Mylène Jansen

312 Chapter 15 Discussion After treatment with KJD or HTO, an increase in cartilage T2 relaxation times was observed throughout the entire joint, similar between the 2 treatments and larger than could be expected as a result of natural OA progression alone. In TKA-indicated KJD patients the T2 value increase was not statistically significant. An increase in T2 relaxation times can be the result of higher water content, lower collagen concentration, loss of collagen framework integrity, or a combination. 9 Remarkably, patients treated with KJD showed an initial T2 value increase in the first year after treatment, but a stabilization or even a decrease between 1 and 2 years post-treatment, especially in TKA- indicated patients. This might be a delayed effect of the 6-week unloading in KJD treatment: articular cartilage may need loading for normal structuring of the collagen framework. A previous study applying T2-mapping of knee cartilage showed that 45 minutes of unloading (lying down) resulted in a T2 relaxation time increase (+0.9 ms), an effect that was even more pronounced in cartilage repair tissue (+4.3 ms) and the authors speculated it was the result of hydration and/or reorganization of the collagen organization. 30 As such, it is not unthinkable that 6-week unloading may still show its effects on the collagen structure 1 year after treatment. Systemic collagen type II markers have previously been evaluated in multiple KJD cohorts, including the RCTs from which patients in the current study were included. Interestingly, all cohorts showed an initial decrease in net collagen type II synthesis (i.e. more breakdown than synthesis), which gradually increased and at 2 years after treatment showed a significant increase in net collagen type II synthesis. 17,31 This corresponds largely with the T2 relaxation times initially increasing and after 1 year decreasing, and suggests a short-term decrease in cartilage collagen content followed by a normalization after 1 year. Only in TKA-indicated KJD patients, the increase in T2 relaxation times goes paired with a volume increase in the MAC. In a previous study optimized for cartilage thickness changes in patients from these RCTs, it was shown that KJD TKA patients showed a significant increase in MAC cartilage thickness and decrease in denuded bone areas, indicating there is indeed new cartilage tissue formation. 18,32 The increase in T2 relaxation time could be the result of newly formed cartilage that needs time to mature. A T2-mapping study in children and adolescents showed that skeletal maturation in children caused a decrease in T2 relaxation times, potentially caused by increasing collagen content as a result of maturation. 33 Furthermore, T2-mapping studies in patients with a cartilage defect showed higher initial T2-values for repair cartilage compared to normal cartilage that decreased over time, and histological studies in dogs treated with KJD suggested a somewhat delayed normalization based on proteoglycan turnover. 7,30,34,35 Newly formed, young, repair cartilage that needs time to mature could explain the 1-year T2 value increase and subsequent normalization that, at least in the MAC of TKA-indicated