Unveiling the <scp>BMI</scp> Risk Threshold for Osteoarthritis: Multi‐Database Causal and Nonlinear Evidence

ABSTRACT Objective To characterize the nonlinear relationship between BMI and osteoarthritis (OA), and to identify BMI thresholds that inform precise prevention strategies. Methods This multi‐database study integrated Global burden of disease 2021, National Health and Nutrition Examination Survey 2007–2018, and Genome‐Wide Association Studies. A generalized additive model was performed to visualize the BMI‐OA relationship, adjusting for multiple confounders. We applied segmented logistic regression models to identify potential threshold effects and used Mendelian randomization to estimate the causal effects of BMI on OA subtypes. Results From 1990 to 2021, the age‐standardized prevalence and years lived with disability rates for OA were highest in regions with high SDI. OA prevalence rose nonlinearly with BMI, with breakpoints at 24.00 and 41.58 kg/m 2 . Each unit increase in BMI was associated with higher odds of OA between 24.00 and 41.58 kg/m 2 (OR = 1.022, 95% CI: 1.003–1.041) and above 41.58 kg/m 2 (OR = 1.055, 95% CI: 1.022–1.090). Women and individuals aged ≥ 45 years exhibited a higher susceptibility to knee osteoarthritis. BMI was causally associated with knee osteoarthritis (OR = 1.63, 95% CI 1.50–1.77) and hip osteoarthritis (OR = 1.54, 95% CI 1.40–1.70). Conclusions These findings suggest that OA risk awareness and weight‐management strategies should begin before BMI reaches the high range, particularly among individuals with BMI exceeding 24.00 kg/m 2 .