title: Treatment of ear and bone disease in the Phex mouse mutant with dietary supplementation.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Otolaryngology, Head and Neck Surgery, University of Texas Southwestern Medical Center, Dallas, TX, U.S.A.. Electronic address: cameron.wick@gmail.com.
authors.forename: Cameron C
authors.initials: CC
authors.lastname: Wick
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, University of California - Davis, Sacramento, CA, U.S.A.
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Lin
authors.affiliation: Ear, Nose, and Throat Institute, University Hospitals Case Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH, U.S.A.
authors.forename: Heping
authors.initials: H
authors.lastname: Yu
authors.affiliation: Ear, Nose, and Throat Institute, University Hospitals Case Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH, U.S.A.
authors.forename: Cliff A
authors.initials: CA
authors.lastname: Megerian
authors.affiliation: Ear, Nose, and Throat Institute, University Hospitals Case Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH, U.S.A.
authors.forename: Qing Yin
authors.initials: QY
authors.lastname: Zheng
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001707:Biopsy, Needle; D001847:Bone Diseases / Q000175:diagnosis / Q000628:therapy*; D002117:Calcitriol / Q000494:pharmacology; D019587:Dietary Supplements; D004195:Disease Models, Animal; D004427:Ear Diseases / Q000175:diagnosis / Q000628:therapy*; D018159:Endolymphatic Hydrops / Q000175:diagnosis / Q000628:therapy; D016057:Evoked Potentials, Auditory, Brain Stem; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis / Q000628:therapy*; D006801:Humans; D007015:Hypophosphatemia, Familial / Q000175:diagnosis / Q000628:therapy*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D010758:Phosphorus / Q000494:pharmacology; D011897:Random Allocation; D016896:Treatment Outcome
chemical_list: D010758:Phosphorus; D002117:Calcitriol