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Because these factors are often ignored when interpreting S-25OHD, assessment of vitamin D associations with disease outcomes may be distorted. We aimed to investigate the impact of season of blood draw and fat mass on the association of S25OHD with fracture risk. We enrolled 5000 women, mean \u00b1 SD age 68\u2009\u00b1\u20097\u2009years, with dual-energy x-ray absorptiometry (DXA) scans and blood collection in a population-based cohort. Proportional hazards regression, stratified by season and fat mass, was used to determine hazard ratios (HRs) of fracture according to categories of S-25OHD. Our secondary exposures were serum 1,25-dihydroxycholecalciferol (1,25-(OH)2 D3), the most active vitamin D metabolite and plasma parathyroid hormone (P-PTH). During an average of 9.2\u2009years of follow-up, 1080 women had a fracture. Women with S-25OHD &amp;lt;30\u2009nmol\/L drawn during sunny months (May\u2013October) had a multivariable-adjusted fracture HR of 2.06 (95% CI, 1.27\u20133.35) compared with those with S-25OHD &amp;gt;60\u2009nmol\/L; those with S-25OHD 30\u201340\u2009nmol\/L had an HR of 1.59 (95% CI, 1.12\u20132.26). In contrast, S-25OHD drawn during November through April was unrelated to fracture risk. The increased risk with low sunny season S-25OHD was seen only among women with body mass index (BMI) \u226525\u2009kg\/m2 or fat mass index (FMI) \u22659.8\u2009kg\/m2. High fat mass and low S-25OHD were independently related to lower S-1,25-dihydroxycholecalciferol, which itself predicted fracture risk with samples collected during the sunny season. Irrespective of season, P-PTH was unrelated to fracture risk. We conclude that S-25OHD is associated with fracture risk only if drawn during periods of seasonally high levels in women with a high BMI. These results have implications for the evaluation of vitamin D status and can explain the lack of effect seen with vitamin D supplementation in many fracture trials. \u00a9 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).<\/jats:p>","DOI":"10.1002\/jbmr.4400","type":"journal-article","created":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T21:29:17Z","timestamp":1624656557000},"page":"1957-1966","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Serum 25-hydroxyvitamin D is associated with fracture risk only during periods of seasonally high levels in women with a high body mass index"],"prefix":"10.1093","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2815-1217","authenticated-orcid":false,"given":"Karl","family":"Micha\u00eblsson","sequence":"first","affiliation":[{"name":"Department of Surgical Sciences Uppsala University Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4421-6466","authenticated-orcid":false,"given":"Liisa","family":"Byberg","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences Uppsala University Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bodil","family":"Svennblad","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences Uppsala University Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna C.","family":"Larsson","sequence":"additional","affiliation":[{"name":"Unit of Cardiovascular and Nutritional EpidemiologyInstitute of Environmental Medicine Karolinska Institutet Stockholm Sweden"},{"name":"Department of Surgical Sciences Uppsala University Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Baron","sequence":"additional","affiliation":[{"name":"Department of EpidemiologyGillings School of Global Public Health University of North Carolina Chapel Hill North Carolina USA"},{"name":"Department of Medicine University of North Carolina School of Medicine Chapel Hill North Carolina USA"},{"name":"Department of Surgical Sciences Uppsala University Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e5kan","family":"Melhus","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences Uppsala University Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,6,25]]},"reference":[{"key":"2024012713461301300_jbmr4400-bib-0001","volume-title":"Dietary reference intakes for calcium and vitamin D","author":"Ross","year":"2011"},{"issue":"11","key":"2024012713461301300_jbmr4400-bib-0002","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/S2213-8587(18)30265-1","article-title":"Effects of vitamin D supplementation on 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