Evaluating Knee Osteoarthritis Induction Methods in Small Translational Animal Models From 1970-2025: A Comprehensive Systematic Review Publisher



Arabzadeh A ; Mossavarali S ; Tavakoli GM ; Mirzaei K ; Tavakoli AM ; Feeley BT ; Nabian MH
Source: Archives of Bone and Joint Surgery Published:2026

Abstract

Objectives: This approaches, for inducing knee osteoarthritis (KOA) in rabbit and rodent models. It also summarizes data study evaluates surgical, mechanical, chemical, genetic, and diet-induced methods, as well as combination-based on post-intervention time points for KOA development, the duration required for osteophyte formation, KOA scoring systems, and relevant histopathological findings. Methods: A systematic search of PubMed, Scopus, and Web of Science (from 1970 to February 2025) was conducted using the PICO framework, focusing on animal models (rabbits and rodents), osteoarthritis induction methods, comparative efficacy, and relevant outcomes. Extracted variables included model characteristics, interventions, and KOA-related findings. The risk of bias was assessed using the Cochrane risk-of-bias tool and the ROBINS-I tool. Results: After screening 5,702 records, 98 studies met the inclusion criteria. Surgical (n = 34), chemical (n = 15), genetic (n = 13), mechanical (n = 19), and high-fat diet–induced (n = 6) models, as well as combination approaches, were reviewed. Among surgical techniques, anterior cruciate ligament transection (ACLT) and medial meniscus destabilization (DMM) were the most frequently used, whereas monosodium iodoacetate (MIA) was the predominant chemical inducer. Genetic models primarily involved gene deletions or mutations in C57BL/6 mice. Mechanical induction methods included joint loading, treadmill running, and immobilization. Histological evaluation—most commonly using the Mankin and Osteoarthritis Research Society International (OARSI) scoring systems—was the predominant approach for KOA assessment, while micro –computed tomography (micro-CT) was employed in selected studies. Osteophyte formation was prominent in surgical and specific chemi cal models and was typically observed within 8 weeks post-intervention. Additionally, each induction method exhibited a distinct time course for osteophyte development and the establishment of KOA. Conclusion: Each approach offers distinct advantages for replicating KOA pathology and for facilitating research into disease mechanisms and therapeutic interventions . Level of evidence: N/A (since this study reviews the laboratory/basic science studies). © 2026 Mashhad University of Medical Sciences.