Abstract

Background and Aim: Osteoarthritis (OA) is a progressive degenerative joint disorder characterized by cartilage loss, sub­chondral bone remodeling, and chronic pain, and remains a leading cause of disability worldwide. Although radiographic imaging and behavioral testing are widely used in preclinical research, few studies have systematically examined their inter­dependence. This study aimed to radiologically characterize OA progression in rats induced by monosodium iodoacetate (MIA) and to correlate structural alterations with functional and nociceptive outcomes, while exploring potential sex-specific differences and therapeutic responses to non-steroidal anti-inflammatory drugs (NSAIDs).

Materials and Methods: Thirty-six Wistar rats (male and female) were divided into six experimental groups: Healthy controls, OA-induced untreated, and OA-induced meloxicam-treated. Over 28 days, animals underwent serial radiolog­ical assessments and validated behavioral tests, including weight-bearing, rotarod, and Von Frey assays. Statistical anal­yses employed analysis of variance with post hoc testing, ensuring methodological rigor with blinded evaluators and sex-stratified comparisons.

Results: Radiographs revealed classical OA features, joint space narrowing, subchondral bone sclerosis, and osteophyte for­mation, with progressive severity across timepoints. NSAID-treated males demonstrated significant improvement in motor coordination and nociceptive thresholds on days 7 and 14 (p < 0.001), whereas females exhibited only modest or delayed responses despite more severe radiological deterioration. Importantly, structural joint damage did not consistently align with behavioral impairments, underscoring a dissociation between radiographic severity and clinical-like manifestations.

Conclusion: This study provides an integrated evaluation of structural and functional outcomes in experimental OA, high­lighting a complex relationship between radiological changes and behavioral impairments. The findings emphasize the necessity of multimodal assessment strategies in preclinical OA models and reveal sex-specific differences in disease progres­sion and therapeutic response. These insights are crucial for refining translational strategies, advocating for sex-conscious approaches and combined structural-functional endpoints in OA research and drug development.

Keywords: behavioral assessment, experimental rat model, non-steroidal anti-inflammatory drugs, osteoarthritis, radiological analysis, sex differences.