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Estimates of the effects of physical activity on osteoporosis using multivariable Mendelian randomization analysis

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Abstract

Summary

This study estimates causality of physical activity (PA) on bone mineral density (BMD) by conducting multivariable Mendelian randomization (MR). The findings suggest that habitual vigorous PA increases lumbar spine BMD, and higher overall acceleration average would improve forearm BMD. The results could promote PA intervention targeting individuals with optimized type.

Introduction

Evidence from epidemiologic studies showed type, frequency, and duration of PA influenced BMD. However, these observational studies may be confounded by many factors, resulting in spurious associations. We aimed to conduct multivariable MR to estimate the causal effect of self-reported and device-measured PA on osteoporosis.

Methods

Three self-reported and two device-measured PA-related traits were selected as exposures. Outcomes were BMD at different skeletal sites: femoral neck BMD (FN BMD), lumbar spine BMD (LS BMD), and forearm BMD (FA BMD). Exposure datasets were obtained from UK Biobank with total 377,234 subjects. Outcome datasets were obtained from GEFOS consortium with 53,236 subjects. Standard MR analysis and multivariable MR were conducted to assess the total and direct causal effect of PA on BMD.

Results

For self-reported PA, inverse-normalized moderate-to-vigorous had a direct causal effect on FN BMD independently (β = − 1.116 (95% confidence interval, 95%CI: − 2.210, − 0.023), P = 0.045); vigorous PA showed a direct effect (β = 3.592 (95%CI: 0.310, 6.874), P = 0.032) on LS BMD independently. While overall acceleration average and fraction of accelerations both had a direct causal effect on FA BMD independently.

Conclusions

Habitual vigorous PA could increase LS BMD. Individuals with higher overall acceleration average would have a higher FA BMD.

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Data availability

The datasets used and/or analyzed during the current study are publicly available. For BMD, data could be downloaded from http://www.gefos.org/?q=content/data-release-2015 and PA data could be downloaded from https://www.ebi.ac.uk/gwas/publications/29899525.

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Acknowledgments

The authors would like to thank the participants, the coordinators, and administrators for their support during the study. The authors would like to thank Jing Zhang for her suggestions and revision of the manuscripts.

Funding

Hong-Wen Deng was partially supported by grants from the National Institutes of Health [AR069055, U19 AG055373, R01 MH104680, R01AR059781, and P20GM109036], and the Edward G. Schlieder Endowment fund to Tulane University. Chang-Qing Sun was partially supported by grants from the Key Research & Development and Promotion Projects of Henan Province [192102310191], and the Major Project of Basic Research of Philosophy and Social Science of Henan Education Department [2015-JCZD-009]. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, 450001, Henan, People’s Republic of China

    F. Xu, Q. Zhang, L.-K. Wang, Q.-X. Tang & C.-Q. Sun

  2. Tulane Center for Biomedical Informatics and Genomics, School of Medicine, Tulane University, New Orleans, LA, 70112, USA

    F. Xu, Q. Zhang & H.-W. Deng

  3. School of Nursing, Zhengzhou University, Zhengzhou, 450001, Henan, People’s Republic of China

    C.-Q. Sun

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  1. F. Xu
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  2. Q. Zhang
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  3. L.-K. Wang
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  4. Q.-X. Tang
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  6. H.-W. Deng
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Correspondence to C.-Q. Sun or H.-W. Deng.

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Contributing studies, where the summary statistics was obtained, received ethical approval from their respective institutional review boards. Informed consent was obtained for all participants in original studies.

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Xu, F., Zhang, Q., Wang, LK. et al. Estimates of the effects of physical activity on osteoporosis using multivariable Mendelian randomization analysis. Osteoporos Int 32, 1359–1367 (2021). https://doi.org/10.1007/s00198-020-05786-2

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  • DOI: https://doi.org/10.1007/s00198-020-05786-2

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