Comparative characterization of monosodium iodoacetate-induced osteoarthritis in rat and rabbit models using micro-computed tomography and histology assessment

Abstract Osteoarthritis (OA) is a progressive joint disease characterized by cartilage degeneration and subchondral bone remodeling. Monosodium iodoacetate (MIA)-induced animal models are widely used for investigating OA pathogenesis and evaluating potential therapies; however, standardized comparative evaluations of commonly used rat and rabbit models using identical structural outcome assessments following species-specific validated MIA induction protocols remain limited. This study compared structural alterations in MIA-induced OA in rats and rabbits using identical macroscopic, micro-computed tomography (micro-CT), and histological assessments. Twelve male Sprague Dawley rats and twelve male New Zealand White rabbits were randomly allocated to sham or OA groups (n = 6/group). OA was induced by intra-articular injection of MIA (3 mg in rats; 8 mg in rabbits), and knee joints were evaluated at a predefined 12-week endpoint. Both species developed characteristic OA pathology, including cartilage degeneration, osteophyte formation, subchondral bone sclerosis, and trabecular microarchitectural alterations. Quantitative micro-CT demonstrated significant OA-associated increases in bone volume fraction (BV/TV), trabecular separation (Tb.Sp), and total porosity (PO) in both species compared with their respective sham controls ( p < 0.05). Under the present experimental conditions, OA-related structural changes were consistently more pronounced in rats, with greater subchondral bone remodeling and more severe cartilage degeneration than in rabbits, as confirmed by micro-CT and histological grading. Although both models successfully reproduced key features of OA, their disease severity differed substantially. These findings provide standardized comparative evidence demonstrating that validated rat and rabbit MIA-induced OA models exhibit distinct structural responses under their respective experimental protocols and may therefore be selected according to specific research objectives rather than assumed biological equivalence.