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ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Endocrinology of Aging
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1450472

α-klotho reduces susceptibility to osteoarthritis: evidence from cross-sectional studies and Mendelian randomization

Provisionally accepted
Zhao Li Zhao Li 1Zhong Li Zhong Li 1*Qisheng Cheng Qisheng Cheng 2Xinlin Nie Xinlin Nie 2Yu Cui Yu Cui 1*Bing Du Bing Du 1*Taotao Ren Taotao Ren 1*Yibo Xu Yibo Xu 1*Teng Ma Teng Ma 1*
  • 1 Honghui Hospital, Xi’an Jiaotong University, Xi‘an, China
  • 2 Department of Orthopedic Center, the First Hospital of Jilin University, Changchun, Hebei Province, China

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

    Abstract Background: Despite extensive research, the association between serum α-klotho levels and osteoarthritis (OA) remains unclear, predominantly relying on findings from OA mouse models. This study used data from the National Health and Nutrition Examination Survey (NHANES) to conduct a cross-sectional study examining the relationship between α-klotho and human OA. In addition, we used Mendelian randomization (MR) to genetically infer a causal relationship between serum α-klotho and the three OA subtypes. Method: A cohort of 12,037 subjects from NHANES (2007-2016) was analyzed. Multivariate logistic regression was utilized to examine the association between α-klotho concentration and OA, alongside subgroup analysis and interaction tests. Additionally, a two-sample bi-directional MR analysis was conducted to evaluate the relationship between serum α-klotho and three OA subtypes, including all OA, hip OA, and knee OA, employing the inverse variance weighting (IVW) method as the primary approach. Results: Following adjustment for covariates, a nonlinear negative correlation between serum α-klotho and OA was observed (OR=0.77; 95% CI, 0.68-0.88, p < 0.0001). The IVW method revealed that higher serum α-klotho levels were associated with decreased susceptibility to hip OA (OR = 0.92, 95% CI: 0.87–0.98, P = 9.64×10-3). However, MR analysis did not establish a causal relationship between serum α-klotho and OA or knee OA. Inverse MR also indicated that the three subtypes of OA do not causally affect serum α-klotho concentrations. Conclusions: In cross-sectional studies, α-klotho showed a nonlinear negative correlation with OA. MR analysis of outcomes was not identical to cross-sectional studies.

    Keywords: α-klotho, Osteoarthritis, NHANES, Mendelian randomization, Causal effect

    Received: 17 Jun 2024; Accepted: 31 Oct 2024.

    Copyright: © 2024 Li, Li, Cheng, Nie, Cui, Du, Ren, Xu and Ma. 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:
    Zhong Li, Honghui Hospital, Xi’an Jiaotong University, Xi‘an, China
    Yu Cui, Honghui Hospital, Xi’an Jiaotong University, Xi‘an, China
    Bing Du, Honghui Hospital, Xi’an Jiaotong University, Xi‘an, China
    Taotao Ren, Honghui Hospital, Xi’an Jiaotong University, Xi‘an, China
    Yibo Xu, Honghui Hospital, Xi’an Jiaotong University, Xi‘an, China
    Teng Ma, Honghui Hospital, Xi’an Jiaotong University, Xi‘an, China

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