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Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors and the Risk of Fracture: A Systematic Review and Meta-analysis of Randomized Controlled Trials

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Abstract

Osteoporosis and hyperlipidemia are closely correlated and statins might be associated with a decreased risk of fracture. We aimed to investigate the association between proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) therapy and the risk of fracture. The PubMed, Cochrane library, and EMBASE databases were systematically searched from the inception dates to October 22, 2022. Randomized clinical trials (RCTs) that addressed to fracture events of participants using alirocumab, evolocumab, bococizumab or inclisiran, with a follow-up of ≥ 24 weeks were included. Meta-analyses were conducted to calculate the odds ratio (OR) with 95% confidence intervals (CIs) for major osteoporotic fracture, hip fracture, osteoporotic non-vertebral fracture, and total fracture. 30 trials assessing PCSK9i among 95, 911 adults were included. There were no significant associations between PCSK9i therapy and the risk of major osteoporotic fracture [OR 1.08 (95% Cl 0.87–1.34), p = 0.49], hip fracture [OR 1.05 (95% Cl 0.73–1.53), p = 0.79], osteoporotic non-vertebral fracture [OR 1.03 (95% Cl 0.80–1.32), p = 0.83], and total fracture [OR 1.03 (95% Cl 0.88–1.19), p = 0.74] over a period of 6–64 months. No significant associations were detected in any of the sensitivity analyses and subgroup analyses stratified by the type of PCSK9i, follow-up duration, age, sex, sample size, and patient profile. Pooled results of our meta-analysis showed that exposure to PCSK9i was not associated with reduced risks of fracture in the short term.

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Data Availability

All data relevant to the study are included in the article or uploaded as supplementary information. This paper is a systematic review and does not report novel primary data.

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Acknowledgements

We appreciate the help from the library staff with finding the literature.

Funding

This work was supported by National Natural Science Foundation of China (Nos. 81970698, 81900805, and 81970708), Beijing Natural Science Foundation (No. 7202216), Peking University People's Hospital Research and Development Funds (Project RS2022-03). The funding agencies had no roles in the study design, data collection or analysis, decision to publish or preparation of the manuscript.

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  1. Department of Endocrinology and Metabolism, Peking University People’s Hospital, No.11 Xizhimen South Street, Xicheng District, Beijing, 100044, China

    Fang Lv, Xiaoling Cai, Chu Lin, Wenjia Yang, Suiyuan Hu & Linong Ji

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Contributions

XLC and LNJ designed this study. FL, WJY and CL searched the literature. FL, WJY, LC and SYH extracted data. FL, CL and WJY analysed data. FL and XLC wrote the first draft of the manuscript. All authors contributed to revisions of the manuscript.

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Correspondence to Xiaoling Cai or Linong Ji.

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Fang Lv, Xiaoling Cai, Chu Lin, Wenjia Yang, Suiyuan Hu, Linong Ji declare that they have no conflict of interest.

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Lv, F., Cai, X., Lin, C. et al. Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors and the Risk of Fracture: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Calcif Tissue Int 113, 175–185 (2023). https://doi.org/10.1007/s00223-023-01085-0

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