Sex differences in the associations of adiposity-related markers with rheumatic and musculoskeletal disease risk: A prospective cohort study

Objectives: Obesity is associated with rheumatic and musculoskeletal diseases (RMDs); however, existing evidence has mostly focused on body mass index (BMI), and sex-specific effects are poorly understood. We aimed to investigate the associations of various adiposity-related markers with incident RMDs in women and men.Methods: This prospective cohort study included 386,008 participants free of RMDs at baseline (2006-2010) from the UK Biobank. We included 12 different adiposity phenotypes that represented body fat accumulation or distribution using anthropometric and bio-impedance measurements. Cox proportional hazards models were used to examine the associations stratified by sex.Results: Over a median follow-up of 12.9 years, 28,384 women (13.5%) and 23,625 men (13.5%) developed RMDs. All but two adiposity-related markers (waist circumference [WC] and waist-to-hip ratio [WHR] adjusted for BMI) were positively associated with the risks of overall and individual RMDs. The associations for certain RMDs remained significant and became strengthened in individuals with a normal BMI. Significant interactions were observed between adiposity markers and sex, with the adiposity-RMDs associations being more pronounced in women. The adjusted hazard ratios per one-standard deviation increment in adiposity markers in women ranged from 1.02 to 1.42 for osteoarthritis and 1.23 to 1.67 for gout, while equivalent HRs in men were 0.93 to 1.38 and 1.13 to 1.42, respectively.Conclusiona: Adiposity-related traits were sex-specifically associated with increased RMD risk regardless of BMI status. The findings highlight the importance of considering different adiposity phenotypes and sex heterogeneity in routine risk assessment and management for precise prevention of RMDs.

研究目的：肥胖与风湿肌肉骨骼疾病（rheumatic and musculoskeletal diseases, RMDs）存在关联，但现有研究证据多聚焦于身体质量指数（body mass index, BMI），且对其性别特异性效应的认知仍较为匮乏。本研究旨在探究不同肥胖相关标志物与男女新发风湿肌肉骨骼疾病的关联。
研究方法：本前瞻性队列研究纳入英国生物银行（UK Biobank）2006-2010年基线时无风湿肌肉骨骼疾病的386008名参与者。我们通过人体测量与生物阻抗测量，获取了12种反映体脂蓄积或分布的肥胖表型指标。采用Cox比例风险模型按性别分层分析上述关联。
研究结果：中位随访12.9年期间，共计28384名女性（占比13.5%）与23625名男性（占比13.5%）新发风湿肌肉骨骼疾病。除两种肥胖相关标志物——校正身体质量指数后的腰围（waist circumference, WC）与腰臀比（waist-to-hip ratio, WHR）——外，其余指标均与总体及各类风湿肌肉骨骼疾病的发病风险呈正相关。在身体质量指数正常的人群中，部分疾病的关联仍具有统计学意义且关联强度进一步增强。我们观察到肥胖标志物与性别间存在显著交互作用，肥胖与风湿肌肉骨骼疾病的关联在女性群体中更为显著。女性群体中，肥胖标志物每增加1个标准差，骨关节炎（osteoarthritis）的校正后风险比（hazard ratios, HR）范围为1.02~1.42，痛风（gout）为1.23~1.67；而男性群体对应的风险比分别为0.93~1.38与1.13~1.42。
研究结论：肥胖相关表型与风湿肌肉骨骼疾病发病风险升高存在性别特异性关联，且不受身体质量指数状态影响。本研究结果提示，在风湿肌肉骨骼疾病的精准预防工作中，应在常规风险评估与管理中纳入不同肥胖表型及性别异质性的考量因素。