{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,4]],"date-time":"2025-10-04T14:41:53Z","timestamp":1759588913765},"reference-count":45,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,5,20]],"date-time":"2016-05-20T00:00:00Z","timestamp":1463702400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Vitamin D<jats:sub>3<\/jats:sub> is important for calcium and phosphate homeostasis. To exert its effects, vitamin D<jats:sub>3<\/jats:sub> has to be enzymatically activated into 1,25D<jats:sub>3<\/jats:sub> (1,25\u2010dihydroxyvitamin D<jats:sub>3<\/jats:sub>). Regulation by endogenous vitamin D metabolites of the activation and inactivation of 1,25D<jats:sub>3<\/jats:sub> is important to maintain adequate amounts of active vitamin D<jats:sub>3<\/jats:sub>. Vitamin D deficiency and low bone mineral density have been linked to treatments with antiretroviral drugs and glucocorticoids. However, the causes of drug\u2010induced osteoporosis remain unclear. The antiretroviral drugs efavirenz and ritonavir as well as the glucocorticoid dexamethasone were included in this study. Their effects on transcription of vitamin D\u2010regulating enzymes in <jats:styled-content style=\"fixed-case\">MG<\/jats:styled-content>\u201063 cells were investigated. Ritonavir and dexamethasone both induced transcription of <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>27B1, the enzyme responsible for the formation of 1,25D<jats:sub>3<\/jats:sub>. Efavirenz, however, suppressed <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>27B1 expression. When administered together with endogenous vitamin D metabolites, dexamethasone and efavirenz counteracted the 1,25D<jats:sub>3<\/jats:sub>\u2010mediated up\u2010regulation of <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>24A1, which inactivates 1,25D<jats:sub>3<\/jats:sub>. This suggests that the drugs may interfere with local regulation of the vitamin D metabolizing system in osteoblasts. Studies on mineralization were performed in <jats:styled-content style=\"fixed-case\">MG<\/jats:styled-content>\u201063 cells and Saos\u20102 cells by measuring calcium concentrations accumulated over time. The effects of efavirenz, ritonavir and dexamethasone and\/or vitamin D metabolites were examined. 1,25D<jats:sub>3<\/jats:sub> induced mineralization in both cell lines. Efavirenz administered alone did not affect mineralization but suppressed the inducing effects of 1,25D<jats:sub>3<\/jats:sub> on mineralization in both <jats:styled-content style=\"fixed-case\">MG<\/jats:styled-content>\u201063 cells and Saos\u20102 cells. In summary, the results suggest that antiretroviral drugs and glucocorticoids may adversely affect bone by interference with the vitamin D system in osteoblasts.<\/jats:p>","DOI":"10.1111\/bcpt.12612","type":"journal-article","created":{"date-parts":[[2016,4,21]],"date-time":"2016-04-21T12:48:29Z","timestamp":1461242909000},"page":"436-442","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Effects of Osteoporosis\u2010Inducing Drugs on Vitamin D\u2010Related Gene Transcription and Mineralization in <scp>MG<\/scp>\u201063 and Saos\u20102 Cells"],"prefix":"10.1111","volume":"119","author":[{"given":"Christine","family":"Wegler","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Biosciences Uppsala University Uppsala Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kjell","family":"Wikvall","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical 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