Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a relatively new class of drugs for treatment of Type 2 Diabetes mellitus (T2DM). They have proven to be excellent drugs not only for the results on glycemic control but also for weight loss, cardiovascular protection and several other potential metabolic effects. In contrast, the effects of GLP-1RAs drugs on bone metabolism and bone mineral density (BMD) remain less clearly defined. This narrative review aimed to explore the relationship between GLP-1RAs and bone in T2DM patients by reviewing clinical studies which assessed the effects of GLP-1RAs on BMD, markers of bone turnover and fragility fractures. In vitro and animal studies have demonstrated that GLP-1RAs treatment promotes bone formation and inhibits bone resorption. However, in humans, GLP-1RAs therapy has been shown to primarily stimulate bone resorption, as evidenced by a significant increase in type I collagen C-terminal cross-linked telopeptide levels, while promoting new bone formation to a lesser extent. Clinical studies indicate that GLP-1RAs therapy, in both diabetic and non-diabetic patients, results in a reduction in BMD, which is more pronounced at skeletal sites subjected to higher mechanical loading, such as the femur and tibia, and appears to correlate with the degree of weight loss. Furthermore, in the studies reviewed, parameters related to bone quality and strength, such as Trabecular bone score (TBS), microindentation, High-resolution peripheral Quantitative Computed Tomography (HR-pQCT), and Radiofrequency Echographic Multi Spectrometry (REMS) remain unaffected by GLP-1RAs. Additionally, the incidence of fragility fractures does not increase.
