Background: Refractory jaw osteonecrosis that occurs in osteoporotic or cancer patients treated with bisphosphonates is called medication-related osteonecrosis of the jaw but its underlying mechanism is unclear. Statins, therapeutic agents for dyslipidemia, lower blood low-density lipoprotein cholesterol. Fluvastatin promotes the healing of tooth extraction sockets and reduces the risk of developing medication-related osteonecrosis of the jaw-like lesions. We used a rat model to investigate whether injecting fluvastatin at extraction sites promoted the healing of medication-related osteonecrosis of the jaw-like lesions. Methods: Upper first molars of rats administered zoledronate and dexamethasone for 2 weeks were extracted. Two weeks after tooth extraction, rats with medication-related osteonecrosis of the jaw-like lesions (bone exposure) were included in this study. A single injection of fluvastatin was administered in the vicinity of the medication-related osteonecrosis of the jaw-like onset site in rats. Results:The distance between the edges of the epithelia, the length of the necrotic bone exposed toward the oral cavity, the area of the necrotic bone, and the necrotic bone ratio were significantly smaller in the fluvastatin-administered group compared with the saline group. A single application of fluvastatin near the site of medication-related osteonecrosis of the jaw onset showed a tendency to close the epithelium, reduce necrotic bone, and form new bone, even when symptoms had already developed. Conclusion:This study suggests that a single topical administration of fluvastatin may be a novel treatment for medication-related osteonecrosis of the jaw.

Medication-related osteonecrosis of the jaw (MRONJ) is an intractable disease that is typically observed in patients with osteoporosis or tumors that have been treated with either bisphosphonate (BP) or antiangiogenic medicine. The mechanism of MRONJ pathogenesis remains unclear, and no effective definitive treatment modalities have been reported to date. Previous reports have indicated that a single injection of benidipine, an antihypertensive calcium channel blocker, in the vicinity of a tooth extraction socket promotes wound healing in healthy rats. The present study was conducted to elucidate the possibility of using benidipine to promote the healing of MRONJ-like lesions. In this study, benidipine was administered near the site of MRONJ symptom onset in a model rat, which was then sacrificed two weeks after benidipine injection, and analyzed using histological sections and CT images. The analysis showed that in the benidipine groups, necrotic bone was reduced, and soft tissue continuity was recovered. Furthermore, the distance between epithelial edges, length of necrotic bone exposed in the oral cavity, necrotic bone area, and necrotic bone ratio were significantly smaller in the benidipine group. These results suggest that a single injection of benidipine in the vicinity of MRONJ-like lesions can promote osteonecrotic extraction socket healing.