Personalized Risk Model and Leveraging of Magnetic Resonance Imaging-Based Structural Phenotypes and Clinical Factors to Predict Incidence of Radiographic Osteoarthritis

Objective: Our study aimed to investigate the association between time to incidence of radiographic osteoarthritis (OA) and magnetic resonance imaging (MRI)-based structural phenotypes proposed by the Rapid Osteoarthritis MRI Eligibility Score (ROAMES). Methods: A retrospective cohort of 2,328 participants without radiographic OA at baseline were selected from the Osteoarthritis Initiative study. Utilizing a deep-learning model, we automatically assessed the presence of inflammatory, meniscus/cartilage, subchondral bone, and hypertrophic phenotypes from MRIs acquired at baseline and 12-, 24-, 36-, 48-, 72-, and 96-month follow-up visits. In addition to 4 structural phenotypes, we examined severe knee injury history and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores as time dependent. We used Cox proportional hazards regression to analyze the association between 4 structural phenotypes and radiographic OA disease-free survival, both univariate and adjusted for known risk factors including age, sex, race, body mass index, presence of Heberden's nodes, and knee malalignment. Results: Inflammatory (hazard ratio [HR] 3.37 [95% confidence interval (95% CI) 2.45-4.63]), meniscus/cartilage (HR 1.55 [95% CI 1.21-1.98]), and subchondral bone (HR 1.84 [95% CI 1.63-2.09]) phenotypes were associated with time to radiographic OA at P < 0.05 when adjusted for the risk factors. Sex was a modifier of hypertrophic phenotype association with time to radiographic OA. Female participants with the hypertrophic phenotype were associated with 2.8 times higher risk of radiographic OA (95% CI 2.25-7.54) compared to male participants without the hypertrophic phenotype. Conclusion: Four ROAMES phenotypes may contribute to time to radiographic OA incidence and if validated could be used as a promising tool for personalized OA management.