Identifying Phenotypes of Knee Osteoarthritis by Separate Quantitative Radiographic Features May Improve Patient Selection for More Targeted Treatment

Objective. Expression of osteoarthritis (OA) varies significantly between individuals, and over time, suggesting the existence of different phenotypes, possibly with specific etiology and targets for treatment. Our objective was to identify phenotypes of progression of radiographic knee OA using separate quantitative features. Methods. Separate radiographic features of OA were measured by Knee Images Digital Analysis (KIDA) in individuals with early knee OA (the CHECK cohort: Cohort Hip & Cohort Knee), at baseline and at 2-year and 5-year followup. Hierarchical clustering was performed to identify phenotypes of radiographic knee OA progression. The phenotypes identified were compared for changes in joint space width (JSW), yarns angle, osteophyte area, eminence height, bone density, for Kellgren-Lawrence (K-L) grade, and for clinical characteristics. Logistic regression analysis evaluated whether baseline radiographic features and demographic/clinical characteristics were associated with each of the specific phenotypes. Results. The 5 clusters identified were interpreted as "Severe" or "No," "Early" or "Late" progression of the radiographic features, or specific involvement of "Bone density." Medial JSW, yarns angle, osteophyte area, eminence height, and bone density at baseline were associated with the Severe and Bone density phenotypes. Lesser eminence height and bone density were associated with Early and Late progression. Larger yarns angle and smaller osteophyte area were associated with No progression. Conclusion. Five phenotypes of radiographic progression of early knee OA were identified using separate quantitative features, which were associated with baseline radiographic features. Such phenotypes might require specific treatment and represent relevant subgroups for clinical trials.