Mylène Jansen

Osteophyte formation after KJD and HTO 353 17 Introduction Osteoarthritis (OA) is characterized by articular cartilage loss, intra-articular inflammation, and osteophyte formation. 1 Osteophytes are often formed at the joint margins, first as cartilage outgrowth and subsequently undergoing ossification. 2 While the exact purpose of osteophytes remains unknown, their presence and size in the knee are associated with joint space width (JSW) decrease and they are an important radiographic feature used to define the severity of knee OA in classifications like the Altman score and Kellgren-Lawrence grade. 3–7 Osteophytes are frequently present in patients with end-stage knee OA receiving surgical treatment such as total knee arthroplasty (TKA). 8 TKA is widely used because of its clinical effectiveness, but in younger patients (<65 years) it has a significantly higher risk of failure and revision surgery later in life. 9,10 Therefore, there is a demand for joint-preserving treatments for (severe) knee OA at a younger age. A joint- preserving alternative for patients with unicompartmental knee OA as a result of malalignment is high tibial osteotomy (HTO), which shows good long-term results and clinical improvement and a certain degree of cartilage repair. 11–13 Knee joint distraction (KJD) is a relatively new joint-preserving treatment for patients with unicompartmental or generalized severe knee OA, where the tibia and femur are temporarily separated using an external fixation frame. 14 An open prospective study (OPS) has shown good long-term treatment results and 2 randomized controlled trials (RCTs), 1 comparing KJD with HTO and 1 with TKA, showed that clinical outcome after KJD is comparable to that after HTO or TKA. 15–20 Furthermore, cartilage repair has been shown on radiographs and on MRI scans, and systemic biomarker analyses suggest beneficial cartilage and bone turnover after KJD treatment. 18,21–23 Cartilage repair activity as a result of treatment could be related to an increase in transforming growth factor- β 1 (TGF β -1), which is generally appreciated to stimulate cartilage repair. 24 During KJD treatment, an increase in synovial fluid TGF β -1 level was observed. 25 While TGF β -1 is associated with joint repair, it has also been shown to induce osteophyte formation, predominantly in experimental animal studies, but in ex vivo human studies as well. 26–31 Interleukin-6 (IL-6) was also observed to increase intra-articularly as a result of KJD treatment and could be positively associated with osteophyte presence as well, showing increased mRNA expression and protein production in in vitro studies with human osteophyte tissue. 25,30,32 As such, we studied osteophyte formation during KJD and compared this to HTO and natural OA progression, hypothesizing that joint-preserving regenerative treatments demonstrating cartilage repair activity lead to tissue (re)generation in general, including osteophyte formation.