Zoledronic acid – Related osteonecrosis of the jaws. Experimental model with dental extractions in rats

Abstract

IntroductionBisphosphonate-related osteonecrosis of the jaws (BRONJ) is a pathologic condition of increasing frequency, with a poorly understood pathophysiology and which can be difficult to manage.The aim of this study was to find a reproducible experimental model that directly relates chronic bisphosphonate administration with the development of osteonecrosis with or without tooth extraction, with no other drug involved. Material and methodsTwenty male Wistar rats were divided into 4 groups (n = 5/group). Animals were injected over 9 weeks with zoledronic acid (0.1 mg/kg). In groups 1 and 2 three times a week intraperitoneally, and in group 3 once a week intravenously. A control group (group 4) received intraperitoneal injections of saline solution three times a week. After 8 weeks of treatment, 3 right upper jaw molars were extracted in groups 1, 3 and 4 and all rats were sacrificed 1 week later. The maxillae were histologically analyzed for presence of osteonecrosis foci, number of osteoclasts, vascularity, bone resorption status and presence of abscess. Radiographic examination was performed with a plain radiograph of each hemi-head. ResultsWe found that group 1 (dental extractions and highest cumulative dose of zoledronic acid) had the highest incidence of osteonecrosis (80%), absence of bone resorption (100%) and lowest number of osteoclasts (mean 7.9/field at 40×). Zoledronic acid-treated groups showed variable degrees of osteosclerosis and trabecular disorganization on X-ray study. ConclusionsWe offer a new animal model of BRONJ after zoledronic acid administration and dental extractions, achieving bone changes similar or superior to previous studies, highlighting the dental extraction as an important trigger factor.