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Association of statin use with osteoporosis risk: a drug-targeted Mendelian randomization study

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Abstract

Background

Hypercholesterolemia and the related inflammatory response promote the development of osteoporosis, but whether targeted interventions are protective against this bone metabolic disease remains unknown. The aim of this study was to investigate the association between the use of statins (one well-recognized cholesterol-lowering drug with anti-inflammatory properties) and the risk of osteoporosis using a drug-targeted Mendelian randomization (MR) approach.

Methods

Instrumental variables predicting three cholesterol-lowering target genes (including HGMCR) and the cholesterol effectors mediated by these genes (i.e., total cholesterol, LDL cholesterol, and non-HDL cholesterol) were extracted from expression quantitative trait loci and genome-wide association studies. Inverse variance-weighted (IVW), summary data-based MR (SMR), multivariate MR, and colocalization analysis were used to determine the association of the interventions represented by these instrumental variables with heel bone mineral density (one diagnostic indicator of osteoporosis).

Results

The IVW reported that increased levels of HGMCR-mediated total cholesterol, LDL cholesterol, and non-HDL cholesterol were associated with the decreased level of heel bone mineral density (P = 4.086e−10, P = 1.487e−09, P = 1.967e−09). The colocalization analysis supported the relationship between HGMCR-mediated non-HDL cholesterol and heel bone mineral density. The SMR reported that higher expression of HGMCR was associated with the decreased level of this osteoporosis indicator (P = 0.036). The multivariate MR further confirmed the role of HGMCR in the correlation between cholesterol traits and heel bone mineral density, and also reported that estrogen played a mediating role in the above correlations.

Conclusion

These evidence supported a protective effect of HMGCR-mediated non-HDL cholesterol reduction or statin use against osteoporosis.

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Acknowledgements

The authors want to acknowledge the participants and investigators of the FinnGen study.

Funding

This study was supported by Shenyang Youth Science and Technology Innovation Talent Cultivation Project (Youth Program for Returning to China), Shenyang Bureau of Science and Technology (project number: RC231169); Shenyang supports the innovation and entrepreneurship funding project for doctoral students returning from studying abroad (Shenyang Municipal Bureau of Human Resources and Social Security).

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Authors and Affiliations

  1. Department of Orthopedics, Shengjing Hospital of China Medical University, No. 36, Sanhao Street, Heping District, Shenyang, 110004, Liaoning Province, China

    Zhaozhou Ren & Long Zhou

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  1. Zhaozhou Ren
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  2. Long Zhou
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Contributions

LZ conducted the study design. ZR and LZ performed the literature research, data collection, data analysis, and manuscript preparation.

Corresponding author

Correspondence to Long Zhou.

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There was no conflict of interest to declare.

Ethics approval

The study was approved by the Ethics Committee of Shengjing Hospital of China Medical University.

Consent to participate

This study is a Mendelian randomized study using public data. Subjects were not directly included in this study.

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This study is a Mendelian randomized study using public data. Subjects were not directly included in this study.

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Ren, Z., Zhou, L. Association of statin use with osteoporosis risk: a drug-targeted Mendelian randomization study. Inflammopharmacol 32, 1253–1261 (2024). https://doi.org/10.1007/s10787-024-01441-y

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