PDF(Pubmed)
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, I2, 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.
CONCLUSIONS: PCSK9 inhibitors increase osteoporosis risk. However, HMGCR inhibitors are unremarkably linked to 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, I2, 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.
CONCLUSIONS: PCSK9 inhibitors increase osteoporosis risk. However, HMGCR inhibitors are unremarkably linked to osteoporosis.
摘要：
背景：前蛋白转化酶枯草杆菌蛋白酶/kexin9型（PCSK9）抑制剂代表了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)分析检查PCSK9抑制剂对骨质疏松的影响.
方法：3-羟基-3-甲基戊二酰辅因子A还原酶（HMGCR）和PCSK9的单核苷酸多态性（SNP）从可用的欧洲家系在线数据库中收集。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，和冠状动脉疾病（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分析结果纳入meta分析，以检查PCSK9和HMGCR抑制剂与骨质疏松症之间的因果关系。
结果：荟萃分析共涉及1,263,102名受试者，表明PCSK9抑制剂可增加骨质疏松风险(P<0.05,I2,39%)。然而,HMGCR抑制剂与骨质疏松症风险无关。此外,使用另一个与暴露相关的GWAS数据集进行了分析的复制，这导致了类似的结论。
结论：PCSK9抑制剂增加骨质疏松风险。然而,HMGCR抑制剂与骨质疏松症无显著关联。
方法：3-羟基-3-甲基戊二酰辅因子A还原酶（HMGCR）和PCSK9的单核苷酸多态性（SNP）从可用的欧洲家系在线数据库中收集。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，和冠状动脉疾病（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分析结果纳入meta分析，以检查PCSK9和HMGCR抑制剂与骨质疏松症之间的因果关系。
结果：荟萃分析共涉及1,263,102名受试者，表明PCSK9抑制剂可增加骨质疏松风险(P<0.05,I2,39%)。然而,HMGCR抑制剂与骨质疏松症风险无关。此外,使用另一个与暴露相关的GWAS数据集进行了分析的复制，这导致了类似的结论。
结论：PCSK9抑制剂增加骨质疏松风险。然而,HMGCR抑制剂与骨质疏松症无显著关联。
