Background:Knee joint distraction (KJD) is a joint-preserving treatment to postpone total knee arthroplasty (TKA) and has shown cartilage repair and clinical improvement in patients with severe knee osteoarthritis (OA), as has high tibial osteotomy (HTO). The observed cartilage repair activity could be related to an increase in transforming growth factor-β1 (TGFβ-1), which increases in the synovial fluid (SF) during KJD treatment.1However, animal and ex vivo human studies have shown that TGFβ-1 also induce formation of osteophytes, generally seen as an OA severity hallmark. Similarly, interleukin-6 (IL-6) was observed to increase in SF during KJD treatment and may also be associated with osteophytosis.As such, we hypothesized that joint-preserving regenerative treatments demonstrating cartilage repair activity lead to general tissue (re)generation, including osteophytosis.Objectives:To analyze osteophytosis after KJD and compare this to HTO and natural progression in knee OA.Methods:63 KJD patients were included in several clinical trials, one of which was a randomized controlled trial comparing patients indicated for HTO, but treated with KJD (KJDHTO; n=23) vs. patients treated with HTO (n=46). All patients received standardized radiographs before and one and two years after treatment, used to measure osteophyte size. Only patients with measurements at baseline and two-year follow-up were included. As a control group for natural progression, untreated knee OA patients from Cohort Hip & Cohort Knee (CHECK; n=1002) were studied. Only patients who received a TKA during follow-up were included, using their last two measurements before treatment to reflect natural two-year progression (n=44).A separate group of 20 patients treated with KJD in regular care underwent SF aspirations before and after treatment, and TGFβ-1 and IL-6 levels were measured by immunoassay (Mesoscale Discovery). Unstandardized radiographs were acquired before and one year after treatment, used to score osteophytes with the revised Altman score, resulting in a 0 (normal) to 12 (severe) whole-joint score. Only patients with radiographs and SF aspirations at both baseline and one-year follow-up were included.Results:After two years, both KJD (n=58) and HTO (n=38) patients showed a significant increase in osteophyte size (+6.2mm2 and +7.0mm2 resp.; both p<0.003; figure 1), with no significant differences between the treatments (p>0.38). Untreated CHECK patients who underwent TKA did not show significant two-year osteophyte changes before treatment (+2.1mm2; p=0.207; figure 1) and showed significant differences compared with KJD and HTO groups (both p<0.044). In the KJD SF aspiration group (n=17), the Altman osteophyte score was not different at one year compared to baseline (+0.2 points; p=0.653) and there was no association between baseline biomarker values and the baseline Altman osteophyte score, or between changes in these parameters (all p≥0.28). Trichotomization of patients in groups with a decrease, no change or increase in total Altman osteophyte score indicated that there was a statistically significant difference between the three groups in changes in TGFβ-1 (p=0.044; figure 2A), but not IL-6 (p=0.898; figure 2B).Conclusion:After KJD treatment, joint space widening and clinical improvement are accompanied by osteophytosis. Similar results were observed after treatment with HTO, suggesting effects occur in regenerative joint-preserving treatments in general. The increased osteophytosis may be a bystander effect of cartilage repair activity related to intra-articular factors like TGFβ-1 and questions whether osteophytosis should necessarily be considered a hallmark of OA worsening.References:[1]Watt et al, Osteoarthritis Cartilage 2020Disclosure of Interests:Mylène Jansen: None declared, Simon Mastbergen: None declared, Fiona Watt: None declared, Elske Willemse: None declared, Tonia Vincent Consultant of: Ad hoc consultancy GSK, Mundipharma, UCB, Sander Spruijt Consultant of: Consultancy to Zimmer Biomet Inc., Pieter Emans Shareholder of: Shareholder and cofounder start-up company Chondropeptix, Roel Custers: None declared, Ronald Van Heerwaarden: None declared, Floris Lafeber Shareholder of: Co-founder and shareholder of ArthroSave BV
Cartilage Repair Activity during Joint-Preserving Treatment May Be Accompanied by Osteophyte Formation
