Department of Orthopaedics, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, 110004, Liaoning, People's Republic of China.
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Calcif Tissue Int. 2018 Nov;103(5):546-553. doi: 10.1007/s00223-018-0452-y. Epub 2018 Jul 14.
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). 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.
观察性研究检查了吸烟和饮酒与骨密度（BMD）之间的关联，这些研究结果不一致，并存在多种方法学局限性。我们旨在使用孟德尔随机化（MR）设计来评估吸烟、饮酒与 BMD 之间是否存在因果关系。使用已发表的全基因组关联研究（GWAS）中确定的与吸烟状况相关的遗传变异（n=142）、每日吸烟量（CPD）（n=3）、吸烟起始（n=1）和饮酒（n=6）作为工具。使用逆方差加权法，使用包含在骨骼遗传因素骨质疏松症联合会或英国生物银行中的 32735、28498、8143 和 445921 名欧洲受试者的汇总统计数据，分别生成遗传预测的吸烟或饮酒与股骨颈（FN-BMD）、腰椎（LS-BMD）、前臂（FA-BMD）和脚跟 BMD 之间关联。BMD 是使用超声（用于脚跟）或双能 X 射线吸收法（用于其他部位）测量的。在我们的分析中，吸烟状况往往与几种类型的 BMD 呈负相关（脚跟 BMD：β=−0.053，p=0.003；FN-BMD：β=−0.139，p=0.053；FA-BMD：β=−0.264，p=0.077），尽管与 LS-BMD 的关联为零。吸烟起始与脚跟 BMD 呈显著负相关（β=−0.201，p=3.60×10）。CPD 仅与 FN-BMD 呈负相关（β=−0.014，p=0.047）。遗传预测的饮酒与 BMD 无明显关联。我们的研究提供了一些证据，表明遗传预测的吸烟与较低的 BMD 之间存在潜在关联，尤其是脚跟 BMD，但与饮酒无关。考虑到与不同类型的 BMD 不一致的发现和当前工作的局限性，需要进一步研究以更好地描述吸烟、饮酒与 BMD 之间的确切关系。
