Effects of Glucagon-Like Peptide-1 receptor agonists on bone health in people living with obesity.

Medications like liraglutide 3.0 mg daily (Saxenda®; Novo Nordisk) and semaglutide 2.4 mg weekly (Wegovy®; Novo Nordisk), which are glucagon-like peptide-1 receptor agonists (GLP-1Ra), have been sanctioned for prolonged weight management in people living with obesity (PwO). Although GLP-1 might enhance bone metabolism and quality, the impact of these receptor agonists on bone health remains uncertain and is the subject of this review. Data on bone health in the context of calorie restriction and bariatric surgery were also summarized. A comprehensive search of the literature on preclinical studies and human data published in English was performed from Jan 2013 to Dec 2024 to identify the various effects of GLP-1Ra on bone health. The effects of intentional weight loss procedures in PwO are well documented; significant weight reduction (~ 7-10%) through calorie restriction, with or without exercise, and bariatric/metabolic surgery results in high turnover bone loss. In different rodent models, liraglutide seems to positively influence bone material properties despite notable weight loss. However, the most favorable effects on bone mineral density and microarchitecture were noted at concentrations much higher than those approved for human obesity treatment. Current evidence on the effects of GLP-1Ra on bone health in PwO is limited. Although initial findings suggest that GLP-1Ra leads to a slight reduction in bone mineral density and promotes bone remodeling, favoring resorption similar to calorie restriction effects, further research is needed to explore the effects of GLP-1Ra on bone metabolism and fracture-related outcomes, as well as dual- and triple-receptor agonists of GLP-1, glucose-dependent insulinotropic polypeptide (GIP), and glucagon in PwO. The impact of glucagon-like peptide-1 receptor agonists (GLP-1Ra) on bone health remains unclear. Although preliminary findings indicate that GLP-1Ra causes modest bone mineral density reduction and enhances bone remodeling, favoring resorption similar to the effects of calorie restriction, further research is needed on fracture-related outcomes in people living with obesity.