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| 孟德尔随机化分析骨质疏松症、骨密度与骨坏死的因果关系 |
| Causal relationship analysis of osteoporosis, bone mineral density, and osteonecrosis using Mendelian randomization |
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| DOI：10.3969/j.issn.1006-7108.2025.12.009 |
| 中文关键词: 骨质疏松症 骨密度 骨坏死 孟德尔随机化 |
| 英文关键词:Osteoporosis Bone mineral density Osteonecrosis Mendelian randomization |
| 基金项目:国家自然科学基金(82374479)；江苏省自然科学基金(BK20211066)； |
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| 中文摘要: |
| 目的?使用孟德尔随机化(mendelian?randomization,MR)方法探讨骨质疏松症(osteoporosis,OP)?、骨密度(bone?mineral?density,BMD)与骨坏死(osteonecrosis,ON)之间的因果关系。方法??使用公开的全基因组关联研究(genome-wide?association?study,GWAS)汇总数据进行?MR?分析。采用逆方差加权法(inverse?variance?weighted,?IVW)、MR-Egger?回归法和加权中位数(weighted?median,WM)等方法估计?OP、BMD?与?ON?之间的因果关系。敏感性分析验证结果的稳定性与可靠性。采用?Bonferroni?法确定显著性阈值(P=8.33×10-3)。结果??正向?MR?研究中，IVW?法表明遗传预测的?OP?与?ON?之间存在显著的因果关系(OR:?1.217,?95%?CI:?1.083~1.368)；在?BMD?方面，全身?BMD(TB-BMD)(OR:?0.733,?95%?CI:?0.625~0.859)、腰椎?BMD(LS-BMD)(OR:?0.758,?95%?CI:?0.626~0.919)、手臂?BMD(Arm-BMD)(OR:?0.751,?95%?CI:?0.614~0.919)、股骨颈?BMD(FN-BMD)(OR:?0.774,?95%?CI:?0.64~0.936)和足跟?BMD(Heel-BMD)(OR:?0.751,?95%?CI:?0.651~0.867)与?ON?之间存在显著的因果关系，经?Bonferroni?法校正后，因果关系依然显著。异质性检验表明，Arm-BMD?与?ON?之间存在异质性，但不影响随机效应?IVW?法得出的结论；OP?和其他部位?BMD?与?ON?之间不存在异质性。MR-Egger?截距法表明无水平多效性。反向?MR?研究未发现?ON?与?OP、不同部位?BMD?之间存在因果关系。异质性检验表明，ON?与?TB-BMD?之间存在异质性，但不影响随机效应?IVW?法得出的结论；ON?与其余结局之间不存在异质性。MR-Egger?截距法表明无水平多效性。结论??遗传预测的OP?是?ON?的危险因素，不同部位?BMD?增加是?ON?的保护因素。这提示?OP?患者应密切关注?ON?好发部位的骨骼情况，以避免ON的发生，本研究为?ON?的预防和治疗提供了新的研究证据和方向。 |
| 英文摘要: |
| Objective??To?explore?the?causal?relationships?between?osteoporosis?(OP)?,bone?mineral?density?(BMD)?and?osteonecrosis?(ON)?using?bidirectional?Mendelian?randomisation?(MR)?analysis.?Methods??Publicly?available?genome-wide?association?study?(GWAS)?summary?data?were?used?to?conduct?the?MR?analysis.The?inverse?variance?weighted?(IVW),?MR-Egger?regression,weighted?median?(WM)?and?other?methods?were?employed?to?investigate?the?causal?relationship?between?OP,?BMD,?and?ON.The?stability?and?reliability?of?the?results?were?verified?using?several?sensitivity?analysis?methods.The?significance?threshold?was?determined?using?the?Bonferroni?method?(P=8.33×10-3).?Results??In?the?forward?MR?study,?the?IVW?method?demonstrated?a?significant?causal?relationship?between?genetically?predicted?OP?and?ON?(OR:?1.217,?95%?CI:?1.083~1.368).?Regarding?BMD,?significant?causal?associations?were?identified?between?ON?and?total?body?BMD?(TB-BMD)?(OR:?0.733,?95%?CI:?0.625~0.859),?lumbar?spine?BMD?(LS-BMD)?(OR:?0.758,?95%?CI:?0.626~0.919),?arm?BMD?(Arm-BMD)?(OR:?0.751,?95%?CI:?0.614~0.919),?femoral?neck?BMD?(FN-BMD)?(OR:?0.774,?95%?CI:?0.640~0.936),?and?heel?BMD?(Heel-BMD)?(OR:?0.751,?95%?CI:?0.651~0.867).?Following?Bonferroni?correction,?these?causal?relationships?remained?statistically?significant.?Heterogeneity?tests?indicated?the?presence?of?heterogeneity?between?Arm-BMD?and?ON;?however,?this?did?not?affect?the?conclusions?derived?from?the?random?effects?IVW?method.?No?heterogeneity?was?found?between?OP?and?BMD?at?other?sites?concerning?ON.?The?MR-Egger?intercept?method?suggested?the?absence?of?horizontal?pleiotropy.?In?contrast,?reverse?MR?study?revealed?no?evidence?of?a?causal?relationship?between?ON?and?OP?or?BMD?at?various?sites.Heterogeneity?tests?indicated?heterogeneity?between?ON?and?TB-BMD,?although?this?did?not?influence?the?conclusions?from?the?random?effects?IVW?method,?and?no?heterogeneity?was?observed?between?ON?and?other?outcomes.?The?MR-Egger?intercept?method?confirmed?the?absence?of?horizontal?pleiotropy.?Conclusion??Genetically?predicted?OP?is?a?risk?factor?for?ON,?while?increased?BMD?at?different?sites?acts?as?a?protective?factor?against?ON.?This?suggests?that?patients?with?OP?should?closely?monitor?the?skeletal?condition?in?areas?prone?to?ON?in?order?to?prevent?its?occurrence.?This?study?provides?new?evidence?and?directions?for?the?prevention?and?treatment?of?ON. |
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