Department of Prevention Medicine, College of Public health, Shanghai University of Medicine & Health Sciences, Shanghai, China.
Jiading Central Hospital, Shanghai University of Medicine & Health Sciences, Shanghai, China.
Front Endocrinol (Lausanne). 2023 Jan 11;13:1021083. doi: 10.3389/fendo.2022.1021083. eCollection 2022.
The causal direction and magnitude of the association between total body bone mineral density (TB-BMD) and osteoarthritis (OA) risk is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. The study aimed to explore the relationships between TB-BMD concentration and OA using Mendelian randomization (MR).
In this study, we used two-sample MR to obtain unconfounded estimates of the effect of TB-BMD on hip and knee OA. Single nucleotide polymorphisms (SNPs) strongly associated with TB-BMD in a large genome-wide association study (GWAS) were identified and selected as instrumental variables (IVs). In addition to the main analysis using inverse-variance weighted (IVW) method, we applied 2 additional methods to control for pleiotropy(MR-Egger regression, weighted median estimator) and compared the respective MR estimates.
MR analyses suggested that genetically predicted higher TB-BMD is associated with risks of hip OA (For IVW: OR=1.199, 95%CI: 1.02-1.42, =0.032; for WM: OR=1.257, 95%CI: 1.09-1.45, =0.002). There was no evidence that the observed causal effect between TB-BMD and the risk of hip OA was affected by genetic pleiotropy(=0.618). Additionally, our study didn't support causal effects of a genetically increased TB-BMD risk on knee OA risk(OR=1.121, 95%CI: 0.99-1.28, =0.084 using IVW; OR=1.132, 95%CI: 0.99-1.29, =0.068 using WM; OR=1.274, 95%CI: 0.88-1.85, =0.217 using MR-Egger).
Our findings support a causal effect that a genetic predisposition to systematically higher TB-BMD was associated with the risk of OA. And, TB-BMD likely exerts an effect on the risk of hip OA not knee OA.
由于观察性研究易受混杂因素和反向因果关系的影响，因此，全身骨密度（TB-BMD）与骨关节炎（OA）风险之间的因果关系方向和程度尚不确定。本研究旨在使用孟德尔随机化（MR）方法来探讨 TB-BMD 浓度与 OA 之间的关系。
本研究采用两样本 MR 方法获得 TB-BMD 对髋部和膝部 OA 影响的无偏估计值。在一项大型全基因组关联研究（GWAS）中，确定并选择与 TB-BMD 密切相关的单核苷酸多态性（SNP）作为工具变量（IVs）。除了使用逆方差加权（IVW）法进行主要分析外，我们还应用了另外两种方法（MR-Egger 回归、加权中位数估计）来控制偏倚，并比较了各自的 MR 估计值。
MR 分析表明，遗传预测的较高 TB-BMD 与髋部 OA 风险相关（IVW：OR=1.199，95%CI：1.02-1.42，=0.032；WM：OR=1.257，95%CI：1.09-1.45，=0.002）。没有证据表明 TB-BMD 与髋部 OA 风险之间的观察到的因果关系受到遗传偏倚的影响（=0.618）。此外，我们的研究不支持遗传上增加的 TB-BMD 风险对膝部 OA 风险的因果效应（IVW：OR=1.121，95%CI：0.99-1.28，=0.084；WM：OR=1.132，95%CI：0.99-1.29，=0.068；MR-Egger：OR=1.274，95%CI：0.88-1.85，=0.217）。
我们的研究结果支持这样一种因果关系，即遗传上易患全身骨密度升高与 OA 风险相关。并且，TB-BMD 可能对髋部 OA 风险而非膝部 OA 风险有影响。
