The Effect of Metformin on Alveolar Bone in Ligature‐Induced Periodontitis in Rats: A Pilot Study

Abstract

The use of metformin, an antidiabetic agent, is associated with a reduced risk of fractures in patients with diabetes, suggesting that metformin exerts a beneficial effect on bone tissues. The objective of this study was to assess the effect of metformin on alveolar bone loss in ligature-induced periodontitis and osteoblast, osteoclast, and adipocyte differentiation. Periodontitis was induced by a ligature around the mandibular first molar of each rat. The rats were divided into two groups: 1) rats with ligature receiving a vehicle (n = 5), and 2) rats with ligature receiving metformin (n = 5). On day 10, after the induction of periodontitis, the alveolar bone volume between the first and second molar was determined via microcomputed tomography. The effect of metformin on osteoblast, osteoclast, and adipocyte differentiation was assessed using MC3T3-E1, cocultures of mouse bone marrow cells and calvaria-derived osteoblasts, and 3T3-L1/C3H10T1/2 cells, respectively. Osteoblast, osteoclast, and adipocyte differentiation was estimated by the degree of mineralization, the formation of tartrate-resistant acid phosphatase-positive multinucleated cells, and the accumulation of triglycerides, respectively. In ligature-induced periodontitis, the metformin treatment of rats induced a significant reduction in alveolar bone loss compared to vehicle-treated rats. With regard to osteoblast differentiation, metformin augmented the mineralization of MC3T3-E1 cells approximately two-fold over the non-treated cells. However, metformin was shown to exert no effects on osteoclast formation induced by 1,25-dihydroxyvitamin D(3), lipopolysaccharide, and prostaglandin E(2). Moreover, metformin exerted no effect on adipocyte differentiation. Our findings suggest that metformin may exert a beneficial effect on alveolar bone in periodontitis by increasing osteoblast differentiation.