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Association between serum soluble α-klotho and bone mineral density (BMD) in middle-aged and older adults in the United States: a population-based cross-sectional study

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Abstract

Background

Osteoporosis is a degenerative disease defined by low bone mineral density, has a high prevalence, and causes fractures at multiple sites throughout the body, greatly affecting the quality of patients. α-Klotho is an endocrine factor involved in the regulation of various metabolic processes in humans, and its role in bone metabolism has attracted widespread attention. The relationship between α-klotho and bone mineral density has not been uniformly recognized, and no large-scale correlation analysis has been conducted in the middle-aged and elderly population.

Objective

To determine the relationship between α-klotho and bone mineral density in middle-aged and elderly people.

Methods

Population data of 3120 individuals aged 40–79 years were obtained from the NHANES database for the period 2011–2016. Regression analysis was performed using a general linear model with serum α-klotho as the independent variable and total bone mineral density, thoracic bone mineral density, lumbar bone mineral density, pelvic bone mineral density, and trunk bone mineral density as the dependent variables, respectively. The generalized additive model was also used for smoothing curve fitting and threshold effect analysis.

Results

Serum α-klotho was positively correlated with total bone mineral density at lg (Klotho) < 2.97 and with thoracic bone mineral density at lg (Klotho) > 2.69 (β = 0.05, p = 0.0006), and negatively correlated (β = −0.27, p = 0.0341) with lumbar bone mineral density at lg (Klotho) < 2.69. It also positively correlated with trunk bone mineral density (β = 0.027, p = 0.03657) and had no segmental effect but did not correlate with pelvic bone mineral density. The positive association of serum α-klotho with those aged 40–49 years, female, non-Hispanic White, and without hypertension was clearer. In the population with diabetes, a significantly positive association between total (β = 0.15, p = 0.01), thoracic (β = 0.23, p = 0.0404), and lumbar (β = 0.22, p = 0.0424) bone mineral density and α-klotho was observed.

Conclusions

α-Klotho has different relationships with total, thoracic, lumbar, and trunk bone mineral density. Among them, the positive correlation between α-klotho and trunk bone mineral density is more valuable for predicting osteoporosis. The significant effect of α-klotho on bone mineral density in diabetes patients suggests its potential as a predictive marker of diabetes progression.

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Data availability

Publicly available datasets were analyzed in this study. These data can be found here: https://www.cdc.gov/nchs/nhanes/.

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Acknowledgements

The authors thank all of the participants, coordinators, and administrators for their support and help during the research.

Funding

This study was supported by the National Natural Science Foundation of China (82270795, 81700658), the Hunan Provincial Natural Science Foundation (2020JJ3058) and the Wisdom Accumulation and Talent Cultivation Project of the Third Xiangya Hospital of Central South University (YX202212).

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Author notes

  1. Yang Zhang and Changtai Zhao have contributed equally to this work.

Authors and Affiliations

  1. Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, 410013, China

    Yang Zhang, Mingcong Chen, Yang Meng, Yuxin Pan & Mingyi Zhao

  2. Transplantation Center, The Third Xiangya Hospital, Central South University, Changsha, 410013, China

    Changtai Zhao & Quan Zhuang

  3. Hunan Provincial Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, Changsha Medical University, Changsha, 410219, China

    Hanyong Zhang

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Contributions

Yang Zhang: conceptualization, methodology, formal analysis, investigation, data curation, writing—review and editing, visualization. Changtai Zhao: conceptualization, methodology, formal analysis, data curation, visualization, writing—original draft. Hanyong Zhang: conceptualization, formal analysis, investigation, supervision, writing—review and editing. Mongcong Chen: conceptualization, formal analysis, investigation, writing—review and editing. Yang Meng: conceptualization, data curation, formal analysis, investigation, methodology. Yuxin Pan: conceptualization, data curation, formal analysis, visualization, writing—review and editing. Quan Zhuang: conceptualization, methodology, funding acquisition, formal analysis, project administration, writing—review and editing, supervision. Mingyi Zhao: conceptualization, methodology, funding acquisition, project administration, writing—review and editing, supervision.

Corresponding authors

Correspondence to Quan Zhuang or Mingyi Zhao.

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The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of this study.

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This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the National Center for Health Statistics (NCHS) Research Ethics Review Board.

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Zhang, Y., Zhao, C., Zhang, H. et al. Association between serum soluble α-klotho and bone mineral density (BMD) in middle-aged and older adults in the United States: a population-based cross-sectional study. Aging Clin Exp Res 35, 2039–2049 (2023). https://doi.org/10.1007/s40520-023-02483-y

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