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Association between fibroblast growth factor 21 and bone mineral density in adults

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Abstract

Purpose

Animal-based studies have reported a decrease in bone mass resulting from high level of fibroblast growth factor 21 (FGF21). However, the correlation between plasma FGF21 levels and bone mineral density (BMD) is paradoxical in previous human-based studies, and the associations between FGF21 gene polymorphisms and BMD haven’t been reported yet. Therefore, here, we evaluated plasma FGF21 levels with sufficient study samples, and performed genetic association test to reveal the physiological and genetic role of FGF21 on BMD in adults.

Methods

Plasma and genetic samples containing 168 and 569 Han Chinese subjects, respectively, were employed in this study. Fasting plasma FGF21 levels were determined using enzyme-linked immunosorbent assay (ELISA). Regional BMD values were measured by dual energy X-ray absorptiometry (DXA). Five variants of FGF21 gene were successfully genotyped.

Results

Physiological association suggested that plasma FGF21 levels were inversely correlated with BMD in femoral neck (Neck-BMD: P = 0.039) and Ward’s triangle (Ward’s-BMD: P = 0.002) of hip region. A FGF21 gene variant, rs490942, was significantly associated with the increase of Ward’s-BMD in total (P = 0.027) and female (P = 0.016) cohorts, as well as Neck-BMD in female cohort (P = 7.45 × 10−3). Meanwhile, eQTL results indicated that this SNP was related to the decreased level of FGF21 gene expression.

Conclusions

Taking together from both physiological and genetic levels, we suggest that FGF21 is inversely associated with regional BMD. And we haven’t observed sex-specific effect in this study.

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Acknowledgements

We wish to thank all the blood donors who participated in the study.

Funding

This work was supported by the National Natural Science Foundation of China (81573241, 31471188, 31771399), China Postdoctoral Science Foundation (2016M602797), Natural Science Basic Research Program Shaanxi Province (2016JQ3026), and the Fundamental Research Funds for the Central Universities.

Author contributions

Y.G. conceived and supervised the project. RH.H. and SS.D. conducted data analysis. M.L., W.H., HN.Y. and DL.Z. contributed to experiments. RH.H wrote the manuscript. JL.G. reproduced data analysis and revised manuscript. All authors discussed the results and commented on the manuscript. All authors agree to be accountable for the work and to ensure that any questions relating to the accuracy and integrity of the paper are investigated and properly resolved.

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Authors and Affiliations

  1. Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, **’an Jiaotong University, **’an, 710049, China

    Ruo-Han Hao, Jun-Ling Gao, Dong-Li Zhu, Hlaing Nwe Thynn, Shan-Shan Dong & Yan Guo

  2. Departments of Orthopaedics, the First Affiliated Hospital, School of Medicine, **’an Jiaotong University, **’an, 710061, China

    Meng Li

  3. Department of Trauma Surgery, Honghui Hospital, College of Medicine, **’an Jiaotong University, **’an, 710054, China

    Wei Huang

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  1. Ruo-Han Hao
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Correspondence to Yan Guo.

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The authors declare that they have no coonflict of interests.

Ethical approval

This study was approved by the Institutional Review Board and Ethics Committee of **’an Jiaotong University. All procedures performed in the study involving human participants were in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Hao, RH., Gao, JL., Li, M. et al. Association between fibroblast growth factor 21 and bone mineral density in adults. Endocrine 59, 296–303 (2018). https://doi.org/10.1007/s12020-017-1507-y

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