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 need to be completely elucidated. Hence, in this study, the impact of a prolonged (3-month) MET treatment was investigated on bone architecture, histomorphometric and biomechanics variables, and osteogenic potential of BMSCs in Wistar rats with or without MetS.

Materials and Methods Young male Wistar rats (n=36) 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 peripheral quantitative computed tomography (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 the structural or mechanical variables of the skeleton.

Conclusion A 3-month treatment with MET (with or without MetS) affects bone architecture and biomechanical variables in Wistar rats.

Keywords

bone architecture - biomechanics - bone marrow stromal cells - metformin - metabolic syndrome

Publication History

Received: 26 December 2023
Received: 16 April 2024

Accepted: 08 May 2024

Accepted Manuscript online:
13 May 2024

Article published online:
13 June 2024

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