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肥胖人群中胰高血糖素样肽-1 受体激动剂对骨骼健康影响的叙述性综述。

Narrative Review of Effects of Glucagon-Like Peptide-1 Receptor Agonists on Bone Health in People Living with Obesity.

机构信息

Service de Rhumatologie, Inserm U 1153, AP-HP Centre, Hôpital Cochin, Université de Paris, Paris, France.

ONIRIS, Inserm, RMeS, UMR 1229, SFR ICAT, Univ Angers, Nantes Université, Angers, France.

出版信息

Calcif Tissue Int. 2024 Feb;114(2):86-97. doi: 10.1007/s00223-023-01150-8. Epub 2023 Nov 24.

Abstract

Glucagon-like peptide-1 Receptor agonists (GLP-1Ras) such as liraglutide and semaglutide have been recently approved as medications for chronic weight management in people living with obesity (PwO); GLP-1 may enhance bone metabolism and improve bone quality. However, the effects of GLP-1Ras on skeletal health remain to be determined and that's the purpose of this narrative review. Nevertheless, bone consequences of intentional weight loss interventions in PwO are well known: (i) significant weight loss induced by caloric restriction and bariatric surgery results in accelerated bone turnover and bone loss, and (ii) unlike caloric restriction interventions, PwO experience a substantial deterioration in bone microarchitecture and strength associated with an increased risk of fracture after bariatric surgery especially malabsorptive procedures. Liraglutide seems to have a positive effect on bone material properties despite significant weight loss in several rodent models. However, most of positive effects on bone mineral density and microarchitecture were observed at concentration much higher than approved for obesity care in humans. No data have been reported in preclinical models with semaglutide. The current evidence of the effects of GLP-1Ra on bone health in PwO is limited. Indeed, studies on the use of GLP-1Ra mostly included patients with diabetes who were administered a dose used in this condition, did not have adequate bone parameters as primary endpoints, and had short follow-up periods. Further studies are needed to investigate the bone impact of GLP-1Ra, dual- and triple-receptor agonists for GLP-1, glucose-dependent insulin releasing polypeptide (GIP), and glucagon in PwO.

摘要

胰高血糖素样肽-1 受体激动剂(GLP-1Ras),如利拉鲁肽和司美格鲁肽,最近已被批准用于肥胖人群(PwO)的慢性体重管理药物;GLP-1 可能增强骨代谢并改善骨质量。然而,GLP-1Ras 对骨骼健康的影响仍有待确定,这就是本综述的目的。然而,PwO 中故意减轻体重干预的骨骼后果是众所周知的:(i)热量限制和减肥手术引起的显著体重减轻导致骨转换和骨丢失加速,(ii)与热量限制干预不同,PwO 在减肥手术后经历与骨折风险增加相关的骨微结构和强度的实质性恶化,特别是吸收不良程序。尽管在几种啮齿动物模型中观察到显著的体重减轻,但利拉鲁肽似乎对骨物质特性有积极影响。然而,在人类肥胖治疗中批准的浓度下观察到大多数对骨矿物质密度和微结构的积极影响。在临床前模型中没有关于司美格鲁肽的数据报告。目前,关于 GLP-1Ra 对 PwO 骨骼健康影响的证据有限。事实上,关于 GLP-1Ra 使用的研究大多包括接受用于该病症的剂量的糖尿病患者,没有作为主要终点的充分骨参数,并且随访时间短。需要进一步的研究来调查 GLP-1Ra、GLP-1、葡萄糖依赖性胰岛素释放肽(GIP)和胰高血糖素的双重和三重受体激动剂在 PwO 中的骨骼影响。

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