Histological and histomorphometric evaluation of the effects of bone morphogenetic protein 2 (BMP 2) and metformin on bone formation in critical size defect models

The aim of this study is to evaluate the possibility of metformin adminstration to achieve increased bone healing in non diabetic patients. It was stated that metformin increases the release of bone morphogenetic protein 2 (BMP 2), a growth factor which is effective in osteoblast differentiation. Recombinant human BMP 2 (rhBMP 2) can be applied with absorbable collagen sponges. In this study osteogenic effects of rhBMP 2 implantation to that of metformin adminstration were compared. Gelatin sponges were used as rhBMP 2 carriers and scaffolds. Forty two Sprague Dawley rats were randomly divided into six groups and a 5 mm calvarium defect was created in the parietal bone of each rat. The defect site was left empty in Group 1. Gelatin sponge was implanted on the defect site in Group 2. Gelatin sponge containing 2.15 μg rhBMP 2 was implanted into the defect site in Group 3. Systemic metformin hydrochloryde (HCl) (255 mg/kg) was administered after the operation once daily for 14 days and the defect was left empty in Group 4. Gelatin sponge was implanted into the defect and systemic metformin HCl was administered after the operation once daily for 14 days in Group 5. 2.15 μg of rhBMP 2 impregnated gelatin sponge was implanted into the defect and systemic metformin HCl (255mg/ kg) was administered after the operation once daily for 14 days in Group 6. All rats were sacrificed on day 28. Calvarial bones were evaluated via histological and histomorphometric methods. The average weight of the rats increased after 28 days in all groups. No foreign body reaction, necrosis or inflammation were observed. During healing period new bone formation gained advantage over fibrosis in all groups, however no pairwise comparisons were statistically significant in terms of mean new bone percentage. The results of this study showed that metformin does not promote osteogenesis as effective as stated in similar studies, yet a relationship between BMP2 and metformin could be possible as the combined theraphy group (Group 6) portrayed the highest levels of new bone formation.