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Is There Causal Relationship of Smoking and Alcohol Consumption with Bone Mineral Density? A Mendelian Randomization Study

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Abstract

Observational studies examining associations of smoking and alcohol consumption with bone mineral density (BMD) have generated inconsistent results and suffer from several methodological limitations. We aim to evaluate whether there are causal associations between smoking, alcohol consumption, and BMD using a Mendelian randomization (MR) design. Genetic variants associated with smoking status (n = 142), no. of cigarettes smoked per day (CPD) (n = 3), smoking initiation (n = 1), and alcohol consumption (n = 6) identified in published genome-wide association studies (GWAS) were used as instruments. Summary statistics data of 32735, 28498, 8143, and 445921 European subjects included in The GEnetic Factors for Osteoporosis Consortium or UK Biobank were used to generate associations of genetically predicted smoking or alcohol consumption with femoral neck (FN-BMD), lumbar spine (LS-BMD), forearm (FA-BMD), and heel BMD, respectively, by using the inverse-variance weighted method. The BMD was measured using either ultrasound (for heel) or Dual-energy X-ray Absorptiometry (for others). In our analyses, smoking status tended to be negatively associated with several types of BMD (heel BMD: β = − 0.053, p = 0.003; FN-BMD: β = − 0.139, p = 0.053; FA-BMD: β = − 0.264, p = 0.077), although the association with LS-BMD was null. Smoking initiation was significantly inversely associated with heel BMD (β = − 0.201, p = 3.60 × 10−8). CPD was associated with a lower FN-BMD (β = − 0.014, p = 0.047) only. There was no clear association of genetically predicted alcohol consumption with BMD. Our study provided some evidence of a potential association between genetically predicted smoking and lower BMD, especially for heel BMD, but not for alcohol consumption. Considering the inconsistent findings with the different types of BMD and limitations of the current work, further studies are needed to better characterize the exact relationship between smoking, alcohol consumption, and BMD.

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Funding

This study was supported by the General project for scientific research of Liaoning Provincial Education Department (No. L2015572 for Ran Guo). The sponsors are not involved in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.

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Authors and Affiliations

  1. Department of Orthopaedics, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, 110004, Liaoning, People’s Republic of China

    Ran Guo & Qin Fu

  2. Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, USA

    Lang Wu

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  1. Ran Guo
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  2. Lang Wu
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Contributions

RG, LW, and QF designed this study. RG and QF performed the catalog and literature search and data extraction with suggestions and help from LW. RG, LW, and QF performed the statistical analyses. All authors contributed to the data interpretation and manuscript writing. QF is responsible for the overall content as the guarantor of the paper.

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Correspondence to Qin Fu.

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Ran Guo, Lang Wu, and Qin Fu declare that they have no conflict of interest.

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Guo, R., Wu, L. & Fu, Q. Is There Causal Relationship of Smoking and Alcohol Consumption with Bone Mineral Density? A Mendelian Randomization Study. Calcif Tissue Int 103, 546–553 (2018). https://doi.org/10.1007/s00223-018-0452-y

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