Evaluating Osteoarthritis Severity in Mice Using μCT-Derived Geometric Indices

Imaging is the gold standard for diagnosing osteoarthritis (OA). However, it remains challenging to precisely assess OA in murine models. The aim of this study is to establish μCT-based geometric indices for assessing the disease severity of post-traumatic OA (PTOA) and age-related OA (AROA). Following medial meniscectomy (MMS) in adult C57BL/6 mice, distal femoral length remained unchanged, whereas its width increased significantly. As a result, distal femoral width-to-length ratio was markedly elevated at 4 and 8 weeks after MMS (1.33 ± 0.05 and 1.47 ± 0.1, n = 7 and 5 joints, respectively) compared to contralateral normal joints (1.19 ± 0.04, n = 9), yielding an area under the curve (AUC) of 1.0 (95% CI, 1.0-1.0). Similarly, the tibial secondary ossification center (IIOC) height decreased, whereas its width increased after MMS. Consequently, the tibial IIOC height-to-width ratio was significantly reduced at 4 and 8 weeks post-MMS (0.25 ± 0.02 and 0.24 ± 0.02, respectively) compared with a normal joint (0.304 ± 0.011), with an AUC of 1.0 (95% CI, 1.0-1.0). Bland-Altman analysis demonstrated strong interrater reproducibility, with intraclass correlation coefficients of 0.853 (95% CI, 0.681-0.936) for the femoral ratio and 0.887 (95% CI, 0.748-0.952) for the tibial ratio. Notably, these MMS-induced changes in femoral and tibial geometric indices were attenuated in mice with genetic deletion of GM-CSF, a key mediator of OA. Importantly, μCT-derived geometric indices were validated by histological analysis. Furthermore, increased distal femoral width-to-length ratio and reduced tibial IIOC height-to-width ratio were also observed in the knee joints of 28-month-old mice with AROA. In addition, an enlarged patella and a calcified synovium-capsule serve as a reference for AROA and PTOA. Collectively, μCT-based geometric indices are useful and easily quantifiable metrics for assessing disease severity and therapeutic response of PTOA and AROA models in murine. Of note is that the distal femoral and proximal tibial geometric indices were developed based on severe OA induced by MMS, and their applicability to mild OA requires further investigation.