您的位置：山东大学 -> 科技期刊社 -> 《山东大学学报（医学版）》

山东大学学报 (医学版) ›› 2025, Vol. 63 ›› Issue (11): 61-67.doi: 10.6040/j.issn.1671-7554.0.2025.0319

• 临床医学 • 上一篇    

孟德尔随机化分析膝骨关节炎疼痛与肌力的因果关联

周坤1,2*,刘婷2*,姜艳菊2,胡泽楷3,李宇佳4,冯武仪2,黄继莉2,叶汪泉2,赵小峰2,胡军1,5   

  1. 1.上海中医药大学康复医学院, 上海 201203;2.上海中冶医院康复医学科, 上海 200941;3.上海第二康复医院康复医学科, 上海 200441;4.复旦大学附属华山医院皮肤科, 上海 200403;5.上海第二康复医院中医康复科, 上海 200441
  • 发布日期:2025-11-28
  • 通讯作者: 胡军. E-mail:jasonhwu@126.com*共同第一作者

Mendelian randomization analysis of the causal association between pain and muscle strength in knee osteoarthritis

ZHOU Kun1,2*, LIU Ting2*, JIANG Yanju2, HU Zekai3, LI Yujia4, FENG Wuyi2, HUANG Jili2, YE Wangquan2, ZHAO Xiaofeng2, HU Jun1,5   

  1. 1. School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China;
    2. Department of Rehabilitation Medicine, Shanghai Zhongye Hospital, Shanghai 200941, China;
    3. Department of Rehabilitation Medicine, Second Rehabilitation Hospital of Shanghai, Shanghai 200441, China;
    4. Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200403, China;
    5. Department of Traditional Chinese Medicine Rehabilitation, Second Rehabilitation Hospital of Shanghai, Shanghai 200441, China
  • Published:2025-11-28

PDF (PC)

11

摘要： 目的 通过临床试验观察膝骨关节炎(knee osteoarthritis, KOA)患者的膝关节屈伸肌力下降情况,并运用全基因组关联性分析(genome-wide association studies, GWAS)膝骨关节炎与大腿肌肉体积之间的因果关系,分析膝骨关节炎患者大腿肌力下降的特征及潜在影响因素。 方法 选取2023年1月至2024年12月上海中冶医院骨科确诊膝骨关节炎女性患者52例,50~80岁,分为双膝关节疼痛组(n=19)和单膝关节疼痛组(n=33),并招募健康成年人作为健康对照组(n=65)。采用方差分析比较各组间膝关节屈伸肌的最大峰值力矩。采用逆方差加权法、MR-Egger法和加权中位数法进行双向双样本孟德尔随机化分析膝骨关节炎、疼痛与大腿前后侧肌肉体积之间的相关性。 结果 双膝关节疼痛组的伸膝和屈膝峰力矩与健康对照组相比差异有统计学意义(P<0.05);单膝关节疼痛组的健侧和患侧峰力矩与健康对照组相比差异有统计学意义(P<0.001);单膝关节疼痛组的健侧与患侧之间差异无统计学意义(P>0.05)。膝骨关节炎和疼痛与大腿前侧肌肉体积间无相关性(膝骨关节炎:P=0.16; 疼痛: P=0.08),而与大腿后侧肌肉体积呈负相关性(膝骨关节炎: P=0.01; 疼痛: P<0.05),大腿前侧肌肉体积和大腿后侧肌肉体积与膝骨关节炎和疼痛均无负相关性。 结论 有疼痛症状的膝骨关节炎患者屈伸肌群最大峰值力矩显著下降,大腿后侧肌肉体积减少可能是屈肌群肌力下降的原因之一,而伸肌群的肌力下降与大腿前侧肌肉体积无关,表明有疼痛症状的膝骨关节炎患者屈伸肌力下降的影响因素不同。

关键词: 膝骨关节炎, 等速肌力, 疼痛, 肌肉体积, 孟德尔随机化

Abstract: Objective To investigate the decline in knee flexor and extensor muscle strength in patients with knee osteoarthritis(KOA)through clinical trials and to explore the causal relationship between KOA and thigh muscle volume using genome-wide association studies(GWAS), as well as to analyse the characteristics and potential factors influencing the decrease in thigh muscle strength in KOA patients. Methods Female patients aged 50 to 80 years diagnosed with KOA who visited the orthopaedic clinic of Shanghai Zhongye Hospital from January 2023 to December 2024 were selected and divided into a bilateral knee pain group(n=19)and a unilateral knee pain group(n=33). Healthy adults were recruited as a healthy control group(n=65). Analysis of variance was used to compare the maximum peak torque of the knee flexor and extensor muscles among 3 groups. Bidirectional two-sample Mendelian randomization analysis was performed using inverse variance weighting, MR-Egger, and weighted median methods to examine the association between knee osteoarthritis, pain, and muscle volume in the anterior and posterior thigh. Results The maximum torque for knee extension and flexion in the bilateral knee pain group was significantly different from that of the healthy control group(P<0.05); peak torque on the unaffected and affected sides in the unilateral knee pain group was significantly different from that of the healthy control group(P<0.001); the difference between the unaffected and affected sides in the unilateral knee pain group was not statistically significant(P>0.05). There was no correlation between knee osteoarthritis and pain and volume of the anterior thigh muscles(KOA: P=0.16; pain: P=0.08), while there was a negative correlation with the volume of the posterior thigh muscles(KOA: P=0.01; pain: P<0.05). There was no negative correlation between the volume of the anterior thigh muscles and the volume of the posterior thigh muscles with KOA and pain. Conclusion Patients with KOA and pain symptoms exhibit a significant decrease in the maximum torque of the flexor muscle group. A reduction in posterior thigh muscle volume may be one of the causes of decreased flexor muscle strength, while a decrease in extensor muscle strength is not related to anterior thigh muscle volume, indicating that factors influencing decreased flexor and extensor muscle strength differ in patients with KOA and pain symptoms.

Key words: Knee osteoarthritis, Isokinetic muscle strength, Pain, Muscle volume, Mendelian randomization

中图分类号: 

  • R684.3
[1] Li M, Xia Q, Nie Q, et al. Burden of knee osteoarthritis in China and globally: 1990-2045[J]. BMC Musculoskelet Disord, 2025, 26(1): 582. doi: 10.1186/s12891-025-08858-8
[2] Du X, Liu ZY, Tao XX, et al. Research progress on the pathogenesis of knee osteoarthritis[J]. Orthop Surg, 2023, 15(9): 2213-2224.
[3] Wojcieszek A, Kurowska A, Majda A, et al. Relationship between optimism, self-efficacy and quality of life: a cross-sectional study in elderly people with knee osteoarthritis[J]. Geriatrics(Basel), 2023, 8(5): 101. doi: 10.3390/geriatrics8050101
[4] Adiguzel L, Kilic D. An investigation of the relationship between the functional status of the individuals with knee osteoarthritis and their quality of life[J]. Niger J Clin Pract, 2022, 25(5): 576-581.
[5] 王斌, 邢丹, 董圣杰, 等. 中国膝骨关节炎流行病学和疾病负担的系统评价[J]. 中国循证医学杂志, 2018, 18(2): 134-142. WANG Bin, XING Dan, DONG Shengjie, et al. Systematic review on epidemiology and disease burden of knee osteoarthritis in China[J]. Chinese Journal of Evidence-Based Medicine, 2018, 18(2): 134-142.
[6] 王莉莎, 王上增, 史栋梁, 等. 乌头汤对膝骨关节炎大鼠模型的治疗作用[J]. 山东大学学报(医学版), 2024, 62(5): 64-71. WANG Lisha, WANG Shangzeng, SHI Dongliang, et al. Therapeutic effect of Wutou decoction on rat model of knee osteoarthritis[J]. Journal of Shandong University(Health Sciences), 2024, 62(5): 64-71.
[7] Lepley AS, Lepley LK. Mechanisms of arthrogenic muscle inhibition[J]. J Sport Rehabil, 2021, 31(6): 707-716.
[8] Culvenor AG, Wirth W, Roth M, et al. Predictive capa-city of thigh muscle strength in symptomatic and/or radiographic knee osteoarthritis progression: data from the foundation for the national institutes of health osteoarthritis biomarkers consortium[J]. Am J Phys Med Rehabil, 2016, 95(12): 931-938.
[9] 夏翠宏, 邢菲, 李洋, 等. 中老年女性膝骨关节炎患者坐-站转换及上下台阶中膝周肌肉激活的观察性研究[J]. 中国康复医学杂志, 2025, 40(6): 909-916. XIA Cuihong, XING Fei, LI Yang, et al. Observation of peri-knee muscle activation during sit-to-stand and stair negotiation in middle-aged and elderly women with knee osteoarthritis[J]. Chinese Journal of Rehabilitation Medicine, 2025, 40(6): 909-916.
[10] Conroy MB, Kwoh CK, Krishnan E, et al. Muscle strength, mass, and quality in older men and women with knee osteoarthritis[J]. Arthritis Care Res(Hoboken), 2012, 64(1): 15-21.
[11] Sattler M, Dannhauer T, Hudelmaier M, et al. Side differences of thigh muscle cross-sectional areas and maximal isometric muscle force in bilateral knees with the same radiographic disease stage, but unilateral frequent pain-data from the osteoarthritis initiative[J]. Osteoarthritis Cartilage, 2012, 20(6): 532-540.
[12] Krishnasamy P, Hall M, Robbins SR. The role of skeletal muscle in the pathophysiology and management of knee osteoarthritis[J]. Rheumatology(Oxford), 2018, 57(Suppl4): 22-33.
[13] Jeong J, Choi DH, Shin CS. Association between the medial-lateral quadriceps and hamstring muscle thickness and the knee kinematics and kinetics during single-leg landing[J]. Sports Health, 2023, 15(4): 519-526.
[14] Mohajer B, Dolatshahi M, Moradi K, et al. Role of thigh muscle changes in knee osteoarthritis outcomes: osteoarthritis initiative data[J]. Radiology, 2022, 305(1): 169-178.
[15] Segal NA, Nilges JM, Oo WM. Sex differences in osteoarthritis prevalence, pain perception, physical function and therapeutics[J]. Osteoarthritis Cartilage, 2024, 32(9): 1045-1053.
[16] van der Meer D, Gurholt TP, Sønderby IE, et al. The link between liver fat and cardiometabolic diseases is highlighted by genome-wide association study of MRI-derived measures of body composition[J]. Commun Biol, 2022, 5(1): 1271. doi: 10.1038/s42003-022-04237-4
[17] Muraki S, Akune T, Oka H, et al. Association of radiographic and symptomatic knee osteoarthritis with health-related quality of life in a population-based cohort study in Japan: the ROAD study[J]. Osteoarthritis Cartilage, 2010, 18(10): 1227-1234.
[18] Ikemoto-Uezumi M, Matsui Y, Hasegawa M, et al. Disuse atrophy accompanied by intramuscular ectopic adipogenesis in vastus medialis muscle of advanced osteoarthritis patients[J]. Am J Pathol, 2017, 187(12): 2674-2685.
[19] Evangelidis PE, Massey GJ, Pain MTG, et al. Strength and size relationships of the quadriceps and hamstrings with special reference to reciprocal muscle balance[J]. Eur J Appl Physiol, 2016, 116(3): 593-600.
[20] Pietrosimone BG, Saliba SA. Changes in voluntary quadriceps activation predict changes in quadriceps strength after therapeutic exercise in patients with knee osteoarthritis[J]. The Knee, 2012, 19(6): 939-943.
[21] Scopaz KA, Piva SR, Gil AB, et al. Effect of baseline quadriceps activation on changes in quadriceps strength after exercise therapy in subjects with knee osteoarthritis[J]. Arthritis Rheum, 2009, 61(7): 951-957.
[22] Rice DA, McNair PJ, Lewis GN. Mechanisms of quadriceps muscle weakness in knee joint osteoarthritis: the effects of prolonged vibration on torque and muscle activation in osteoarthritic and healthy control subjects[J]. Arthritis Res Ther, 2011, 13(5): 151. doi: 10.1186/ar3467
[23] Bacon KL, Segal NA, Øiestad BE, et al. Concurrent change in quadriceps strength and physical function over five years in the multicenter osteoarthritis study[J]. Arthritis Care Res(Hoboken), 2019, 71(8): 1044-1051.
[24] Lopes HS, Waiteman MC, Priore LB, et al. There is more to the knee joint than just the quadriceps: a systematic review with meta-analysis and evidence gap map of hamstring strength, flexibility, and morphology in individuals with gradual-onset knee disorders[J]. J Sport Health Sci, 2024, 13(4): 521-536.
[25] Zhang LY, Zhang C, Zhang JT, et al. A bidirectional mendelian randomization study of sarcopenia-related traits and knee osteoarthritis[J]. Clin Interv Aging, 2023, 18: 1577-1586.
[26] Jin Z, Wang R, Jin L, et al. Causal relationship between sarcopenia with osteoarthritis and the mediating role of obesity: a univariate, multivariate, two-step Mendelian randomization study[J]. BMC Geriatr, 2024, 24(1): 469. doi: 10.1186/s12877-024-05098-8
[27] Kumar D, Karampinos DC, MacLeod TD, et al. Quadriceps intramuscular fat fraction rather than muscle size is associated with knee osteoarthritis[J]. Osteoarthr Cartil, 2014, 22(2): 226-234.
[28] 曹龙军, 章礼勤, 周石, 等. 膝关节骨性关节炎患者股四头肌动员能力和肌力储备改变的研究[J]. 中国康复医学杂志, 2012, 27(1): 30-34. CAO Longjun, ZHANG Liqin, ZHOU Shi, et al. Changes in quadriceps recruitment capacity and strength reserve in patients with knee osteoarthritis[J]. Chinese Journal of Rehabilitation Medicine, 2012, 27(1): 30-34.
[29] 王玫懿, 张长杰, 程铁峰, 等. 膝骨关节炎患者下肢肌群表面肌电信号改变的研究进展[J]. 中国康复医学杂志, 2025, 40(5): 782-789. WANG Meiyi, ZHANG Changjie, CHENG Tiefeng, et al. Research progress on surface electromyographic changes of lower-limb muscles in patients with knee osteoarthritis[J]. Chinese Journal of Rehabilitation Medicine, 2025, 40(5): 782-789.
[30] Serrão PR, Vasilceac FA, Gramani-Say K, et al. Men with early degrees of knee osteoarthritis present functional and morphological impairments of the quadriceps femoris muscle[J]. Am J Phys Med Rehabil, 2015, 94(1): 70-81.
[1] 王乐,罗清馨,吴思佳,吴雨桐,葛祎蕾,俞一凡,韦云,吉寒冰,刘铁梅,张紫妍,修佳伟,薛付忠,李洪凯. 虚弱和癫痫关联研究:前瞻性队列和孟德尔随机化分析[J]. 山东大学学报 (医学版), 2025, 63(9): 20-30.
[2] 王雪梅,杨豪,宋洋,程世超,张婷婷,王艳春. 抗糖尿病药物与女性恶性肿瘤的因果关联:一项两样本孟德尔随机化分析[J]. 山东大学学报 (医学版), 2025, 63(6): 67-77.
[3] 黄馨,王梦雪,付书璠,张琦悦,徐力. 代谢综合征及其组分与消化系统恶性肿瘤的因果关联:两样本孟德尔随机化研究[J]. 山东大学学报 (医学版), 2025, 63(5): 86-94.
[4] 王小磊,方骏,王安,朱武晖,史光军. 两样本孟德尔随机化分析肠道菌群与肝外胆管癌的因果关系[J]. 山东大学学报 (医学版), 2025, 63(4): 44-50.
[5] 李建锋,张展,丁新华,高奋堂,何勤利,谢萍. 欧洲人群饮食因素与认知功能障碍关系的孟德尔随机化分析[J]. 山东大学学报 (医学版), 2025, 63(4): 36-43.
[6] 张彭,杨鹏,赵菁,钟俊桥,万绍勇. 多角度等速肌力训练对膝关节置换术后膝关节活动度及本体感觉恢复效果[J]. 山东大学学报 (医学版), 2025, 63(3): 36-43.
[7] 常宇,胡云峰,王会丰,郭静,张跳,郝雅琴,刘雨. 阑尾切除术与结直肠癌发病风险关联的孟德尔随机化研究[J]. 山东大学学报 (医学版), 2025, 63(2): 77-83.
[8] 杨慧,苏士晶,李芬. 基于双向孟德尔随机化法探讨组织蛋白酶与衰弱的因果关联[J]. 山东大学学报 (医学版), 2025, 63(2): 67-76.
[9] 梁炎春,严莹,麦华希,姚书忠. 地诺孕素在子宫内膜异位症相关性疼痛中的治疗作用:从基础到临床[J]. 山东大学学报 (医学版), 2025, 63(10): 27-33.
[10] 刘振花,连雅囡,米国琳. 子宫内膜异位症疼痛的心理因素及干预措施的研究进展[J]. 山东大学学报 (医学版), 2025, 63(10): 43-51.
[11] 赵书睿,赵烨. 围绝经期及绝经后期子宫内膜异位症的诊疗现状[J]. 山东大学学报 (医学版), 2025, 63(10): 20-26.
[12] 薛铭,梁静,凌斌. 各种类型子宫内膜异位症疼痛特点及治疗研究进展[J]. 山东大学学报 (医学版), 2025, 63(10): 13-19.
[13] 徐萍,张信美. 子宫内膜异位症疼痛的机制[J]. 山东大学学报 (医学版), 2025, 63(10): 1-7.
[14] 袁宗怀,潘广晔,迟曰梅,安传国,张永刚. 孟德尔随机化分析低级别浆液性卵巢癌与乳腺癌的因果关系[J]. 山东大学学报 (医学版), 2025, 63(1): 99-107.
[15] 张展,李建锋,李燕玲,王博雯,昂文成林龙珠,王鑫,张小明,谢萍. 饮食因素与子痫前期因果关系的孟德尔随机化分析[J]. 山东大学学报 (医学版), 2024, 62(8): 59-66.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
版权所有 © 2018 《山东大学学报(医学版)》编辑部　
地址:山东大学科技期刊社（济南市历城区山大南路27号山东大学中心校区明德楼B座721室） 电话: 0531-88366918 E-mail: xbyxb@sdu.edu.cn
本系统由北京玛格泰克科技发展有限公司设计开发