{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:38:41Z","timestamp":1779237521164,"version":"3.51.4"},"reference-count":45,"publisher":"The Endocrine Society","issue":"2","license":[{"start":{"date-parts":[[2023,9,20]],"date-time":"2023-09-20T00:00:00Z","timestamp":1695168000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000063","name":"National Institutes of Health Office of Dietary Supplements","doi-asserted-by":"crossref","award":["(Nos. R01DK118942"],"award-info":[{"award-number":["(Nos. R01DK118942"]}],"id":[{"id":"10.13039\/100000063","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000063","name":"National Institutes of Health Office of Dietary Supplements","doi-asserted-by":"crossref","award":["R01DK118942-02S1"],"award-info":[{"award-number":["R01DK118942-02S1"]}],"id":[{"id":"10.13039\/100000063","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000063","name":"National Institutes of Health Office of Dietary Supplements","doi-asserted-by":"crossref","award":["T32DK098107)."],"award-info":[{"award-number":["T32DK098107)."]}],"id":[{"id":"10.13039\/100000063","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,1,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Canagliflozin has been reported to increase the risk of bone fracture\u2014possibly mediated by decreasing 1,25-dihydroxyvitamin D (1,25(OH)2D) and increasing parathyroid hormone (PTH).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This work investigated whether baseline vitamin D (VitD) deficiency renders individuals vulnerable to this adverse effect and whether VitD3 supplementation is protective.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This community-based, outpatient study had a paired design comparing individual participants before and after VitD3 supplementation. Eleven VitD-deficient (25-hydroxyvitamin D [25(OH)D] \u2264 20 ng\/mL) individuals were recruited from the Amish population in Lancaster, Pennsylvania. Participants underwent 2 canagliflozin challenge protocols (300 mg daily for 5 days): the first before and the second after VitD3 supplementation. In the VitD3 supplementation protocol, participants received VitD3 supplementation (50 000 IU once or twice a week depending on body mass index for 4-6 weeks) to achieve 25(OH)D of 30 ng\/mL or greater. Two coprimary end points were identified: effects of VitD3 supplementation on canagliflozin-induced changes in 1,25(OH)2D and PTH. Secondary end points included effects of VitD3 supplementation on baseline levels of VitD metabolites and PTH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>VitD3 supplementation increased mean 25(OH)D from 16.5 \u00b1 1.6 to 44.3 \u00b1 5.5 ng\/mL (P = .0006) and 24,25-dihydroxyvitamin D (24,25(OH)2D) from 1.0 \u00b1 0.1 to 4.3 \u00b1 0.6 ng\/mL (P = .0002). Mean 1,25(OH)2D and PTH were unchanged. VitD3 supplementation decreased the magnitude of canagliflozin-induced changes in 1,25(OH)2D (from \u221231.3%\u00b14.7% to \u22129.3%\u00b18.3%; P = .04) and PTH (from +36.2%\u00b16.2% to +9.7%\u00b13.7%; P = .005).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>VitD deficiency rendered individuals more vulnerable to adverse effects of canagliflozin on biomarkers associated with bone health. VitD3 supplementation was protective against canagliflozin's short-term adverse effects on 1,25(OH)2D and PTH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgad554","type":"journal-article","created":{"date-parts":[[2023,9,18]],"date-time":"2023-09-18T17:04:17Z","timestamp":1695056657000},"page":"e646-e656","source":"Crossref","is-referenced-by-count":5,"title":["Vitamin D Deficiency Increases Vulnerability to Canagliflozin-induced Adverse Effects on 1,25-Dihydroxyvitamin D and PTH"],"prefix":"10.1210","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1056-4523","authenticated-orcid":false,"given":"Zhinous","family":"Shahidzadeh Yazdi","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine , Baltimore, MD 21201 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth A","family":"Streeten","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine , Baltimore, MD 21201 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hilary B","family":"Whitlatch","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine , Baltimore, MD 21201 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"May E","family":"Montasser","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine , Baltimore, MD 21201 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amber L","family":"Beitelshees","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine , Baltimore, MD 21201 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7500-7854","authenticated-orcid":false,"given":"Simeon I","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine , Baltimore, MD 21201 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2023,9,20]]},"reference":[{"issue":"24","key":"2024070116370351500_dgad554-B1","doi-asserted-by":"crossref","first-page":"2295","DOI":"10.1056\/NEJMoa1811744","article-title":"Canagliflozin and renal outcomes in type 2 diabetes and nephropathy","volume":"380","author":"Perkovic","year":"2019","journal-title":"N Engl J 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