The starting point for bisphosphonate-related osteonecrosis of the jaw: Alveolar bone or oral mucosa? A randomized, controlled experimental study

- Zoledronate therapy does not induce any histological changes in jaw bone and does not lead to BRONJ in rats if no injury to mucosa or bone occurs.
- In rats under zoledronate therapy, pure alveolar mucosal injury may induce histological osteonecrosis in the non-injured underlying bone but does not lead to BRONJ.
- Tooth extraction is a strong triggering factor for initiation of BRONJ in rats receiving zoledronate, causing osteonecrosis in 80% of the cases.
- The findings of this experimental study support the “inside-out” theory of BRONJ development.

ObjectiveAlthough over a decade has passed since first introduction of BRONJ, the exact pathophysiology of this disease is still unclear. The present experimental study aimed to determine whether the oral mucosa or alveolar bone serves as the starting point for BRONJ development.Subjects and methodsSixty male Wistar rats were randomly assigned into study and control groups (each, n = 30), and received intraperitoneal injection of 0.06 mg/kg zoledronate and saline, respectively, once a week for 12 weeks. At the end of the week 4 of the experiment, all 60 rats underwent unilateral mandibular first molar extraction. A 4 mm defect was made in the contralateral canine alveolar mucosa. At the end of the experiment, rats were sacrificed, and the three areas of interest including extraction, soft tissue defect, and the non-intervention (canine area on the same side of extraction) sites were assessed clinically for presence of bone exposure/fistula, and histologically for status of bone remodeling (only at extraction site) and osteonecrosis.ResultsIn the study group, the frequency of bone exposure/fistula was 80%, 0%, and 0%; and the rate of histological bone necrosis was 83.3%, 20%, and 0%; at the extraction, soft tissue defect, and non-intervention sites, respectively. No clinical and histological sign of bone necrosis was found in the control group. Normal bone remodeling was observed in 0% and 100% of the extraction sockets in the study and control groups, respectively.ConclusionInjury to alveolar bone was a stronger trigger for BRONJ development compared to oral mucosal damages.