Role of periodontal disease in bisphosphonate-related osteonecrosis of the jaws in ovariectomized rats.

Abstract

This study aimed to investigate the role of progressive periodontal disease in inducing bisphosphonate-related osteonecrosis of the jaws (BRONJ) using an ovariectomized (OVX) rat model mimicking human intracortical remodeling process. Thirty 12-week-old Spraque-Dawly (SD) female rats were randomly assigned into two groups. All rats underwent bilateral ovariectomy. Six weeks after surgery, zoledronic acid (ZA) or vehicle control was administered intraperitoneally for 12 weeks. On the same day of injection, a cotton ligature was placed subgingivally around the first left lower molar to induce periodontitis. All animals were sacrificed 12 weeks after injection. The entire mandibles were harvested for micro-computed tomography (micro-CT) and histological examinations. Micro-CT examination showed that ligature placement caused significant alveolar bone loss both in ZA (0.63 ± 0.13 vs. 0.38 ± 0.06 mm, P < 0.001) and in control (0.88 ± 0.19 vs. 0.40 ± 0.06 mm, P < 0.001) groups. Whereas in the ZA group, bone loss was attenuated compared with the control group (P < 0.01); the bone mineral density in the ZA group (1.00 ± 0.02 g/cm(3)) was significantly higher than that in vehicle control group (0.96 ± 0.03 g/cm(3), P < 0.001). Histological examination found necrotic bone tissue with extensive, empty lacunae in two of 15 rats in ZA group, but in none of the control group. Bisphosphonates inhibit alveolar bone resorption in progressive periodontal disease, which might benefit the management of periodontitis, but increase the risk of developing BRONJ.