Mylène Jansen

SF biomarker changes upon KJD 325 16 Introduction Osteoarthritis (OA) affects all joint tissues, with articular cartilage loss being 1 of the hallmarks of progressive disease 1 . It is likely that excessive mechanical load or loss of mechanoprotective mechanisms in the joint is an underlying process in many cases of disease, but that there are other superimposed factors such as inflammation that modify its course. 2–6 Longitudinal cohorts such as the Osteoarthritis Initiative and Clinical Assessment of the Knee (CAS-K) show that in ∼ 40% of individuals with early knee OA, pain may stabilize or improve over time, suggesting that the disease may remit and is not inevitably progressive. 7 Interventions that mechanically off-load the joint, such as strengthening exercises, weight loss, orthotics such as bracing or surgical interventions such as osteotomy or unloading devices all reduce knee symptoms. 1,8 It is often stated that adult articular cartilage is unable to repair but a body of literature is emerging that challenges this concept. This is best exemplified by traumatic focal cartilage defects that can repair spontaneously in young joints (reviewed in 9 ), but in individuals undergoing high tibial or distal femoral osteotomy for OA, structural modification has also been observed. 10 The other evidence comes from studies of surgical knee joint distraction (KJD). The primary goal of this treatment is to improve symptoms sufficiently to delay knee arthroplasty. This is especially the case in younger patients, since these individuals have an increased risk of revision arthroplasty. 11 KJD is a technique where, under anesthesia, an external fixation frame is placed on both sides of the joint, allowing distraction (gradual pulling apart of the joint’s bony ends by ∼ 5 mm for 6 weeks). During distraction, the patient is encouraged to weight-bear on the extended knee. Such weight-bearing creates intermittent joint fluid pressure changes, due to built-in springs in the frame enabling a maximal 3 mm axial displacement under full body weight. 12 Studies of joint distraction have shown sustained and clinically significant improvement at a number of joint sites. 13,14 For knee OA, joint distraction improved knee symptoms for 5–9 years in individuals with established OA. 15,16 Remarkably, the 6 week intervention also led to apparent cartilage regeneration in the subsequent months and years, with increase in joint space width on X-ray, and increased articular cartilage thickness on magnetic resonance imaging (MRI). 14,16– 18 These studies suggest that, by temporarily off-loading the joint, KJD might somehow be responsible for ‘priming’ the joint to enable intrinsic cartilaginous repair. The biological mechanisms which underlie such a response are not understood but may include changes in the periarticular bone and enhanced mesenchymal stem cell attachment to the damaged joint surface. 19,20 KJD is therefore an attractive mechanistic model in which to investigate potential reparative pathways and identify novel associated markers of clinical response. Synovial fluid (SF) represents an accessible fluid that contains molecules reflecting biological processes within the joint. These molecules are joint tissue-agnostic; likely being derived from all the tissues interfacing the joint cavity and can be sampled repeatedly to monitor change