Revealing early subchondral bone structural changes in osteoarthritis progression in a collagenase-induced mouse model using microCT

Osteoarthritis (OA) is the most prevalent joint disorder affecting millions of people worldwide, and involves deterioration to subchondral bone. This study aims to reveal the early bone microstructural changes at high temporal resolution in a small animal model of OA with joint laxity and inflammation. Seventy-five male C57BI/10 mice aged nine weeks were recruited and assigned to three cross-sectional cohorts, baseline, control, and OA. Of these, forty-seven ten-week-old mice assigned to the OA cohort received intra-articular injection of collagenase on the right knee to destabilize the right tibiofemoral joint. Micro-computed tomography (microCT) scan was performed after humanely killing the mice at nine time points (eight weeks in total). Quantitative morphometric analysis (QMA) was performed to measure structure of subchondral cortical and epiphyseal femoral and tibial bone, and osteophyte activity. Early pathological changes caused by collagenase-injection were characterized by bone morphometry measures and osteophyte detection. Compared to control joints, bone loss, lower bone volume fraction, thinner trabeculae, larger trabecular spacing, smaller trabecular number, thinner cortical bone, and osteophyte formation were observed in osteoarthritic joints at multiple time points, with changes detectable as early as one week post disease induction. Additionally, a non-linear pattern of structural changes was observed throughout the experiment, with a critical transition occurring within three weeks after disease induction. These findings underscore the necessity of early and frequent quantification to capture rapidly changing bone microstructure alterations in early stage of OA, potentially enabling earlier diagnosis, intervention, and treatment of OA.