Both diabetes mellitus and osteoporosis constitute a notable burden in terms of quality of life and healthcare costs. Diabetes mellitus affecting the skeletal system has been gaining attention in recent years and is now getting recognized as yet another complication of the disease, known as diabetic bone disease. As this condition with weaker bone strength increases fracture risk and reduces the quality of life, so much attention is being paid to investigate the molecular pathways through which both diabetes and its therapy are affecting bone metabolism. Out of many therapeutic agents currently available for managing diabetes mellitus, metformin is one of the most widely accepted first choices worldwide. The purpose of this review is to describe the effects of biguanide-metformin on bone metabolism in type 2 diabetes mellitus including its plausible mechanisms of action on the skeleton. In vitro studies suggest that metformin directly stimulates osteoblasts differentiation and may inhibit osteoclastogenesis by increasing osteoprotegerin expression, both through activation of the AMPK signaling pathway. Several studies in both preclinical and clinical settings report the favorable effects of metformin on bone microarchitecture, bone mineral density, bone turnover markers, and fracture risk. However, animal studies were not specific in terms of the diabetic models used and clinical studies were associated with several confounders. The review highlights some of these limitations and provide future recommendations for research in this area which is necessary to better understand the role of metformin on skeletal outcomes in diabetes.

就生活质量和医疗保健费用而言，糖尿病和骨质疏松症都构成了显着的负担。影响骨骼系统的糖尿病近年来受到越来越多的关注，现在被认为是该疾病的另一种并发症，称为糖尿病性骨病。由于这种骨强度较弱的情况会增加骨折风险并降低生活质量，因此人们非常关注研究糖尿病及其治疗影响骨代谢的分子途径。在目前可用于治疗糖尿病的许多治疗药物中，二甲双胍是全球最广泛接受的首选药物之一。本综述的目的是描述双胍-二甲双胍对 2 型糖尿病骨代谢的影响，包括其对骨骼的可能作用机制。体外研究表明，二甲双胍直接刺激成骨细胞分化，并可能通过激活 AMPK 信号通路增加骨保护素表达来抑制破骨细胞生成。临床前和临床环境中的几项研究报告了二甲双胍对骨微结构、骨矿物质密度、骨转换标志物和骨折风险的有利影响。然而，动物研究在所使用的糖尿病模型方面并不具体，临床研究与几个混杂因素有关。