Background: To explore the anti-osteoporosis and anti-diabetes effects and potential underlying mechanisms of treatment with metformin and alendronate in diabetes mellitus mice.

Methods: Eight-week-old C57 BL/KS db/db and db/+ female mice were evaluated according to the following treatment group for 12 weeks: control group, diabetes mellitus group, diabetes mellitus with metformin group, diabetes mellitus with Alendronate group, diabetes mellitus with metformin plus alendronate group. Glucose level, glucose tolerance test, bone mineral density, bone microarchitecture, bone histomorphometry, serum biomarkers, and qPCR analysis.

Results: Combined metformin and alendronate can improve progression in glucose metabolism and bone metabolism, including blood glucose levels, blood glucose levels after 4 and 16 hours fasting, glucose tolerance test results, insulin sensitivity and reduces bone loss than the diabetes group. The use of alendronate alone can increase significantly serum glucagon-like peptide-1 levels than the diabetes group. The use of metformin alone can improve bone microstructure such as Tb.Sp and Tb.N of spine in diabetic mice.

Conclusion: The combined use of alendronate and metformin has an anti-diabetes and anti-osteoporotic effect compared with diabetic mice, but they appear to act no obvious synergistically between alendronate and metformin.