Mylène Jansen

Clinical evidence and molecular mechanisms of KJD 195 10 The use of radiographic JSW does not provide a direct measure for cartilage thickness. E.g. partial meniscus extrusion may normalize because of the temporary increase in JSW, enabling the meniscus to reposition, resulting in an increased JSW but not cartilage thickening per se. Actual cartilaginous tissue repair is supported byMRI or post-treatment arthroscopy evaluation. The studies by Deie et al. and Abouheif et al. evaluated the treated knees arthroscopically, and showed hyaline-like cartilage being formed after treatment, confirmed on an MRI scan in the study by Abouheif et al. 14,19 In most studies arthroscopy was not used, as to not disturb the joint and the processes occurring, and since patients are reluctant to interfere with the well- functioning joint. MRI evaluation by Intema et al. showed that the average cartilage thickness measured by quantitative MRI evaluation of the most affected compartment increased significantly from 2.4 mm pre-treatment to 3.0 mm post-treatment. 21 As for the first-year radiographic JSW change, the first-year cartilage thickness change (when corrected for baseline) was shown to predict long-term survival. 23 Also, the percentage of denuded bone area, i.e. the percentage of subchondral bone without cartilage, decreased from 22% to 5%. 21 Two years after treatment these beneficial changes were still significant, and while they prolonged to five years after treatment, they were no longer significant at that point. 16 When the five-year changes were compared to natural progression from matched patients from the Osteoarthritis Initiative (OAI), who showed a significant five year deterioration in both MRI parameter (and in the radiographic JSW parameters), patients treated with KJD showed significantly better five-year results. 16 Even if long-term cartilage restoration results are no longer significantly improved, patients treated with KJD apparently still respond significantly better than if they would not have been treated conventionally with natural OA progression instead. KJD patients from the RCTs have been evaluated by MRI showing a two-year increase in cartilage thickness and decrease in denuded bone area in the most affected compartment. 36 Lastly, preliminary long-term results in the prospective study of Intema et al . show that, while after an initial increase one and two years after treatment the cartilage thickness gradually decreased, even ten years after treatment it was still increased compared to pre-treatment in both the tibia and femur. 37 Unfortunately, the two most recent (ongoing) KJD studies have not included MRI scans as a primary outcome in their protocol because of the costs related to repeated scanning of these patients’ knees. With respect to the quality of the cartilage regenerated after KJD, data are limited. In the prospective study and both RCTs, systemic collagen type II biomarkers (serum N-propeptide of type IIA procollagen (PIIANP) as synthesis marker, and urinary C-telopeptide of type II collagen (CTXII) as degradation marker) were evaluated. A ratio between the two showed that the net collagen type II synthesis was significantly decreased in the first months after treatment (i.e. more degradation than synthesis), but slowly increased to significance two years after treatment, in all studies. 21,22,25 This suggests that the regenerated tissue may be of hyaline nature. 38 From a subgroup of patients from the two RCTs, the change in cartilage