Key result
Anti-obesity medications preserve bone mineral density without increasing fracture risk.
Why the study?
Do anti-obesity medications affect bone metabolism in people living with obesity?
Do anti-obesity medications affect bone metabolism in people living with obesity?
This review highlights that while GLP-1R agonists do not appear to increase fracture risk despite potential minor negative effects on bone density, the bone effects of newer anti-obesity medications require further clinical investigation.
The development of novel sophisticated medications that induce weight loss has revolutionized the management of people living with obesity (PwO). However, when body weight is reduced, muscle and bone are lost along with fat. In the present review, we quote and discuss existing evidence on the effects of the major anti-obesity medications on bone metabolism. Glucagon-like peptide-1 receptor (GLP-1R) agonists have shown a positive impact in preclinical studies but a neutral or negative, albeit not clinically significant, effect on bone turnover markers and bone mineral density in clinical studies. Nevertheless, fracture risk does not seem to increase with GLP-1R agonists use, at least in clinically relevant doses. Limited, mostly preclinical, data suggest that other incretin analogues, including dual GLP-1R and glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) agonists, dual GLP-1R and glucagon receptor (GCGR) agonists, and triple GLP-1R, GIPR and GCGR agonists, may have a positive effect on bone. Preclinical data with amylin analogues imply the same. Activin type II receptor (ActRII) antagonists may combine anti-obesity effects with simultaneous muscle and bone mass preservation and could be used either as monotherapy or in combination with incretin analogues. The bone effects of opioid receptor antagonists and setmelanotide are largely unknown, while the impact of the combination of phentermine with topiramate is assumed to be negative. Finally, very limited clinical evidence suggests that orlistat may have a neutral effect on bone metabolism.
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Anastasilakis et al. (2025) conducted a review in Obesity. Anti-obesity medications was evaluated on Bone metabolism and fracture risk. Anti-obesity medications such as GLP-1R agonists demonstrate a neutral or negative but not clinically significant effect on bone mineral density, without increasing fracture risk.
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