Evaluating Osteoarthritis Severity in Mice Using μCT-Derived Geometric Indices

Area of Science:

• Biomedical Engineering
• Orthopedics
• Medical Imaging

Background:

• Osteoarthritis (OA) diagnosis relies heavily on imaging, but precise assessment in murine models remains challenging.
• Developing accurate and reproducible methods to evaluate OA severity in preclinical studies is crucial for understanding disease mechanisms and testing therapeutics.

Purpose of the Study:

• To establish micro-computed tomography (μCT)-based geometric indices for assessing disease severity in post-traumatic OA (PTOA) and age-related OA (AROA) mouse models.
• To validate the reproducibility and utility of these indices in quantifying OA progression and therapeutic responses.

Main Methods:

• Medial meniscectomy (MMS) was performed on adult C57BL/6 mice to induce PTOA.
• μCT imaging was used to measure distal femoral and tibial secondary ossification center (IIOC) geometric parameters.
• Geometric indices, including width-to-length ratios, were calculated and compared between OA-induced and contralateral normal joints.
• Bland-Altman analysis assessed interrater reproducibility, and histological analysis validated μCT findings.
• Age-related OA (AROA) was assessed in 28-month-old mice.

Main Results:

• MMS significantly increased distal femoral width-to-length ratio and decreased tibial IIOC height-to-width ratio, demonstrating high diagnostic accuracy (AUC=1.0).
• These geometric indices exhibited strong interrater reproducibility (ICC > 0.85).
• MMS-induced changes were attenuated in mice lacking GM-CSF, a key OA mediator.
• Similar geometric index alterations were observed in AROA models, along with enlarged patella and calcified synovium-capsule.

Conclusions:

• μCT-based geometric indices provide a reliable, quantifiable method for assessing OA severity in murine models.
• These metrics are valuable for evaluating therapeutic interventions in PTOA and AROA.
• Further investigation is needed to confirm the applicability of these indices to milder forms of OA.