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Because the cardiovascular effect of alfacalcidol could be modulated by bone turnover status, this post-hoc analysis of the J-DAVID examined how alkaline phosphatase (ALP), a more precise marker of bone turnover than parathyroid hormone (PTH), modifies the impact of alfacalcidol. The J-DAVID was a 48-month, open-label, randomized controlled trial comparing oral alfacalcidol with no vitamin D receptor activators use in terms of cardiovascular events among 976 hemodialysis patients without secondary hyperparathyroidism. This post-hoc analysis included 959 patients with available data on baseline ALP. The median [25\u201375th percentile] baseline ALP level was 234 [183\u2013296] U\/L. In a Cox proportional hazards model, ALP did not significantly modify the effect of alfacalcidol on the rate of cardiovascular events or all-cause death (<jats:italic>P<\/jats:italic> for effect modification\u2009=\u20090.54 and 0.74, respectively). The effect of alfacalcidol on time-series changes in calcium, phosphate, and intact PTH were similar across ALP subgroups. In conclusion, oral alfacalcidol did not significantly affect cardiovascular outcomes irrespective of bone turnover status.<\/jats:p>","DOI":"10.1038\/s41598-022-19820-2","type":"journal-article","created":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T15:03:03Z","timestamp":1663167783000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Effects of alfacalcidol on cardiovascular outcomes according to alkaline phosphatase levels in the J-DAVID trial"],"prefix":"10.1038","volume":"12","author":[{"given":"Tatsufumi","family":"Oka","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yusuke","family":"Sakaguchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshitaka","family":"Isaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haruka","family":"Ishii","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daijiro","family":"Kabata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayumi","family":"Shintani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinya","family":"Nakatani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoaki","family":"Morioka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katsuhito","family":"Mori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaaki","family":"Inaba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masanori","family":"Emoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuo","family":"Shoji","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,9,14]]},"reference":[{"key":"19820_CR1","doi-asserted-by":"publisher","first-page":"422","DOI":"10.7326\/M17-2640","volume":"168","author":"M Ketteler","year":"2018","unstructured":"Ketteler, M. et al. 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Y.S. received personal fees and research grant from Chugai Pharmaceutical, Kyowa Kirin, Bayer Yakuhin, Ono Pharmaceutical, Kissei Pharmaceutical, Torii Pharmaceutical, Mitsubishi Tanabe, and Fuso Pharmaceutical, outside the submitted work. Y.I. received grants and personal fees from Chugai Pharmaceutical, grants and personal fees from Kyowa Kirin, and personal fees from Kissei Pharmaceutical outside the submitted work. H.I. was employee of Kyowa Kirin. D.K. received personal fees from Chugai Pharmaceutical; research grant and consultation fee for statistical analysis from Kyowa Kirin; and personal fees and research grant from Bayer Yakuhin outside the submitted work. A.S. received personal fees from Chugai Pharmaceutical, Bayer Yakuhin, and Ono Pharmaceutical; and personal fees and research grants from Kyowa Kirin, Takeda Pharmaceutical, and Daiichi Sankyo outside the submitted work. S.N. received personal fees from Chugai Pharmaceutical, Kyowa Kirin, Bayer Yakuhin, Ono Pharmaceutical, Kissei Pharmaceutical, and Torii Pharmaceutical. T. M. received personal fees from Ono Pharmaceutical. K.M. received personal fees from Ono Pharmaceutical; he served as the principal investigator of a clinical trial for Kyowa Kirin; and personal fees and research grant from Mitsubishi Tanabe outside the submitted work. M.I. received personal fees from Chugai Pharmaceutical, Kyowa Kirin, Bayer Yakuhin, Ono Pharmaceutical, Kissei Pharmaceutical, and Torii Pharmaceutical outside the submitted work. M.E. received personal fees from Kissei Pharmaceutical, AstraZeneca, and Torii Pharmaceutical; and personal fees and research grants from Chugai Pharmaceutical, Kyowa Kirin, Ono Pharmaceutical, Nippon Boehringer Ingelheim, and Mitsubishi Tanabe outside the submitted work. T.S. received personal fees from Chugai Pharmaceutical, Kyowa Kirin, and Kissei Pharmaceutical; and personal fees and research grants from Bayer Yakuhin, and Ono Pharmaceutical outside the submitted work.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"15463"}}