In situ profiling of nanoscale displacements uncovers mechano-architectural predictors of osteoarthritis emergence

Mechanical and anatomical interplay between the distinct tissues of the knee joint is essential for maintaining functional integrity during healthy ageing and contributes to the mechanisms that drive osteoarthritis (OA). In this study, we investigate how age- and disease-associated alterations in joint anatomy influence load transmission and tissue-level strain distribution. Using full-field synchrotron X-ray computed tomography coupled with digital volume correlation, we hierarchically characterised in situ nanoscale strains generated in response to mechanical loading across the tibial epiphysis. Our findings show that greater compressive strains accumulate in the articular condyle of male OA-prone (STR/Ort) epiphyses. Finite element modelling further demonstrated that these strain concentrations are associated with reduced load-bearing capacity, which arise from architectural differences localised to the subchondral bone plate. By coupling high-resolution imaging with computational modelling, our work provides new insights into how structural-function changes to joint anatomy contribute to the initiation and progression of mechanically driven OA. Our approach offers a means to identify early imaging biomarkers prior to OA diagnosis and has potential for monitoring interventions aimed at preserving joint mechanics while promoting healthy joint ageing.