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ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Bone Research
Volume 15 - 2024 |
doi: 10.3389/fendo.2024.1386556
Effects of circulating inflammatory proteins on osteoporosis and fractures: evidence from genetic correlation and Mendelian randomization study
Provisionally accepted- 1 Fujian Medical University, Fuzhou, Fujian Province, China
- 2 Peking University, Beijing, Beijing Municipality, China
- 3 University of Calgary, Calgary, Canada
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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