Abstract
BackgroundTo evaluate the independent and combined effects of metabolic abnormalities and obesity on the risk of knee and hand osteoarthritis (KOA and HOA).MethodsParticipants from the UK Biobank were classified into four phenotypes: metabolically healthy non-obesity (MHN), metabolically healthy obesity (MHO), metabolically unhealthy non-obesity (MUN), and metabolically unhealthy obesity (MUO). Accelerated failure time (AFT) models were applied to assess the associations of these phenotypes with the risk of KOA and HOA.Results389,807 participants (mean 56.4 years, 54.0% female) without KOA or HOA at baseline were included. Compared to MHN, both MHO and MUO significantly accelerated the incidence of KOA (MHO: Time Ratio [TR] = 0.37, 95% confidence interval [CI]: 0.33-0.40; MUO: TR = 0.37, 95%CI: 0.35-0.39), and MUO accelerated the risk of HOA (TR = 0.81, 95%CI: 0.70-0.93) over 13.0 years. The incidence of KOA was also higher in MUN participants (TR = 0.87, 95%CI: 0.83-0.91), although the effect of metabolic abnormalities on KOA risk disappeared after controlling for body mass index (BMI) (TR = 1.03, 95%CI: 0.99-1.07). There was a significant interaction between metabolic status and BMI for KOA risk, where the association between BMI and the risk of KOA was stronger in metabolically healthy participants (TR = 0.88 per 1 kg/m2 increase in BMI, 95%CI: 0.87-0.89).ConclusionsHigh BMI elevates the risk of both KOA and HOA irrespective of metabolic status, and the increased risk of KOA attributed to high BMI is more evident in metabolically healthy participants. Weight management remains a key to OA prevention, especially for weight-bearing joints.Clinical trial numberNot applicable.</p>