Mylène Jansen

264 Chapter 13 Discussion Ten years after treatment with KJD, in patients who did not convert to TKA, the beneficial effects of this treatment still appear visible, even in this relatively small cohort. In these end-stage knee OA patients, KJD treatment resulted in significant short-term (1 to 2 years) cartilage regeneration in the most affected compartment. While after 2 years this initial gain in cartilage thickness is gradually lost, 10 years after treatment the cartilage remains thicker than before treatment. This is seen in the whole-joint changes as indicated in Figure 1, but also compartmentally as seen in Figure 3 and Supplementary Figures 3 and 4. Even individually, all patients with data at 10 years showed an increase of at least 0.1 mm in one or more compartments, and 6 of 8 patients showed a 10-year increase when averaging all compartments (data not shown). The gradual decrease after 2 years is likely the result of natural progression in loss occurring again after the 2-year regenerative response, potentially in combination with normal or even increased weight-bearing and movement, as a result of successful treatment and the experienced clinical improvement shown previously. 15 However, as we have no untreated control group, this cannot be verified. A good control group for these patients is difficult to find, since purposefully not treating patients with an indication for TKA, especially over multiple years, is impractical and ethically unsound. In the LAC, a delayed cartilage response seems to take place, with significantly increased cartilage thickness in the long term on the whole-joint analyses. This is surprising, since thus far it was concluded that KJD did not have a clear effect on the cartilage in the LAC. 16 The compartmental analyses did not show a significant long-term increase in the LAC, but only a minimal increase between 5 and 10 years after treatment. For the analyses in all patients these results could be affected by survivorship bias, but a similar effect was seen when looking only at patients with full 10-year data-sets. Apparently, the LAC areas with a significant long-term increase are compensated for by a decrease in the remaining space of the LAC, resulting in the LAC barely changing in the compartmental analyses. This highlights the value of analytical approaches which fully reflect the spatial distribution of changes in articular cartilage. Still, looking at Figures 1 and 3, the slight long-term increase in the LAC goes in parallel with a decrease in the MAC, which for the MAC tibia was statistically significant. This may indicate increased loading on the MAC and decreased loading on the LAC over time, allowing regeneration in the LAC, either in a delayed response to the processes in the joint initiated by KJD treatment (described previously 19,20 ) or as a natural response that might occur even in untreated patients. It is also surprising that only the 10-year cartilage thickness change in the LAC tibia had a significant influence on the clinical outcome over 10 years. Previously, no association between clinical and structural changes was found, and it is unexpected that changes in the LAC instead of the MAC could be related to better clinical response. Importantly, these analyses should be repeated in a larger group of patients to verify these results, especially since the effect was not significant over the first 2 years after treatment.