Mylène Jansen

34 Chapter 2 Despite multiple studies showing cartilage regeneration after KJD, the mechanism enabling the regenerative process is not yet clear. Systemic biomarker analysis showed that KJD causes a decrease in collagen type II degeneration marker CTXII and an increase in collagen type II synthesis marker PIIANP. 16,20 Synovial fluid biomarkers showed changes in degenerative and regenerative pathways, and cartilage quality measurements (dGEMRIC) showed no changes over 2 years post-treatment, while cartilage volume increased and untreated patients might have shown a cartilage quality decrease. 30,31 These results suggest that joint unloading by KJD stimulates intrinsic intra-articular conditions that promote cartilaginous tissue regeneration with an optimum between 1 and 2 years. Patients treated with KJD show clearly better results than patients without KJD, while results were comparable between KJD and HTO. TKA patients often showed more clinical improvement but lost their native knee. Adding KJD to microfracture and debridement significantly improved results as well. Apart from pin tract infections, complications were not different in severity and number than those in other treatments. Knee contracture after 6-week fixation seemed no significant risk (on the contrary, flexion was regained quicker than after TKA). 19 Our study had several limitations. First, the number of patients was limited. Although the effect sizes were generally large, a larger number of patients would allow for stronger conclusions, especially for long-term results. Also, the treatment protocol (distraction duration) differed between studies. Furthermore, only 2 studies performed patient randomization, and none of the studies had a completely low risk of bias. Also, most studies were conducted by 1 research group, although in multi-center approach. Nevertheless, there were no indications for publication bias, and patient characteristics were generally very similar between the different studies. All studies seem to have included younger patients with severe knee OA, which is the target group for KJD treatment in regular care, increasing the likelihood that results found in this review may be expected in regular care as well. In conclusion, this review analyzed data of available KJD studies for an extensive meta-analysis with multiple outcome measures, cohorts, and follow-up periods. Despite clear effects, it remains important that more patients are studied with longer follow-up, preferably in dedicated medical centers. This may also support treatment indication and patient selection. Better understanding of the underlying mechanisms of tissue structure repair and clinical benefit due to KJD might add to the above. Irrespectively, KJD provides for an additional option in joint- preserving treatments for osteoarthritis and a viable alternative to joint replacement, especially in younger patients.