thyroid cancer and many more
*Over 600 illustrations and figures available on CD
- Издатель:
- Academic Press
- Издано:
- May 12, 2011
- ISBN:
- 9780123819796
- Формат:
- Книге
Связано с Vitamin D
Отрывок книги
Vitamin D
Vitamin D
Third Edition
Volume I
Editor-in-Chief
David Feldman
Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
Associate Editors
J. Wesley Pike
Department of Biochemistry, University of Wisconsin, Madison, WI, USA
John S. Adams
UCLA-Orthopaedic Hospital Department of Orthopaedic Surgery, University of California, Los Angeles, CA, USA
Vitamin D
Third Edition
Volume II
Editor-in-Chief
David Feldman
Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
Associate Editors
J. Wesley Pike
Department of Biochemistry, University of Wisconsin, Madison, WI, USA
John S. Adams
UCLA-Orthopaedic Hospital Department of Orthopaedic Surgery, University of California, Los Angeles, CA, USA
Table of Contents
Cover image
Title page
Title page_1
Copyright
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
Copyright
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Preface to the 3rd Edition
The 3rd edition of Vitamin D was written at a time of great interest, exuberant hype, and even commotion in the public and lay press about vitamin D as a potential drug to treat and/or prevent multiple important and common diseases. Recent noteworthy events impacting the vitamin D field were the launching of the VITAL trial to discover whether vitamin D supplementation can reduce the risk of severe and life-threatening disease and the Institute of Medicine (IOM) report setting new dietary reference intakes (DRIs) for calcium and vitamin D. The IOM report expressed doubt on how well current data supported the beneficial actions of vitamin D on nonskeletal sites and called for more research to prove the hypothesis. This volume marshals the currently available data on basic mechanisms, normal physiology, and effects on disease and lays out for the reader up-to-date and expert information on the role of vitamin D in health and many disorders. These and other current trends in vitamin D research are extensively covered in this new edition.
The editors have continued our basic plan to constantly renew and remodel this book with each successive edition. To this end, we have added a new editor, Dr. John Adams, who has broad skill and knowledge in many areas of vitamin D research at both the basic science and clinical levels. John replaces Francis Glorieux who has undertaken to edit a separate book on pediatric bone disease. We thank Francis for his years of exemplary service to this book and wish him well in his new endeavors. John adds new energy and expertise to the editorial team.
The 3rd edition has 105 chapters, making the book approximately the same size as the 2nd edition. However, the editors have worked very hard to revise and update this edition with new material and the presentation of fresh and different perspectives from respected authors. Some chapters covered in the 2nd edition have not been continued in this edition because relatively little new research was added in those areas. We thank the authors who are no longer contributing to this edition for their previous efforts. They may well be asked to write in the next edition as we continue our strategy of rotating authors. All chapters have been revised and updated and new references added. In our revitalization of the material in the book we have added 32 new chapters to cover previously uncovered areas of research. In addition, we have changed the authorship of 20 additional chapters that are now written by different authors who have been charged with revising and updating previous chapters. These extensive modifications, with major updates and expansion of the content and the addition of totally new material in half of the chapters, has resulted in a substantially reorganized, modified, and modernized book compared to the 2nd edition. Finally, the expanded internet availability of the text and the figures will make access to the material easier and more flexible.
Among the areas given new emphasis are nutrition, additional diseases that may be affected by vitamin D, and newly recognized biological pathways that regulate or are regulated by vitamin D. As we appreciate the full scope of vitamin D action, it has become clearer that the vitamin D endocrine system affects most if not all tissues in the body. We have tried to keep up with these advances in the state of knowledge about vitamin D by increasing our coverage of these newly recognized areas. We have enlisted the leading investigators in each area to provide truly expert opinion about each field.
We would like to thank the excellent team at Elsevier/Academic Press for their outstanding support of our efforts to produce this new edition. We especially thank Mara Conner and Megan Wickline for their indispensable contributions to make this edition possible. We also want to extend our thanks and appreciation to the many authors who contributed to this volume. Without their hard work there of course would be no new edition. We therefore wish to express our gratitude for their willingness to offer their time and knowledge to make this book a success. Finally, we hope that this book will provide for our readers the authoritative information that they seek about the significance and importance of vitamin D in health and disease and serve as the means to keep their knowledge current about the continuing growth of the field of vitamin D biology.
David Feldman
J. Wesley Pike
John S. Adams
Preface to the 2nd Edition
Those interested in the vitamin D field will not be surprised that this second edition is considerably larger than the first edition. A great deal of progress has been made since the first edition was published in 1997. However, our goal in planning this updated version remains the same. We have endeavored to provide investigators, clinicians, and students with a comprehensive, definitive, and up-to-date compendium of the diverse scientific and clinical aspects of vitamin D, each area covered by experts in the field. Our hope for the second edition is that this book will continue to serve as both a resource for current researchers, as well as a guide to assist those in related disciplines to enter the realm of vitamin D research. We hope that this book will illuminate the vitamin D field and help investigators identify areas where new research is needed as well as educate them about what is currently known. We believe that the first edition succeeded in stimulating interactions between researchers and clinicians from different disciplines and that it facilitated collaborations. As we move from basic science and physiology to the use of vitamin D and its analogs as pharmacological agents to treat various diseases, the need for cross-collaborations between researchers and clinicians from different disciplines will increase. We hope that this new volume will continue to be a valuable resource that plays a role in this advancement and stimulates and facilitates these interactions.
Enormous progress in the study of vitamin D has been made in the approximately eight years since the first edition was written and we hope that this book has contributed in some way to this progress. The first edition proved to be highly valuable to its readers and the chapters have been cited frequently as authoritative reviews of the field. However, it became clear to us that the time was ripe to organize a second edition. Building on the original, we hope this second edition will incorporate all of the progress made in the field since the first edition was published so that our objective of an up-to-date compendium containing everything you wanted to know about vitamin D will continue.
The second edition is essentially a new and reinvigorated book. We have changed the symbol on the cover to reflect its updated content and the field’s continued evolution into the molecular world. This new edition now includes 104 chapters. In order to cover the growth of new information on vitamin D, we have had to publish this new edition in two volumes. In addition, the book has undergone some major remodeling. There are 33 completely new chapters and 18 other chapters have had major changes in authorship and are totally rewritten. While approximately half of the chapters have some of the same authors, all have had major updates and many have new co-authors with new perspectives. We have endeavored to attract the leading investigators in each field to author the chapter covering their area. We are especially pleased with the roster of authors who have written for the second edition. They really are the leaders in their respective fields.
We wish to express our thanks to Tari Paschall, Judy Meyer, and Sarah Hajduk as well as the rest of the Elsevier/Academic Press staff for their expertise and indispensable contribution to bringing this revised edition to fruition. Most of all, we thank the authors for their contributions. We hope that our readers will find this updated volume useful and informative and that it will contribute to the burgeoning growth of the vitamin D field.
David Feldman
J. Wesley Pike
Francis H. Glorieux
Preface to the 1st Edition
Our reasons for deciding to publish an entire book devoted to vitamin D can be found in the rapid and extensive advances currently being made in this important field of research. Enormous progress in investigating many aspects of vitamin D, from basic science to clinical medicine, has been made in recent years. The ever-widening scope of vitamin D research has created new areas of inquiry so that even workers immersed in the field are not fully aware of the entire spectrum of current investigation. Our goal in planning this book was to bring the diverse scientific and clinical fields together in one definitive and up-to-date volume. It is our hope that this compendium on vitamin D will serve as both a resource for current researchers and a guide to stimulate and assist those in related disciplines to enter this field of research. In addition, we hope to provide clinicians and students with a comprehensive source of information for the varied and extensive material related to vitamin D.
The explosion of information in the vitamin D sphere has led to new insights into many different areas, and in our treatment of each subject in this book we have tried to emphasize the recent advances as well as the established concepts. The classic view of vitamin D action, as a hormone limited to calcium metabolism and bone homeostasis, has undergone extensive revision and amplification in the past few years. We now know that the vitamin D receptor (VDR) is present in most tissues of the body and that vitamin D actions, in addition to the classic ones, include important effects on an extensive array of other target organs. To cover this large number of subjects, we have organized the book in the following manner: Section I, the enzymes involved in vitamin D metabolism and the activities of the various metabolites; Section II, the mechanism of action of vitamin D, including rapid, nongenomic actions and the role of the VDR in health and disease; Section III, the effects of vitamin D and its metabolites on the various elements that constitute bone and the expanded understanding of vitamin D actions in multiple target organs, both classic and nonclassic; Section IV, the role of vitamin D in the physiology and regulation of calcium and phosphate metabolism and the multiplicity of hormonal, environmental, and other factors influencing vitamin D metabolism and action; and Sections V and VI, the role of vitamin D in the etiology and treatment of rickets, osteomalacia, and osteoporosis and the pathophysiological basis, diagnosis, and management of numerous clinical disorders involving vitamin D.
The recent recognition of an expanded scope of vitamin D action and the new investigational approaches it has generated were part of the impetus for developing this volume on vitamin D. It has become clear that in addition to the classic vitamin D actions, a new spectrum of vitamin D activities that include important effects on cellular proliferation, differentiation, and the immune system has been identified. This new information has greatly expanded our understanding of the breadth of vitamin D action and has opened for investigation a large number of new avenues of research that are covered in Sections VII and VIII of this volume. Furthermore, these recently recognized nonclassic actions have led to a consideration of the potential application of vitamin D therapy to a range of diseases not previously envisioned. This therapeutic potential has spawned the search for vitamin D analogs that might have a more favorable therapeutic profile, one that is less active in causing hypercalcemia and hypercalciuria while more active in a desired application such as inducing antiproliferation, prodifferentiation, or immunosuppresion. Since 1α,25-dihydroxyvitamin D [1,25(OH)2D] and its analogs are all presumed to act via a single VDR, a few years ago most of us probably would have thought that it was impossible to achieve a separation of these activities. Yet today, many analogs that exhibit different profiles of activity relative to 1,25(OH)2D have already been produced and extensively studied. The development of analogs with an improved therapeutic index has opened another large and complex area of vitamin D research. This work currently encompasses three domains: (1) the design and synthesis of vitamin D analogs exhibiting a separation of actions with less hypercalcemic and more antiproliferative or immunosuppressive activity, (2) the interesting biological question of the mechanism(s) by which these analogs achieve their differential activity, and (3) the investigation of the potential therapeutic applications of these analogs to treat various disease states. These new therapeutic applications, from psoriasis to cancer, from immunosuppression to neurodegenerative diseases, have drawn into the field an expanded population of scientists and physicians interested in vitamin D.
Our goal in editing this book was to create a comprehensive resource on vitamin D that would be of use to a mix of researchers in different disciplines. To achieve this goal, we sought authors who had contributed greatly to their respective fields of vitamin D research. The book has a large number of chapters to accommodate many contributors and provide expertise in multiple areas. Introductory chapters in each section of the book are designed to furnish an overview of that area of vitamin D research, with other chapters devoted to a narrowly focused subject. Adjacent and closely related subjects are often covered in separate chapters by other authors. While this intensive style may occasionally create some redundancy, it has the advantage of allowing the reader to view the diverse perspectives of the different authors working in overlapping fields. In this regard, we have endeavored to provide many cross-references to guide the reader to related information in different chapters.
We express our thanks to Jasna Markovac (Editor-in-Chief), for encouraging us to develop this book and guiding us through the process; to Tari Paschall (Acquisitions Editor) and the Academic Press staff for their diligence, expertise, and patience in helping us complete this work. Most of all, we thank the authors for their contributions that have made this book possible.
David Feldman
Francis H. Glorieux
J. Wesley Pike
Contributors
Steven A. Abrams, USDA/ARS Children’s Nutrition Research Center, Houston, TX, USA (647)
John S. Adams, UCLA-Orthopaedic Hospital, Los Angeles, CA, USA (251, 777)
Judith E. Adams, Manchester Royal Infirmary, Manchester, UK and Imaging Science and Biomedical Engineering, The University, Manchester, UK (861)
Luciano Adorini, Intercept Pharmaceuticals, Perugia, Italy (1789, 1931)
Paul H. Anderson, SA Pathology, Adelaide, South Australia, Australia and University of South Australia, Adelaide, South Australia, Australia (411)
Lenore Arab, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA (1009)
Gerald J. Atkins, University of Adelaide, Adelaide, South Australia, Australia (411)
Ariane Berdal, Universities Paris 5, Paris 6 and Paris 7, Paris, France and Rothchild Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France (521)
Ishir Bhan, Massachusetts General Hospital, Boston, MA, USA (1555)
Daniel Bikle, Veterans Affairs Medical Center and University of California, San Francisco, CA, USA (1299)
John P. Bilezikian, Columbia University College of Physicians and Surgeons, New York, NY, USA (1381)
Heike Bischoff-Ferrari, University of Zurich, Switzerland and University Hospital Zurich, Switzerland (1145)
Adele L. Boskey, Hospital for Special Surgery, affiliated with Weil College of Cornell Medical School, New York, NY, USA (381)
Roger Bouillon, Laboratory of Experimental Medicine and Endocrinology, K.U. Leuven, Leuven, Belgium (57, 1067, 1461)
Barbara D. Boyan, Georgia Institute of Technology, Atlanta, GA, USA (507)
Alex J. Brown, Washington University School of Medicine, St. Louis, MO, USA (1437)
Edward M. Brown, Brigham and Women’s Hospital, Boston, MA, USA (425)
Danny Bruce, The Pennsylvania State University, University Park, PA, USA (1879)
Andrew J. Burghardt, University of California, San Francisco, CA, USA (891)
Thomas Burne, The Park Centre for Mental Health, Wacol, Australia and University of Queensland, St. Lucia, Australia (565)
Mona S. Calvo, US Food and Drug Administration, Laurel, MD, USA (979)
Carlos A. Camargo Jr., Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA (1999)
Margherita Cantorna, The Pennsylvania State University, University Park, PA, USA (1879)
Carsten Carlberg, University of Luxembourg, Luxembourg and University of Eastern Finland, Kuopio, Finland (211)
Thomas O. Carpenter, Yale University School of Medicine, New Haven, CT, USA (1091)
Matthew W. Carson, Lilly Research Laboratories, Indianapolis, IN, USA (1497)
Lisa Ceglia, Tufts University, Boston, MA, USA (2023)
Hong Chen, Emory University School of Medicine, Atlanta, GA, USA (251)
Songcang Chen, University of California at San Francisco, San Francisco, CA, USA (541)
Sylvia Christakos, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ, USA (363)
Fredric L. Coe, The University of Chicago Pritzker School of Medicine, Chicago, IL, USA (1359)
Juliet Compston, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK (845)
Heide S. Cross, Retired, Medical University of Vienna, Austria (1711)
Natalie E. Cusano, Columbia University College of Physicians and Surgeons, New York, NY, USA (1381)
Bess Dawson-Hughes, Tufts University, Boston, MA, USA (1145, 1907)
Pierre De Clercq, Universiteit Gent, Vakgroep voor Organische Chemie, Gent, Belgium (1461)
Hector DeLuca, University of Wisconsin-Madison, WI, USA (1429)
Michael Danilenko, Ben-Gurion University of the Negev, Beer-Sheva, Israel (1625)
Valentin David, University of Tennessee Health Science Center, Memphis, TN, USA (747)
Hector F. Deluca, University of Wisconsin-Madison, Madison, WI, USA (3)
Marie B. Demay, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA (533)
Francisco J.A. de Paula, Maine Medical Center Research Institute and Department of Internal Medicine, School of Medicine of Ribeirão Preto, USP, Ribeirão Preto, SP, Brazil (769)
Vianney Descroix, Universities Paris 5, Paris 6 and Paris 7, Paris, France and Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, Paris France (521)
Puneet Dhawan, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ, USA (363)
Katie M. Dixon, University of Sydney, NSW, Australia (1943)
Harald Dobnig, Medical University of Graz, Graz, Austria (1973)
Jeffrey A. Dodge, Lilly Research Laboratories, Indianapolis, IN, USA (1497)
Eve Donnelly, Hospital for Special Surgery, affiliated with Weil College of Cornell Medical School, New York, NY, USA (381)
Maryam Doroudi, Georgia Institute of Technology, Atlanta, GA, USA (507)
Diane R. Dowd, Case Western Reserve University, Cleveland, OH, USA (193)
Marc K. Drezner, William H. Middleton Veterans Administration Medical Center, Madison, WI, USA (1155)
Adriana S. Dusso, Experimental Nephrology Laboratory, Lleida, Spain (1325)
Peter R. Ebeling, University of Melbourne, Victoria, Australia (1129)
Thomas Edouard, Shriners Hospital for Children, Montreal, Quebec, Canada (1187)
Guy Eelen, Katholieke Universiteit Leuven, Leuven, Belgium (1461)
John A. Eisman, Garvan Institute of Medical Research, Sydney, Australia (1129)
Tina Epps, Cytochroma Inc., Markham, Ontario, Canada (1525)
Ervin H. Epstein Jr., Children’s Hospital Oakland Research Institute, Oakland, CA, USA (1751)
Sol Epstein, Mount Sinai School of Medicine, New York, NY, USA (1245)
Darryl Eyles, The Park Centre for Mental Health, Wacol, Australia and University of Queensland, St. Lucia, Australia (565)
Mary C. Farach-Carson, Rice University, Houston, TX, USA (457)
Murray J. Favus, The University of Chicago Pritzker School of Medicine, Chicago, IL, USA (1359)
David Feldman, Stanford University School of Medicine, Stanford, CA, USA (1197, 1591, 1675)
David M. Findlay, University of Adelaide, Adelaide, South Australia, Australia (411)
James C. Fleet, Purdue University, West Lafayette, IN, USA (349)
Renny T. Franceschi, University of Michigan, Ann Arbor, MI, USA (321)
Ryoji Fujiki, University of Tokyo, Tokyo, Japan (227)
David G. Gardner, University of California at San Francisco, San Francisco, CA, USA (541)
Adit A. Ginde, University of Colorado Denver School of Medicine, Aurora, CO, USA (1999)
Edward Giovannucci, Harvard School of Public Health, Boston, MA, USA and Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA (1569)
Denis J. Glenn, University of California at San Francisco, San Francisco, CA, USA (541)
Francis H. Glorieux, Shriners Hospital for Children, Montreal, Quebec, Canada (1187)
Elzbieta Gocek, University of Wroclaw, Wroclaw, Poland (1625)
David Goltzman, McGill University and Royal Victoria Hospital of the McGill University Health Centre, Montreal, Quebec, Canada (583)
José Manuel González-Sancho, Universidad Autónoma de Madrid, Madrid, Spain (235)
Clare Gordon-Thomson, University of Sydney, NSW, Australia (1943)
Conny Gysemans, Katholieke Universiteit Leuven, Leuven, Belgium (1825)
Karen E. Hansen, University of Wisconsin, Madison, WI, USA (1155)
Carol A. Haussler, University of Arizona, Phoenix, AZ, USA (137)
Mark R. Haussler, University of Arizona, Phoenix, AZ, USA (137)
Colleen E. Hayes, University of Wisconsin-Madison, Madison, WI, USA (1843)
Robert P. Heaney, Creighton University, Omaha, NE, USA (607)
Christian Helvig, Cytochroma Inc., Markham, Ontario, Canada (1525)
Geoffrey N. Hendy, McGill University and Royal Victoria Hospital of the McGill University Health Centre, Montreal, Quebec, Canada (583)
Martin Hewison, UCLA-Orthopaedic Hospital, Los Angeles, CA, USA (251, 777)
Arnold Lippert Hirsch, AGD Nutrition LLC, Lewisville, Texas, USA (73)
Michael F. Holick, Boston Medical Center and Boston University School of Medicine, Boston, MA, USA (13, 1891)
Bruce W. Hollis, Medical University of South Carolina, Charleston, SC, USA (823)
Elizabeth Holt, Yale University School of Medicine, New Haven, CT, USA (725)
Jui-Cheng Hsieh, University of Arizona, Phoenix, AZ, USA (137)
Karl L. Insogna, Yale University School of Medicine, New Haven, CT, USA (1091)
Candace Johnson, Roswell Park Cancer Institute, Buffalo, NY, USA (1763)
Glenville Jones, Queen’s University, Kingston, Ontario, Canada (23)
Peter W. Jurutka, Arizona State University at the West Campus, Glendale, AZ, USA (137)
Heidi J. Kalkwarf, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA (679)
Shigeaki Kato, University of Tokyo, Tokyo, Japan (227)
Steven A. Kliewer, University of Texas Southwestern Medical Center, Dallas, TX, USA (763)
H. Phillip Koeffler, Division of Hematology and Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA and National University of Singapore, Singapore (1731)
Hannelie Korf, Katholieke Universiteit Leuven, Leuven, Belgium (1825)
Alexander Kouzmenko, University of Tokyo, Tokyo, Japan and Alfaisal University, Riyadh, Kingdom of Saudi Arabia (227)
Christopher S. Kovacs, Memorial University of Newfoundland, Health Sciences Centre, St. John’s, Newfoundland, Canada (625)
Barbara E. Kream, University of Connecticut Health Center, Farmington, CT, USA (403)
Richard Kremer, McGill University and Royal Victoria Hospital of the McGill University Health Centre, Montreal, Quebec, Canada (583)
Aruna V. Krishnan, Stanford University School of Medicine, Stanford, CA, USA (1675)
Roland Krug, University of California, San Francisco, CA, USA (891)
Noboru Kubodera, Chugai Pharmaceutical Co., Ltd, Tokyo, Japan, present address: International Institute of Active Vitamin D Analogs (1489)
Rajiv Kumar, Mayo Clinic and Foundation, Rochester, MN, USA (471)
Emma M. Laing, University of Georgia, Athens, GA, USA (657)
Joseph M. Lane, Hospital for Special Surgery, New York, NY, USA (927)
María Jesús Larriba, Consejo Superior de Investigaciońes Cientificas (235)
Seong Min Lee, University of Wisconsin-Madison, Madison, WI, USA (97)
Richard D. Lewis, University of Georgia, Athens, GA, USA (657)
Yan Li, University of Michigan, Ann Arbor, MI, USA (321)
Yan Chun Li, The University of Chicago, Chicago, IL, USA (707)
Jane B. Lian, University of Massachusetts Medical School, Worcester, MA, USA (301)
Alexander C. Lichtler, University of Connecticut Health Center, Farmington, CT, USA (403)
Paul Lips, VU University Medical Center, Amsterdam, The Netherlands (947)
Philip T. Liu, University of California at Los Angeles, CA, USA (1811)
Thomas S. Lisse, UCLA-Orthopaedic Hospital, Los Angeles, CA, USA (251)
Yanfei L. Ma, Lilly Research Laboratories, Indianapolis, IN, USA (1497)
Paul N. MacDonald, Case Western Reserve University, Cleveland, OH, USA (193)
Leila Mady, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ, USA (363)
Mario Maggi, University of Florence, Florence, Italy (1931)
Sharmila Majumdar, University of California, San Francisco, CA, USA (891)
Makoto Makishima, Nihon University School of Medicine, Tokyo, Japan (1509)
Peter J. Malloy, Stanford University School of Medicine, Stanford, CA, USA (1197)
David J. Mangelsdorf, University of Texas Southwestern Medical Center, Dallas, TX, USA (763)
Jonathan M. Mansbach, Children’s Hospital Boston, Harvard Medical School, Boston, MA, USA (1999)
JoAnn E. Manson, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA (2043)
Rebecca S. Mason, University of Sydney, NSW, Australia (1943)
Chantal Mathieu, Katholieke Universiteit Leuven, Leuven, Belgium (1825)
Christopher G. Mayne, Medical College of Wisconsin, Milwaukee, WI, USA (1843)
Timothy M. McAlindon, Tufts Medical Center and Tufts University School of Medicine, Boston, Massachusetts (1955)
John McGrath, The Park Centre for Mental Health, Wacol, Australia and University of Queensland, St. Lucia, Australia (565)
Mark B. Meyer, University of Wisconsin-Madison, Madison, WI, USA (97)
Mathew T. Mizwicki, University of California, Riverside, CA, USA (271)
Muriel Molla, Universities Paris 5, Paris 6 and Paris 7, Paris, France and Rothchild Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France (521)
Martin Montecino, Universidad Andres Bello, Santiago, Chile (301)
Dino Moras, Université de Strasbourg, 67404 Illkirch, France (171)
Annamaria Morelli, University of Florence, Florence, Italy (1931)
Howard A. Morris, SA Pathology, Adelaide, South Australia, Australia and University of South Australia, Adelaide, South Australia, Australia (411)
Alberto Muñoz, Consejo Superior de Investigaciońes Cientificas, Madrid, Spain (1591)
Mark S. Nanes, Emory University School of Medicine, Atlanta, GA, USA (251)
Faye E. Nashold, University of Wisconsin-Madison, Madison, WI, USA (1843)
Tally Naveh-Many, Hadassah Hebrew University Medical Center, Hadassah Hospital, Jerusalem, Israel (493)
Wei Ni, University of California at San Francisco, San Francisco, CA, USA (541)
Corwin D. Nelson, University of Wisconsin-Madison, Madison, WI, USA (1843)
Anthony W. Norman, University of California, Riverside, CA, USA (271)
Fumiaki Ohtake, University of Tokyo, Tokyo, Japan (227)
Ryoko Okamoto, Division of Hematology and Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA (1731)
Olivia I. Okereke, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA (2043)
Lubna Pal, Yale University School of Medicine, New Haven, CT, USA (695)
Martin Petkovich, Cytochroma Inc., Markham, Ontario, Canada and Queen’s University, Kingston, Ontario, Canada (1525)
John M. Pettifor, University of the Witwatersrand and Chris Hani Baragwanath Hospital, South Africa (1107)
J. Wesley Pike, University of Wisconsin-Madison, Madison, WI, USA (97)
Anastassios G. Pittas, Tufts Medical Center, Boston, MA, USA (1907)
Lori A. Plum, University of Wisconsin-Madison, WI, USA (1429)
David E. Prosser, Queen’s University, Kingston, Ontario, Canada (23)
L. Darryl Quarles, University of Tennessee Health Science Center, Memphis, TN, USA (747)
Brian J. Rebolledo, Weill Cornell Medical College, New York, NY, USA (927)
Jörg Reichrath, Universitätsklinikum des Saarlandes, Homburg, Germany (1891)
Natacha Rochel, Université de Strasbourg, Illkirch, France (171)
Clifford J. Rosen, School of Medicine of Ribeirão Preto, USP, Ribeirão Preto, SP, Brazil (769)
F. Patrick Ross, Washington University School of Medicine, St. Louis, MO, USA (335)
Philip Sambrook, University of Sydney, Sydney, NSW, Australia (1233)
Daniel R. Schmidt, University of Texas Southwestern Medical Center, Dallas, TX, USA (763)
Ryan D. Schoch, Purdue University, West Lafayette, IN, USA (349)
Gary G. Schwartz, Wake Forest University School of Medicine, Winston-Salem, NC, USA (965)
Zvi Schwartz, Georgia Institute of Technology, Atlanta, GA, USA (507)
Vanessa Sequeira, University of Sydney, NSW, Australia (1943)
Elizabeth Shane, Columbia University College of Physicians & Surgeons, New York, NY, USA (1291)
M. Kyla Shea, Wake Forest University School of Medicine, Winston-Salem, NC, USA (1955)
Justin Silver, Hadassah Hebrew University Medical Center, Hadassah Hospital, Jerusalem, Israel (493)
Robert U. Simpson, University of Michigan Medical School, Ann Arbor, MI, USA (2203)
Linda Skingle, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK (845)
Eduardo Slatopolsky, Washington University School of Medicine, St. Louis, MO, USA (1325)
Harald Sourij, Medical University of Graz, Graz, Austria (1973)
Justin A. Spanier, University of Wisconsin-Madison, Madison, WI, USA (1843)
Bonny L. Specker, South Dakota State University, Brookings, SD, USA (679)
René St-Arnaud, Shriners Hospital for Children, Montreal, Quebec, Canada and McGill University, Montreal, Quebec Canada (43, 1187)
Keith R. Stayrook, Indiana University School of Medicine, Indianapolis, IN, USA (1497)
Emily M. Stein, Columbia University College of Physicians & Surgeons, New York, NY, USA (1291)
Gary S. Stein, University of Massachusetts Medical School, Worcester, MA, USA (301)
Janet L. Stein, University of Massachusetts Medical School, Worcester, MA, USA (301)
George P. Studzinski, UMD-New Jersey Medical School, Newark, NJ, USA (1625)
Fumiaki Takahashi, Chugai Pharmaceutical Co., Ltd, Tokyo, Japan (1489)
Jean Y. Tang, Stanford University School of Medicine, Stanford, CA, USA (1751)
Hugh S. Taylor, Yale University School of Medicine, New Haven, CT, USA (695)
Peter Tebben, Mayo Clinic and Foundation, Rochester, MN, USA (471)
Ravi Thadhani, Massachusetts General Hospital, Boston, MA, USA (1555)
Natalie W. Thiex, South Dakota State University, Brookings, SD, USA (679)
William R. Thompson, University of Delaware, Newark, DE, USA (457)
Susan Thys-Jacobs, Columbia University College of Physicians and Surgeons, New York, NY, USA (1381)
Dov Tiosano, Meyer Children’s Hospital, Rambam Medical Center, Haifa, Israel (1197)
Dwight A. Towler, Washington University in St. Louis, St. Louis, MO, USA (1403)
Donald Trump, Roswell Park Cancer Institute, Buffalo, NY, USA (1763)
André G. Uitterlinden, Erasmus Medical Center, Rotterdam, The Netherlands (1025)
Aasis Unnanuntana, Hospital for Special Surgery, New York, NY, USA and Siriraj Hospital, Mahidol University, Bangkok, Thailand (927)
Maurits Vandewalle, Universiteit Gent, Vakgroep voor Organische Chemie, Gent, Belgium (1461)
Marjolein van Driel, Erasmus Medical Center, Rotterdam, The Netherlands (1591)
Johannes P.T.M. van Leeuwen, Erasmus Medical Center, Rotterdam, The Netherlands (1591)
Andre J. van Wijnen, University of Massachusetts Medical School, Worcester, MA, USA (301)
Natasja van Schoor, VU University Medical Center, Amsterdam, The Netherlands (947)
Lieve Verlinden, Katholieke Universiteit Leuven, Leuven, Belgium (1461)
Annemieke Verstuyf, Laboratorium voor Experimentele Geneeskunde en Endocrinologie, Leuven, Belgium (1461)
Reinhold Vieth, University of Toronto, Toronto, Canada and Mount Sinai Hospital, Toronto, Canada (1041)
Connie M. Weaver, Purdue University, West Lafayette, IN, USA (657)
Barrie M. Weinstein, Mount Sinai School of Medicine, New York, NY, USA (1245)
JoEllen Welsh, University at Albany, Rensselaer, NY, USA (1657)
John H. White, McGill University, Montreal, Canada (1777)
G. Kerr Whitfield, University of Arizona, Phoenix, AZ, USA (137)
Susan J. Whiting, University of Saskatchewan, Saskatoon, Saskatchewan, Canada (979)
Michael P. Whyte, Shriners Hospital for Children and Washington University School of Medicine
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