{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T02:15:05Z","timestamp":1784168105042,"version":"3.55.0"},"reference-count":76,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:00:00Z","timestamp":1693526400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"China\u2013Australia Centre for Health Sciences Research"},{"name":"Bone Health Foundation"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Cancers"],"abstract":"<jats:p>Vitamin D deficiency or insufficiency is prevalent in childhood cancer patients and survivors after chemotherapy; further studies are needed to investigate the underlying aetiology and effectiveness of vitamin D supplementation in preventing chemotherapy-induced bone loss. This study used a rat model of treatment with antimetabolite methotrexate to investigate whether methotrexate chemotherapy causes vitamin D deficiency and if vitamin D supplementation attenuates the resultant bone loss. Methotrexate treatment (five daily injections) decreased serum vitamin D levels (from 52 to &lt;30 ng\/mL), reduced body and bone lengthening and tibial trabecular bone volume, and altered intestinal vitamin D metabolism, which was associated with intestinal mucosal damage known to cause malabsorption of nutrients, including dietary vitamin D and calcium. During the early stage after chemotherapy, mRNA expression increased for vitamin D activation enzyme CYP27B1 and for calcium-binding protein TRPV6 in the intestine. During the intestinal healing stage, expression of vitamin D catabolism enzyme CYP24 increased, and that of TRPV6 was normalised. Furthermore, subcutaneous calcitriol supplementation diminished methotrexate-induced bone loss due to its effect suppressing methotrexate-induced increased bone resorption. Thus, in young rats, methotrexate chemotherapy causes vitamin D deficiency, growth impairments, bone loss, and altered intestinal vitamin D metabolism, which are associated with intestinal damage, and vitamin D supplementation inhibits methotrexate-induced bone loss.<\/jats:p>","DOI":"10.3390\/cancers15174367","type":"journal-article","created":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T08:45:31Z","timestamp":1693557931000},"page":"4367","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Methotrexate Chemotherapy Causes Growth Impairments, Vitamin D Deficiency, Bone Loss, and Altered Intestinal Metabolism\u2014Effects of Calcitriol Supplementation"],"prefix":"10.3390","volume":"15","author":[{"given":"Yu-Wen","family":"Su","sequence":"first","affiliation":[{"name":"UniSA Clinical and Health Sciences, University of South Australia, Adelaide, SA 5001, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice M. C.","family":"Lee","sequence":"additional","affiliation":[{"name":"UniSA Clinical and Health Sciences, University of South Australia, Adelaide, SA 5001, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xukang","family":"Xu","sequence":"additional","affiliation":[{"name":"UniSA Clinical and Health Sciences, University of South Australia, Adelaide, SA 5001, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Belinda","family":"Hua","sequence":"additional","affiliation":[{"name":"UniSA Clinical and Health Sciences, University of South Australia, Adelaide, SA 5001, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"Tapp","sequence":"additional","affiliation":[{"name":"Department of Haematology & Oncology, Women\u2019s and Children\u2019s Hospital, North Adelaide, SA 5006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue-Sen","family":"Wen","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8467-2845","authenticated-orcid":false,"given":"Cory J.","family":"Xian","sequence":"additional","affiliation":[{"name":"UniSA Clinical and Health Sciences, University of South Australia, Adelaide, SA 5001, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1038\/sj.leu.2402078","article-title":"Bone mineral decrements in survivors of childhood acute lymphoblastic leukemia: Frequency of occurrence and risk factors for their development","volume":"15","author":"Kaste","year":"2001","journal-title":"Leukemia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1002\/pbc.21408","article-title":"Skeletal toxicities of treatment in children with cancer","volume":"50","author":"Kaste","year":"2008","journal-title":"Pediatr. 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