Mylène Jansen

Osteophyte formation after KJD and HTO 355 17 Control group of untreated osteoarthritis patients The only relevant OA cohort using the same standardized radiographic analyses, with quantification of osteophyte area, is CHECK (Cohort Hip & Cohort Knee), a cohort of 1002 participants with early symptomatic knee or hip OA who were followed for 10 years and had radiographs of both knees at baseline, 2, 5, 8 and 10 years follow-up. 37 From this cohort, patients that received a TKA during the follow-up period were selected to be compared with KJD patients, since most KJD patients were indicated for TKA but received KJD. For each knee that was treated with TKA in CHECK, all pre-TKA radiographic osteophyte measurements were analyzed to evaluate linearity of osteophyte formation using a linear regression model, with osteophyte size as dependent variable and the ‘years before TKA’ and ‘years before TKA squared’ as independent variables. The change in osteophyte area during the last 2 measurements before TKA, corrected to represent a 2-year period, was used as control osteophyte progression rate. WOMAC questionnaires from the last time point before TKA and 2 years prior were used to evaluate 2-year clinical changes. Radiographic analysis The standardized radiographs were analyzed by 1 experienced observer, blinded to patient characteristics, using KIDA software. 38 The osteophyte size (area on the 2D image) was measured in mm 2 for 4 regions: the lateral and medial femur and tibia. The sum of these regions gives the whole-joint osteophyte size in mm 2 . The JSW of the most affected compartment (MAC; determined pre-treatment) in mm provided by the KIDA measurement was evaluated as a representative of the cartilage regenerative activity of the treatment. In CHECK the compartment with the smallest JSW was chosen as MAC. Synovial fluid aspirations Between 2014 and 2015, 20 patients treated with KJD in regular care were included for synovial fluid (SF) aspirations in an ethically approved study (protocol number 15/160). The treatment protocol and in- and exclusion criteria in regular care were similar as explained above and have been described elsewhere 39 , with the addition that patients in this study needed to have a successful baseline SF aspiration. At baseline (during frame placement surgery) and after treatment (during frame removal surgery) an SF sample of maximum 2 mL was aspirated from the treated knee. Biomarker levels were measured according to protocols described previously. 25 In short, samples were centrifuged for 20 min at 3000G and stored in 200 μl aliquots at -80°C. The supernatants were measured by immunoassay for 10 predefined mechanosensitive molecules; mean analyte concentrations were calculated from duplicate assay reads for each participant and time point. For the present evaluation, only TGF β -1 and IL-6 were used as predefined potential candidates for association with osteophyte formation as only those have been related to osteophyte formation in literature.