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We performed this two-sample Mendelian randomization (MR) analysis to investigate the causal effect of vitamin D on BMD. We extracted 143 single-nucleotide polymorphisms from a recent GWAS on 417,580 participants of European ancestry as instrumental variables, and used summary statistics for BMD at forearm (n\u2009=\u200910,805), femoral neck (n\u2009=\u200949,988), lumbar spine (n\u2009=\u200944,731) and total-body of different age-stages (&lt;\u200915, 15\u201330, 30\u201345, 45\u201360,\u2009&gt;\u200960) (n\u2009=\u200967,358). We explored the direct effect of vitamin D on BMD with an adjusted body mass index (BMI) in a multivariable MR analysis. We found no support for causality of 25-hydroxyvitamin D on BMD at forearm, femoral neck, lumbar spine, and total-body BMD across the lifespan. There was no obvious difference between the total and direct effect of vitamin D on BMD after adjusting for BMI. Our MR analysis provided evidence that genetically determined vitamin D was not causally associated with BMD in the general population. Large-scale randomized controlled trials are warranted to investigate the role of vitamin D supplementation in preventing osteoporosis in the high-risk population.<\/jats:p>","DOI":"10.1038\/s41598-022-14548-5","type":"journal-article","created":{"date-parts":[[2022,6,21]],"date-time":"2022-06-21T10:04:03Z","timestamp":1655805843000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Absence of causal association between Vitamin D and bone mineral density across the lifespan: a Mendelian randomization study"],"prefix":"10.1038","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0371-9216","authenticated-orcid":false,"given":"Yanchao","family":"Tang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9728-7997","authenticated-orcid":false,"given":"Miao","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8149-1002","authenticated-orcid":false,"given":"Yongqiang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyong","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5284-6097","authenticated-orcid":false,"given":"Xiaoguang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,6,21]]},"reference":[{"key":"14548_CR1","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1016\/j.beem.2008.06.001","volume":"22","author":"C Holroyd","year":"2008","unstructured":"Holroyd, C., Cooper, C. & Dennison, E. 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