Resurrection of vitamin D deficiency and rickets.

The epidemic scourge of rickets in the 19th century was caused by vitamin D deficiency due to inadequate sun exposure and resulted in growth retardation, muscle weakness, skeletal deformities, hypocalcemia, tetany, and seizures. The encouragement of sensible sun exposure and the fortification of milk with vitamin D resulted in almost complete eradication of the disease. Vitamin D (where D represents D2 or D3) is biologically inert and metabolized in the liver to 25-hydroxyvitamin D [25(OH)D], the major circulating form of vitamin D that is used to determine vitamin D status. 25(OH)D is activated in the kidneys to 1,25-dihydroxyvitamin D [1,25(OH)2D], which regulates calcium, phosphorus, and bone metabolism. Vitamin D deficiency has again become an epidemic in children, and rickets has become a global health issue. In addition to vitamin D deficiency, calcium deficiency and acquired and inherited disorders of vitamin D, calcium, and phosphorus metabolism cause rickets. This review summarizes the role of vitamin D in the prevention of rickets and its importance in the overall health and welfare of infants and children.

[1]  M. Holick,et al.  Vitamin D Deficiency in a Healthy Group of Mothers and Newborn Infants , 2007, Clinical pediatrics.

[2]  J. Adams,et al.  Toll-Like Receptor Triggering of a Vitamin D-Mediated Human Antimicrobial Response , 2006, Science.

[3]  A. Litonjua,et al.  Prospective Study Of Maternal Intake Of Vitamin D During Pregnancy And Risk Of Wheezing Illnesses In Children At Age 2 Years , 2006 .

[4]  J. Carlin,et al.  Maternal 25-hydroxyvitamin D and parathyroid hormone concentrations and offspring birth size. , 2006, The Journal of clinical endocrinology and metabolism.

[5]  M. Holick High prevalence of vitamin D inadequacy and implications for health. , 2006, Mayo Clinic proceedings.

[6]  S. Seton Collected Writings: Volume 3a , 2006 .

[7]  C. Modlesky,et al.  Serum 25-hydroxyvitamin D concentrations in girls aged 4-8 y living in the southeastern United States. , 2006, The American journal of clinical nutrition.

[8]  H. Tenenhouse,et al.  Dietary and serum phosphorus regulate fibroblast growth factor 23 expression and 1,25-dihydroxyvitamin D metabolism in mice. , 2005, Endocrinology.

[9]  M. Haussler,et al.  1alpha,25-Dihydroxyvitamin D3 upregulates FGF23 gene expression in bone: the final link in a renal-gastrointestinal-skeletal axis that controls phosphate transport. , 2005, American journal of physiology. Gastrointestinal and liver physiology.

[10]  R. Scragg,et al.  Relationship between serum 25-hydroxyvitamin d and pulmonary function in the third national health and nutrition examination survey. , 2005, Chest.

[11]  F. Tylavsky,et al.  Vitamin D, parathyroid hormone, and bone mass in adolescents. , 2005, The Journal of nutrition.

[12]  C. Cooper,et al.  Developmental origins of osteoporotic fracture: the role of maternal vitamin D insufficiency. , 2005, The Journal of nutrition.

[13]  M. Holick The vitamin D epidemic and its health consequences. , 2005, The Journal of nutrition.

[14]  D. Roth,et al.  Are National Vitamin D Guidelines Sufficient to Maintain Adequate Blood Levels in Children? , 2005, Canadian journal of public health = Revue canadienne de sante publique.

[15]  H. Adami,et al.  Family history of hematopoietic malignancy and risk of lymphoma. , 2005, Journal of the National Cancer Institute.

[16]  M. Holick,et al.  Colon cancer and solar ultraviolet B radiation and prevention and treatment of colon cancer in mice with vitamin D and its Gemini analogs , 2005, The Journal of Steroid Biochemistry and Molecular Biology.

[17]  Edward Giovannucci,et al.  Vitamin D and prevention of colorectal cancer , 2005, The Journal of Steroid Biochemistry and Molecular Biology.

[18]  L. Ben-Porat,et al.  Sun exposure and mortality from melanoma. , 2005, Journal of the National Cancer Institute.

[19]  N. Tandon,et al.  Vitamin D and bone mineral density status of healthy schoolchildren in northern India , 2005 .

[20]  M. Holick VITAMIN D IN HEALTH AND DISEASE: Vitamin D for Health and in Chronic Kidney Disease , 2005, Seminars in dialysis.

[21]  M. Holick,et al.  Adolescent girls in Maine are at risk for vitamin D insufficiency. , 2005, Journal of the American Dietetic Association.

[22]  W. Grant,et al.  Benefits and requirements of vitamin D for optimal health: a review. , 2005, Alternative medicine review : a journal of clinical therapeutic.

[23]  P. Lips,et al.  Estimates of optimal vitamin D status , 2005, Osteoporosis International.

[24]  P. Merkel,et al.  Consensus statement: Guide to bone health and disease in cystic fibrosis , 2005 .

[25]  D. Bikle CHAPTER 35 – Vitamin D: Role in Skin and Hair , 2005 .

[26]  M. Econs CHAPTER 70 – Disorders of Phosphate Metabolism: Autosomal Dominant Hypophosphatemic Rickets, Tumor Induced Osteomalacia, Fibrous Dysplasia, and the Pathophysiological Relevance of FGF23 , 2005 .

[27]  Yan Zhu,et al.  Vitamin D status, 1,25-dihydroxyvitamin D3, and the immune system. , 2004, The American journal of clinical nutrition.

[28]  H. DeLuca Overview of general physiologic features and functions of vitamin D. , 2004, The American journal of clinical nutrition.

[29]  C. Wagner,et al.  Vitamin D requirements during lactation: high-dose maternal supplementation as therapy to prevent hypovitaminosis D for both the mother and the nursing infant. , 2004, The American journal of clinical nutrition.

[30]  C. Barton,et al.  Vitamin D fortification in the United States and Canada: current status and data needs. , 2004, The American journal of clinical nutrition.

[31]  S. Emans,et al.  Prevalence of vitamin D deficiency among healthy adolescents. , 2004, Archives of pediatrics & adolescent medicine.

[32]  M. Saad,et al.  Hypovitaminosis D is associated with insulin resistance and β cell dysfunction , 2004 .

[33]  F. Glorieux,et al.  Resolution of severe, adolescent-onset hypophosphatemic rickets following resection of an FGF-23-producing tumour of the distal ulna. , 2004, Bone.

[34]  R. Vieth Why the optimal requirement for Vitamin D3 is probably much higher than what is officially recommended for adults , 2004, The Journal of Steroid Biochemistry and Molecular Biology.

[35]  C. Wagner,et al.  Assessment of dietary vitamin D requirements during pregnancy and lactation. , 2004, The American journal of clinical nutrition.

[36]  Bess Dawson-Hughes,et al.  Effect of Vitamin D on falls: a meta-analysis. , 2004, JAMA.

[37]  M. Holick,et al.  Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. , 2004, The American journal of clinical nutrition.

[38]  L. C. Stene,et al.  Use of cod liver oil during the first year of life is associated with lower risk of childhood-onset type 1 diabetes: a large, population-based, case-control study. , 2003, The American journal of clinical nutrition.

[39]  M. DeLucia,et al.  Nutritional rickets with normal circulating 25-hydroxyvitamin D: a call for reexamining the role of dietary calcium intake in North American infants. , 2003, The Journal of clinical endocrinology and metabolism.

[40]  Kumaravel Rajakumar,et al.  Vitamin D, cod-liver oil, sunlight, and rickets: a historical perspective. , 2003, Pediatrics.

[41]  J. Bouwes Bavinck,et al.  The influence of painful sunburns and lifetime sun exposure on the risk of actinic keratoses, seborrheic warts, melanocytic nevi, atypical nevi, and skin cancer. , 2003, The Journal of investigative dermatology.

[42]  J. Adams,et al.  Heterogeneous nuclear ribonucleoprotein (hnRNP) binding to hormone response elements: A cause of vitamin D resistance , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[43]  F. Greer,et al.  Prevention of rickets and vitamin D deficiency: new guidelines for vitamin D intake. , 2003, Pediatrics.

[44]  P. Dhawan,et al.  New insights into the mechanisms of vitamin D action , 2003, Journal of cellular biochemistry.

[45]  P. Malloy,et al.  Hereditary 1,25-Dihydroxyvitamin D-resistant rickets. , 1997, Endocrine development.

[46]  G. Tenderich,et al.  Low vitamin D status: a contributing factor in the pathogenesis of congestive heart failure? , 2003, Journal of the American College of Cardiology.

[47]  A. Ponsonby,et al.  Ultraviolet radiation and autoimmune disease: insights from epidemiological research. , 2002, Toxicology.

[48]  Shu Q. Liu,et al.  1,25-Dihydroxyvitamin D3 is a negative endocrine regulator of the renin-angiotensin system , 2002 .

[49]  B. Dawson-Hughes,et al.  Serum 25-hydroxyvitamin D status of adolescents and adults in two seasonal subpopulations from NHANES III. , 2002, Bone.

[50]  C. Mathieu,et al.  The coming of age of 1,25-dihydroxyvitamin D(3) analogs as immunomodulatory agents. , 2002, Trends in molecular medicine.

[51]  W. Grant An estimate of premature cancer mortality in the U.S. due to inadequate doses of solar ultraviolet‐B radiation , 2002, Cancer.

[52]  S. Khosla,et al.  Minireview: the OPG/RANKL/RANK system. , 2001, Endocrinology.

[53]  Elina Hyppönen,et al.  Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study , 2001, The Lancet.

[54]  M. Podgornik,et al.  Pseudo‐(Tumor‐Induced) Rickets , 2001, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[55]  P. Vestergaard,et al.  Vitamin D status and its adequacy in healthy Danish perimenopausal women: relationships to dietary intake, sun exposure and serum parathyroid hormone , 2001, British Journal of Nutrition.

[56]  K. Frayn Effects of fat on carbohydrate absorption: more is not necessarily better. , 2001, The British journal of nutrition.

[57]  S. Takeda,et al.  Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[58]  G. Fuleihan,et al.  Hypovitaminosis D in Healthy Schoolchildren , 2001, Pediatrics.

[59]  J. McGrath,et al.  Does 'imprinting' with low prenatal vitamin D contribute to the risk of various adult disorders? , 2001, Medical hypotheses.

[60]  A. Parisi,et al.  Vitamin D insufficiency in south‐east Queensland , 2001, The Medical journal of Australia.

[61]  R. Bouillon Vitamin D: From Photosynthesis, Metabolism, and action to Clinical Applications , 2001 .

[62]  D. Peehl,et al.  Vitamin D and prostate cancer. , 1995, Advances in experimental medicine and biology.

[63]  R. Schwartz,et al.  Nutritional rickets in African American breast-fed infants. , 2000, The Journal of pediatrics.

[64]  L. Freedman,et al.  Mechanisms of gene regulation by vitamin D(3) receptor: a network of coactivator interactions. , 2000, Gene.

[65]  I. McCutcheon,et al.  Use of long-term intravenous phosphate infusion in the palliative treatment of tumor-induced osteomalacia. , 2000, The Journal of clinical endocrinology and metabolism.

[66]  D. Feldman,et al.  Editorial/Mini-Review: Vitamin D and Prostate Cancer. , 2000, Endocrinology.

[67]  M. Hernán,et al.  Geographic variation of MS incidence in two prospective studies of US women , 1999, Neurology.

[68]  G. Chan,et al.  A comparison of calcium, vitamin D, or both for nutritional rickets in Nigerian children. , 1999, The New England journal of medicine.

[69]  M. Garabédian,et al.  Rickets and Vitamin D Deficiency , 1999 .

[70]  M. Holick,et al.  Suberythemal UV-Irradiation Increases Immunological Capacity in Children With Frequent Cold , 1999 .

[71]  T. Dwyer,et al.  Bone mass in prepubertal children: gender differences and the role of physical activity and sunlight exposure. , 1998, The Journal of clinical endocrinology and metabolism.

[72]  Arya M. Sharma,et al.  Ultraviolet B and blood pressure , 1998, The Lancet.

[73]  T. Chen,et al.  Human prostate cells synthesize 1,25-dihydroxyvitamin D3 from 25-hydroxyvitamin D3. , 1998, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[74]  J. Riancho,et al.  Seasonal Deficiency of Vitamin D in Children: A Potential Target for Osteoporosis‐Preventing Strategies? , 1998, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[75]  S. Kato,et al.  Inactivating mutations in the 25-hydroxyvitamin D3 1alpha-hydroxylase gene in patients with pseudovitamin D-deficiency rickets. , 1998, The New England journal of medicine.

[76]  S. Rostand Ultraviolet light may contribute to geographic and racial blood pressure differences. , 1997, Hypertension.

[77]  M. Gascon-Barré CHAPTER 4 – The Vitamin D 25-Hydroxylase , 1997 .

[78]  S. Kooh,et al.  Persistence of Vitamin D-deficiency rickets in Toronto in the 1990s. , 1996, Canadian journal of public health = Revue canadienne de sante publique.

[79]  S. E. Brodie New York, New York, USA , 1996 .

[80]  W. Koo,et al.  Effect of three levels of vitamin D intake in preterm infants receiving high mineral-containing milk. , 1995, Journal of pediatric gastroenterology and nutrition.

[81]  W. Wassif,et al.  Continuing clinically severe vitamin D deficiency in Asians in the UK (Leicester). , 1994, Postgraduate medical journal.

[82]  L. Finberg,et al.  Single-day therapy for nutritional vitamin D-deficiency rickets: a preferred method. , 1994, The Journal of pediatrics.

[83]  B. Specker,et al.  Seasonal and geographical variations in the growth rate of infants in China receiving increasing dosages of vitamin D supplements. , 1994, Journal of Tropical Pediatrics.

[84]  M. Holick,et al.  A possible genetic defect in 25-hydroxylation as a cause of rickets. , 1994, The Journal of pediatrics.

[85]  M. Hediger,et al.  Cloning and characterization of an extracellular Ca2+-sensing receptor from bovine parathyroid , 1993, Nature.

[86]  R. Sherwood,et al.  Role of Plasma Phosphate Measurements in Detecting Rickets of Prematurity and in Monitoring Treatment , 1993, Annals of clinical biochemistry.

[87]  A. K. Bhattacharyya Nutritional rickets in the tropics. , 1992, World review of nutrition and dietetics.

[88]  T. Markestad,et al.  Serum Concentrations of Vitamin D Metabolites in Rachitic Libyan Children , 1989, Journal of pediatric gastroenterology and nutrition.

[89]  R. Bouillon,et al.  Vitamin D Metabolism in Breast-Fed Infants and their Mothers , 1989, Pediatric Research.

[90]  R. Swaminathan,et al.  Vitamin D Status of Hong Kong Chinese Infants , 1989, Acta paediatrica Scandinavica.

[91]  M. Holick,et al.  Influence of season and latitude on the cutaneous synthesis of vitamin D3: exposure to winter sunlight in Boston and Edmonton will not promote vitamin D3 synthesis in human skin. , 1988, The Journal of clinical endocrinology and metabolism.

[92]  M. Stein,et al.  Nutritional rickets in San Diego. , 1987, American journal of diseases of children.

[93]  A. Hasanoğlu,et al.  Serum-25-hydroxycholecalciferol levels in children and adolescents. , 1987, The Turkish journal of pediatrics.

[94]  M. Holick,et al.  Sunscreens suppress cutaneous vitamin D3 synthesis. , 1987, The Journal of clinical endocrinology and metabolism.

[95]  T. Cole,et al.  Etiology of rickets in Egyptian children. , 1987, Human nutrition. Clinical nutrition.

[96]  J. B. Henderson,et al.  The importance of limited exposure to ultraviolet radiation and dietary factors in the aetiology of Asian rickets: a risk-factor model. , 1987, The Quarterly journal of medicine.

[97]  S. Wientroub,et al.  Seasonal variation in paired maternal-newborn serum 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D concentrations in Israel. , 1987, Israel journal of medical sciences.

[98]  E. Mawer,et al.  VITAMIN D NUTRITION AND VITAMIN D METABOLISM IN THE PREMATURE HUMAN NEONATE , 1986, Clinical endocrinology.

[99]  C. Ricour,et al.  Long-term nocturnal calcium infusions can cure rickets and promote normal mineralization in hereditary resistance to 1,25-dihydroxyvitamin D. , 1986, The Journal of clinical investigation.

[100]  R. Morris,et al.  Oral intake of phosphorus can determine the serum concentration of 1,25-dihydroxyvitamin D by determining its production rate in humans. , 1986, The Journal of clinical investigation.

[101]  R. Simpson,et al.  Identification of 1,25-dihydroxyvitamin D3 receptors and activities in muscle. , 1985, The Journal of biological chemistry.

[102]  L. Räsänen,et al.  The vitamin D intake of children and adolescents in Finland. , 1984, Human nutrition. Applied nutrition.

[103]  S. Taha,et al.  25-Hydroxyvitamin D and Total Calcium: Extraordinarily Low Plasma Concentrations in Saudi Mothers and Their Neonates , 1984, Pediatric Research.

[104]  T. Markestad,et al.  Plasma Concentrations of Vitamin D Metabolites before and during Treatment of Vitamin D Deficiency Rickets in Children , 1984, Acta paediatrica Scandinavica.

[105]  Nestlé Nutrition S.A Nestlé Nutrition workshop series , 1983 .

[106]  R. Anderson,et al.  Spectral character of sunlight modulates photosynthesis of previtamin D3 and its photoisomers in human skin. , 1982, Science.

[107]  J. Adams,et al.  INCREASED SKIN PIGMENT REDUCES THE CAPACITY OF SKIN TO SYNTHESISE VITAMIN D3 , 1982, The Lancet.

[108]  F. Glorieux,et al.  Early Oral Administration of Vitamin D and its Metabolites in Premature Neonates. Effect on Mineral Homeostasis , 1982, Pediatric Research.

[109]  M. Holick,et al.  Regulation of cutaneous previtamin D3 photosynthesis in man: skin pigment is not an essential regulator. , 1981, Science.

[110]  H. DeLuca,et al.  Vitamin-D-dependent rickets type II. Resistance of target organs to 1,25-dihydroxyvitamin D. , 1978, The New England journal of medicine.

[111]  H. DeLuca,et al.  Pathogenesis of Hereditary Vitamin-D-Dependent Rickets , 1973 .

[112]  Arthur Ab,et al.  Rickets in the welfare state. , 1969 .

[113]  V. Kelley,et al.  Brennemann's practice of pediatrics , 1969 .

[114]  A. Abbie ART AND SCIENCE IN MEDICINE , 1948 .

[115]  W. Mozoåowski Jäccaron;drzej Sniadecki (1768–1838) on the Cure of Rickets , 1939, Nature.

[116]  W. Mozołowski Jędrzej Sniadecki (1768–1838) on the Cure of Rickets , 1939, Nature.

[117]  A. Hess Rickets, Including Osteomalacia and Tetany , 1930, The Indian Medical Gazette.

[118]  W. S. Thayer,et al.  Antirachitic Properties Imparted to Inert Fluids and to Green Vegetables by Ultraviolet Irradiation , 1925 .

[119]  A. Hess,et al.  ANTIRACHITIC PROPERTIES IMPARTED TO INERT FLUIDS AND TO GREEN VEGETABLES BY ULTRA-VIOLET IRRADIATION , 1924 .

[120]  H. Steenbock THE INDUCTION OF GROWTH PROMOTING AND CALCIFYING PROPERTIES IN A RATION BY EXPOSURE TO LIGHT. , 1924, Science.

[121]  H. Steenbock,et al.  FAT-SOLUBLE VITAMINS XVII. THE INDUCTION OF GROWTH-PROMOTING AND CALCIFYING PROPERTIES IN A RATION BY EXPOSURE TO ULTRA-VIOLET LIGHT , 1924 .

[122]  E. V. Mccollum,et al.  STUDIES ON EXPERIMENTAL RICKETS. , 2009 .

[123]  E. V. Mccollum,et al.  STUDIES ON EXPERIMENTAL RICKETS XXI. AN EXPERIMENTAL DEMONSTRATION OF THE EXISTENCE OF A VITAMIN WHICH PROMOTES CALCIUM DEPOSITION , 1922 .

[124]  A. Hess,et al.  The cure of infantile rickets by artificial light and by sunlight , 1921 .

[125]  K. Huldschinsky Heilung von Rachitis durch künstliche Höhensonne , 1919 .

[126]  Sir Edward Mellanby The part played by an accessory factor in the production of experimental rickets. , 1918 .