Biomechanical and Biological Predictors of Cartilage Health Following Meniscus Injury

Abstract Injury of the meniscus is frequently associated with early onset osteoarthritis (OA). Partial meniscectomy to remove the damaged meniscal tissue is the most commonly performed orthopaedic procedure. While this procedure can provide symptomatic relief in the short term, nearly 35% of patients develop radiographic evidence of OA within 5-7 years following surgery. However, the causes for this early onset OA are unknown. One potential pathway for the progression of knee OA following meniscectomy is through altered loading of the articular cartilage. However, other studies suggest that biological factors, such as joint inflammation may play an important role. Recently, through a combination of MR imaging, 3D modeling, and biplanar radiography, our team has shown that medial meniscal injury alters the cartilage-to-cartilage contact strains in both the medial and lateral compartments. In addition, we found that increased strain was correlated with increased levels of matrix metalloproteinase (MMP) activity in the synovial fluid, a biomarker which may be indicative of joint degradation. Together, these results suggest that biomechanical and biological factors play an important role in the development of OA after meniscal injury. However, the role of partial meniscectomy on these changes is unclear. Thus, a comprehensive evaluation of the biomechanical and biological environment of the joint before and after partial meniscectomy will elucidate the factors that contribute to early onset OA. Our overall hypothesis is that following partial meniscectomy, both biomechanical and biological changes in the joint will predict cartilage degeneration. Furthermore, when biomechanical and biological predictors are combined together with patient demographics and clinical characteristics, we will identify well-defined clinical phenotypes of patients at high risk of cartilage degeneration. Cartilage degeneration will be assessed through MR-based measures of cartilage thickness and composition. Using high speed biplanar x-ray and MR imaging, in vivo cartilage strains in both knees of patients with unilateral medial meniscus injury will be measured in response to treadmill walking prior to surgery and after surgery. Synovial fluid and serum will also be collected and a panel of pro-inflammatory mediators and tissue metabolic biomarkers will be measured. Synovial fluid immune cell analyses will be performed by flow cytometry. Using these biomechanical and biological factors, we will identify participants at increased risk for cartilage degeneration at two years after surgery. Then, using predictive models combining biomechanical factors, biological factors, demographics, and clinical characteristics, we will develop well-defined clinical phenotypes of cartilage degeneration risk. Importantly, the development of these phenotypes will enable targeted treatment approaches focused on surgery, pharmaceutical targets, and non-pharmacological interventions, such as physical rehabilitation strategies or weight loss, to prevent cartilage degeneration.