Ovariectomy stimulates and bisphosphonates inhibit intracortical remodeling in the mouse mandible

D. J. Kubek, D. B. Burr, M. R. Allen

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Objective - The pathophysiology of osteonecrosis of the jaw (ONJ) is thought to be linked to suppression of intracortical remodeling. The aim of this study was to determine whether mice, which normally do not undergo appreciable amounts of intracortical remodeling, could be stimulated by ovariectomy to remodel within the cortex of the mandible and if bisphosphonates (BPs) would suppress this intracortical remodeling. Material and Methods - Skeletally mature female C3H mice were either ovariectomized (OVX) or SHAM operated and treated with two intravenous doses of zoledronic acid (ZOL, 0.06 mg/kg body weight) or vehicle (VEH). This ZOL dose corresponds to the dose given to patients with cancer on a mg/kg basis, adjusted for body weight. Calcein was administered prior to sacrifice to label active formation sites. Dynamic histomorphometry of the mandible and femur was performed. Results - Vehicle-treated OVX animals had significantly higher (eightfold) intracortical remodeling of the alveolar portion of the mandible compared to sham - this was significantly suppressed by ZOL treatment. At all skeletal sites, overall bone formation rate was lower with ZOL treatment compared to the corresponding VEH group. Conclusions - Under normal conditions, the level of intracortical remodeling in the mouse mandible is minimal but in C3H mice it can be stimulated to appreciable levels with ovariectomy. Based on this, if the suppression of intracortical remodeling is found to be part of the pathophysiology of ONJ, the ovariectomized C3H mouse could serve as a useful tool for studying this condition.

Original languageEnglish (US)
Pages (from-to)214-222
Number of pages9
JournalOrthodontics and Craniofacial Research
Volume13
Issue number4
DOIs
StatePublished - Nov 1 2010

Keywords

  • BRONJ
  • Jaw necrosis
  • Osteonecrosis
  • Osteonecrosis of the jaw
  • Zoledronic acid

ASJC Scopus subject areas

  • Orthodontics
  • Oral Surgery
  • Otorhinolaryngology
  • Surgery

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