Anastasilakis Athanasios D, Paccou Julien, Palermo Andrea, Polyzos Stergios A
Department of Endocrinology, Diabetes and Metabolism, 424 General Military Hospital, Thessaloniki, Greece.
Department of Rheumatology, University Lille, CHU Lille, Lille, France.
Diabetes Obes Metab. 2025 Sep;27(9):4674-4688. doi: 10.1111/dom.16541. Epub 2025 Jun 24.
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.
新型高效减肥药的研发彻底改变了肥胖症患者的治疗方式。然而，体重减轻时，肌肉和骨骼会与脂肪一同流失。在本综述中，我们引用并讨论了现有证据，以说明主要抗肥胖药物对骨代谢的影响。胰高血糖素样肽-1受体（GLP-1R）激动剂在临床前研究中显示出积极作用，但在临床研究中对骨转换标志物和骨密度的影响呈中性或负面，尽管在临床上并不显著。尽管如此，至少在临床相关剂量下，使用GLP-1R激动剂似乎不会增加骨折风险。有限的、大多为临床前的数据表明，其他肠促胰岛素类似物，包括双GLP-1R和葡萄糖依赖性促胰岛素多肽（GIP）受体（GIPR）激动剂、双GLP-1R和胰高血糖素受体（GCGR）激动剂以及三联GLP-1R、GIPR和GCGR激动剂，可能对骨骼有积极作用。淀粉样蛋白类似物的临床前数据也表明了同样的情况。激活素II型受体（ActRII）拮抗剂可能将抗肥胖作用与同时保留肌肉和骨量相结合，可作为单一疗法或与肠促胰岛素类似物联合使用。阿片受体拮抗剂和setmelanotide对骨骼的影响在很大程度上尚不清楚，而 phentermine与托吡酯联合使用的影响被认为是负面的。最后，非常有限的临床证据表明，奥利司他可能对骨代谢有中性影响。
