Skip to main content

ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Bone Research
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1439255
This article is part of the Research Topic The Endocrine Role of the Musculoskeletal System View all 6 articles

Effects of FGF21 overexpression in osteoporosis and bone mineral density: a two-sample, mediating Mendelian analysis

Provisionally accepted
Jingjing Liu Jingjing Liu 1*Lirong Yang Lirong Yang 1*Yunjia Li Yunjia Li 1*Qiaojun Chen Qiaojun Chen 1*Ting Yang Ting Yang 1*Yanfa Lei Yanfa Lei 1*Zewei He Zewei He 1*Xiaowei Wang Xiaowei Wang 1*Qiang Na Qiang Na 2*Changtao Lao Changtao Lao 2*xinlei luo xinlei luo 1*Jun Jiang Jun Jiang 1*Zhengchang Yang Zhengchang Yang 1*
  • 1 Southern Central Hospital of Yunnan Province, Honghe, China
  • 2 People's Hospital of Yuxi City, Yuxi, China

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

    Abstract： Objective Fibroblast growth factor 21 (FGF21) is a secreted protein that regulates body metabolism. In recent years, many observational studies have found that FGF21 is closely related to bone mineral density and osteoporosis, but the causal relationship between them is still unclear. Therefore, this study used two-sample, mediated Mendelian randomization (MR) analysis to explore the causal relationship between FGF21 and osteoporosis and bone mineral density. Methods We conducted a two-sample, mediator MR Analysis using genetic data from publicly available genome-wide association studies (GWAS) that included genetic variants in the inflammatory cytokine FGF21, and Total body bone mineral density, Heel bone mineral density, Forearm bone mineral density, Femoral neck bone mineral density, osteoporosis. The main analysis method used was inverse variance weighting (IVW) to investigate the causal relationship between exposure and outcome. In addition, weighted median, simple median method, weighted median method and MR-Egger regression were used to supplement the explanation, and sensitivity analysis was performed to evaluate the reliability of the results. Results MR Results showed that FGF21 overexpression reduced bone mineral density: Total body bone mineral density (OR=0.920, 95%CI: 0.876-0.966), P=0.001), Heel bone mineral density (OR=0.971, 95%CI (0.949-0.993); P=0.01), Forearm bone mineral density (OR=0.882, 95%CI(0.799-0.973); P=0.012), Femoral neck bone mineral density (OR=0.952, 95%CI(0.908-0.998), P=0.039); In addition, it also increased the risk of osteoporosis (OR=1.003, 95%CI (1.001-1.005), P=0.004). Sensitivity analysis supported the reliability of these results. The effect of FGF21 overexpression on osteoporosis may be mediated by type 2 diabetes mellitus and basal metabolic rate, with mediating effects of 14.96% and 12.21%, respectively. Conclusions Our study suggests that the overexpression of FGF21 may lead to a decrease in bone mineral density and increase the risk of osteoporosis, and the effect of FGF21 on osteoporosis may be mediated through type 2 diabetes and basal metabolic rate. This study can provide a reference for analyzing the potential mechanism of osteoporosis and is of great significance for the prevention and treatment of osteoporosis. Key words：Fibroblast growth factor 21; osteoporosis; GWAS; Mendelian randomization.

    Keywords: fibroblast growth factor 21, Osteoporosis, GWAS, Mendelian randomization, bone mineral density

    Received: 27 May 2024; Accepted: 21 Aug 2024.

    Copyright: © 2024 Liu, Yang, Li, Chen, Yang, Lei, He, Wang, Na, Lao, luo, Jiang and Yang. 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:
    Jingjing Liu, Southern Central Hospital of Yunnan Province, Honghe, China
    Lirong Yang, Southern Central Hospital of Yunnan Province, Honghe, China
    Yunjia Li, Southern Central Hospital of Yunnan Province, Honghe, China
    Qiaojun Chen, Southern Central Hospital of Yunnan Province, Honghe, China
    Ting Yang, Southern Central Hospital of Yunnan Province, Honghe, China
    Yanfa Lei, Southern Central Hospital of Yunnan Province, Honghe, China
    Zewei He, Southern Central Hospital of Yunnan Province, Honghe, China
    Xiaowei Wang, Southern Central Hospital of Yunnan Province, Honghe, China
    Qiang Na, People's Hospital of Yuxi City, Yuxi, China
    Changtao Lao, People's Hospital of Yuxi City, Yuxi, China
    xinlei luo, Southern Central Hospital of Yunnan Province, Honghe, China
    Jun Jiang, Southern Central Hospital of Yunnan Province, Honghe, China
    Zhengchang Yang, Southern Central Hospital of Yunnan Province, Honghe, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.