The Incidence and Severity of Medication Related Osteonecrosis of the Jaws is Similar in Male and Female Mice

Abstract

Medication related osteonecrosis of the jaws (MRONJ), a rare side-effect of antiresorptive medications, is described as exposed bone in the oral cavity that lasts for at least 8weeks. Most studies report a female predilection for MRONJ; these findings could be due to the increased use of antiresorptives in females, or due to inherent differences between male versus female patients. The purpose of this study was to measure and compare the incidence and severity of osteonecrosis of the jaws (ONJ) between male and female mice. We designed a randomized in-vivo animal study utilizing male and female mice treated with zoledronic acid (ZA). Experimental periodontitis was induced in 24 male and 24 female mice using a silk ligature following administration of saline or a potent bisphosphonate. After 8weeks, animals were evaluated radiographically and histologically. The independent variables were sex (male vs female) and treatment group (ZA vs saline control). Treatment was randomly assigned with balanced distribution between male and female animals. The main outcome variable was ONJ status coded as present or absent. ONJ was defined as present if there was histologic contact between the ligature and the alveolar bone. Secondary outcomes of interest were radiographic and histologic parameters. Statistical differences were analyzed using a two-way analysis of variance with Tukey's post hoc test using a P value of 0.05 for significance. The final sample was composed of 24 vehicle treated and 24ZA treated animals. In vehicle treated animals, 8% of female and 8% of male animals developed ONJ. In ZA treated animals, 83% of female and 92% of male animals developed ONJ. Sex was not associated with the risk (measured as incidence of disease) for developing ONJ or in the radiographic or histologic parameters that were assessed (P values >.1). Sex does not appear to affect the incidence of MRONJ or the severity of the disease as assessed by the radiographic and histologic parameters.