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Meta-Analysis
. 2024 Jul 16;25(1):548.
doi: 10.1186/s12891-024-07674-w.

PCSK9 inhibitors and osteoporosis: mendelian randomization and meta-analysis

Affiliations
Meta-Analysis

PCSK9 inhibitors and osteoporosis: mendelian randomization and meta-analysis

Ding-Qiang Chen et al. BMC Musculoskelet Disord. .

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.

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

Keywords: HMGCR; Mendelian randomization; Osteoporosis; PCSK9.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
MR study design conceptual diagram
Fig. 2
Fig. 2
The impact of PCSK9 and HMGCR inhibitors on CHD and osteoporosis
Fig. 3
Fig. 3
Meta-analytic forest figure showing the effect of PCSK9 inhibitors on osteoporosis. (A) Initial analysis; (B) Repeat analysis
Fig. 4
Fig. 4
Meta-analytic forest figure showing the effect of HMGCR inhibitors on osteoporosis. (A) Initial analysis; (B) Repeat analysis

References

    1. Hu L, Yin C, Zhao F, Ali A, Ma J, Qian A. Mesenchymal stem cells: cell fate decision to osteoblast or adipocyte and application in osteoporosis treatment. Int J Mol Sci. 2018;19(2):360. doi: 10.3390/ijms19020360. - DOI - PMC - PubMed
    1. Föger-Samwald U, Kerschan-Schindl K, Butylina M, Pietschmann P. Age related osteoporosis: Targeting Cellular Senescence. Int J Mol Sci. 2022;23(5):2701. doi: 10.3390/ijms23052701. - DOI - PMC - PubMed
    1. Laskou F, Fuggle NR, Patel HP, Jameson K, Cooper C, Dennison E. Associations of osteoporosis and sarcopenia with frailty and multimorbidity among participants of the Hertfordshire Cohort Study. J Cachexia Sarcopenia Muscle. 2022;13(1):220–9. doi: 10.1002/jcsm.12870. - DOI - PMC - PubMed
    1. Anagnostis P, Florentin M, Livadas S, Lambrinoudaki I, Goulis DG. Bone Health in patients with Dyslipidemias: an underestimated aspect. Int J Mol Sci. 2022;23(3):1639. doi: 10.3390/ijms23031639. - DOI - PMC - PubMed
    1. Duan Y, Gong K, Xu S, Zhang F, Meng X, Han J. Regulation of cholesterol homeostasis in health and diseases: from mechanisms to targeted therapeutics. Signal Transduct Target Ther. 2022;7(1):265. doi: 10.1038/s41392-022-01125-5. - DOI - PMC - PubMed

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