Cameron C Wick1, Sharon J Lin2, Heping Yu3, Cliff A Megerian3, Qing Yin Zheng3. 1. Department of Otolaryngology, Head and Neck Surgery, University of Texas Southwestern Medical Center, Dallas, TX, U.S.A.. Electronic address: cameron.wick@gmail.com. 2. Department of Otolaryngology, Head and Neck Surgery, University of California - Davis, Sacramento, CA, U.S.A. 3. Ear, Nose, and Throat Institute, University Hospitals Case Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH, U.S.A.
Abstract
HYPOTHESIS: Phosphorus and vitamin D (calcitriol) supplementation in the Phex mouse, a murine model for endolymphatic hydrops (ELH), will improve otic capsule mineralization and secondarily ameliorate the postnatal development of ELH and sensorineural hearing loss (SNHL). BACKGROUND: Male Phex mice have X-linked hypophosphatemic rickets (XLH), which includes osteomalacia of the otic capsule. The treatment for XLH is supplementation with phosphorus and calcitriol. The effect of this treatment has never been studied on otic capsule bone and it is unclear if improving the otic capsule bone could impact the mice's postnatal development of ELH and SNHL. METHODS: Four cohorts were studied: 1) wild-type control, 2) Phex control, 3) Phex prevention, and 4) Phex rescue. The control groups were not given any dietary supplementation. The Phex prevention group was supplemented with phosphorus added to its drinking water and intraperitoneal calcitriol from postnatal day (P) 7-P40. The Phex rescue group was also supplemented with phosphorus and calcium but only from P20 to P40. At P40, all mice underwent auditory brainstem response (ABR) testing, serum analysis, and temporal bone histologic analysis. Primary outcome was otic capsule mineralization. Secondary outcomes were degree of SNHL and presence ELH. RESULTS: Both treatment groups had markedly improved otic capsule mineralization with less osteoid deposition. The improved otic capsule mineralized did not prevent the development of ELH or SNHL. CONCLUSION: Supplementation with phosphorus and calcitriol improves otic capsule bone morphology in the Phex male mouse but does not alter development of ELH or SNHL.
HYPOTHESIS: Phosphorus and vitamin D (calcitriol) supplementation in the Phexmouse, a murine model for endolymphatic hydrops (ELH), will improve otic capsule mineralization and secondarily ameliorate the postnatal development of ELH and sensorineural hearing loss (SNHL). BACKGROUND: Male Phexmice have X-linked hypophosphatemic rickets (XLH), which includes osteomalacia of the otic capsule. The treatment for XLH is supplementation with phosphorus and calcitriol. The effect of this treatment has never been studied on otic capsule bone and it is unclear if improving the otic capsule bone could impact the mice's postnatal development of ELH and SNHL. METHODS: Four cohorts were studied: 1) wild-type control, 2) Phex control, 3) Phex prevention, and 4) Phex rescue. The control groups were not given any dietary supplementation. The Phex prevention group was supplemented with phosphorus added to its drinking water and intraperitoneal calcitriol from postnatal day (P) 7-P40. The Phex rescue group was also supplemented with phosphorus and calcium but only from P20 to P40. At P40, all mice underwent auditory brainstem response (ABR) testing, serum analysis, and temporal bone histologic analysis. Primary outcome was otic capsule mineralization. Secondary outcomes were degree of SNHL and presence ELH. RESULTS: Both treatment groups had markedly improved otic capsule mineralization with less osteoid deposition. The improved otic capsule mineralized did not prevent the development of ELH or SNHL. CONCLUSION: Supplementation with phosphorus and calcitriol improves otic capsule bone morphology in the Phex male mouse but does not alter development of ELH or SNHL.
Authors: Erik A Imel; Linda A DiMeglio; Siu L Hui; Thomas O Carpenter; Michael J Econs Journal: J Clin Endocrinol Metab Date: 2010-02-15 Impact factor: 5.958
Authors: Anna Benet-Pagès; Bettina Lorenz-Depiereux; Hans Zischka; Kenneth E White; Michael J Econs; Tim M Strom Journal: Bone Date: 2004-08 Impact factor: 4.398
Authors: Bettina Lorenz-Depiereux; Victoria E Guido; Kenneth R Johnson; Qing Yin Zheng; Leona H Gagnon; Joiel D Bauschatz; Muriel T Davisson; Linda L Washburn; Leah Rae Donahue; Tim M Strom; Eva M Eicher Journal: Mamm Genome Date: 2004-03 Impact factor: 2.957
Authors: Maximilian M Delsmann; Richard Seist; Julian Stürznickel; Felix N Schmidt; Amer Mansour; Margaret M Kobelski; Gabriel Broocks; Jonathan Peichl; Ralf Oheim; Mark Praetorius; Thorsten Schinke; Michael Amling; Marie B Demay; Konstantina M Stankovic; Tim Rolvien Journal: J Bone Miner Res Date: 2021-10-04 Impact factor: 6.741