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

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.