In a study of periodontitis on male Wistar rats that had low doses of metformin (50 mg/kg), RANKL and OPG were visualized using a colorimetric-based detection kit; they found weak staining of RANKL (reduced) but strong staining of OPG, which indicated a decrease in bone resorption with reduction of osteoclasts number and an increase of osteoblasts.23 This evidence concerns the gene TNFSF11 and periodontitis.