Does metformin administration improve fracture healing? A systematic review of preclinical studies

Abstract

Introduction: Fracture healing plays a critical role in the recovery from bone injuries and functional mobility. However, conditions such as diabetes mellitus increase the vulnerability to disruptions in this process. Diabetes, a systemic inflammatory disorder, is associated with impaired osseus healing and increased fracture vulnerability. Metformin, an oral antidiabetic medication, has shown potential in enhancing fracture healing; however, its clinical effectiveness remains controversial. We aim to elucidate the effects of metformin on fracture healing and explore potential mechanisms of action.

Methods: Systematic literature search was performed in PubMed, ScienceDirect, and Google Scholar until January 17, 2024. Criteria encompassed English-language, peer-reviewed articles using in vivo models. This systematic review was conducted in accordance with PRISMA guideline.

Results: A total of 7 studies were included in this study. Diabetes impedes fracture healing through inflammation- induced osteoblast cell death, and metformin, commonly prescribed for diabetes, exhibits anti-inflammatory properties. Studies indicated metformin’s positive effects on bone repair through AMPK activation, increased collagen production, and enhanced angiogenesis. However, some studies reported inferior bone quality and limited impact on normoglycemic conditions.

Conclusion: Metformin emerges as a promising adjunct in fracture healing, particularly in diabetic patients, by promoting osteogenesis and controlling chronic inflammation. Contradictory findings necessitate further research to clarify metformin’s effects on bone healing, urging a comprehensive understanding for potential clinical applications and improved patient outcomes.