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ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Bone Research
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1386556
This article is part of the Research Topic Insights in Bone Research: 2023 View all 5 articles

Effects of circulating inflammatory proteins on osteoporosis and fractures: evidence from genetic correlation and Mendelian randomization study

Provisionally accepted
Qingcong Zheng Qingcong Zheng 1Du Wang Du Wang 2Rongjie Lin Rongjie Lin 1Zhechen Li Zhechen Li 1Yuchao Chen Yuchao Chen 1Rongsheng Chen Rongsheng Chen 1Chunfu Zheng Chunfu Zheng 3*Weihong Xu Weihong Xu 1*
  • 1 Fujian Medical University, Fuzhou, Fujian Province, China
  • 2 Peking University, Beijing, Beijing Municipality, China
  • 3 University of Calgary, Calgary, Canada

The final, formatted version of the article will be published soon.

    Objective: There is a controversy in studies of circulating inflammatory proteins (CIPs) in association with osteoporosis (OP) and fractures, and it is unclear if these two conditions are causally related. This study used MR analyses to investigate the causal associations between 91 CIPs and OP and 9 types of fractures. Methods: Genetic variants data for CIPs, OP, and fractures were obtained from the publicly available genome-wide association studies (GWAS) database. We used inverse variance weighted (IVW) as the primary analysis, pleiotropy, and heterogeneity tests to analyze the validity and robustness of causality and reverse MR analysis to test for reverse causality. Results: The IVW results with Bonferroni correction indicated that CXCL11 (OR = 1.2049; 95% CI: 1.0308-1.4083; P = 0.0192) can increase the risk of OP; IL-4 (OR = 1.2877; 95% CI: 1.1003-1.5070; P = 0.0016), IL-7 (OR = 1.2572; 95% CI: 1.0401-1.5196; P = 0.0180) , IL-15RA (OR = 1.1346; 95% CI: 1.0163-1.2668; P = 0.0246) , IL-17C (OR = 1.1353; 95% CI: 1.0272-1.2547; P = 0.0129) , CXCL10 (OR = 1.2479; 95% CI: 1.0832-1.4377; P = 0.0022), eotaxin/CCL11 (OR = 1.1552; 95% CI: 1.0525-1.2678; P = 0.0024), and FGF23 (OR = 1.9437; 95% CI: 1.1875-3.1816; P = 0.0082) can increase the risk of fractures; whereas IL-10RB (OR = 0.9006; 95% CI: 0.8335-0.9730; P = 0.0080), CCL4 (OR = 0.9101; 95% CI: 0.8385-0.9878; P = 0.0242) , MCP-3/CCL7 (OR = 0.8579; 95% CI: 0.7506-0.9806; P = 0.0246) , IFN-γ [shoulder and upper arm (OR = 0.7832; 95% CI: 0.6605-0.9287; P = 0.0049); rib(s), sternum and thoracic spine (OR = 0.7228; 95% CI: 0.5681-0.9197; P = 0.0083)], β-NGF (OR = 0.8384; 95% CI: 0.7473-0.9407; P = 0.0027) , and SIRT2 (OR = 0.5167; 95% CI: 0.3296-0.8100; P = 0.0040) can decrease fractures risk. Conclusions: Mendelian randomization (MR) analyses indicated the causal associations between multiple genetically predicted CIPs and the risk of OP and fractures.

    Keywords: Osteoporosis, Fracture, Bone homeostasis, Circulating inflammatory proteins, Mendelian randomization

    Received: 15 Feb 2024; Accepted: 16 Apr 2024.

    Copyright: © 2024 Zheng, Wang, Lin, Li, Chen, Chen, Zheng and Xu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Chunfu Zheng, University of Calgary, Calgary, Canada
    Weihong Xu, Fujian Medical University, Fuzhou, 350108, Fujian Province, China

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