Role of Metformin in Reversing the Negative Impact of Hyperglycemia on Bone Healing Around Implants Inserted in Type 2 Diabetic Rats

Purpose: There is interest in establishing hypoglycemiant agents able to contain/revert the impact of diabetes mellitus on osseointegration. The purpose of this study was to assess the possible effect of metformin in reversing the negative effects of hyperglycemia on the healing of bone surrounding implants inserted in rats. Materials and Methods: Rats (10 per group) were assigned to one of the following groups: DM group: type 2 diabetic rats deprived of metformin (M) treatment; MDM group: type 2 diabetic rats under M treatment (40 mg/kg/day, starting on the 15th day after implant placement); control group: nondiabetic rats without M treatment. At 30 days after streptozotocin injection, titanium implants were placed in tibiae. Animals were euthanized 30 days after implant surgery. Bone-to-implant contact (BIC), bone area (BA), and the number of receptor activator of nuclear factor kappa B ligand (RANKL)- and osteoprotegerin (OPG)-stained cells were assessed in cortical and medullary areas. Results: The percentages of BIC and BA in the cortical bone were reduced in the DM and MDM groups compared with the control group (P < .05). The percentage of BA in the medullary region was reduced in the DM group compared with the control group (P < .05). The MDM group showed the greatest number of OPG-stained cells, while the DM group presented the greatest ratio of RANKL/OPG in the medullary area (P < .05). Conclusion: Metformin did not modulate the damaging effect of hyperglycemia on bone healing around implants at histometric levels, but increased the expression of OPG and decreased the RANKL/OPG ratio in the medullary area, yielding some molecular benefits in the osseointegration of implants under the hyperglycemic state.