Protective Effect of Metformin on Periapical Lesions in Rats by Decreasing the Ratio of Receptor Activator of Nuclear Factor Kappa B Ligand/Osteoprotegerin

Introduction: Metformin, one of the antihyperglycemic agents commonly used for the treatment of type 2 diabetes, was shown to inhibit osteoclast formation. The current study aimed to investigate the effects of systemically administered metformin on alveolar bone resorption and on the ratio of receptor activator of nuclear factor kappa B ligand/osteoprotegerin (RANKL/OPG) in rats subjected to experimental periapical lesions. Methods: Forty adult male Wistar rats were divided equally into control and experimental groups, and the pulp chambers of their mandibular first molars were exposed to the oral environment to induce periapical lesions. The experimental group received daily intramuscular injections of metformin at 40 mg/kg doses, whereas the control group received only the saline vehicle. The injections were initiated 1 day before the periapical lesion induction and then were continued daily throughout the entire experimental period. Two or 4 weeks after pulp exposure, the rats were killed, and the mandibles were prepared for histologic analysis, enzyme histochemistry, immunohistochemistry, and immunofluorescence. Results: The number of RANKL-positive and tartrate-resistant acid phosphatase (TRAP) positive cells in the metformin-treated groups decreased on day 14, whereas the number of OPG-positive cells increased on day 28. The periapical bone loss area in the metformin-treated group significantly decreased on day 28 compared with the control group. Conclusions: Metformin inhibits the periapical lesions possibly by lowering the RANKL/OPG ratio, subsequently reducing the number of osteoclasts and bone resorption areas. (J Endod 2012;38:943-947)