{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T14:35:11Z","timestamp":1756996511803,"version":"3.41.2"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,6]],"date-time":"2022-06-06T00:00:00Z","timestamp":1654473600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>Intact mineralization of the auditory ossicles - the smallest bones in the body - is essential for sound transmission in the middle ear, while ossicular hypomineralization is associated with conductive hearing loss. Here, we performed a high-resolution analysis of the ossicles in vitamin D receptor deficient mice (<jats:italic>Vdr<jats:sup>-\/-<\/jats:sup><\/jats:italic>), which are characterized by hypocalcemia and skeletal mineralization defects, and investigated whether local hypomineralization can be prevented by feeding a calcium-rich rescue diet (<jats:italic>Vdr<jats:sup>-\/- res<\/jats:sup><\/jats:italic>). In <jats:italic>Vdr<jats:sup>-\/-<\/jats:sup><\/jats:italic> mice fed a regular diet (<jats:italic>Vdr<jats:sup>-\/- reg<\/jats:sup><\/jats:italic>), quantitative backscattered electron imaging (qBEI) revealed an increased void volume (porosity, p&amp;lt;0.0001) along with lower mean calcium content (CaMean, p=0.0008) and higher heterogeneity of mineralization (CaWidth, p=0.003) compared to WT mice. Furthermore, a higher osteoid volume per bone volume (OV\/BV; p=0.0002) and a higher osteocyte lacunar area (Lc.Ar; p=0.01) were found in histomorphometric analysis in <jats:italic>Vdr<jats:sup>-\/- reg<\/jats:sup><\/jats:italic> mice. In <jats:italic>Vdr<jats:sup>-\/- res<\/jats:sup><\/jats:italic> mice, full rescue of OV\/BV and Lc.Ar (both p&amp;gt;0.05 vs. WT) and partial rescue of porosity and CaWidth (p=0.02 and p=0.04 vs. WT) were observed. Compared with <jats:italic>Hyp<\/jats:italic> mice, a model of X-linked hypophosphatemic rickets, <jats:italic>Vdr<jats:sup>-\/- reg<\/jats:sup><\/jats:italic> mice showed a lower osteoid volume in the ossicles (p=0.0002), but similar values in the lumbar spine. These results are consistent with later postnatal impairment of mineral homeostasis in <jats:italic>Vdr<jats:sup>-\/-<\/jats:sup><\/jats:italic> mice than in <jats:italic>Hyp<\/jats:italic> mice, underscoring the importance of intact mineral homeostasis for ossicle mineralization during development. In conclusion, we revealed a distinct phenotype of hypomineralization in the auditory ossicles of <jats:italic>Vdr<jats:sup>-\/-<\/jats:sup><\/jats:italic> mice that can be partially prevented by a rescue diet. Since a positive effect of a calcium-rich diet on ossicular mineralization was demonstrated, our results open new treatment strategies for conductive hearing loss. Future studies should investigate the impact of improved ossicular mineralization on hearing function.<\/jats:p>","DOI":"10.3389\/fendo.2022.901265","type":"journal-article","created":{"date-parts":[[2022,6,6]],"date-time":"2022-06-06T09:41:03Z","timestamp":1654508463000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Prevention of Hypomineralization In Auditory Ossicles of Vitamin D Receptor (Vdr) Deficient Mice"],"prefix":"10.3389","volume":"13","author":[{"given":"Maximilian M.","family":"Delsmann","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Peichl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timur A.","family":"Yorgan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank 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