This study aimed to investigate the causal relationship between bone mineral density (BMD) and intervertebral disk degeneration (IVDD) using a two-sample bidirectional Mendelian randomization analysis. Summary-level data from the Genome-Wide Association Study (GWAS) were used. Instrumental variables (IVs) for IVDD were selected from the large-scale Genome-Wide Association Study (GWAS) (20,001 cases and 164,682 controls). Bone mineral density (BMD) at five different sites (heel (n = 426,824), total body (TB) (n = 56,284), forearm (FA) (n = 8143), femoral neck (FN) (n = 32,735), and lumbar spine (LS) (n = 28,498)) was used as a phenotype for OP. Bidirectional causality between IVDD and BMD was assessed using inverse variance weighting (IVW) and other methods. Related sensitivity analyses were performed. Myopia was also analyzed as a negative control result to ensure the validity of IVs. Heel bone mineral density (heel BMD), total body bone mineral density (TB-BMD), femoral neck bone mineral density (FN-BMD), and lumbar spine bone mineral density (LS-BMD) have a direct causal relationship on intervertebral disk degeneration (IVDD) [heel BMD-related analysis: beta = 0.06, p = 0.03; TB-BMD-related analysis: beta = 0.18, p = 8.72E-08; FN-BMD-related analysis: beta = 0.15, p = 4.89E-03; LS-BMD-related analysis: beta = 0.16, p = 1.43E-04]. There was no evidence of a significant causal effect of IVDD on BMD. In conclusion, our study found a significant positive causal effect of lower BMD on IVDD, and we identified significant causal effects of heel, TB-, FN-, and LS-BMD on IVDD, but there was no evidence of a significant causal effect of IVDD on BMD.

本研究旨在利用两样本双向孟德尔随机化分析探讨骨矿物质密度 (BMD) 与椎间盘退变 (IVDD) 之间的因果关系。使用全基因组关联研究 (GWAS) 的摘要级数据。IVDD 的工具变量 (IV) 选自大规模全基因组关联研究 (GWAS)（20,001 例病例和 164,682 例对照）。五个不同部位的骨矿物质密度 (BMD)（脚跟 ( n  = 426,824)、全身 (TB) ( n  = 56,284)、前臂 (FA) ( n  = 8143)、股骨颈 (FN) ( n  = 32,735)、腰椎 (LS) ( n  = 28,498)) 被用作 OP 的表型。使用逆方差加权 (IVW) 和其他方法评估 IVDD 和 BMD 之间的双向因果关系。进行了相关敏感性分析。近视也作为阴性对照结果进行分析，以确保 IV 的有效性。足跟骨密度（heel BMD）、全身骨密度（TB-BMD）、股骨颈骨密度（FN-BMD）、腰椎骨密度（LS-BMD）与椎间盘有直接因果关系退化（IVDD）[足跟 BMD 相关分析：beta = 0.06，p  = 0.03；TB-BMD相关分析：beta = 0.18，p  = 8.72E-08；FN-BMD相关分析：beta = 0.15，p  = 4.89E-03；LS-BMD相关分析：beta = 0.16，p  = 1.43E-04]。没有证据表明 IVDD 对 BMD 有显着因果影响。总之，我们的研究发现较低的 BMD 对 IVDD 具有显着的正因果效应，并且我们确定了足跟、TB-、FN- 和 LS-BMD 对 IVDD 的显着因果效应，但没有证据表明以下因素具有显着的因果效应： BMD 上的 IVDD。