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Objective: To summarize proceedings of a workshop convened to discuss the current state of science in the disease of osteoarthritis (OA), identify the knowledge gaps, and examine the developmental and regulatory challenges in bringing these products to market. Design: Summary of the one-day workshop held virtually on June 22nd, 2021. Results: Speakers selected by the Planning Committee presented data on the current approach to assessment of OA therapies, biomarkers in OA drug development, and the assessment of disease progression and long-term benefit. Conclusions: Demonstrated by numerous failed clinical trials, OA is a challenging disease for which to develop therapeutics. The challenge is magnified by the slow time of onset of disease and the need for clinical trials of long duration and/or large sample size to demonstrate the effect of an intervention. The OA science community, including academia, pharmaceutical companies, regulatory agencies, and patient communities, must continue to develop and test better clinical endpoints that meaningfully reflect disease modification related to long-term patient benefit.

Background: Finite element modelling can be used to evaluate altered loading conditions and failure locations in knee joint tissues. One limitation of this modelling approach has been experimental comparison. The aims of this proof-of-concept study were: 1) identify areas susceptible to osteoarthritis progression in anterior cruciate ligament reconstructed patients using finite element modelling; 2) compare the identified areas against changes in T₂ and T₁ₚ values between 1-year and 3-year follow-up timepoints. Methods: Two patient-specific finite element models of knee joints with anterior cruciate ligament reconstruction were created. The knee geometry was based on clinical magnetic resonance imaging and joint loading was obtained via motion capture. We evaluated biomechanical parameters linked with cartilage degeneration and compared the identified risk areas against T₂ and T₁ₚ maps. Findings: The risk areas identified by the finite element models matched the follow-up magnetic resonance imaging findings. For Patient 1, excessive values of maximum principal stresses and shear strains were observed in the posterior side of the lateral tibial and femoral cartilage. For Patient 2, high values of maximum principal stresses and shear strains of cartilage were observed in the posterior side of the medial joint compartment. For both patients, increased T₂ and T₁ₚ values between the follow-up times were observed in the same areas. Interpretation: Finite element models with patient-specific geometries and motions and relatively simple material models of tissues were able to identify areas susceptible to post-traumatic knee osteoarthritis. We suggest that the methodology presented here may be applied in large cohort studies.