Effectiveness of local application of simvastatin for prevention of bisphosphonate-related osteonecrosis of the jaw: An animal study on rats

Objectives: This study aimed to assess the efficacy of topical application of simvastatin for the prevention of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in rats. Materials and methods: In this interventional animal study, 44 rats were placed in 4 groups (n = 11). The rats in the first three groups received weekly intraperitoneal injection of 0.06 mg/kg zoledronic acid for 4 weeks. The fourth group served as the control group and received saline injections. After extraction of maxillary first molars in all rats, Gelfoam containing 0.5 mg/mL simvastatin was placed in the extraction socket in group 1 and plain Gelfoam in group 2. The extraction socket in groups 3 and 4 did not receive any intervention and was sutured. After one month, the rats were sacrificed and biopsy samples were obtained from the extraction sockets and underwent histological analysis to assess angiogenesis, osteonecrosis, degree of inflammation, and the number of osteoclasts. Data were analyzed by the Kruskal-Wallis, Mann-Whitney, and Fisher's exact tests and Bonferroni adjustment (alpha = 0.05). Results: Angiogenesis was significantly higher in the simvastatin group than in other groups (P < 0.001). Maximum inflammation was noted in the saline group. The use of Gelfoam in groups 1 and 2 did not increase the inflammation compared with other groups (P = 0.011), and the maximum number of osteoclasts (P = 0.01) were noted in the saline group. No significant difference existed in osteonecrosis among the four groups (P > 0.05). Conclusions: It appears that the local application of single-dose simvastatin can decrease the risk of BRONJ by increasing angiogenesis.