The Cartilage Thickness score (CTh-Score) Captures High-resolution Cartilage Thickness Patterns Associated with Osteoarthritis Onset, Progression, and Knee Replacement: Data from the Osteoarthritis Initiative

Objective To evaluate the Cartilage Thickness Score (CTh-Score) as a quantitative measure of cartilage damage severity by assessing its association with three osteoarthritis (OA) milestones and comparing its performance with conventional morphometric measures (radiographic minimum joint space width (JSW) and regional average cartilage thickness). Methods Data were obtained from the Osteoarthritis Initiative (OAI) and the publicly available OAI CTh-Maps and CTh-Score dataset. Three matched case-control designs were used to represent major OA milestones: (i) incident radiographic OA onset, (ii) combined pain and structural progression, and (iii) knee replacement (KR) in the coming 2 years. Progression subjects were extracted from the FNIH Biomarkers Consortium cohort. Cases and controls were compared at 4 years (T-4Y), 2 years (T-2Y), and 0 years (T0) before the milestone. MRI-based CTh-Score and regional average cartilage thickness, as well as JSW, were analyzed cross-sectionally and longitudinally. Associations with case status were assessed using adjusted logistic regression models, and responsiveness was evaluated using longitudinal change and standardized response means. Results The onset cohort included 307 matched case-control pairs, the progression cohort 164 cases and 369 controls, and the KR cohort 81 cases and 324 controls. Across all three study designs, the CTh-Score significantly differentiated cases from controls at all timepoints. In the onset cohort, the CTh-Score was higher in future cases than controls at T-4Y (16.2 vs 12.6, p=0.007), T-2Y (23.5 vs 16.7, p<0.001), and T0 (39.8 vs 18.6, p<0.001), whereas JSW and regional thickness measures showed limited or later discrimination. Similar findings were observed for progression (43.2 vs 33.0 at T-4Y; p<0.001) and KR (55.4 vs 46.1 at T-4Y; p=0.02) cohorts. Longitudinally, CTh-Score changes differentiated cases from controls earlier and more consistently than JSW or regional average thickness, and its responsiveness was consistently the highest across OA milestones and time intervals. In adjusted models, the CTh-Score was independently associated with all outcomes at T-4Y and T-2Y, with odds ratios per standard deviation increase ranging from 1.3 to 2.2. Conclusion The CTh-Score captures high-resolution cartilage thickness patterns associated with OA onset, progression, and future knee replacement, outperforming conventional morphometric measures in early discrimination, responsiveness, and predictive association. These findings support CTh-Score as a sensitive quantitative marker of cartilage damage severity across the OA continuum.