PCSK9 抑制剂与骨质疏松症：孟德尔随机化与荟萃分析。

PCSK9 inhibitors and osteoporosis: mendelian randomization and meta-analysis.

机构信息

Department of Orthopedics, The First Affiliated Hospital of Xiamen University, Xiamen, China.

The School of Clinical Medicine, Fujian Medical University, Fuzhou, China.

出版信息

BMC Musculoskelet Disord. 2024 Jul 16;25(1):548. doi: 10.1186/s12891-024-07674-w.

DOI:10.1186/s12891-024-07674-w

PMID:39010016

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11251371/

Abstract

BACKGROUND

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors represent an effective strategy for reducing cardiovascular disease risk. Yet, PCSK9's impact on osteoporosis remains unclear. Hence, we employed Mendelian randomization (MR) analysis for examining PCSK9 inhibitor effects on osteoporosis.

METHODS

Single nucleotide polymorphisms (SNPs) for 3-hydroxy-3-methylglutaryl cofactor A reductase (HMGCR) and PCSK9 were gathered from available online databases for European pedigrees. Four osteoporosis-related genome-wide association studies (GWAS) data served as the main outcomes, and coronary artery disease (CAD) as a positive control for drug-targeted MR analyses. The results of MR analyses examined by sensitivity analyses were incorporated into a meta-analysis for examining causality between PCSK9 and HMGCR inhibitors and osteoporosis.

RESULTS

The meta-analysis involving a total of 1,263,102 subjects, showed that PCSK9 inhibitors can increase osteoporosis risk (P < 0.05, I, 39%). However, HMGCR inhibitors are not associated with osteoporosis risk. Additionally, a replication of the analysis was conducted with another exposure-related GWAS dataset, which led to similar conclusions.

CONCLUSION

PCSK9 inhibitors increase osteoporosis risk. However, HMGCR inhibitors are unremarkably linked to osteoporosis.

摘要

背景

前蛋白转化酶枯草溶菌素 9（PCSK9）抑制剂是降低心血管疾病风险的有效策略。然而，PCSK9 对骨质疏松的影响尚不清楚。因此，我们采用孟德尔随机化（MR）分析来研究 PCSK9 抑制剂对骨质疏松的影响。

方法

从可用的在线数据库中收集 3-羟基-3-甲基戊二酰基辅酶 A 还原酶（HMGCR）和 PCSK9 的单核苷酸多态性（SNP），用于欧洲血统。四项与骨质疏松症相关的全基因组关联研究（GWAS）数据作为主要结果，冠心病（CAD）作为药物靶向 MR 分析的阳性对照。通过敏感性分析检查的 MR 分析结果被纳入荟萃分析，以检验 PCSK9 和 HMGCR 抑制剂与骨质疏松症之间的因果关系。