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利拉鲁肽是一种胰高血糖素样肽-1受体激动剂,在伴有或不伴有糖尿病的骨质疏松动物模型中均能抑制骨质流失。

Liraglutide, a glucagon-like peptide-1 receptor agonist, inhibits bone loss in an animal model of osteoporosis with or without diabetes.

作者信息

Wu Zongyi, Deng Wei, Ye Yiming, Xu Jie, Han Deyu, Zheng Yu, Zheng Qun

机构信息

Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.

Department of Rheumatology Immunology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.

出版信息

Front Endocrinol (Lausanne). 2024 May 29;15:1378291. doi: 10.3389/fendo.2024.1378291. eCollection 2024.

Abstract

INTRODUCTION

Liraglutide (Lrg), a novel anti-diabetic drug that mimics the endogenous glucagon-like peptide-1 to potentiate insulin secretion, is observed to be capable of partially reversing osteopenia. The aim of the present study is to further investigate the efficacy and potential anti-osteoporosis mechanisms of Lrg for improving bone pathology, bone- related parameters under imageology, and serum bone metabolism indexes in an animal model of osteoporosis with or without diabetes.

METHODS

Eight databases were searched from their inception dates to April 27, 2024. The risk of bias and data on outcome measures were analyzed by the CAMARADES 10-item checklist and Rev-Man 5.3 software separately.

RESULTS

Seventeen eligible studies were ultimately included in this review. The number of criteria met in each study varied from 4/10 to 8/10 with an average of 5.47. The aspects of blinded induction of the model, blinding assessment of outcome and sample size calculation need to be strengthened with emphasis. The pre-clinical evidence reveals that Lrg is capable of partially improving bone related parameters under imageology, bone pathology, and bone maximum load, increasing serum osteocalcin, N-terminal propeptide of type I procollagen, and reducing serum c-terminal cross-linked telopeptide of type I collagen (P<0.05). Lrg reverses osteopenia likely by activating osteoblast proliferation through promoting the Wnt signal pathway, p-AMPK/PGC1α signal pathway, and inhibiting the activation of osteoclasts by inhibiting the OPG/RANKL/RANK signal pathway through anti-inflammatory, antioxidant and anti-autophagic pathways. Furthermore, the present study recommends that more reasonable usage methods of streptozotocin, including dosage and injection methods, as well as other types of osteoporosis models, be attempted in future studies.

DISCUSSION

Based on the results, this finding may help to improve the priority of Lrg in the treatment of diabetes patients with osteoporosis.

摘要

引言

利拉鲁肽(Lrg)是一种新型抗糖尿病药物,可模拟内源性胰高血糖素样肽-1以增强胰岛素分泌,据观察它能够部分逆转骨质减少。本研究的目的是在伴有或不伴有糖尿病的骨质疏松动物模型中,进一步研究Lrg改善骨病理、影像学骨相关参数以及血清骨代谢指标的疗效和潜在抗骨质疏松机制。

方法

检索了8个数据库,检索时间从各数据库建库起至2024年4月27日。分别采用CAMARADES 10项清单和Rev-Man 5.3软件分析偏倚风险和结局指标数据。

结果

本综述最终纳入17项符合条件的研究。每项研究符合的标准数量从4/10到8/10不等,平均为5.47。模型的盲法诱导、结局的盲法评估和样本量计算等方面需要重点加强。临床前证据表明,Lrg能够部分改善影像学骨相关参数、骨病理和骨最大负荷,增加血清骨钙素、I型前胶原N端前肽,并降低血清I型胶原C端交联末肽(P<0.05)。Lrg可能通过促进Wnt信号通路、p-AMPK/PGC1α信号通路激活成骨细胞增殖,并通过抗炎、抗氧化和抗自噬途径抑制OPG/RANKL/RANK信号通路来抑制破骨细胞的激活,从而逆转骨质减少。此外,本研究建议在未来的研究中尝试更合理的链脲佐菌素使用方法,包括剂量和注射方法,以及其他类型的骨质疏松模型。

讨论

基于这些结果,这一发现可能有助于提高Lrg在治疗骨质疏松糖尿病患者中的优先级。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29ab/11167098/1cd22abd6a95/fendo-15-1378291-g001.jpg

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