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Life sciences · Journal article
Journal of the Endocrine Society · October 21, 2026
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Abstract Purpose Obesity causes mechanical stress and metabolic dysfunction. However, the relationship between obesity and osteoarthritis (OA) pain still needs further investigation. This study aims to examine the effect of weight loss on pain and function through a secondary analysis of a randomized, double-blind, multicenter OA trial and to evaluate obesity's impact on OA pain using a rat model. Methods In a post-hoc analysis of an RCT (NCT00486434), we evaluated baseline BMI and WOMAC scores (n=1175) and examined the impact of 5% weight loss on WOMAC scores after 2 years using a factorial ANCOVA (n=674). In a preclinical model of metabolic OA induced by meniscectomy, pain-like behavior was assessed with the von Frey and cold plate tests. Results Participants who lost >5% of weight within 2 years experienced a mean decrease of -567.1 [95% CI -666.7 - -467.6], -399.2 [-505.8 - -292.5] in total WOMAC scores for their target and non-target knees, respectively, whereas individuals who gained >5% in weight had a smaller decrease of -364.6 [-496.5 - -232.7], -135 [277.4–6.3], respectively. Additionally, the high-fat diet-fed rat model showed more pain-like behavior than the lean model. Main conclusions These studies indicate that weight loss could decrease OA pain in both target and non-target knees of patients with obesity, supporting the inclusion of obesity in OA animal models to improve the translatability of OA treatments.