Osteogenic action of anti-diabetic drug metformin in periodontal disease

Sir,

Metformin (MF) a biguanide, is widely prescribed as the first line anti-diabetic agent for the treatment of type 2 diabetes mellitus. MF is considered an insulin-sensitizing drug, lowering glycemic level without increasing insulin secretion. Cortizo et al. investigated action of MF on the development of osteoblasts like cell lines and showed for the first time a direct osteogenic effect of MF of osteoblast in cell culture.[1]

Recent studies have demonstrated that MF is useful for improvement in clinical and radiological parameter of chronic periodontitis as compared with the placebo group in randomized clinical trials.[2] Histopathologic and micro-computed tomography findings, which suggest that MF may reduce inflammatory cell infiltration and alveolar bone loss in periodontal tissues, indicate that MF may exert a beneficial effect on periodontitis.[3]

It was reported that MF can induce MC3T3-E1 osteoblastic cells differentiation and bone matrix synthesis through adenosine 5’-monophosphate-activated protein kinase activation and subsequent induction of endothelial nitric oxide synthase and bone morphogenetic protein-2 (BMP-2) expression.[4] The action of MF on bone marrow mesenchymal progenitors BMP cells (BMPCs) has also been investigated and MF caused an osteogenic effect, suggesting a possible action in promoting a shift of BMPCs toward osteoblastic differentiation. In contrast, in vitro studies have shown no effect of MF on the osteogenic differentiation of bone marrow derived mesenchymal stem cells and matrix mineralization of both MC3T3-E1 cells and primary osteoblasts. A high concentration of MF (2 mm) even clearly inhibited osteoblast differentiation.[4]

Since MF benefits on fracture reduction and takes positive action on osteoblasts, it appears possible that this agent may have protective effects on bone loss. Recent in vivo and in vitro studies suggest that MF reduces receptor activator for nuclear factor-kappa B ligand and stimulates osteoprotegerin expression in osteoblasts, further inhibits osteoclast differentiation and prevents bone loss in ovariectomized rats. In a recent study, MF treatment of rats induced a significant reduction in alveolar bone loss compared with vehicle treated rats. A possible bone sparing and bone formative effect of MF has been shown to postulated as MF has been shown to significantly decrease the intracellular reactive oxygen species and apoptosis and also have a direct osteogenic effect on osteoblasts, which could be partially mediated through promotion of Runx 2 and insulin-like growth factor-1 expression.[5] Further more studies in periodontal environment should carry out for exploring the beneficial role of MF in periodontal therapy.