Establishment of osteonecrosis of the jaw lesion in rats

Objectives: Aim: Medication related osteonecrosis of the jaw (MRONJ) is a debilitating bone disorder defined as exposed bone that persists for more than 8 weeks. The prevalence of MRONJ following intravenous administration of bisphosphonate (BP) has been reported as 0.8% to 12%. To date, the pathogenesis of MRONJ still remains unclear and there isn't a definitive treatment for MRONJ. The aim of this study is to establish MRONJ experimental model in order to further investigate the pathogenesis, prevention and treatment of the disease.
Methods: Materials and Methods: Nineteen rats were randomly allocated into test or control groups. Rats in the test group were administered weekly with zolendronic acid (ZA) (7.5Mg/kg) +dexamethasone (1mg/kd) for 11 weeks. Control rats were treated with saline. Three weeks following first drug administration, all rats underwent extraction of first maxillary molar. Rats were euthanized at 11 weeks. Healing of extraction socket was evaluated clinically, radiographically (using Peri-apical and micro-CT analyses) and histologically.
Results: Results: All rats survived throughout the study. However, rats in the test group lost weight compared with control rat. At euthanasia, body weight of control rats was 10.4% higher than test rats. Impaired healing and MRONJ-like lesions were observed in 50% of the rats in the test group; while all rats in control group demonstrated normal healing pattern with soft tissue closure of the extraction sites. Furthermore, radiographic analysis of the MRONJ-like lesions revealed areas of bone fragments surrounded by radiolucent borders, suggesting sequestra formation.
Conclusions: Conclusion: administration of BP and Dexamethasone coupled with tooth extraction is a reliable model for MRONJ induction in rats. Thus, Future studies will be using it to gain understanding of the pathogenesis and investigating possible treatment modalities for MRONJ.