Relationship between intra-articular gentamicin dosage and damage to cartilage structure and synovial tissue: An in vivo experimental study in rabbits
Husnul F. Albar, Otman Siregar, Tommy TommyObjectives:
Intra-articular antibiotic delivery can generate high local concentrations, but the short-term safety of intra-articular gentamicin for articular cartilage and synovium remains insufficiently defined. This study tested the hypothesis that increasing intra-articular gentamicin concentration is associated with greater histopathological cartilage damage and synovial inflammation in a rabbit knee model.
Methods:
A pure experimental in vivo post-test-only control study was conducted in 28 male New Zealand white rabbits. Animals were randomized into four groups ( n = 7/group): Sham control receiving 2 mL of 0.9% sodium chloride and three treatment groups receiving 2 mL of intra-articular gentamicin at 0.02, 0.04, or 0.08 mg/mL. After 14 days, the knee joints were harvested. Cartilage was evaluated using the Osteoarthritis Research Society International (OARSI) rabbit histopathology scale and Modified Mankin score, while synovial inflammation was assessed using the Krenn score. Group comparisons used Kruskal–Wallis testing, followed by Mann–Whitney U-tests with Bonferroni correction.
Results:
All animals completed the study. Kruskal–Wallis testing showed significant between-group differences for OARSI, Modified Mankin, and Krenn outcomes (all p < 0.001). Mean ranks increased with gentamicin exposure, and the 0.08 mg/mL group showed the most severe changes across all three scoring systems. After Bonferroni correction ( p < 0.0083), not all pairwise comparisons were significant; comparisons involving the high-dose group remained the most consistently different from control or lower-dose groups.
Conclusion:
Within the limits of this short-term rabbit model, higher intra-articular gentamicin concentration was associated with greater histopathological cartilage deterioration and synovial inflammation at 14 days. These preclinical findings should not be directly translated into human dosing recommendations without pharmacokinetic and longer-term confirmatory studies.