Honghui-hospital, Xi'an Jiaotong University, Xi'an, 710054, China.
Shannxi Key Laboratory of Spine Bionic Treatment, Xi'an, China.
BMC Musculoskelet Disord. 2024 Feb 12;25(1):130. doi: 10.1186/s12891-024-07195-6.
Observational studies have suggested that type 2 Diabetes Mellitus (DM2) is a potentially modifiable risk factor for lower BMD, but the causal relationship is unclear. This study aimed to examine whether the association of DM2 with lower BMD levels was causal by using Mendelian randomization (MR) analyses.
We collected genome-wide association study data for DM2 and BMD of total body and different skeletal sites from the IEU database. Subsequently, we performed a two-sample Mendelian randomization analysis using the Two Sample MR package.
We identified a positive association between DM2 risk (61,714 DM2 cases and 596,424 controls) and total BMD, and other skeletal sites BMD, such as femoral neck BMD, ultra-distal forearm BMD and heel BMD. However, non-significant trends were observed for the effects of DM2 on lumbar-spine BMD.
In two-sample MR analyses, there was positive causal relationship between DM2 and BMD in both overall samples. In summary, while observational analyses consistently indicate a strong association between DM2 and low BMD, our MR analysis introduces a nuanced perspective. Contrary to the robust association observed in observational studies, our MR analysis suggests a significant link between DM2 and elevated BMD.
观察性研究表明 2 型糖尿病（DM2）是骨密度降低的潜在可改变危险因素，但因果关系尚不清楚。本研究旨在通过孟德尔随机化（MR）分析来检验 DM2 与较低的 BMD 水平之间的关联是否存在因果关系。
我们从 IEU 数据库中收集了 DM2 和全身及不同骨骼部位 BMD 的全基因组关联研究数据。然后，我们使用 Two Sample MR 包进行了两样本 MR 分析。
我们发现 DM2 风险（61714 例 DM2 病例和 596424 例对照）与总体 BMD 以及其他骨骼部位 BMD（如股骨颈 BMD、远段前臂 BMD 和足跟 BMD）呈正相关。然而，DM2 对腰椎 BMD 的影响则呈现出非显著的趋势。
在两样本 MR 分析中，DM2 与 BMD 之间存在正相关的因果关系。总的来说，虽然观察性分析一致表明 DM2 与低 BMD 之间存在很强的关联，但我们的 MR 分析引入了一个细微的视角。与观察性研究中观察到的稳健关联相反，我们的 MR 分析表明 DM2 与较高的 BMD 之间存在显著联系。
