Zoledronic acid - related osteonecrosis of the jaws. Experimental model with dental extractions in rats.

INTRODUCTION: Bisphosphonate-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 METHODS: Twenty 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.

RESULTS: We 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.

CONCLUSIONS: We 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.