{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T22:15:12Z","timestamp":1794262512368,"version":"4.9.0"},"reference-count":390,"publisher":"The Endocrine Society","issue":"4","license":[{"start":{"date-parts":[[2018,10,12]],"date-time":"2018-10-12T00:00:00Z","timestamp":1539302400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FWO Flanders and KU leuven","award":["G0A2416N"],"award-info":[{"award-number":["G0A2416N"]}],"id":[{"id":"https:\/\/ror.org\/05f950310","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK32333"],"award-info":[{"award-number":["DK32333"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["NIH RO1 AR051930"],"award-info":[{"award-number":["NIH RO1 AR051930"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["VA 1 I01 BX003814-01"],"award-info":[{"award-number":["VA 1 I01 BX003814-01"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"name":"USDA Agriculture Research","award":["# 58-1950-7-707"],"award-info":[{"award-number":["# 58-1950-7-707"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The etiology of endemic rickets was discovered a century ago. Vitamin D is the precursor of 25-hydroxyvitamin D and other metabolites, including 1,25(OH)2D, the ligand for the vitamin D receptor (VDR). The effects of the vitamin D endocrine system on bone and its growth plate are primarily indirect and mediated by its effect on intestinal calcium transport and serum calcium and phosphate homeostasis. Rickets and osteomalacia can be prevented by daily supplements of 400 IU of vitamin D. Vitamin D deficiency (serum 25-hydroxyvitamin D &lt;50 nmol\/L) accelerates bone turnover, bone loss, and osteoporotic fractures. These risks can be reduced by 800 IU of vitamin D together with an appropriate calcium intake, given to institutionalized or vitamin D\u2013deficient elderly subjects. VDR and vitamin D metabolic enzymes are widely expressed. Numerous genetic, molecular, cellular, and animal studies strongly suggest that vitamin D signaling has many extraskeletal effects. These include regulation of cell proliferation, immune and muscle function, skin differentiation, and reproduction, as well as vascular and metabolic properties. From observational studies in human subjects, poor vitamin D status is associated with nearly all diseases predicted by these extraskeletal actions. Results of randomized controlled trials and Mendelian randomization studies are supportive of vitamin D supplementation in reducing the incidence of some diseases, but, globally, conclusions are mixed. These findings point to a need for continued ongoing and future basic and clinical studies to better define whether vitamin D status can be optimized to improve many aspects of human health. Vitamin D deficiency enhances the risk of osteoporotic fractures and is associated with many diseases. We review what is established and what is plausible regarding the health effects of vitamin D.<\/jats:p>","DOI":"10.1210\/er.2018-00126","type":"journal-article","created":{"date-parts":[[2018,10,12]],"date-time":"2018-10-12T14:03:00Z","timestamp":1539352980000},"page":"1109-1151","source":"Crossref","is-referenced-by-count":1026,"title":["Skeletal and Extraskeletal Actions of Vitamin D: Current Evidence and Outstanding Questions"],"prefix":"10.1210","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6446-3763","authenticated-orcid":false,"given":"Roger","family":"Bouillon","sequence":"first","affiliation":[{"name":"Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6568-8588","authenticated-orcid":false,"given":"Claudio","family":"Marcocci","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8324-4462","authenticated-orcid":false,"given":"Geert","family":"Carmeliet","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1040-475X","authenticated-orcid":false,"given":"Daniel","family":"Bikle","sequence":"additional","affiliation":[{"name":"Veterans Affairs Medical Center and University of California San Francisco, San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4785-2687","authenticated-orcid":false,"given":"John H","family":"White","sequence":"additional","affiliation":[{"name":"Department of Physiology, McGill University, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bess","family":"Dawson-Hughes","sequence":"additional","affiliation":[{"name":"Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2627-8145","authenticated-orcid":false,"given":"Paul","family":"Lips","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Endocrine Section, VU University Medical Center, HV Amsterdam, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig F","family":"Munns","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital at Westmead, Sydney, New South Wales, Australia"},{"name":"Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9186-2834","authenticated-orcid":false,"given":"Marise","family":"Lazaretti-Castro","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Escola Paulista de Medicina, Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Giustina","sequence":"additional","affiliation":[{"name":"Chair of Endocrinology, Vita-Salute San Raffaele University, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Bilezikian","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Columbia University College of Physicians and Surgeons, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2018,10,12]]},"reference":[{"issue":"19","key":"2019071308555101200_B1","doi-asserted-by":"crossref","first-page":"7392","DOI":"10.1073\/pnas.0402207101","article-title":"Ribozyme knockdown functionally links a 1,25(OH)2D3 membrane binding protein (1,25D3-MARRS) and phosphate uptake in intestinal cells","volume":"101","author":"Nemere","year":"2004","journal-title":"Proc Natl Acad Sci USA"},{"issue":"4","key":"2019071308555101200_B2","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.beem.2011.05.010","article-title":"Vitamin D receptor (VDR)-mediated actions of 1\u03b1,25(OH)2vitamin D3: genomic and non-genomic mechanisms","volume":"25","author":"Haussler","year":"2011","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"issue":"8","key":"2019071308555101200_B3","doi-asserted-by":"crossref","first-page":"3546","DOI":"10.1172\/JCI98093","article-title":"Optimal bone fracture repair requires 24R,25-dihydroxyvitamin D3 and its effector molecule FAM57B2","volume":"128","author":"Martineau","year":"2018","journal-title":"J Clin Invest"},{"key":"2019071308555101200_B4","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.jsbmb.2017.05.004","article-title":"RCTS are the only appropriate way to demonstrate the role of vitamin D in health","volume":"177","author":"Jorde","year":"2018","journal-title":"J Steroid Biochem Mol Biol"},{"key":"2019071308555101200_B5","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.jsbmb.2017.06.006","article-title":"Limitations of vitamin D supplementation trials: why observational studies will continue to help determine the role of vitamin D in health","volume":"177","author":"Scragg","year":"2018","journal-title":"J Steroid Biochem Mol 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