Identification of Biochemical and Biomechanical Markers for Cartilage Degeneration in the Knee Joint (IBBM-CKJ)

Osteoarthritis (OA) is a painful and debilitating disease of the synovial joints, affecting the structural and functional integrity of articular cartilage, subchondral bone, synovium and the adjacent supporting connective tissue . It is a degenerative disorder characterized by cartilage loss with high prevalence in individuals over an age of 55 years. The most affected region in OA is the medial compartment of the knee. The symptoms of OA include joint pain, stiffness, and swelling which may lead to impaired physical function and muscle weakness . The etiology of the disease is multifactorial and not fully understood. Traditionally, OA was regarded as a "wear and tear" disease caused by ageing, but both non-physiological mechanical loading (e.g. malalignment, obesity, trauma or joint instability) of a normal joint or physiological mechanical loading of a pathological joint can induce OA .

Joint misalignment has been identified as a potential biomechanical risk factor for development and progression of knee OA. Although determination of malalignment might provide important information about the load distribution in static conditions , dynamic loading parameters have been analyzed during gait to provide information about the total extrinsic load at the knee during the stance phase. According to Andriacchi, the external knee adduction moment can be used to predict load distribution between the medial and lateral compartments of the knee during dynamic activities. Increased external adduction moments are associated with increased joint forces on the medial plateau. During walking, forces are not evenly distributed across the joint surface and approximately 70% of the total load passes through the medial compartment. This may contribute to the higher prevalence of OA in this compartment . It can be expected that in patients with a varus deformity an even higher proportion of load is supported by the medial compartment. This may result in acceleration of articular cartilage degeneration.

The link between mechanical loading and the severity and progression of medial OA has been shown by many studies. Disease severity was found to correlate with the knee adduction moment , knee adduction angular impulse and knee extension moment . Miyazaki et al. analyzed the disease progression of OA patients during seven years. Patients that showed radiographic disease progression in the medial knee compartment also presented more severe knee pain and greater knee adduction moment than patients without disease progression. Baliunas et al. observed a significant greater knee adduction moment in OA patients with different levels of disease severity, but no significant differences were found in the sagittal moments. Thorp et al. analyzed not only the knee adduction moment but also the knee adduction angular impulse for the stance phase in healthy subjects and OA patients with mild and moderate disease progression in the medial knee compartment. The peak knee adduction moment and the knee adduction angular impulse were significant different between the control group, mild and moderate OA patients. Furthermore, the parameter knee adduction angular impulse was significantly different between mild and moderate OA patients, suggesting that this parameter can describe functional changes between different stages of disease progression.

While the relationship of varus malalignment and OA of the medial compartment is well described in the literature, little information is available if and how varus malalignment affects the lateral compartment. Fantini Pagani recently demonstrated that cartilage mechanical quality is not related to the knee adduction moment during gait in patients with severe OA.

Authors further reported that mechanical properties of osteoarthritic cartilage are highly variable indicating a complex relationship between joint loading and tissue changes during degenerative processes of articular cartilage. In clinical practice, patients with an identical mechanical varus malalignement of the lower extremity may show either isolated osteoarthritis of the medial compartment of the knee (example 1), or OA of the medial, lateral and patellofemoral compartment (example 2). This entity suggests that osteoarthritic disease in varus malaligned knees, in which the medial compartment is submitted to excessive overload, progress from medial to lateral over time. It could be assumed that mechanobiological factors and inflammatory reactions rather than mechanical load transmission play a major role in disease progression in the osteoarthritic knee.