Mylène Jansen

Summary and general discussion 407 19 and hip distraction 21,22 , which could be related to hormonally controlled bone differences between men and (mostly post-menopausal) women. 34 Patients with more severe OA seemed to show a better response in cartilage regeneration and quality ( chapter 13 , chapter 14 , and chapter 15 ), which in turn results in better long-term success ( chapter 3 ), indicating that pre-treatment patient selection is crucial. Treating patients with severe complaints but only mild joint damage with KJD will likely not give the positive effect that the treatment can potentially bring. Still, there will be other characteristics, components or processes that are important in KJD treatment that we have not yet discovered or simply have not been studied yet. For example, the possible influence of muscles, ligaments and menisci has thus far not been investigated. The menisci, especially, could be of relevance, since they have an important role in load distribution during weight-bearing and in the structural progression of knee OA. 35 Also, including a well-matched, untreated control group as comparison when evaluating structural changes would be helpful in unraveling the mechanisms behind KJD and identifying important characteristics. Unfortunately, this is difficult, since a good control group would need to have similar, severely progressed, knee OA, and not treating such patients would be unethical. Performing advanced imaging of ideally larger groups of patients on more time points especially shorter after treatment, since that could allow linking SF biomarker and MSC response with structural bone and cartilage changes, would likely further improve understanding of the joint repair processes as well. Importantly, when further elucidating these processes they might be of direct help to development of other OA treatment modalities, where placement of a frame may be obsolete, in case the relevant process can be influenced without distraction (see Figure 2). Moving forward with KJD also means looking beyond the original goal of using it to treat OA patients, and applying the knowledge gained from the repair processes that occur on the general field of OA. The regenerative processes upon KJD occur very fast compared with the slow rate degenerative processes in OA, as they show relatively large structural and clinical changes in a short amount of time. Having a treatment with clear regenerative capacity allows us to step off the old paradigm of trial and error of investigating targets and medication often aiming at a single molecule, pathway or tissue (such as cartilage) in the OA joint. Instead, we can learn of the integrated effects induced by distraction and use this knowledge, as summarized in Figure 2. Many researchers select (and rarely combine) components, mechanical, cellular and/or chemical, of supposed relevance to induce cartilage tissue repair. In this process, many components are discarded and several will be missed because they act only in synergy with others that have not been considered or are prematurely discarded. Moreover, researchers generally have either biochemical, cellular or mechanical expertise and seldom a combination of them. After decades, we still only have limited insight in the requirements needed for cartilage tissue repair, as they have to be found and combined by trial and error. Apparently KJD provides a joint homeostasis, both mechanically, cellular and chemically, with all required components,