Negative effects of semaglutide on bone in obese mice

GLP1 receptor agonists, such as semaglutide, are used in the management of obesity. While causing weight loss, these drugs reduce both fat and lean mass. The impact of GLP1 receptor agonists on bone health has not been explored. Femur mass, stiffness, and strength are lower in obese male C57BL/6J mice treated with semaglutide, and these effects are more pronounced than in mice that are calorically restricted to the same extent. Decrements in bone are paralleled by lower circulating levels of markers of osteoblast activity. In an additional cohort, femur weight, strength, and stiffness are the same 6 weeks following the discontinuation of semaglutide compared to vehicle. Our findings provide evidence that bone mass and strength decrease with semaglutide and that this effect is dependent upon continued exposure to the drug. Clinical investigations are needed to determine if GLP1 receptor agonists have similar impacts on bone in patient populations.