Skeletal effects of a prolonged oral metformin treatment in adult Wistar rats

Abstract

Introduction: We previously showed that a 3-week oral Metformin (MET) treatment enhances the osteogenic potential of bone marrow stromal cells (BMSCs) and improves several bone histomorphometric parameters in Wistar rats with metabolic syndrome (MetS). However, the skeletal effects of extended periods of MET are still not completely elucidated. Hence, we investigated the impact of a prolonged (3-month) MET treatment on bone architecture, histomorphometric and biomechanics variables and osteogenic potential of BMSCs in Wistar rats with or without MetS. Materials and Methods: 36 young male Wistar rats were randomized into four groups (n=9) that received either 20% fructose ( F); MET (MET); F plus MET treatments (FMET); or drinking water alone (Veh). Rats were euthanized, blood was collected, and bones were dissected and processed for pQCT analysis, static and dynamic histomorphometry and bone biomechanics. In addition, BMSCs were isolated to determine their osteogenic potential. Results: MET affected trabecular and cortical bone, altering bone architecture and biomechanics. Furthermore, MET increased the pro-resorptive profile of BMSCs. In addition, fructose-induced MetS practically did not affect the skeleton's structural or mechanical variables. Conclusion: A 3-month treatment with MET (with or without MetS) affects bone architecture and biomechanical variables in Wistar rats.