Karam Léa, Mabilleau Guillaume, Paccou Julien
Department of Rheumatology, Univ. Lille, CHU Lille, MABlab ULR 4490, 59000, Lille, France.
Rheumatology Department, Saint-Joseph University, Beirut, Lebanon; Rheumatology Department, Hôtel-Dieu de France Hospital, Beirut, Lebanon.
Osteoporos Int. 2025 Sep 8. doi: 10.1007/s00198-025-07664-1.
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.
像每日3.0毫克利拉鲁肽（司美格鲁肽；诺和诺德公司）和每周2.4毫克司美格鲁肽（维戈维；诺和诺德公司）这类药物，属于胰高血糖素样肽-1受体激动剂（GLP-1Ra），已被批准用于肥胖症患者的长期体重管理。尽管GLP-1可能会增强骨代谢和骨质，但这些受体激动剂对骨骼健康的影响仍不确定，这也是本综述的主题。同时还总结了热量限制和减肥手术背景下的骨骼健康数据。对2013年1月至2024年12月期间发表的英文临床前研究和人体数据文献进行了全面检索，以确定GLP-1Ra对骨骼健康的各种影响。肥胖症患者进行有意减肥程序的效果已有充分记录；通过热量限制（无论是否进行运动）以及减肥/代谢手术实现显著体重减轻（约7-10%）会导致高转换型骨质流失。在不同的啮齿动物模型中，尽管体重显著减轻，但利拉鲁肽似乎对骨材料特性有积极影响。然而，对骨密度和微结构最有利的影响是在远高于批准用于人类肥胖治疗的浓度下观察到的。目前关于GLP-1Ra对肥胖症患者骨骼健康影响的证据有限。尽管初步研究结果表明GLP-1Ra会导致骨密度略有降低并促进骨重塑，有利于吸收，类似于热量限制的效果，但仍需要进一步研究来探索GLP-1Ra对骨代谢和骨折相关结局的影响，以及GLP-1、葡萄糖依赖性促胰岛素多肽（GIP）和胰高血糖素的双受体和三受体激动剂对肥胖症患者的影响。胰高血糖素样肽-1受体激动剂（GLP-1Ra）对骨骼健康的影响仍不明确。尽管初步研究结果表明GLP-1Ra会导致骨密度适度降低并增强骨重塑，有利于吸收，类似于热量限制的效果，但仍需要对肥胖症患者的骨折相关结局进行进一步研究。
