Methodological quality criteria are of importance to reveal an association between radiographic and clinical OA.

Changing PP and acquisition settings in clinical practice can have profound effect on outcome. If done with care, accurate BD measurement is feasible using plain digital radiography.

In these subjects with no or doubtful radiographic knee OA, uCTX-II might not only reflect articular cartilage degradation but also endochondral ossification in osteophytes. Furthermore, sCOMP and sHA relate to osteophytes, maybe because synovitis drives osteophyte development. High bone turnover may aggravate articular cartilage loss. Metabolic activity in osteophytes and synovial tissue, but not in articular cartilage may be related to knee pain.

In this early OA cohort, different radiographic features were identified that progressed at different rates between timepoints. The relations between radiographic features and with clinical outcome varied over time. This implies that longitudinal evaluation of different features can improve insight into progression of OA.

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.