{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T13:20:41Z","timestamp":1791638441655,"version":"4.3.4"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2023,7,17]],"date-time":"2023-07-17T00:00:00Z","timestamp":1689552000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["asbmr.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Bone & Mineral Res"],"published-print":{"date-parts":[[2023,9]]},"abstract":"ABSTRACT<\/jats:title>\n \n In a 36\u2010month randomized controlled trial examining the effect of high\u2010dose vitamin D\n 3<\/jats:sub>\n on radial and tibial total bone mineral density (TtBMD), measured by high\u2010resolution peripheral quantitative tomography (HR\u2010pQCT), participants (311 healthy males and females aged 55\u201370\u2009years with dual\u2010energy X\u2010ray absorptiometry T\u2010scores > \u22122.5 without vitamin D deficiency) were randomized to receive 400\u2009IU (\n N<\/jats:italic>\n \u2009=\u2009109), 4000\u2009IU (\n N<\/jats:italic>\n \u2009=\u2009100), or 10,000\u2009IU (\n N<\/jats:italic>\n \u2009=\u2009102) daily. Participants had HR\u2010pQCT radius and tibia scans and blood sampling at baseline, 6, 12, 24, and 36\u2009months. This secondary analysis examined the effect of vitamin D dose on plasma measurements of the vitamin D metabolome by liquid chromatography\u2013tandem mass spectrometry (LC\u2010MS\/MS), exploring whether the observed decline in TtBMD was associated with changes in four key metabolites [25\u2010(OH)D\n 3<\/jats:sub>\n ; 24,25\u2010(OH)\n 2<\/jats:sub>\n D\n 3<\/jats:sub>\n ; 1,25\u2010(OH)\n 2<\/jats:sub>\n D\n 3<\/jats:sub>\n ; and 1,24,25\u2010(OH)\n 3<\/jats:sub>\n D\n 3<\/jats:sub>\n ]. The relationship between peak values in vitamin D metabolites and changes in TtBMD over 36\u2009months was assessed using linear regression, controlling for sex. Increasing vitamin D dose was associated with a marked increase in 25\u2010(OH)D\n 3<\/jats:sub>\n , 24,25\u2010(OH)\n 2<\/jats:sub>\n D\n 3<\/jats:sub>\n and 1,24,25\u2010(OH)\n 3<\/jats:sub>\n D\n 3<\/jats:sub>\n , but no dose\u2010related change in plasma 1,25\u2010(OH)\n 2<\/jats:sub>\n D\n 3<\/jats:sub>\n was observed. There was a significant negative slope for radius TtBMD and 1,24,25\u2010(OH)\n 3<\/jats:sub>\n D\n 3<\/jats:sub>\n (\u22120.05, 95% confidence interval [CI] \u22120.08, \u22120.03,\n p<\/jats:italic>\n \u2009<\u20090.001) after controlling for sex. A significant interaction between TtBMD and sex was seen for 25\u2010(OH)D\n 3<\/jats:sub>\n (female: \u22120.01, 95% CI \u22120.12, \u22120.07; male: \u22120.04, 95% CI \u22120.06, \u22120.01,\n p<\/jats:italic>\n \u2009=\u20090.001) and 24,25\u2010(OH)\n 2<\/jats:sub>\n D\n 3<\/jats:sub>\n (female: \u22120.75, 95% CI \u22120.98, \u22120.52; male: \u22120.35, 95% CI \u22120.59, \u22120.11,\n p<\/jats:italic>\n \u2009<\u20090.001). For the tibia there was a significant negative slope for 25\u2010(OH)D\n 3<\/jats:sub>\n (\u22120.03, 95% CI \u22120.05, \u22120.01,\n p<\/jats:italic>\n \u2009<\u20090.001), 24,25\u2010(OH)\n 2<\/jats:sub>\n D\n 3<\/jats:sub>\n (\u22120.30, 95% CI \u22120.44, \u22120.16,\n p<\/jats:italic>\n \u2009<\u20090.001), and 1,24,25\u2010(OH)\n 3<\/jats:sub>\n D\n 3<\/jats:sub>\n (\u22120.03, 95% CI \u22120.05, \u22120.01,\n p<\/jats:italic>\n \u2009=\u20090.01) after controlling for sex. These results suggest vitamin D metabolites other than 1,25\u2010(OH)\n 2<\/jats:sub>\n D\n 3<\/jats:sub>\n may be responsible for the bone loss seen in the Calgary Vitamin D Study. Although plasma 1,25\u2010(OH)\n 2<\/jats:sub>\n D\n 3<\/jats:sub>\n did not change with vitamin D dose, it is possible rapid catabolism to 1,24,25\u2010(OH)\n 3<\/jats:sub>\n D\n 3<\/jats:sub>\n prevented the detection of a dose\u2010related rise in plasma 1,25\u2010(OH)\n 2<\/jats:sub>\n D\n 3<\/jats:sub>\n . \u00a9 2023 The Authors.\n Journal of Bone and Mineral Research<\/jats:italic>\n published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).\n <\/jats:p>","DOI":"10.1002\/jbmr.4876","type":"journal-article","created":{"date-parts":[[2023,7,6]],"date-time":"2023-07-06T08:49:17Z","timestamp":1688633357000},"page":"1312-1321","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Measurements of the Vitamin D Metabolome in the Calgary Vitamin D Study: Relationship of Vitamin D Metabolites to Bone 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Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7402-3473","authenticated-orcid":false,"given":"Glenville","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Molecular Sciences Queen's University Kingston Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma O.","family":"Billington","sequence":"additional","affiliation":[{"name":"McCaig Institute for Bone and Joint Health, Cumming School of Medicine University of Calgary Calgary Alberta Canada"},{"name":"Division of Endocrinology & Metabolism, Cumming School of Medicine University of Calgary Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2930-5997","authenticated-orcid":false,"given":"Steven K.","family":"Boyd","sequence":"additional","affiliation":[{"name":"McCaig Institute for Bone and Joint Health, Cumming School of Medicine 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