Treatment of ear and bone disease in the Phex mouse mutant with dietary supplementation

Publication date: Available online 28 September 2016
Source:American Journal of Otolaryngology
Author(s): Cameron C. Wick, Sharon J. Lin, Heping Yu, Cliff A. Megerian, Qing Yin Zheng
HypothesisPhosphorous 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).BackgroundMale Phex mice have X-linked hypophosphatemic rickets (XLH), which includes osteomalacia of the otic capsule. The treatment for XLH is supplementation with phosphorous 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.MethodsFour 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 phosphorous added to its drinking water and intraperitoneal calcitriol from postnatal day (P) 7 – P40. The Phex Rescue group was also supplemented with phosphorous and calcium but only from P20 – 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.ResultsBoth treatment groups had markedly improved otic capsule mineralization with less osteoid deposition. The improved otic capsule mineralize did not prevent the development of ELH or SNHL.ConclusionSupplementation with phosphorous and calcitriol improves otic capsule bone morphology in the Phex male mouse but does not alter development of ELH or SNHL.



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