# Radiological–behavioral disparities in experimental osteoarthritis: Sex-specific progression and therapeutic response in a rat model

## TL;DR

This study shows that radiological changes in osteoarthritis in rats don't always match behavioral symptoms, and that males and females respond differently to treatment.

## Contribution

The study reveals sex-specific differences in OA progression and NSAID response, and highlights a dissociation between radiological and behavioral outcomes.

## Key findings

- NSAID-treated males showed significant improvement in motor coordination and nociceptive thresholds at days 7 and 14.
- Females exhibited modest or delayed responses despite more severe radiological deterioration.
- Structural joint damage did not consistently align with behavioral impairments.

## Abstract

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).

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.

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.

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.