{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:26:28Z","timestamp":1787063188842,"version":"build-2736575974"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T00:00:00Z","timestamp":1696118400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"},{"start":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T00:00:00Z","timestamp":1691452800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100007146","name":"Allgemeine Unfallversicherungsanstalt","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007146","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Austrian Social Health Insurance Fund"},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["AR049069"],"award-info":[{"award-number":["AR049069"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007146","name":"Allgemeine Unfallversicherungsanstalt","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007146","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["AR049069"],"award-info":[{"award-number":["AR049069"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["asbmr.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,10,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Vitamin C (VitC) is essential for bone health, and low VitC serum levels increase the risk for skeletal fractures. If and how VitC affects bone mineralization is unclear. Using micro-computed tomography (\u03bcCT), histologic staining, as well as quantitative backscattered electron imaging (qBEI), we assessed the effects of VitC on femoral structure and microarchitecture, bone formation, and bone mineralization density distribution (BMDD) in the VitC incompetent Gulo\u2212\/\u2212 mouse model and wild-type mice. In particular, VitC-supplemented, 20-week-old mice were compared with age-matched counterparts where dietary VitC intake was excluded from week 15. VitC depletion in Gulo\u2212\/\u2212 mice severely reduced cortical thickness of the diaphyseal shaft and bone volume around the growth plate (eg, bone volume of the primary spongiosa \u221243%, p\u2009&amp;lt;\u20090.001). Loss of VitC also diminished the amount of newly formed bone tissue as visualized by histology and calcein labeling of the active mineralization front. BMDD analysis revealed a shift to higher calcium concentrations upon VitC supplementation, including higher average (~10% increase in female VitC deficient mice, p\u2009&amp;lt;\u20090.001) and peak calcium concentrations in the epiphyseal and metaphyseal spongiosa. These findings suggest higher bone tissue age. Importantly, loss of VitC had significantly more pronounced effects in female mice, indicating a higher sensitivity of their skeleton to VitC deficiency. Our results reveal that VitC plays a key role in bone formation rate, which directly affects mineralization. We propose that low VitC levels may contribute to the higher prevalence of bone-degenerative diseases in females and suggest leveraging this vitamin against these conditions. \u00a9 2023 American Society for Bone and Mineral Research (ASBMR).<\/jats:p>\n                  <jats:p>Abstract<\/jats:p>\n                  <jats:p>Vitamin C deficiency disrupts bone microarchitecture, as well as bone formation and mineralization in Gulo\u2212\/\u2212 mice, which emphasizes the importance of this micronutrient for the skeleton. Importantly, the female skeleton is significantly more sensitive to vitamin C deficiency than the male skeleton, indicating sex-specific differences in vitamin C requirements for bone.<\/jats:p>","DOI":"10.1002\/jbmr.4889","type":"journal-article","created":{"date-parts":[[2023,7,26]],"date-time":"2023-07-26T10:30:20Z","timestamp":1690367420000},"page":"1509-1520","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Vitamin C Deficiency Deteriorates Bone Microarchitecture and Mineralization in a Sex-Specific Manner in Adult Mice"],"prefix":"10.1093","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6575-8443","authenticated-orcid":false,"given":"St\u00e9phane","family":"Blouin","sequence":"first","affiliation":[{"name":"Ludwig Boltzmann Institute of Osteology at Hanusch Hospital of OEGK and AUVA Trauma Centre Meidling 1st Med. Dept. Hanusch Hospital Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farzaneh","family":"Khani","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Molecular Biology Mayo Clinic Rochester MN USA"},{"name":"Department of Orthopedic Surgery Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phaedra","family":"Messmer","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute of Osteology at Hanusch Hospital of OEGK and AUVA Trauma Centre Meidling 1st Med. Dept. Hanusch Hospital Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Roschger","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute of Osteology at Hanusch Hospital of OEGK and AUVA Trauma Centre Meidling 1st Med. Dept. Hanusch Hospital Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6046-0365","authenticated-orcid":false,"given":"Markus A.","family":"Hartmann","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute of Osteology at Hanusch Hospital of OEGK and AUVA Trauma Centre Meidling 1st Med. Dept. Hanusch Hospital Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4458-0946","authenticated-orcid":false,"given":"Andre J.","family":"van Wijnen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry University of Vermont Burlington VT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5515-8719","authenticated-orcid":false,"given":"Roman","family":"Thaler","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Molecular Biology Mayo Clinic Rochester MN USA"},{"name":"Department of Orthopedic Surgery Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9923-4920","authenticated-orcid":false,"given":"Barbara M.","family":"Misof","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute of Osteology at Hanusch Hospital of OEGK and AUVA Trauma Centre Meidling 1st Med. Dept. Hanusch Hospital Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,10,1]]},"reference":[{"key":"2024022211040084600_jbmr4889-bib-0001","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1002\/jbmr.2709","article-title":"The roles and mechanisms of actions of vitamin C in bone: new developments","volume":"30","author":"Aghajanian","year":"2015","journal-title":"J Bone Miner Res"},{"key":"2024022211040084600_jbmr4889-bib-0002","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.3945\/ajcn.2008.27016","article-title":"Serum vitamin C and the prevalence of vitamin C deficiency in the United States: 2003-2004 National Health and nutrition examination survey (NHANES)","volume":"90","author":"Schleicher","year":"2009","journal-title":"Am J Clin Nutr"},{"key":"2024022211040084600_jbmr4889-bib-0003","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1093\/pubmed\/fdn076","article-title":"Estimated prevalence and predictors of vitamin C deficiency within UK's low-income population","volume":"30","author":"Mosd\u00f8l","year":"2008","journal-title":"J Public Health (Oxf)"},{"key":"2024022211040084600_jbmr4889-bib-0004","doi-asserted-by":"crossref","first-page":"2394","DOI":"10.3390\/nu12082394","article-title":"Role of vitamin C in osteoporosis development and treatment\u2014a literature review","volume":"12","author":"Brzezi\u0144ska","year":"2020","journal-title":"Nutrients"},{"key":"2024022211040084600_jbmr4889-bib-0005","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.3390\/nu13031012","article-title":"Evidence of a positive link between consumption and supplementation of ascorbic acid and bone mineral density","volume":"13","author":"Rondanelli","year":"2021","journal-title":"Nutrients"},{"key":"2024022211040084600_jbmr4889-bib-0006","doi-asserted-by":"crossref","first-page":"5883","DOI":"10.1038\/s41467-022-32915-8","article-title":"Vitamin C epigenetically controls osteogenesis and bone mineralization","volume":"13","author":"Thaler","year":"2022","journal-title":"Nat Commun"},{"key":"2024022211040084600_jbmr4889-bib-0007","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1007\/BF02555792","article-title":"Bone histomorphometric analysis for the cause of osteopenia in vitamin C-deficient rat (ODS rat)","volume":"48","author":"Tsunenari","year":"1991","journal-title":"Calcif Tissue Int"},{"key":"2024022211040084600_jbmr4889-bib-0008","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1073\/pnas.97.2.841","article-title":"Aortic wall damage in mice unable to synthesize ascorbic acid","volume":"97","author":"Maeda","year":"2000","journal-title":"Proc Natl Acad Sci USA"},{"key":"2024022211040084600_jbmr4889-bib-0009","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1254\/jjp.68.255","article-title":"Alteration of bone status with ascorbic acid deficiency in ODS (osteogenic disorder Shionogi) rats","volume":"68","author":"Togari","year":"1995","journal-title":"Jpn J Pharmacol"},{"key":"2024022211040084600_jbmr4889-bib-0010","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1359\/JBMR.050406","article-title":"Spontaneous fractures in the mouse mutant sfx are caused by deletion of the gulonolactone oxidase gene, causing vitamin C deficiency","volume":"20","author":"Mohan","year":"2005","journal-title":"J Bone Miner Res"},{"key":"2024022211040084600_jbmr4889-bib-0011","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/S0021-9258(18)64830-6","article-title":"Biosynthesis of collagen; 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