Mylène Jansen

64 Chapter 4 Radiographic evaluation As tertiary measure, the change in joint space width (JSW) was evaluated. Standardized weight-bearing, semi-flexed posterior-anterior radiographs were obtained at baseline (0), 12, and 24 months post-treatment to assess structural outcome for the KJD TKA , KJD HTO , and HTO groups. An aluminum step wedge was used as a reference standard for linear measures and density. The images were evaluated using knee images digital analysis (KIDA) software 16 to analyze the minimum and mean JSW of the most affected compartment (MAC) of the knee. All image analyses were performed by a single, experienced observer, blinded to patient characteristics, and the intra-observer variation of this measurement method was shown to be good (ICC 0.73–0.99). 16 Systemic biochemical marker analyses In a smaller, open prospective study on KJD, a beneficial change in systemic cartilage biomarkers (serum/urine collagen type II biomarkers) was observed between 6 and 12 months of follow- up. 8 Therefore, in the present study, systemic collagen type II biomarkers were measured again in this combined for both studies, larger group of KJD patients. Serum and urine samples were collected from all KJD patients at baseline (0), 3, 6, 12, 18, and 24 months and stored at −80°C. Cartilage collagen type II synthesis and breakdown were determined by serum N-propeptide of type IIA procollagen (PIIANP; Linco, EZPIIANP - 53K) and urinary C-telopeptide of type II collagen (CTXII; Cartilaps; corrected for urine creatinine), respectively. Longitudinal samples of each patient were analyzed in the same micro-titter plate to prevent influence of variability between kits. Statistical analyses Two-sided paired t -tests were used to evaluate changes between 2 years follow-up and baseline scores, for each group separately. Differences in changes between groups were evaluated using linear regression, corrected for baseline. For all graphs, the mean and standard error of the mean (SEM) are given. For the changes over 2 years’ time, the mean and 95% confidence interval (95%CI) are given as well. Biochemical marker measurements outside the 95%CI of each group (KJD TKA or KJD HTO ) were defined as outliers and removed. Outlier exclusion was validated by a sensitivity analysis. Since there were no differences in relative biochemical marker response between the 2 KJD groups anticipated, the groups were combined to increase statistical power. For both biomarkers, combined normalized Z-scores were calculated, and the net collagen type II synthesis was expressed as a Z-index (Z index = Z PIIANP - Z CTXII ). P- values <0.05 were considered statistically significant. SPSS v.22 software (IBM, Armonk, New York) was used to perform statistical analyses.