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Vitamin D in the New Millennium

  • Current Therapeutics (SL Silverman, Section Editor)
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Abstract

The incidence of vitamin D deficiency is rising worldwide, yet in the vast majority of patients, the condition remains undiagnosed and untreated. Current evidence overwhelmingly indicates that supplemental doses greater than 800 IU/day have beneficial effects on the musculoskeletal system, improving skeletal homeostasis, thus leading to fewer falls and fractures. Evidence is also accumulating on the beneficial effects of vitamin D on extraskeletal systems, such as improving immune health, autoimmune disorders, cancer, neuromodulation, diabetes, and metabolic syndrome. The cause-effect relationship of vitamin D deficiency with increasing incidences of nonskeletal disorders is being investigated. Published reports support the definition of sufficiency, serum levels of 25-hydroxyvitamin D [25(OH)D] greater than 30 ng/mL (75 nmol/L). To achieve this, most people need vitamin D supplementation ranging from 600 to 2000 IU/day; consumption up to of 5000 international units (IU) per day of vitamin D is reported as safe. Although light-skinned individuals need 1000 IU/day of vitamin D, elderly and dark-skinned individuals are likely to need approximately 2000 IU/day to maintain serum 25(OH)D levels greater than 30 ng/mL. Other vulnerable patients, such as the obese, those who have undergone bariatric surgery, and those with gastrointestinal malabsorption syndromes, may require higher doses of vitamin D to maintain normal serum levels and be healthy.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Bosomworth NJ. Mitigating epidemic vitamin D deficiency: The agony of evidence. Can Fam Physician. 2011;57(1):16–20.

    PubMed  CAS  Google Scholar 

  2. Ginde AA, Liu MC, Camargo Jr CA. Demographic differences and trends of vitamin D insufficiency in the US population, 1988–2004. Arch Intern Med. 2009;169(6):626–32.

    Article  PubMed  CAS  Google Scholar 

  3. Goldstein D. The epidemic of vitamin D deficiency. J Pediatr Nurs. 2009;24(4):345–6.

    Article  PubMed  Google Scholar 

  4. Bodnar LM, Catov JM, Simhan HN, et al. Maternal vitamin D deficiency increases the risk of preeclampsia. J Clin Endocrinol Metab. 2007;92(9):3517–22.

    Article  PubMed  CAS  Google Scholar 

  5. Bodnar LM, Catov JM, Zmuda JM, et al. Maternal serum 25-hydroxyvitamin D concentrations are associated with small-for-gestational age births in white women. J Nutr. 2010;140(5):999–1006.

    Article  PubMed  CAS  Google Scholar 

  6. Lewis S, Lucas RM, Halliday J, et al. Vitamin D deficiency and pregnancy: from preconception to birth. Mol Nutr Food Res. 2010;54(8):1092–102.

    PubMed  CAS  Google Scholar 

  7. Nnoaham KE, Clarke A. Low serum vitamin D levels and tuberculosis: a systematic review and meta-analysis. Int J Epidemiol. 2008;37(1):113–9.

    Article  PubMed  Google Scholar 

  8. Ginde AA, Mansbach JM, Camargo Jr CA. Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. Arch Intern Med. 2009;169(4):384–90.

    Article  PubMed  CAS  Google Scholar 

  9. Chesney RW. Vitamin D and The Magic Mountain: the anti-infectious role of the vitamin. J Pediatr. 2010;156(5):698–703.

    Article  PubMed  Google Scholar 

  10. Levin AD, Wadhera V, Leach ST, et al. Vitamin D Deficiency in Children with Inflammatory Bowel Disease. Dig Dis Sci 2011.

  11. Garland CF, Garland FC, Gorham ED, et al. The role of vitamin D in cancer prevention. Am J Public Health. 2006;96(2):252–61.

    Article  PubMed  Google Scholar 

  12. Giovannucci E, Liu Y, Willett WC. Cancer incidence and mortality and vitamin D in black and white male health professionals. Cancer Epidemiol Biomarkers Prev. 2006;15(12):2467–72.

    Article  PubMed  CAS  Google Scholar 

  13. Hisatake J, O’Kelly J, Uskokovic MR, et al. Novel vitamin D(3) analog, 21-(3-methyl-3-hydroxy-butyl)-19-nor D(3), that modulates cell growth, differentiation, apoptosis, cell cycle, and induction of PTEN in leukemic cells. Blood. 2001;97(8):2427–33.

    Article  PubMed  CAS  Google Scholar 

  14. Morales-Tirado V, Wichlan DG, Leimig TE, et al. 1alpha,25-dihydroxyvitamin D3 (vitamin D3) catalyzes suppressive activity on human natural regulatory T cells, uniquely modulates cell cycle progression, and augments FOXP3. Clin Immunol. 2011;138(2):212–21.

    Article  PubMed  CAS  Google Scholar 

  15. Ng KY, Ma MT, Leung KK, et al. Vitamin D and vitamin A receptor expression and the proliferative effects of ligand activation of these receptors on the development of pancreatic progenitor cells derived from human fetal pancreas. Stem Cell Rev. 2011;7(1):53–63.

    Article  PubMed  CAS  Google Scholar 

  16. Kilpinen-Loisa P, Nenonen H, Pihko H, et al. High-dose vitamin D supplementation in children with cerebral palsy or neuromuscular disorder. Neuropediatrics. 2007;38(4):167–72.

    Article  PubMed  CAS  Google Scholar 

  17. Bolland MJ, Bacon CJ, Horne AM, et al. Vitamin D insufficiency and health outcomes over 5 y in older women. Am J Clin Nutr. 2010;91(1):82–9.

    Article  PubMed  CAS  Google Scholar 

  18. Tai K, Need AG, Horowitz M, et al. Glucose tolerance and vitamin D: effects of treating vitamin D deficiency. Nutrition. 2008;24(10):950–6.

    Article  PubMed  CAS  Google Scholar 

  19. Sneve M, Figenschau Y, Jorde R. Supplementation with cholecalciferol does not result in weight reduction in overweight and obese subjects. Eur J Endocrinol. 2008;159(6):675–84.

    Article  PubMed  CAS  Google Scholar 

  20. Binkley N. Is vitamin D the fountain of youth? Endocr Pract. 2009;15(6):590–6.

    Article  PubMed  Google Scholar 

  21. Norman AW, Bouillon R, Whiting SJ, et al. 13th Workshop consensus for vitamin D nutritional guidelines. J Steroid Biochem Mol Biol. 2007;103(3–5):204–5.

    Article  PubMed  CAS  Google Scholar 

  22. Binkley N. Does low vitamin D status contribute to “age-related” morbidity? J Bone Miner Res. 2007;22 Suppl 2:V55–8.

    Article  PubMed  Google Scholar 

  23. Holick MF. High prevalence of vitamin D inadequacy and implications for health. Mayo Clin Proc. 2006;81(3):353–73.

    Article  PubMed  CAS  Google Scholar 

  24. Holick MF. Vitamin D: a D-Lightful health perspective. Nutr Rev. 2008;66(10 Suppl 2):S182–94.

    Article  PubMed  Google Scholar 

  25. Bischoff-Ferrari HA, Dietrich T, Orav EJ, et al. Higher 25-hydroxyvitamin D concentrations are associated with better lower-extremity function in both active and inactive persons aged > or =60 y. Am J Clin Nutr. 2004;80(3):752–8.

    PubMed  CAS  Google Scholar 

  26. Pfeifer M, Begerow B, Minne HW. Vitamin D and muscle function. Osteoporos Int. 2002;13(3):187–94.

    Article  PubMed  CAS  Google Scholar 

  27. Bischoff-Ferrari HA, Willett WC, Wong JB, et al. Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA. 2005;293(18):2257–64.

    Article  PubMed  CAS  Google Scholar 

  28. Porthouse J, Cockayne S, King C, et al. Randomised controlled trial of calcium and supplementation with cholecalciferol (vitamin D3) for prevention of fractures in primary care. BMJ. 2005;330(7498):1003.

    Article  PubMed  CAS  Google Scholar 

  29. Avenell A, Gillespie WJ, Gillespie LD, et al. Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis. Cochrane Database Syst Rev 2009, (2):CD000227.

  30. Bischoff-Ferrari HA, Willett WC, Wong JB, et al. Prevention of nonvertebral fractures with oral vitamin D and dose dependency: a meta-analysis of randomized controlled trials. Arch Intern Med. 2009;169(6):551–61.

    Article  PubMed  CAS  Google Scholar 

  31. Zhang HL, Wu J. Role of vitamin D in immune responses and autoimmune diseases, with emphasis on its role in multiple sclerosis. Neurosci Bull. 2010;26(6):445–54.

    Article  PubMed  CAS  Google Scholar 

  32. Blaney GP, Albert PJ, Proal AD. Vitamin D metabolites as clinical markers in autoimmune and chronic disease. Eur J Clin Invest. 2005;35:290–304.

    Article  Google Scholar 

  33. Semba RD, Houston DK, Bandinelli S, et al. Relationship of 25-hydroxyvitamin D with all-cause and cardiovascular disease mortality in older community-dwelling adults. Eur J Clin Nutr. 2010;64(2):203–9.

    Article  PubMed  CAS  Google Scholar 

  34. Wang L, Manson JE, Song Y, et al. Systematic review: Vitamin D and calcium supplementation in prevention of cardiovascular events. Ann Intern Med. 2010;152(5):315–23.

    PubMed  Google Scholar 

  35. Drechsler C, Pilz S, Obermayer-Pietsch B, et al. Vitamin D deficiency is associated with sudden cardiac death, combined cardiovascular events, and mortality in haemodialysis patients. Eur Heart J. 2010;31(18):2253–61.

    Article  PubMed  CAS  Google Scholar 

  36. Pilz S, Tomaschitz A, Drechsler C, et al. Vitamin D supplementation: a promising approach for the prevention and treatment of strokes. Curr Drug Targets. 2011;12(1):88–96.

    Article  PubMed  CAS  Google Scholar 

  37. •• Wimalawansa SJ. Vitamin D: Everything You Need to Know. Homagama, Sri Lanka. Publisher: Karunaratne & Sons, 2011. This is a comprehensive book on vitamin D primarily directed for the primary care physicians.

    Google Scholar 

  38. Jenab M, Bueno-de-Mesquita HB, Ferrari P, et al. Association between pre-diagnostic circulating vitamin D concentration and risk of colorectal cancer in European populations:a nested case–control study. BMJ. 2010;340:b5500.

    Article  PubMed  Google Scholar 

  39. Karlsson S, Olausson J, Lundh D, et al. Vitamin D and prostate cancer: the role of membrane initiated signaling pathways in prostate cancer progression. J Steroid Biochem Mol Biol. 2010;121(1–2):413–6.

    Article  PubMed  CAS  Google Scholar 

  40. Holick MF, Siris ES, Binkley N, et al. Prevalence of Vitamin D inadequacy among postmenopausal North American women receiving osteoporosis therapy. J Clin Endocrinol Metab. 2005;90(6):3215–24.

    Article  PubMed  CAS  Google Scholar 

  41. Seton M, Jackson V, Lasser KE, et al. Low 25-hydroxyvitamin D and osteopenia are prevalent in persons > or =55 yr with fracture at any site: a prospective, observational study of persons fracturing in the community. J Clin Densitom. 2005;8(4):454–60.

    Article  PubMed  Google Scholar 

  42. Kuchuk NO, Pluijm SM, van Schoor NM, et al. Relationships of serum 25-hydroxyvitamin D to bone mineral density and serum parathyroid hormone and markers of bone turnover in older persons. J Clin Endocrinol Metab. 2009;94(4):1244–50.

    Article  PubMed  CAS  Google Scholar 

  43. Orwoll E, Nielson CM, Marshall LM, et al. Vitamin D deficiency in older men. J Clin Endocrinol Metab. 2009;94(4):1214–22.

    Article  PubMed  CAS  Google Scholar 

  44. Trivedi DP, Doll R, Khaw KT. Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. BMJ. 2003;326(7387):469–72.

    Article  PubMed  CAS  Google Scholar 

  45. Holick MF, Biancuzzo RM, Chen TC, et al. Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D. J Clin Endocrinol Metab. 2008;93(3):677–81.

    Article  PubMed  CAS  Google Scholar 

  46. •• Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin d deficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2011, 96(7):1911–1930. These recommendations are primarily directed to individual patients; not intended for populations.

    Article  PubMed  CAS  Google Scholar 

  47. Romagnoli E, Mascia ML, Cipriani C, et al. Short and long-term variations in serum calciotropic hormones after a single very large dose of ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3) in the elderly. J Clin Endocrinol Metab. 2008;93(8):3015–20.

    Article  PubMed  CAS  Google Scholar 

  48. Armas LA, Hollis BW, Heaney RP. Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004;89(11):5387–91.

    Article  PubMed  CAS  Google Scholar 

  49. Binkley N, Gemar D, Engelke J, et al. Evaluation of Ergocalciferol or Cholecalciferol Dosing, 1,600 IU Daily or 50,000 IU Monthly in Older Adults. J Clin Endocrinol Metab 2011.

  50. Wimalawansa SJ. Vitamin D: An essential component for skeletal health. Annals of NYAS. 2011;1240(1):90–104.

    Google Scholar 

  51. Chun RF, Adams JS, Hewison M. Back to the future: a new look at ‘old’ vitamin D. J Endocrinol. 2008;198(2):261–9.

    Article  PubMed  CAS  Google Scholar 

  52. Strushkevich N, Usanov SA, Plotnikov AN, et al. Structural analysis of CYP2R1 in complex with vitamin D3. J Mol Biol. 2008;380(1):95–106.

    Article  PubMed  CAS  Google Scholar 

  53. Fernandesdeabreu DA, Eyles D, Feron F. Vitamin D, a neuro-immunomodulator: implications for neurodegenerative and autoimmune diseases. Psychoneuroendocrinology. 2009;34(1):265–77.

    Article  CAS  Google Scholar 

  54. Bravo S, Paredes R, Izaurieta P, et al. The classic receptor for 1alpha,25-dihydroxy vitamin D3 is required for non-genomic actions of 1alpha,25-dihydroxy vitamin D3 in osteosarcoma cells. J Cell Biochem. 2006;99(4):995–1000.

    Article  PubMed  CAS  Google Scholar 

  55. De Boland AR, Boland RL. Non-genomic signal transduction pathway of vitamin D in muscle. Cell Signal. 1994;6(7):717–24.

    Article  PubMed  Google Scholar 

  56. Pitcher T, Buffenstein R. Intestinal calcium transport in mole-rats (Cryptomys damarensis and Heterocephalus glaber) is independent of both genomic and non-genomic vitamin D mediation. Exp Physiol. 1995;80(4):597–608.

    PubMed  CAS  Google Scholar 

  57. Vazquez G, de Boland AR, Boland R. Stimulation of Ca2+ release-activated Ca2+ channels as a potential mechanism involved in non-genomic 1,25(OH)2-vitamin D3-induced Ca2+ entry in skeletal muscle cells. Biochem Biophys Res Commun. 1997;239(2):562–5.

    Article  PubMed  CAS  Google Scholar 

  58. Dawson-Hughes B, Heaney RP, Holick MF, et al. Estimates of optimal vitamin D status. Osteoporos Int. 2005;16(7):713–6.

    Article  PubMed  CAS  Google Scholar 

  59. Okazaki R. Vitamin D deficiency and vitamin D insufficiency. Nippon Naika Gakkai Zasshi. 2007;96(4):742–7.

    PubMed  CAS  Google Scholar 

  60. Hollis BW. Circulating 25-hydroxyvitamin D levels indicative of vitamin D sufficiency: implications for establishing a new effective dietary intake recommendation for vitamin D. J Nutr. 2005;135(2):317–22.

    PubMed  CAS  Google Scholar 

  61. Li B, Byrjalsen I, Glendenning P, et al. Selective monitoring of vitamin D2 and D3 supplementation with a highly specific 25-hydroxyvitamin D3 immunoassay with negligible cross-reactivity to 25-hydroxyvitamin D2. Clin Chim Acta. 2009;404(2):144–8.

    Article  PubMed  CAS  Google Scholar 

  62. Binkley N, Krueger D. Evaluation and correction of low vitamin D status. Curr Osteoporos Rep. 2008;6(3):95–9.

    Article  PubMed  Google Scholar 

  63. Heaney RP, and Weaver CM. Calcium and vitamin D. Endocrinol Metab Clin North Am 2003, 32(1):181–194, vii-viii.

  64. Holick MF. Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease. Am J Clin Nutr. 2004;80(6 Suppl):1678S–88.

    PubMed  CAS  Google Scholar 

  65. Kleerekoper M, Schleicher RL, Eisman J, et al. Clinical applications for vitamin d assays: what is known and what is wished for. Clin Chem. 2011;57(9):1227–32.

    Article  PubMed  CAS  Google Scholar 

  66. Kushnir MM, Ray JA, Rockwood AL, et al. Rapid analysis of 25-hydroxyvitamin D(2) and D(3) by liquid chromatography-tandem mass spectrometry and association of vitamin D and parathyroid hormone concentrations in healthy adults. Am J Clin Pathol. 2010;134(1):148–56.

    Article  PubMed  CAS  Google Scholar 

  67. van den Ouweland JM, Beijers AM, Demacker PN, et al. Measurement of 25-OH-vitamin D in human serum using liquid chromatography tandem-mass spectrometry with comparison to radioimmunoassay and automated immunoassay. J Chromatogr B Analyt Technol Biomed Life Sci. 2010;878(15–16):1163–8.

    PubMed  Google Scholar 

  68. Adamec J, Jannasch A, Huang J, et al. Development and optimization of an LC-MS/MS-based method for simultaneous quantification of vitamin D2, vitamin D3, 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3. J Sep Sci. 2011;34(1):11–20.

    Article  PubMed  CAS  Google Scholar 

  69. El-Khoury JM, Reineks EZ, Wang S. Progress of liquid chromatography-mass spectrometry in measurement of vitamin D metabolites and analogues. Clin Biochem. 2011;44(1):66–76.

    Article  PubMed  CAS  Google Scholar 

  70. • Jafri L, Khan AH, Siddiqui AA, et al. Comparison of high performance liquid chromatography, radio immunoassay and electrochemiluminescence immunoassay for quantification of serum 25 hydroxy vitamin D. Clin Biochem 2011, 44(10–11):864–868. These are detailed discussions and comparisons of various methodologies currenlty avaiable for the measurement of serum vitamin D.

    Article  PubMed  CAS  Google Scholar 

  71. Flicker L, Mead K, MacInnis RJ, et al. Serum vitamin D and falls in older women in residential care in Australia. J Am Geriatr Soc. 2003;51(11):1533–8.

    Article  PubMed  Google Scholar 

  72. MacLaughlin J, Holick MF. Aging decreases the capacity of human skin to produce vitamin D3. J Clin Invest. 1985;76(4):1536–8.

    Article  PubMed  CAS  Google Scholar 

  73. Sambrook PN, Cameron ID, Cumming RG, et al. Vitamin D deficiency is common in frail institutionalised older people in northern Sydney. Med J Aust. 2002;176(11):560.

    PubMed  Google Scholar 

  74. Harris SS. Vitamin D and African Americans. J Nutr. 2006;136(4):1126–9.

    PubMed  CAS  Google Scholar 

  75. Zubillaga P, Garrido A, Mugica I, et al. Effect of vitamin D and calcium supplementation on bone turnover in institutionalized adults with Down’s Syndrome. Eur J Clin Nutr. 2006;60(5):605–9.

    Article  PubMed  CAS  Google Scholar 

  76. Deplas A, Debiais F, Alcalay M, et al. Bone density, parathyroid hormone, calcium and vitamin D nutritional status of institutionalized elderly subjects. J Nutr Health Aging. 2004;8(5):400–4.

    PubMed  CAS  Google Scholar 

  77. Harinarayan CV, Ramalakshmi T, Prasad UV, et al. High prevalence of low dietary calcium, high phytate consumption, and vitamin D deficiency in healthy south Indians. Am J Clin Nutr. 2007;85(4):1062–7.

    PubMed  CAS  Google Scholar 

  78. Klein GL, Wimalawansa SJ, Kulkarni G, et al. The efficacy of acute administration of pamidronate on the conservation of bone mass following severe burn injury in children: a double-blind, randomized, controlled study. Osteoporos Int. 2005;16(6):631–5.

    Article  PubMed  CAS  Google Scholar 

  79. Roy DK, Berry JL, Pye SR, et al. Vitamin D status and bone mass in UK South Asian women. Bone. 2007;40(1):200–4.

    Article  PubMed  CAS  Google Scholar 

  80. van der Meer IM, Middelkoop BJ, Boeke AJ, et al. Prevalence of vitamin D deficiency among Turkish, Moroccan, Indian and sub-Sahara African populations in Europe and their countries of origin: an overview. Osteoporos Int 2010.

  81. Korpershoek HW, Witteman EM, Meinardi JR, et al. Severe vitamin D deficiency and hypocalcaemia after bariatric surgery. Ned Tijdschr Geneeskd. 2010;154:A827.

    PubMed  Google Scholar 

  82. Arvold DS, Odean MJ, Dornfeld MP, et al. Correlation of symptoms with vitamin D deficiency and symptom response to cholecalciferol treatment: a randomized controlled trial. Endocr Pract. 2009;15(3):203–12.

    PubMed  Google Scholar 

  83. Marti F, Naumann UK, Suter PM, et al. [Vitamin D deficiency (in adults). Main symptoms: bone pain]. Praxis (Bern 1994) 2006, 95(50):1953–1959; quiz 1960.

  84. Nogues X, Servitja S, Pena MJ, et al. Vitamin D deficiency and bone mineral density in postmenopausal women receiving aromatase inhibitors for early breast cancer. Maturitas. 2010;66(3):291–7.

    Article  PubMed  CAS  Google Scholar 

  85. Messinger-Rapport B, Dumas LG. Falls in the nursing home: a collaborative approach. Nurs Clin North Am. 2009;44(2):187–95.

    Article  PubMed  Google Scholar 

  86. Dharmarajan TS, Akula M, Kuppachi S, et al. Vitamin D deficiency in community older adults with falls of gait imbalance: an under-recognized problem in the inner city. J Nutr Elder. 2005;25(1):7–19.

    Article  PubMed  CAS  Google Scholar 

  87. Joop PW, van den Bergh, Bours SPG, et al. Optimal Use of Vitamin D When Treating Osteoporosis. Osteoporos Rep. 2011;9(1):36–42.

    Article  Google Scholar 

  88. Broe KE, Chen TC, Weinberg J, et al. A higher dose of vitamin d reduces the risk of falls in nursing home residents: a randomized, multiple-dose study. J Am Geriatr Soc. 2007;55(2):234–9.

    Article  PubMed  Google Scholar 

  89. Greenspan SL, Resnick NM, Parker RA. Vitamin D supplementation in older women. J Gerontol A Biol Sci Med Sci. 2005;60(6):754–9.

    Article  PubMed  Google Scholar 

  90. Kalyani RR, Stein B, Valiyil R, et al. Vitamin D treatment for the prevention of falls in older adults: systematic review and meta-analysis. J Am Geriatr Soc. 2010;58(7):1299–310.

    Article  PubMed  Google Scholar 

  91. Fleet JC, Schoch RD. Molecular mechanisms for regulation of intestinal calcium absorption by vitamin D and other factors. Crit Rev Clin Lab Sci. 2010;47(4):181–95.

    Article  PubMed  CAS  Google Scholar 

  92. Heaney RP, Dowell MS, Hale CA, et al. Calcium absorption varies within the reference range for serum 25-hydroxyvitamin D. J Am Coll Nutr. 2003;22(2):142–6.

    PubMed  CAS  Google Scholar 

  93. Lips P. Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications. Endocr Rev. 2001;22(4):477–501.

    Article  PubMed  CAS  Google Scholar 

  94. Bischoff-Ferrari HA, Kiel DP, Dawson-Hughes B, et al. Dietary calcium and serum 25-hydroxyvitamin D status in relation to BMD among U.S. adults. J Bone Miner Res. 2009;24(5):935–42.

    Article  PubMed  CAS  Google Scholar 

  95. Cauley JA, Lacroix AZ, Wu L, et al. Serum 25-hydroxyvitamin D concentrations and risk for hip fractures. Ann Intern Med. 2008;149(4):242–50.

    PubMed  Google Scholar 

  96. Gerdhem P, Ringsberg KA, Obrant KJ, et al. Association between 25-hydroxy vitamin D levels, physical activity, muscle strength and fractures in the prospective population-based OPRA Study of Elderly Women. Osteoporos Int. 2005;16(11):1425–31.

    Article  PubMed  CAS  Google Scholar 

  97. Parfitt A. Osteomalacia and related disorders. In: Metabolic bone disease and clinically related disorders, Edited by Avioli LV, and Krane SM. Philadelphia: WB Saunders Company; 1990: 329–396.

  98. Bischoff-Ferrari HA, Dawson-Hughes B, Willett WC, et al. Effect of Vitamin D on falls: a meta-analysis. JAMA. 2004;291(16):1999–2006.

    Article  PubMed  CAS  Google Scholar 

  99. Chapuy MC, Arlot ME, Duboeuf F, et al. Vitamin D3 and calcium to prevent hip fractures in the elderly women. N Engl J Med. 1992;327(23):1637–42.

    Article  PubMed  CAS  Google Scholar 

  100. Adams JS, Kantorovich V, Wu C, et al. Resolution of vitamin D insufficiency in osteopenic patients results in rapid recovery of bone mineral density. J Clin Endocrinol Metab. 1999;84(8):2729–30.

    Article  PubMed  CAS  Google Scholar 

  101. Heaney RP. Barriers to optimizing vitamin D3 intake for the elderly. J Nutr. 2006;136(4):1123–5.

    PubMed  CAS  Google Scholar 

  102. Pattanaungkul S, Riggs BL, Yergey AL, et al. Relationship of intestinal calcium absorption to 1,25-dihydroxyvitamin D [1,25(OH)2D] levels in young versus elderly women: evidence for age-related intestinal resistance to 1,25(OH)2D action. J Clin Endocrinol Metab. 2000;85(11):4023–7.

    Article  PubMed  CAS  Google Scholar 

  103. Song Y, Kato S, Fleet JC. Vitamin D receptor (VDR) knockout mice reveal VDR-independent regulation of intestinal calcium absorption and ECaC2 and calbindin D9k mRNA. J Nutr. 2003;133(2):374–80.

    PubMed  CAS  Google Scholar 

  104. Christakos S, Dhawan P, Porta A, et al. Vitamin D and intestinal calcium absorption. Mol Cell Endocrinol 2011.

  105. Christakos S, Dhawan P, Peng X, et al. New insights into the function and regulation of vitamin D target proteins. J Steroid Biochem Mol Biol. 2007;103(3–5):405–10.

    Article  PubMed  CAS  Google Scholar 

  106. Benn BS, Ajibade D, Porta A, et al. Active intestinal calcium transport in the absence of transient receptor potential vanilloid type 6 and calbindin-D9k. Endocrinology. 2008;149(6):3196–205.

    Article  PubMed  CAS  Google Scholar 

  107. Christakos S, Dhawan P, Benn B, et al. Vitamin D: molecular mechanism of action. Ann N Y Acad Sci. 2007;1116:340–8.

    Article  PubMed  CAS  Google Scholar 

  108. Richard C, Huo R, Samadfam R, et al. The calcium-sensing receptor and 25-hydroxyvitamin D-1alpha-hydroxylase interact to modulate skeletal growth and bone turnover. J Bone Miner Res. 2010;25(7):1627–36.

    Article  PubMed  CAS  Google Scholar 

  109. Khosla S. Minireview: the OPG/RANKL/RANK system. Endocrinology. 2001;142(12):5050–5.

    Article  PubMed  CAS  Google Scholar 

  110. Lewiecki EM MP, McClung MR, Cohen SB, Liu Y, Wang A, Fitzpatrick LA. Rank ligand inhibition with denosuman (AMG 162) increase bone mineral density (BMD) in postmenopausal women after two-years of treatment. In: American College of Rheumatology (ACR/ARHP) Annual Meeting2005.

  111. Bischoff-Ferrari HA, Dawson-Hughes B, Staehelin HB, et al. Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomised controlled trials. BMJ. 2009;339:b3692.

    Article  PubMed  CAS  Google Scholar 

  112. Bergman GJ, Fan T, McFetridge JT, et al. Efficacy of vitamin D3 supplementation in preventing fractures in elderly women: a meta-analysis. Curr Med Res Opin. 2010;26(5):1193–201.

    Article  PubMed  CAS  Google Scholar 

  113. Salovaara K, Tuppurainen M, Karkkainen M, et al. Effect of vitamin D(3) and calcium on fracture risk in 65- to 71-year-old women: a population-based 3-year randomized, controlled trial–the OSTPRE-FPS. J Bone Miner Res. 2010;25(7):1487–95.

    Article  PubMed  CAS  Google Scholar 

  114. Gillespie LD, Robertson MC, Gillespie WJ, et al. Interventions for preventing falls in older people living in the community. Cochrane Database Syst Rev 2009, (2):CD007146.

  115. Tang BM, Eslick GD, Nowson C, et al. Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis. Lancet. 2007;370(9588):657–66.

    Article  PubMed  CAS  Google Scholar 

  116. Bischoff-Ferrari HA, Dawson-Hughes B, Baron JA, et al. Calcium intake and hip fracture risk in men and women: a meta-analysis of prospective cohort studies and randomized controlled trials. Am J Clin Nutr. 2007;86(6):1780–90.

    PubMed  CAS  Google Scholar 

  117. •• Ross AC, Manson JE, Abrams SA, et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab 2011, 96(1):53–58. This summary of the IOM report includes evidence-based recommendations for vitamin D.

    Article  PubMed  CAS  Google Scholar 

  118. Lappe JM, Travers-Gustafson D, Davies KM, et al. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr. 2007;85(6):1586–91.

    PubMed  CAS  Google Scholar 

  119. Elwood JM. Who gets skin cancer: individual risk factors. In: Prevention of Skin Cancer, Edited by Hill DJ, Elwood JM, and English DR. Dordrecht, the Netherlands: Kluwer Academic Publishers; 2004: 3–20.

  120. Bogh MK, Schmedes AV, Philipsen PA, et al. Vitamin D production depends on ultraviolet-B dose but not on dose rate: a randomized controlled trial. Exp Dermatol. 2011;20(1):14–8.

    Article  PubMed  CAS  Google Scholar 

  121. Bogh MK, Schmedes AV, Philipsen PA, et al. Interdependence between body surface area and ultraviolet B dose in vitamin D production: a randomized controlled trial. Br J Dermatol. 2011;164(1):163–9.

    Article  PubMed  CAS  Google Scholar 

  122. Robberecht E, Vandewalle S, Wehlou C, et al. Sunlight is an important determinant of vitamin D serum concentrations in cystic fibrosis. Eur J Clin Nutr. 2011;65(5):574–9.

    Article  PubMed  CAS  Google Scholar 

  123. Godar DE, Pope SJ, Grant WB, et al. Solar UV Doses of Young Americans and Vitamin D3 Production. Environ Health Perspect 2011.

  124. Bonevski B, Girgis A, Magin P, et al. Prescribing sunshine: A cross-sectional survey of 500 Australian general practitioners’ practices and attitudes about vitamin D. Int J Cancer 2011.

  125. Clipp SL, Burke A, Hoffman-Bolton J, et al. Sun-seeking behavior to increase cutaneous vitamin D synthesis: when prevention messages conflict. Public Health Rep. 2011;126(4):533–9.

    PubMed  Google Scholar 

  126. Ahmed SF, Franey C, McDevitt H, et al. Recent trends and clinical features of childhood vitamin D deficiency presenting to a children’s hospital in Glasgow. Arch Dis Child. 2011;96(7):694–6.

    Article  PubMed  CAS  Google Scholar 

  127. Eastell R, Arnold A, Brandi ML, et al. Diagnosis of asymptomatic primary hyperparathyroidism: proceedings of the third international workshop. J Clin Endocrinol Metab. 2009;94(2):340–50.

    Article  PubMed  CAS  Google Scholar 

  128. Khazai NB, Judd SE, Jeng L, et al. Treatment and prevention of vitamin D insufficiency in cystic fibrosis patients: comparative efficacy of ergocalciferol, cholecalciferol, and UV light. J Clin Endocrinol Metab. 2009;94(6):2037–43.

    Article  PubMed  CAS  Google Scholar 

  129. Chel VG, Ooms ME, Pavel S, et al. Prevention and treatment of vitamin D deficiency in Dutch psychogeriatric nursing home residents by weekly half-body UVB exposure after showering: a pilot study. Age Ageing. 2011;40(2):211–4.

    Article  PubMed  CAS  Google Scholar 

  130. Hart PH, Gorman S, Finlay-Jones JJ. Modulation of the immune system by UV radiation: more than just the effects of vitamin D? Nat Rev Immunol. 2011;11(9):584–96.

    Article  PubMed  CAS  Google Scholar 

  131. Olds WJ, McKinley AR, Moore MR, et al. In vitro model of vitamin D3 (cholecalciferol) synthesis by UV radiation: dose–response relationships. J Photochem Photobiol B. 2008;93(2):88–93.

    Article  PubMed  CAS  Google Scholar 

  132. Kumar J, Muntner P, Kaskel FJ, et al. Prevalence and associations of 25-hydroxyvitamin D deficiency in US children: NHANES 2001–2004. Pediatrics. 2009;124(3):e362–70.

    Article  PubMed  Google Scholar 

  133. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266–81.

    Article  PubMed  CAS  Google Scholar 

  134. Looker AC, Pfeiffer CM, Lacher DA, et al. Serum 25-hydroxyvitamin D status of the US population: 1988–1994 compared with 2000–2004. Am J Clin Nutr. 2008;88(6):1519–27.

    Article  PubMed  CAS  Google Scholar 

  135. Adami S, Viapiana O, Gatti D, et al. Relationship between serum parathyroid hormone, vitamin D sufficiency, age, and calcium intake. Bone. 2008;42(2):267–70.

    Article  PubMed  CAS  Google Scholar 

  136. Karakelides H, Geller JL, Schroeter AL, et al. Vitamin D-mediated hypercalcemia in slack skin disease: evidence for involvement of extrarenal 25-hydroxyvitamin D 1alpha-hydroxylase. J Bone Miner Res. 2006;21(9):1496–9.

    Article  PubMed  Google Scholar 

  137. Hewison M, Burke F, Evans KN, et al. Extra-renal 25-hydroxyvitamin D3-1alpha-hydroxylase in human health and disease. J Steroid Biochem Mol Biol. 2007;103(3–5):316–21.

    Article  PubMed  CAS  Google Scholar 

  138. Waele BD, Smitz J, Willems G. Recurrent pancreatitis secondary to hypercalcemia following vitamin D poisoning. Pancreas. 1989;4(3):378–80.

    Article  PubMed  CAS  Google Scholar 

  139. Hathcock JN, Shao A, Vieth R, et al. Risk assessment for vitamin D. Am J Clin Nutr. 2007;85(1):6–18.

    PubMed  CAS  Google Scholar 

  140. Pietras SM, Obayan BK, Cai MH, et al. Vitamin D2 treatment for vitamin D deficiency and insufficiency for up to 6 years. Arch Intern Med. 2009;169(19):1806–8.

    Article  PubMed  Google Scholar 

  141. Koutkia P, Chen TC, Holick MF. Vitamin D intoxication associated with an over-the-counter supplement. N Engl J Med. 2001;345(1):66–7.

    Article  PubMed  CAS  Google Scholar 

  142. Kaptein S, Risselada AJ, Boerma EC, et al. Life-threatening complications of vitamin D intoxication due to over-the-counter supplements. Clin Toxicol (Phila). 2010;48(5):460–2.

    Article  Google Scholar 

  143. Institute of Medicine. Dietary reference intakes for calcium and vitamin D Washington, DC. Washington, DC.: Food and Nutrition Board 1997.

  144. Food and Nutrition Board. Dietary reference intakes. Nutr Rev. 1997;55(9):319–26.

    Google Scholar 

  145. Vieth R, Bischoff-Ferrari H, Boucher BJ, et al. The urgent need to recommend an intake of vitamin D that is effective. Am J Clin Nutr. 2007;85(3):649–50.

    PubMed  CAS  Google Scholar 

  146. Norman AW. A vitamin D nutritional cornucopia: new insights concerning the serum 25-hydroxyvitamin D status of the US population. Am J Clin Nutr. 2008;88(6):1455–6.

    Article  PubMed  CAS  Google Scholar 

  147. Moore CE, Murphy MM, Holick MF. Vitamin D intakes by children and adults in the United States differ among ethnic groups. J Nutr. 2005;135(10):2478–85.

    PubMed  CAS  Google Scholar 

  148. Holick MF. Vitamin D: evolutionary, physiological and health perspectives. Curr Drug Targets. 2011;12(1):4–18.

    Article  PubMed  CAS  Google Scholar 

  149. Chung M, Balk EM, Brendel M, et al. Vitamin D and calcium a systematic review of health outcomes. Evid Rep Technol Assess Full Rep. 2009;183:1–420.

    PubMed  Google Scholar 

  150. Heaney RP. The Vitamin D requirement in health and disease. J Steroid Biochem Mol Biol. 2005;97(1–2):13–9.

    Article  PubMed  CAS  Google Scholar 

  151. U.S. Department of Health and Human Services. Healthy People U.S. Department of Health and Human Services. Available at http://www.healthypeople.gov/document/html/objectives/03-09.htm.

  152. Reis JP, von Muhlen D, Miller 3rd ER, et al. Vitamin D Status and Cardiometabolic Risk Factors in the United States Adolescent Population. Pediatrics. 2009;124:e371–9.

    Article  PubMed  Google Scholar 

  153. Chel VG, Ooms ME, Popp-Snijders C, et al. Ultraviolet irradiation corrects vitamin D deficiency and suppresses secondary hyperparathyroidism in the elderly. J Bone Miner Res. 1998;13(8):1238–42.

    Article  PubMed  CAS  Google Scholar 

  154. Shah N, Bernardini J, Piraino B. Prevalence and correction of 25(OH) vitamin D deficiency in peritoneal dialysis patients. Perit Dial Int. 2005;25(4):362–6.

    PubMed  CAS  Google Scholar 

  155. Semba RD, Houston DK, Ferrucci L, et al. Low serum 25-hydroxyvitamin D concentrations are associated with greater all-cause mortality in older community-dwelling women. Nutr Res. 2009;29(8):525–30.

    Article  PubMed  CAS  Google Scholar 

  156. Autier P, Gandini S. Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials. Arch Intern Med. 2007;167(16):1730–7.

    Article  PubMed  CAS  Google Scholar 

  157. Melamed ML, Michos ED, Post W, et al. 25-hydroxyvitamin D levels and the risk of mortality in the general population. Arch Intern Med. 2008;168(15):1629–37.

    Article  PubMed  Google Scholar 

  158. Giovannucci E, Liu Y, Hollis BW, et al. 25-hydroxyvitamin D and risk of myocardial infarction in men: a prospective study. Arch Intern Med. 2008;168(11):1174–80.

    Article  PubMed  CAS  Google Scholar 

  159. Chiu KC, Chu A, Go VL, et al. Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction. Am J Clin Nutr. 2004;79(5):820–5.

    PubMed  CAS  Google Scholar 

  160. Choi HS, Kim KA, Lim CY, et al. Low serum vitamin D is associated with high risk of diabetes in Korean adults. J Nutr. 2011;141(8):1524–8.

    Article  PubMed  CAS  Google Scholar 

  161. Gupta AK, Brashear MM, Johnson WD. Prediabetes and prehypertension in healthy adults are associated with low vitamin D levels. Diabetes Care. 2011;34(3):658–60.

    Article  PubMed  Google Scholar 

  162. Hamed EA, Abu Faddan NH, Adb Elhafeez HA, et al. Parathormone - 25(OH)-vitamin D axis and bone status in children and adolescents with type 1 diabetes mellitus. Pediatr Diabetes. 2011;12(6):536–46.

    PubMed  CAS  Google Scholar 

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Disclosure

Conflicts of interest: S.J. Wimalawansa: has published a book for primary care physicians on vitamin D; no sponsorships to date, and no other conflicts exist.

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  1. Physiology & Integrative Biology, Endocrinology, Metabolism & Nutrition, UMDNJ–Robert Wood Johnson Medical School, New Brunswick, NJ, USA

    Sunil J. Wimalawansa

  2. Regional Osteoporosis Center, MEB-372, Division of Endocrinology, Robert Wood Johnson Medical School, New Brunswick, NJ, 08903-0019, USA

    Sunil J. Wimalawansa

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Wimalawansa, S.J. Vitamin D in the New Millennium. Curr Osteoporos Rep 10, 4–15 (2012). https://doi.org/10.1007/s11914-011-0094-8

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