Mylène Jansen

General introduction 11 1 Knee osteoarthritis Osteoarthritis Osteoarthritis (OA) is the most common chronic musculoskeletal disorder, affecting more than 300 million people worldwide. 12 Prevalence is expected to rise with an aging population and increasing obesity, as both are related to incidence and prevalence of OA. 13 The knee is a frequent site of OA, involving the entire joint, encompassing bone, cartilage, and synovium. 14 Bone changes include an increase in subchondral bone density, formation of osteophytes, and bone shape alterations. 15 Cartilage volume decrease is perhaps the most well-known characteristic of OA, but the quality of cartilage deteriorates as well, as the collagen type II in the ECM is affected. 16 Both the bone and cartilage alterations influence the joint mechanically and biochemically. Often synovial inflammation, or synovitis, is present, affecting the composition of the synovium and synovial fluid. 17,18 Not all changes occur similarly in all patients: they show heterogeneity, leading to attempts to define different subgroups or phenotypes. 19 Diagnosis and monitoring Diagnosis of knee OA starts with the symptoms that bring patients to visit their doctor, including pain, reduced function, and stiffness. A definitive diagnosis is made based on these symptoms, in combination with physical examination, and a radiograph of the knee. 20 Classification and monitoring of disease progression is usually done with plain radiographs as well, often using relatively rough grading scales. 21 However, while radiographs have the advantage of being fast and cheap, they only provide a 2D image and do not show soft tissue such as cartilage. Alternative imaging techniques can be used, such as computed tomography (CT) for a 3D image of the bones or magnetic resonance imaging (MRI) for a 3D image of hard and soft tissue, including synovial tissue and cartilage, enabling measurement of not only cartilage quantity but also quality using specialized scans. 22 While these imaging techniques are applied more and more in research, radiography is still dominant in regular care. Treatment Treatment of tibiofemoral knee OA usually starts with conservative, non-surgical options such as weight loss, bracing, use of oral pain medication and anti-inflammatories, and, if that fails, intra-articular injections. 23 Eventually, as the disease progresses towards end-stage knee OA, many patients need a joint replacement, a partial or total knee arthroplasty (UKA/TKA). While TKA and more recently also UKA are applied often and have shown good clinical results, still around 20% of patients express dissatisfaction after TKA surgery. 24 Furthermore, the prosthesis itself has a limited life span, meaning it could eventually need replacement in an expensive and usually less clinically successful revision surgery. The chance for revisions surgery increases significantly when the arthroplasty is performed in relatively young patients,