Mylène Jansen

Osteophyte formation after KJD and HTO 363 17 osteophyte size or Kellgren-Lawrence grade had a significant influence on the change in osteophyte size (CHECK: p= 0.391 and p= 0.457, respectively). For patients who had SF aspirations, the osteophyte formation after KJD seems to be associated with the increase in TGF β -1 during the 6 weeks of treatment, based on dividing patients into groups showing an increase, no change or a decrease in Altman osteophyte score after KJD. However, there were no associations between the (changes in) actual Altman scores and TGF β - 1 values. These results are as such indicative and not conclusive, corroborating the reported role of TGF β -1 in osteophyte formation. While both TGF β -1 and IL-6 significantly increased during treatment, the change in IL-6 was not associated with osteophyte formation. This study has several limitations. First, the different cohorts were not initiated and powered for the presented statistical evaluations and should therefore be considered exploratory. Second, retrospectively comparing patient cohorts that have not been randomized or carefully matched, as was done when comparing KJD patients with CHECK, provides a risk for coincidental findings. Despite selecting the most relevant subgroup from CHECK, there was a clear difference in OA severity with KJD patients. Also, although the comparison between KJD and CHECK was corrected for baseline osteophyte size and the Kellgren-Lawrence grade was shown to not be on influence on the change in osteophyte size, it could still be that the results in CHECK patients underestimate the natural progression in more severe knee OA patients. CHECK was used since it was a well-established cohort of untreated knee OA patients of which radiographs were evaluated with KIDA, but patients generally had mild OA. Patients with a more comparable severity would make a better comparison, although purposefully not treating severe knee OA patients for multiple years would be ethically unsound. Another limitation was the fact that no KIDA evaluations were available for the SF patient group. The Altman osteophyte score may not have been sensitive enough to show 1-year changes in osteophyte size after KJD, especially in this small group of patients. As TGF β -1 has previously been associated with both cartilage repair and osteophyte formation, morphometric MRI scans in sufficient numbers of patients could be of added value in future studies. The present study provides an indication that a rise in TGF β -1 might be a mediator in tissue repair activity upon KJD leading to osteophyte formation in addition to cartilage repair, but future studies would have to proof this concept. Lastly, osteophyte formation was measured on 2D images. In a future study, it would be interesting to measure osteophyte formation after regenerative treatments like KJD and HTO in 3-dimensional CT images as well, to improve sensitivity (to change) and to add to pathobiological mechanisms regarding osteophytosis during natural progression compared to these joint regenerative treatments.