Effect of Zoledronic Acid Combined With Metformin on Bone of Db/db Mice

Abstract

Background Diabetic Osteoporosis (DO) is a complication of diabetes. As a first-line medication for diabetes, metformin combined with the anti-osteoporosis drug zoledronic acid is still unclear whether it is effective in treating DO. In this work, we explored the effect of metformin combined with zoledronic acid in the treatment of DO.Methods 12-week-old db/db mice were randomly divided into db/db group, ZA (zoledronic acid) group, MET (metformin) group, CMT (combination therapy group) group, Set WT (wild-type) mice of the same strain and age as the blank control group. Body weight and blood glucose were measured every 2 weeks. After 10 weeks, samples were taken for pathology and imaging related tests.Results (1) The body weight of db/db mice treated with metformin was stable and blood glucose was decreased. (2) After HE staining, db/db mice treated with metformin showed decreased adipocytes, increased blood cells and blood vessels in bone marrow cavity; db/db mice treated with zoledronic acid showed increased trabeculae. The number of bone trabeculae and blood vessels in the bone increased after the combined use of the two drugs. (3) By OPG staining and semi-quantitative analysis, db/db mice had the lowest osteoblastic activity. db/db mice treated with metformin had higher osteoblastic activity than those treated with zoledronic acid, and the osteoblastic activity of CMT was higher than that treated with ZA group or MET group. (4) After TE staining, semi-quantitative analysis showed that the number of bone lacunae in WT group was the least, the number of bone lacunae in ZA group and CMT group was significantly lower than that in db/db group, but the number of bone lacunae in MET group was not significant. (5) The bone morphological analysis of db/db mice in the CMT group was significantly better than that of MET or ZA alone by micro-CT scanning and bone tissue parameters determination.Conclusion ZA combined with MET has better anti-bone loss effect than zoledronic acid or metformin alone in db/db mice.