Objective: To analyze and synthesize the information available from five pivotal, large-scale, multicenter, observational studies (CHECK, OAI, FNIH Biomarkers Consortium, IMI-APPROACH, and MOST) focusing on knee osteoarthritis (OA), which can be used to elucidate disease progression, risk factors, and the effectiveness of potential interventions. Design: For this narrative review, a comprehensive literature search and data extraction from official web pages and scientific databases were conducted to compare methodologies, in- and exclusion criteria, outcomes, and cohort characteristics across the studies. Thematic, comparative, and qualitative analyses were employed to identify trends, commonalities, and disparities among the findings. Results: The studies collectively enhanced understanding of the onset and progression of knee OA, and in several of the studies, hip OA, emphasizing the importance of both systemic and local risk factors. Advanced imaging and biomarkers are important components in all the cohorts, with the goal of aiding early diagnosis and tracking disease progression. All cohorts evaluated unique markers generally not available in the other cohorts, while other factors overlap, suggesting possibilities for combining or cross-validating between cohorts. Conclusions: The collaborative efforts of major OA research significantly advance our understanding of knee OA. These studies highlight the importance of a multifaceted approach, integrating advanced imaging, biomarkers, and longitudinal data to tackle the complexities of OA. By synthesizing findings and addressing knowledge gaps such as heterogeneity of patients and used measurements, and use of novel pain measures, future research can develop more effective diagnostic tools and treatments, ultimately enhancing the quality of life for OA patients.

Objective: Fibulin-3 is a glycoprotein highly expressed in osteoarthritic cartilage and inhibits angiogenesis and chondrocyte differentiation. Recent studies have indicated that fibulin-3 has potential value as a biomarker in osteoarthritis. The aim of the present study is to examine the role of 3 fibulin-3 peptides (Fib3-1, Fib3-2, and Fib3-3) and a type II collagen degradation product in a rat osteoarthritis model with systemic metabolic alterations combined with local cartilage damage. Design: Forty, 12-week-old male, Wistar rats were randomly divided over 2 groups: a standard or a high-fat diet inducing metabolic dysregulation. After 12 weeks, articular cartilage damage was induced on the femoral condyles (groove model), in 1 knee joint in 14 rats of each diet group. At endpoint, blood was collected and serum was isolated. Enzyme-linked immunosorbent assay on all selected fibulin-3 fragments was performed from serum samples in addition to immunohistochemical analysis for Fib3-3. Results: Serum concentrations of Fib3-3 were increased by 29.9%, when cartilage damage was induced in addition to a high-fat diet. Fib3-3 was also associated with an increased histological total joint degeneration (r = 0.435) and cartilage degeneration (r = 0.435). Immunostainings demonstrated increased Fib3-3 in the superficial cartilage of animals with high-fat diet and/or cartilage damage. Conclusions: In the rat groove model combined with high-fat diet–induced metabolic dysregulation an increased Fib3-3 concentration was observed systemically, which is associated with local joint degeneration. This suggests that systemic Fib3-3 concentrations can indicate the status of joint degeneration and function as a biomarker in osteoarthritis.