Vitamin D

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. 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.

• VOLUME ONESECTION I: CHEMISTRY, METABOLISM, CIRCULATION 1 Historical Overview of Vitamin DHector F. Deluca2 Photobiology of Vitamin D Michael F. Holick3 The Activating Enzymes of Vitamin D Metabolism (25- and 1a-Hydroxylases)Glenville Jones and David E. Prosser4 CYP24A1: Structure, Function, and Physiological RoleRene St. Arnaud5 The Vitamin D Binding Protein: DBPRoger Bouillon 6 Industrial Aspects of Vitamin D Arnold L. HirschSECTION II: MECHANISMS OF ACTION7 VDR J. Wesley Pike8 Nuclear Vitamin D Receptor: Natural Ligands, Molecular Structure-Function, and Transcriptional Control of Vital Genes Mark R. Haussler, Carol A. Haussler, Jui-Cheng Hsieh, Peter W. Jurutka, and G. Kerr Whitfield9 Structural Basis for Ligand Activity in VDRDino Moras and Natacha Rochel10 Coregulators of VDR-mediated Gene Expression Paul McDonald and Diane R. Dowd11 Target Genes of Vitamin D: Spatio-temporal Interaction of Chromatin, VDR and Response Elements Carsten Carlberg12 Epigenetic Modifications in Vitamin D Receptor Mediated TransrepressionShigeaki Kato, Alexander Kouzmenko, Fumiaki Ohtake, and Ryoji Fujiki13 Vitamin D and Wnt/ß-Catenin SignalingAlbert Munoz, José Manuel González-Sancho, and María Jesús Larriba14 Vitamin D Response Element Binding Protein John S. Adams, Thomas S. Lisse, Hong Chen, Mark S. Nanes, and Martin Hewison15 Vitamin D Sterol/VDR Conformational Dynamics and Nongenomic ActionsAnthony W. Norman and Mathew T. MizwickiSECTION III: MINERAL AND BONE HOMEOSTASIS 16 Development of the SkeletonJane B. Lian, Gary S. Stein, Martin Montecino, Janet L. Stein, Andre J. van Wijnen17 Vitamin D Regulation of Osteoblast FunctionRenny Franchesci and Yan Li18 OsteoclastsF. Patrick Ross19 Molecular Mechanisms for Regulation of Intestinal Calcium and Phosphate Absorption by Vitamin DJames Fleet and Ryan D. Schoch20 The Calbindins: Calbindin-D28K and Calbindin-D9K and the Epithelial Calcium Channels TRPV5 and TRPV6 Sylvia Christakos, Leila Mady, and Puneet Dhawan21 MineralizationAdele Boskey and Eve Donnelly22 VITAMIN D Regulation of Type I Collagen Expression in Bone Barbara Kream and Alexander Lichtler23 Target Genes: Bone Proteins Howard Morris, Paul H. Anderson, Gerald J. Atkins, and David M. Findlay24 Vitamin D and the Calcium-Sensing Receptor Edward M. Brown25 Effects of 1,25-Dihydroxyvitamin D3 on Voltage-Sensitive Calcium Channels in Osteoblast Differentiation and Morphology Mary Farach-Carson and William R. ThompsonSECTION IV: TARGETS26 Vitamin D and the KidneyRajiv Kumar and Peter Tebben27 Vitamin D and the Parathyroids Justin Silver and Tally Neveh-Many28 Cartilage Barbara D. Boyan, Maryam Doroudi and Zvi Schwartz29 Vitamin D and Oral Heath Ariane Berdal, Muriel Molla, Vianney Descroix30 The Role of Vitamin D and its Receptor in Skin and Hair Follicle BiologyMarie B. Demay31 Vitamin D and the Cardiovascular SystemDavid Gardner, Songcang Chen, Denis Glenn, and Wei Ni32 Vitamin D: A Neurosteroid Affecting Brain Development and Function; Implications for Neurological and Psychiatric DisordersJohn McGrath, Darryl Eyles, and Thomas Burne33 Contributions of Genetically Modified Mouse Models to Understanding the Physiology and Pathophysiology of the 25-hydroxyvitamin D-1-alpha Hydroxylase Enzyme [1a(OH)ase] and the Vitamin D Receptor (VDR) David Goltzman, Geoffrey N. Hendy, and Richard KremerSECTION V: HUMAN PHYSIOLOGY34 Vitamin D: Role in the Calcium and Phosphorus EconomiesRobert P. Heaney35 Fetus, Neonate and InfantChris Kovacs36 Vitamin D Deficiency and Calcium Absorption During Childhood Steven A. Abrams37 Adolescence and Acquisition of Peak Bone MassConnie Weaver, Rick Lewis, and Emma Liang38 Vitamin D Metabolism in Pregnancy and Lactation Bonny Specker, Natalie W. Thiex, and Heidi J. Kalkwarf 39 Vitamin D: Relevance in Reproductive Biology and Pathophysiological Implications in Reproductive DysfunctionHugh S. Taylor and Lubna Pal40 Vitamin D and the Renin-Angiotensin System Yan Chun Li41 Parathyroid Hormone, Parathyroid Hormone-Related Protein and CalcitoninJohn J. Wysolmerski and Elizabeth Holt42 FGF23/Klotho New Regulators of Vitamin D Metabolism L. Darryl Quarles and Valentin David43 The Role of the Vitamin D Receptor in Bile Acid HomeostasisDavid J. Mangelsdorf, Daniel R. Schmidt, Steven A. Kliewer44 Vitamin D and FatClifford J. Rosen and Francisco J. A. de Paula45 Extra-renal 1a-hydroxylase Martin Hewison and John S. AdamsSection VI: Diagnosis and Management 46 Approach to the Patient Michael P. Whyte47 Detection of Vitamin D and Its Major MetabolitesBruce W. Hollis48 Bone HistomorphometryJuliet E. Compston and Linda Skingle49 Radiology Judith E. Adams50 High-Resolution Imagine Techniques for Bone Quality AssessmentSharmila Majumdar, Andrew J. Burghardt, and Roland Krug51 The Role of Vitamin D in Orthopaedic SurgeryJoseph M. Lane, Aasis Unnanuntana, and Brian J. RebolledoSECTION VII: NUTRITION, SUNLIGHT, GENETICS, AND VITAMIN D DEFICIENCY52 Worldwide Vitamin D StatusPaul Lips and Natasja van Schoor53 Sunlight, Vitamin D and Prostate Cancer Epidemiology Gary G. Schwartz54 Nutrition and lifestyle effects on vitamin D status Susan J. Whiting and Mona S. Calvo55 Bone Loss, Vitamin D and Bariatric Surgery: Nutrition, Obesity and Bariatric Surgery Lenore Arab and Ian Yip56 Genes and Risk of DiseaseAndré G. Uitterlinden57 The Pharmacology of Vitamin D Reinhold Vieth58 How to Define Optimal Vitamin D Status?Roger Bouillon VOLUME TWOSECTION VIII: DISORDERS59 The Hypocalcemic Disorders: Differential Diagnosis and Therapeutic Use of Vitamin DThomas O. Carpenter and Karl L. Insogna60 Vitamin D Deficiency and Nutritional Rickets in ChildrenJohn M. Pettifor61 Vitamin D and OsteoporosisPeter R. Ebeling and John A. Eisman62 Relevance of Vitamin D Deficiency in Adult Fracture and Fall Prevention Heike Bischoff-Ferrari and Bess Dawson-Hughes63 Clinical Disorders of Phosphate HomeostasisMarc K. Drezner and Karen E. Hansen64 Pseudo-vitamin D Deficiency Francis H. Glorieux, Thomas Edouard, and René St-Arnaud65 Hereditary 1,25-Dihydroxyvitamin D Resistant RicketsPeter J. Malloy, David Feldman, and Dov Tiosano66 Glucocorticoids and Vitamin D Philip Sambrook67 Drug and Hormone Effects on Vitamin D MetabolismSol Epstein and Barrie M. Weinstein68 Vitamin D and Organ TransplantationElizabeth Shane and Emily M. Stein69 Vitamin D and Bone Mineral Metabolism in Hepatogastrointestinal Diseases Daniel Bikle70 Vitamin D and Renal Disease Adriana S. Dusso and Eduardo Slatopolsky71 Idiopathic Hypercalciuria and NephrolithiasisMurray J. Favus and Fredric L. Coe72 Hypercalcemia Due to Vitamin D ToxicityJohn P. Bilezikian, Natalie E. Cusano, and Susan Thys-Jacobs73 Vitamin D: Cardiovascular Effects and Vascular Calcification Dwight A. TowlerSECTION IX: ANALOGS74 New AnalogsHector DeLuca and Lori A. Plum75 Mechanisms for the Selective Actions of Vitamin D AnalogsAlex J. Brown 76 Analogs of Calcitriol Annemieke Verstuyf, Pierre De Clercq, Roger Bouillon, Lieve Verlinden, Guy Eelen, and Maurits Vandewalle77 Analogs and Fx PreventionNoboru Kubodera and Fumiaki Takahashi78 Non-Secosteroidal Ligands and ModulatorsKeith R. Stayrook, Yanfei L. Ma, Matthew W. Carson, and Jeffrey A. Dodge79 The bile acid derivatives lithocholic acid acetate and lithocholic acid propionate are functionally selective vitamin D receptor ligands Makoto Makishima and Sachiko Yamada80 CYP24A1 Regulation in Health and DiseaseMartin Petkovich, Tina Epps, and Christian Helvig81 Calcitriol and Analogs in the Treatment of Chronic Kidney DiseaseRavi Thadhani and Ishir BhanSECTION X: CANCER82 The Epidemiology of Vitamin D and Cancer RiskEdward Giovannucci83 Vitamin D: Cancer and Differentiation Johannes P. T. M. van Leeuwen, Alberto Munoz, Marjolein van Driel, and David Feldman84 Vitamin D Effects on Differentiation and Cell CycleGeorge P. Studzinski, Elzbieta Gocek, and Michael Danilenko85 Vitamin D Actions in Mammary Gland and Breast Cancer Joellen Welsh86 Vitamin D and Prostate CancerDavid Feldman and Aruna V. Krishnan87 The VITAMIN D System and Colorectal Cancer PreventionHeide S. Cross88 Hematological MalignancyH. Phillip Koeffler and Ryoko Okamoto89 Vitamin D and Skin Cancer Jean Y. Tang and Ervin H. Epstein90 The Anti-Tumor Effects of Vitamin D in Other CancersDonald Trump and Candace JohnsonSECTION XI: IMMUNITY, INFLAMMATION, AND DISEASE 91 Vitamin D and Innate ImmunityJohn H. White92 Control of Adaptive Immunity by Vitamin D Receptor AgonistsLuciano Adorini93 The role of vitamin D in innate immunity: Antimicrobial Activity, Oxidative Stress and Barrier FunctionPhilip T. Liu94 Vitamin D and DiabetesChantal Mathieu, Conny Gysemans, and Hannelie Korf95 Vitamin D and Multiple SclerosisColleen E. Hayes, Faye E. Nashold, Justin A. Spanier, Corwin D. Nelson, and Christopher G. Mayne96 Vitamin D and Inflammatory Bowel Disease Margherita Cantorna and Danny Bruce97 Psoriasis and other Skin DiseasesJörg Reichrath and Michael F. HolickSECTION XII: THERAPEUTIC APPLICATIONS AND NEW ADVANCES 98 The Role of Vitamin D in Type 2 Diabetes and HypertensionBess Dawson-Hughes and Anastassios G. Pittas99 Vitamin D Receptor Agonists in the Treatment of Benign Prostatic Hyperplasia Mario Maggi, Annamaria Morelli, and Luciano Adorini100 Sunlight protection by Vitamin D CompoundsRebecca S. Mason, Katie M. Dixon, Vanessa Sequiera, and Clare Gordon-Thomas101 The Role of Vitamin D in Osteoarthritis and Rheumatic DiseaseTimothy M. McAlindon and M. Kyla Shea102 Vitamin D and cardiovascular Disease Harald Dobnig and Harald Sourij103 Vitamin D, Childhood Wheezing, Asthma, and Chronic Obstructive Pulmonary DiseaseCarlos A. Camargo, Jonathan Mansbach, and Adit Ginde104 Vitamin D and Skeletal Muscle Function Robert U. Simpson and Lisa Ceglia105 VITAL JoAnn E. Manson

"In this brief review, it is impossible to cover all the nuances of vitamin D addressed in this book. Interested readers may want to peruse the book chapters to assess relevance to their personal interests. I regard this impressive text as a ‘‘must have’’ in the medical libraries of most hospitals. Clinicians and researchers with an interest in vitamin D may want their own personal copy for ready reference. I highly recommend it and congratulate the authors and editors in providing a much needed reference text on arguably one of the more important nutrients to our species." --American Journal of Human Biology"In this remarkable compendium, the editors provide a fresh and comprehensive review of a multifaceted and sometimes controversial vitamin D. This third edition is not just an update, but a greatly expanded work organized to authoritatively cover the evidence for new roles of vitamin D in cardiovascular health, immunity, psychiatric disorders, and much more. In more than 100 chapters, experts span the history of vitamin D, update its molecular mechanism and chemistry, provide specifics of clinical use in disorders of the skeleton, and review progress in an array of diseases including diabetes, inflammatory bowel disease, multiple sclerosis, and psoriasis. In this edition one finds new information for a broad audience including internal medicine, nutrition, orthopedics, basic scientists, and teachers. How does one define optimal vitamin D status? How does vitamin D affect innate immunity? What are the epigenetic modifications of the vitamin D receptor that contribute to its function? Are there other natural ligands for the vitamin D receptor? These are a part of the new increased scope of Vitamin D, Third Edition. If you are interested in vitamin D, you should have this book." --Mark S. Nanes, MD, PhD, Professor of Medicine, Emory University, Atlanta, GA, USA"The Third Edition of the classic text Vitamin D is a superb summary of an important and topical issue. Its contributors are truly experts in the field and they have managed to comprehensively describe the biochemistry, pharmacology and effects of vitamin D as well as to eloquently weave in the relevant biology of bone, muscle, immunology and other relevant tissues. The 105 readable chapters offer a complete and well balanced mix of basic and clinical topics that provides an opportunity to understand the full breadth of vitamin D action. Each section represents an excellent summary of up-to-date information and, as a whole, this text offers an outstanding resource that will appeal to a broad spectrum of readers – from students to established clinicians and investigators." --Eric Orwoll, MD, Department of Medicine, Division of Endocrinology, Diabetes, and Clinical Nutrition, Oregon Health and Science University, Portland, OR, USA"The Third Edition of Vitamin D is well written, comprehensive and balanced. Several of the new chapters, such as Epigenetic Modifications and Wnt/ß-Catenin Signaling, have strayed away from the "traditional" vitamin D but the authors have put these topics very clearly into perspective in ways that will be valuable to those studying vitamin D action. The overall list of authors for this book is a virtual '"who's who" of vitamin D research, and the coverage of the topic is appropriately broad, including those matters in nutrition and epidemiology that have been the subject of much interest in recent years." --T. Jack Martin, AO MD DSC FRACP FRCPA FAA FRS, John Holt Fellow, Emeritus Professor of Medicine, Bone, Joint & Cancer Unit, St Vincent's Institute, Victoria, Australia