不同部位骨密度与椎间盘退变的因果关联
Causal association between bone mineral density and intervertebral disc degeneration at different sites
  
DOI:10.3969/j.issn.1006-7108.2024.05.009
中文关键词:  骨密度  骨质疏松症  椎间盘退变  孟德尔随机化
英文关键词:bone mineral density  osteoporosis  intervertebral disc degeneration  Mendelian randomization
基金项目:国家自然科学基金面上项目(82372431);上海市卫健委“卫生健康领军人才”计划(2022LJ007);上海市科委“科技创新行动计划”自然科学基金(22ZR1476700);上海市科委“科技创新行动计划”科技支撑项目(201409003200)
作者单位
石明亮1 谢栋1,2 杨立利1,2* 1海军军医大学第二附属医院(上海长征医院)脊柱外科上海 200003 2中国人民解放军海军第九零五医院骨科上海 200052 
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中文摘要:
      目的 采用双向和多变量孟德尔随机化方法探讨不同部位骨密度与椎间盘退变的因果关联。方法 椎间盘退变的遗传工具变量来自FinnGen数据库;骨质疏松症、腰椎骨密度、股骨颈骨密度、全身骨密度和足跟骨密度5个独立遗传工具变量来自GEFOS联盟和英国生物银行。逆方差加权法作为主要分析方法,并采用了严格的框架,包括双向、多变量孟德尔随机化和多种敏感性分析,以避免潜在的混杂偏倚。结果 遗传预测骨质疏松症是椎间盘退变发生的负向影响因素(OR=0.017,P=1.718E-02)。此外,正向孟德尔随机化分析表明,腰椎骨密度(OR=1.131,95% CI:1.053~1.214,P=6.915E-04)、全身骨密度(OR=1.148,95% CI:1.093~1.206,P=4.221E-08)和足跟骨密度(OR=1.061,95% CI:1.016~1.109,P=7.871E-03)与椎间盘退变发生显著正相关。而在多变量模型中,仅发现腰椎骨密度与椎间盘退变具有正向因果效应(OR=1.120,95% CI:1.003~1.250,P=4.493E-02)。反向分析结果表明,椎间盘退变可影响腰椎骨密度(Beta=0.142,95% CI:0.052~0.233,P=2.078E-03),而未发现对其他部位骨密度具有类似影响。异质性、多效性和统计效能分析结果肯定了上述发现的稳健性。结论 遗传预测骨质疏松症是椎间盘退变发生的负向影响因素。此外,本研究还强调腰椎骨密度与椎间盘退变具有双向因果关联。
英文摘要:
      Objective Bidirectional and multivariable Mendelian randomization (MR) methods were employed to investigate the causal association between bone mineral density (BMD) and intervertebral disc degeneration (IVDD) at different sites. Methods Genetic instrumental variables for IVDD were sourced from the FinnGen database. Five independent genetic instrumental variables for osteoporosis, including lumbar spine BMD, femoral neck BMD, total body BMD, and heel BMD, were acquired from the GEFOS consortium and the UK Biobank. Our primary analytical approach was based on inverse-variance weighted, and we adhered to a robust framework that encompassed bidirectional, multivariable, and multiple sensitivity analyses to mitigate the risk of potential confounding biases. Results The occurrence of IVDD was negatively influenced by genetically predicted osteoporosis (OR=0.017, P=1.718E-02). Univariable MR analyses revealed significant positive associations between lumbar spine BMD (OR=1.131, 95% CI: 1.053–1.214, P=6.915E-04), total body BMD (OR=1.148, 95% CI: 1.093–1.206, P=4.221E-08), heel BMD (OR=1.061, 95% CI: 1.016–1.109, P=7.871E-03), and the occurrence of IVDD. However, in the multivariable model, only genetically predicted lumbar spine BMD demonstrated a positive causal effect on the risk of IVDD (OR=1.120, 95% CI: 1.003–1.250, P=4.493E-02). Results from the reverse causality study suggested a potential reverse causal association between lumbar spine BMD and IVDD (Beta=0.142, 95% CI: 0.052–0.233, P=2.078E-03), with no similar associations found for BMD at other sites. Sensitivity analysis affirmed the robustness of our findings. Conclusion Genetically predicted osteoporosis is a negative influence on the occurrence of IVDD. In addition, this study emphasizes a bidirectional causal association between lumbar spine BMD and IVDD.
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