Mylène Jansen

Summary and general discussion 409 19 been used in the past, such as the currently ongoing APPROACH (Applied Public-Private Research enabling Osteoarthritis Clinical Headway) trial aiming for better identification of fast and slow progressors. 41 Repair-inducing treatments like KJD show a uniquely rapid response that provide a relatively large contrast between patients, which could be generalized to degenerative processes in OA. By analyzing and combining structural (imaging) markers and clinical outcome of a large number of these patients, concrete OA phenotypes might finally be identified. For example, those that do and do not respond to a certain treatment (such as distraction) might be related to a certain phenotype (for example, a bone phenotype that shows optimal regeneration in case of distraction). This would improve patient-specific prognosis and allow for more personalized medicine, but could also improve design of future studies, as it is believed that many therapeutic OA trials may have failed due to the unidentified phenotypic heterogeneity of included patients. 42,43 Ultimately, this might even lead to successful development of DMOADs. In conclusion, work in this thesis has moved the field forward with clinical evaluation of KJD as a treatment for severe knee OA and improving understanding of the working mechanisms behind this treatment. KJD can bring long-lasting clinical efficacy and cartilage regeneration, and increasingly patient-friendly implementation in regular care is possible. KJD induces significant anabolic and catabolic changes in joint homeostasis, showing whole-joint modifications involving bone, cartilage, and synovial fluid, subsequently followed by overall repair. Future studies should focus on deepening comprehension of the mechanisms induced by KJD to improve patient selection, as well as using this unique population showing high rate structural and clinical response to improve understanding of different OA pathways in general.