中国组织工程研究

中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (23): 6030-6039.doi: 10.12307/2026.371

• 组织工程相关大数据分析 Big data analysis in tissue engineering • 上一篇    下一篇

肌少症与骨质疏松症：欧洲人群全基因组数据分析

尹兴晓1，蒋  阳1，宋艳萍2，姚  娜2，申  震2，李艳琪1，宋粤渝1，彭  皓1，陈奇刚2   

  1. 1云南师范大学体育学院，云南省昆明市   650500；2云南中医药大学第三附属医院康复科，云南省昆明市   650011


  • 收稿日期:2025-07-09 接受日期:2025-09-07 出版日期:2026-08-18 发布日期:2025-12-31
  • 通讯作者: 陈奇刚，主任医师，教授，硕士生导师，云南中医药大学第三附属医院康复科，云南省昆明市 650011 通讯作者：彭皓，在读博士，云南师范大学体育学院，云南省昆明市 650500
  • 作者简介:尹兴晓，男，1998年生，云南省保山市人，汉族，在读硕士，主要从事肌骨康复、运动康复研究。
  • 基金资助:
    国家自然科学基金(82360943)，项目负责人：申震；云南省“兴滇英才支持计划”青年人才专项项目(XDYC-QNRC-2022-0609)，项目负责人：申震；云南省科学技术厅中医联合专项课题项目(202101AZ070001-257、202101AZ070001-123)，项目负责人：申震；云南省科学技术厅基础研究专项课题项目(202201AU070120)，项目负责人：申震

Association between sarcopenia and osteoporosis: a genome-wide data analysis in European populations

Yin Xingxiao1, Jiang Yang1, Song Yanping2, Yao Na2, Shen Zhen2, Li Yanqi1, Song Yueyu1, Peng Hao1, Chen Qigang2   

  1. 1School of Physical Education, Yunnan Normal University, Kunming 650500, Yunnan Province, China; 2Department of Rehabilitation, The Third Affiliated Hospital of Yunnan University of Chinese Medicine, Kunming 650011, Yunnan Province, China
  • Received:2025-07-09 Accepted:2025-09-07 Online:2026-08-18 Published:2025-12-31
  • Contact: Chen Qigang, Chief physician, Professor, Master’s supervisor, Department of Rehabilitation, The Third Affiliated Hospital of Yunnan University of Chinese Medicine, Kunming 650011, Yunnan Province, China Corresponding author: Peng Hao, PhD candidate, School of Physical Education, Yunnan Normal University, Kunming 650500, Yunnan Province, China
  • About author:Yin Xingxiao, MS candidate, School of Physical Education, Yunnan Normal University, Kunming 650500, Yunnan Province, China
  • Supported by:
    National Natural Science Foundation of China, No. 82360943 (to SZ); Yunnan Province Youth Talent Special Project - “Xingdian Talent Support Program,” No. XDYC-QNRC-2022-0609 (to SZ); Traditional Chinese Medicine Joint Special Project of Yunnan Provincial Department of Science and Technology, Nos. 202101AZ070001-257 and 202101AZ070001-123 (both to SZ); Basic Research Special Project of Yunnan Provincial Department of Science and Technology, No. 202201AU070120 (to SZ)

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摘要：



文题释义：
孟德尔随机化：是一种以遗传变异为工具变量，推断暴露因素与健康结局的因果关系，具有规避混杂偏倚和反向因果的独特优势，为病因推断开辟了新途径。
骨质疏松症：是一种以骨量减少、骨组织微结构破坏为特征的全身性骨骼疾病，是导致骨骼脆性增加、骨折风险显著升高的代谢性骨病。

背景：肌少症和骨质疏松症因高发病率及导致的严重不良后果而备受学界关注，尽管现有研究表明肌少症与骨质疏松症可能存在因果关联，但相关研究证据仍显不足。
目的：基于大型全基因组数据，采用双向孟德尔随机化分析探究遗传预测的肌少症与骨质疏松症之间的双向因果关系。
方法：从UK Biobank数据库(由英国政府、医学研究委员会、威康信托基金会等共同开发的开放数据库)筛选与肌少症相关特征显著关联的全基因组显著性位点(P < 5×10-8)，进行连锁不平衡分析。骨质疏松症数据来自GEFOS数据库(由欧盟科研框架计划资助，荷兰伊拉斯谟大学医学中心等机构联合主导建设，为开放数据库)，共纳入28 498例欧洲血统受试者，重点分析骨质疏松性骨折易发部位的相关数据。研究采用逆方差加权法作为主要分析方法，辅以MR-Egger回归、加权中位数法和MR-RAPS进行多重验证。为确保研究结果的可靠性，进行了多重敏感性分析。
结果与结论：逆方差加权分析结果显示，全身无脂肪质量与骨密度之间存在双向因果关系(P < 0.05)。正向因果分析表明，全身无脂肪质量与腰椎骨密度呈正向关联(OR=1.124，95%CI：1.008-1.253，P=0.035)，与前臂骨密度呈负向关联(OR=0.821，95%CI：0.699-0.966，P=0.017)。反向因果分析显示，前臂骨密度(OR=1.033，95%CI：1.002-1.066，P=0.036)、腰椎骨密度(OR=1.054，95%CI：1.025-1.084，P < 0.001)及股骨颈骨密度(OR=1.059，95%CI：1.008-1.113，P=0.021)均与全身无脂肪质量呈正向关联。全身无脂肪质量的减少可导致腰椎骨密度降低，而各部位骨密度的下降又会进一步加剧全身无脂肪质量流失。尽管此次研究数据主要来源于欧洲人群，但由于全基因组关联分析方法的普适性及遗传背景的共性，研究结果对中国人群肌少症与骨质疏松症的发病机制探索、临床干预策略制定及遗传风险评估仍具有重要参考价值。
https://orcid.org/0009-0007-5536-7757 (尹兴晓)


中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

关键词: 肌少症, 骨质疏松症, 肌肉骨骼减少症, 因果关系, 骨密度, 遗传学, 孟德尔随机化, 肌骨交互机制

Abstract: BACKGROUND: Sarcopenia and osteoporosis have attracted significant attention in the academic community due to their high prevalence and severe adverse outcomes. Although existing studies have suggested a potential causal relationship between sarcopenia and osteoporosis, the evidence remains insufficient. 
OBJECTIVE: Based on large-scale genome-wide data, to explore the causal relationship between genetically predicted sarcopenia and osteoporosis through a bidirectional Mendelian randomization approach. 
METHODS: Genome-wide significant loci (P < 5×10-8) associated with sarcopenia-related traits were selected from the UK Biobank database (an open database jointly developed by the UK government, the Medical Research Council, and the Wellcome Trust), followed by linkage disequilibrium analysis. Osteoporosis data were obtained from the GEnetic Factors for OSteoporosis Consortium (GEFOS; an open database funded by the EU Framework Program for Research and Development, jointly led by Erasmus University Medical Center in the Netherlands), including 28 498 participants of European ancestry, with a focus on osteoporotic fracture-prone skeletal sites. The inverse-variance weighted method served as the primary analytical approach, supplemented by MR-Egger regression, weighted median method, and MR-RAPS for robustness validation. Multiple sensitivity analyses were conducted to ensure the reliability of the findings. 
RESULTS AND CONCLUSION: The inverse-variance weighted analysis revealed bidirectional causal relationships between fat-free mass and bone mineral density (P < 0.05). Forward causality analysis indicated that fat-free mass was positively associated with lumbar spine bone mineral density [odds ratio (OR)=1.124, 95% confidence interval (CI): 1.008-1.253, P=0.035) but negatively associated with forearm bone mineral density (OR=0.821, 95% CI: 0.699-0.966, P=0.017). Reverse causality analysis demonstrated that forearm bone mineral density (OR=1.033, 95% CI: 1.002-1.066, P=0.036), lumbar spine bone mineral density (OR=1.054, 95% CI: 1.025-1.084, P < 0.001), and femoral neck bone mineral density (OR=1.059, 95% CI: 1.008-1.113, P=0.021) were all positively associated with fat-free mass. A reduction in fat-free mass may lead to decreased lumbar spine bone mineral density, while lower bone mineral density at various skeletal sites may further exacerbate the loss of fat-free mass. Although the study primarily utilized data from European populations, the generalizability of genome-wide association studies and shared genetic backgrounds suggest that these findings hold significant reference value for understanding the pathogenesis of sarcopenia and osteoporosis in Chinese populations, informing clinical intervention strategies, and assessing genetic risks.

Key words: sarcopenia, osteoporosis, osteosarcopenia, causal relationship, bone mineral density, genetics, Mendelian randomization, muscle-bone interaction mechanism

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