Xu Fei, Zhang XiuRong, Zhang YinRong, Chen WenHui, Liao ZiCong
General Surgery Department, Zhongshan Boai Hospital, Zhongshan, Guangdong, 528400, People's Republic of China.
Breast Surgery Department, Zhongshan Boai Hospital, Zhongshan, Guangdong, 528400, People's Republic of China.
Nat Sci Sleep. 2024 Mar 22;16:325-333. doi: 10.2147/NSS.S443557. eCollection 2024.
Observational studies have yielded conflicting evidence concerning the relationships between obstructive sleep apnea (OSA) and bone mineral density (BMD). As the exact causal inferences remain inconclusive, we conducted a two-sample Mendelian randomization (MR) to identify the causal associations between OSA and BMD.
Single-nucleotide polymorphisms associated with OSA were extracted from the FinnGen study. Summary statistics for 10 BMD measured at different age or skeletal sites were obtained from the publicly available IEU GWAS database. Inverse-variance weighted (IVW) method was chosen as the primary analysis, combined with several sensitivity analyses to evaluate the robustness of results. The study design included two-sample MR and network MR.
Our primary MR analysis revealed that genetically predicted OSA was positively linked to increased forearm BMD (β = 0.24, 95% confidence interval [CI]: 0.06-0.41, p = 0.009) and heel BMD (β=0.10, 95% CI = 0.02-0.18, p = 0.018), while no significant causal relationships were observed between OSA and total body BMD, lumbar spine BMD, or femoral neck BMD (all p > 0.05). Network MR suggests that OSA might act as a mediating factor in the effect of BMI on forearm BMD and heel BMD, with a mediated portion estimated at 73% and 84%, respectively.
Our findings provide support for a causal relationship between genetically predicted OSA and increased forearm BMD and heel BMD. Furthermore, our results suggest that OSA may play a role in mediating the influence of BMI on BMD.
观察性研究关于阻塞性睡眠呼吸暂停（OSA）与骨矿物质密度（BMD）之间的关系得出了相互矛盾的证据。由于确切的因果推断仍无定论，我们进行了一项两样本孟德尔随机化（MR）研究以确定OSA与BMD之间的因果关联。
从芬兰基因研究中提取与OSA相关的单核苷酸多态性。从公开可用的IEU全基因组关联研究（GWAS）数据库中获取在不同年龄或骨骼部位测量的10种BMD的汇总统计数据。选择逆方差加权（IVW）方法作为主要分析方法，并结合几种敏感性分析来评估结果的稳健性。研究设计包括两样本MR和网络MR。
我们的主要MR分析显示，基因预测的OSA与前臂骨密度增加呈正相关（β = 0.24，95%置信区间[CI]：0.06 - 0.41，p = 0.009）以及足跟骨密度增加呈正相关（β = 0.10，95%CI = 0.02 - 0.18，p = 0.018），而在OSA与全身骨密度、腰椎骨密度或股骨颈骨密度之间未观察到显著的因果关系（所有p > 0.05）。网络MR表明，OSA可能在体重指数（BMI）对前臂骨密度和足跟骨密度的影响中起中介作用，中介部分估计分别为73%和84%。
我们的研究结果支持基因预测的OSA与前臂骨密度增加和足跟骨密度增加之间存在因果关系。此外，我们的结果表明OSA可能在介导BMI对骨密度的影响中发挥作用。
