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In XLH, increased circulating fibroblast growth factor 23 (FGF23) levels cause renal phosphate wasting and low concentrations of 1,25-dihydroxyvitamin D, leading to an early clinical manifestation of rickets. Importantly, hearing loss is commonly observed in XLH patients. We present here data from two XLH patients with marked conductive hearing loss. To decipher the underlying pathophysiology of hearing loss in XLH, we utilized the Hyp mouse model of XLH and measured auditory brain stem responses (ABRs) and distortion product otoacoustic emissions (DPOAEs) to functionally assess hearing. As evidenced by the increased ABR\/DPOAE threshold shifts in the mid-frequency range, these measurements indicated a predominantly conductive hearing loss in Hyp mice compared to wild-type (WT) mice. Therefore, we carried out an in-depth histomorphometric and scanning electron microscopic analysis of the auditory ossicles. Quantitative backscattered electron imaging (qBEI) indicated a severe hypomineralization of the ossicles in Hyp mice, evidenced by lower calcium content (CaMean) and higher void volume (ie, porosity) compared to WT mice. Histologically, voids correlated with unmineralized bone (ie, osteoid), and the osteoid volume per bone volume (OV\/BV) was markedly higher in Hyp mice than WT mice. The density of osteocyte lacunae was lower in Hyp mice than in WT mice, whereas osteocyte lacunae were enlarged. Taken together, our findings highlight the importance of ossicular mineralization for hearing conduction and point toward the potential benefit of improving mineralization to prevent hearing loss in XLH. \u00a9 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).<\/jats:p>","DOI":"10.1002\/jbmr.4443","type":"journal-article","created":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T09:13:24Z","timestamp":1631697204000},"page":"2317-2328","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Conductive Hearing Loss in the <i>Hyp<\/i> Mouse Model of X-Linked Hypophosphatemia Is Accompanied by Hypomineralization of the Auditory Ossicles"],"prefix":"10.1093","volume":"36","author":[{"given":"Maximilian M.","family":"Delsmann","sequence":"first","affiliation":[{"name":"Department of Trauma and Orthopaedic Surgery, Division of Orthopaedics University Medical Center Hamburg-Eppendorf Hamburg Germany"},{"name":"Department of Osteology and Biomechanics University Medical Center Hamburg Eppendorf Hamburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Seist","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery Stanford University School of Medicine Stanford CA USA"},{"name":"Department of Otolaryngology-Head and Neck Surgery Massachusetts Eye and Ear and Harvard Medical School Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julian","family":"St\u00fcrznickel","sequence":"additional","affiliation":[{"name":"Department of Trauma and Orthopaedic Surgery, Division of Orthopaedics University Medical Center Hamburg-Eppendorf Hamburg Germany"},{"name":"Department of Osteology and Biomechanics University Medical Center Hamburg Eppendorf Hamburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felix N.","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Department of Osteology and Biomechanics University Medical Center Hamburg Eppendorf Hamburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amer","family":"Mansour","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery Massachusetts Eye and Ear and Harvard Medical School Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margaret M.","family":"Kobelski","sequence":"additional","affiliation":[{"name":"Endocrine Unit Massachusetts General Hospital, Harvard Medical School Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriel","family":"Broocks","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Interventional Neuroradiology University Medical Center Hamburg-Eppendorf Hamburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Peichl","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology University Medical Center Hamburg-Eppendorf Hamburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9449-5013","authenticated-orcid":false,"given":"Ralf","family":"Oheim","sequence":"additional","affiliation":[{"name":"Department of Osteology and Biomechanics University Medical Center Hamburg Eppendorf Hamburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Praetorius","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology University Medical Center Hamburg-Eppendorf Hamburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thorsten","family":"Schinke","sequence":"additional","affiliation":[{"name":"Department of Osteology and Biomechanics University Medical Center Hamburg Eppendorf Hamburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2382-8348","authenticated-orcid":false,"given":"Michael","family":"Amling","sequence":"additional","affiliation":[{"name":"Department of Osteology and Biomechanics University Medical Center Hamburg Eppendorf Hamburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5845-5479","authenticated-orcid":false,"given":"Marie B","family":"Demay","sequence":"additional","affiliation":[{"name":"Endocrine Unit Massachusetts General Hospital, Harvard Medical School Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Konstantina M","family":"Stankovic","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery Stanford University School of Medicine Stanford CA USA"},{"name":"Department of Otolaryngology-Head and Neck Surgery Massachusetts Eye and Ear and Harvard Medical School Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1058-1307","authenticated-orcid":false,"given":"Tim","family":"Rolvien","sequence":"additional","affiliation":[{"name":"Department of Trauma and Orthopaedic Surgery, Division of Orthopaedics University Medical Center Hamburg-Eppendorf Hamburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,9,15]]},"reference":[{"issue":"3","key":"2024012713454643200_jbmr4443-bib-0001","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1530\/EJE-08-0818","article-title":"Incidence and prevalence of nutritional and hereditary rickets in southern Denmark","volume":"160","author":"Beck-Nielsen","year":"2009","journal-title":"Eur J Endocrinol"},{"issue":"39","key":"2024012713454643200_jbmr4443-bib-0002","doi-asserted-by":"crossref","first-page":"37419","DOI":"10.1074\/jbc.M304544200","article-title":"Regulation of 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