The role of metabolic syndrome in osteoarthritis development: Is obesity the key driver?

Objective: Investigate the role of metabolic syndrome and obesity in incident osteoarthritis (OA). Methods: Prospective cohort study with up to 11 years follow-up. From a general population cohort of 28,786 individuals from Sweden aged 45 to 75, we selected individuals without OA diagnosis and without joint pain during the year prior to the baseline. Metabolic syndrome was defined at baseline by the presence of at least three out of five components: elevated waist circumference (WC), elevated plasma triglycerides, reduced HDL-cholesterol, elevated blood pressure, and hyperglycaemia. Individuals were followed from baseline until incident OA diagnosis in any joint (outcome), death, relocation outside Region Skåne/Region Uppsala, or December 31, 2022. Associations between metabolic syndrome and OA incidence were estimated using parametric survival models with restricted cubic splines and adjusted for sex, age, education, immigration status, marital status, physical activity, and diet score. Results: Among the 10,633 individuals, 1167 (11 %) received an OA diagnosis (median follow-up 8.6 years). Metabolic syndrome was associated with an increased risk of OA (hazard ratio [HR] 1.17, confidence intervals [1.04, 1.33]). Elevated WC alone was associated with a similar risk of OA (HR 1.42 [1.06, 1.90]), while metabolic syndrome without elevated WC did not show a conclusive association (HR 1.02 [0.73, 1.43]). Substituting WC with BMI led to similar results. Conclusions: Metabolic syndrome leads to an increased risk of developing OA even in individuals free of joint pain at baseline. The association is largely driven by obesity, which underscores the importance of weight management to mitigate OA development.