The Incidence of Medication-Related Osteonecrosis of the Jaws (Mronj) in Rodent Animal Models: A Systematic Review and Meta-Analysis

This systematic review with meta-analysis aimed to identify the main factors influencing the incidence of medication-related osteonecrosis of the jaws (MRONJ) in rodent models. A systematic search of experimental studies involving rat and mouse models of MRONJ was conducted across multiple databases up to April 2025. Risk of bias was assessed using Systematic Review Center for Laboratory animal Experimentation (SYRCLE) tool. Primary outcomes were the incidence of histological osteonecrosis and/or exposed bone or fistula in the oral cavity. A total of 119 studies were included, with 105 were eligible for meta-analysis. The pooled incidence of histological osteonecrosis was 28.60% (95% CI 20.24%–37.61%; I² = 90.3%) in rats and 23.81% (95% CI 8.24%–43.05%; I² = 88.6%) in mice. The overall incidence of bone exposure was 19.96% (95% CI 13.20%–27.50%; I² = 88.9%) in rats and 8.6% (95% CI 3.2%–15.5%; I² = 75.7%) in mice. Across both species, the MRONJ induction protocol and cumulative zoledronic acid (ZOL) dose were the main determinants of histological osteonecrosis, with higher incidences observed in ZOL plus tooth extraction protocols. In rats, the highest bone exposure rates occurred in ZOL-plus-extraction protocols associated with bone regularization, infection, or dexamethasone. In mice, greater bone exposure was associated with ZOL combined with cyclophosphamide or dexamethasone. Meta-regression models explained up to 78% of between-study heterogeneity. Statistically significant publication bias was detected only for bone exposure in rats. The induction protocol and ZOL dose are critical determinants of MRONJ incidence in rodent models. • Induction protocol and zoledronic acid dose determine MRONJ incidence in rodents • Zoledronic acid plus tooth extraction yields the highest MRON rates • Inflammatory and immunosuppressive cofactors increase bone exposure incidence • Meta-regression explained up to 78% of between-study heterogeneity • Results support standardization of experimental MRONJ rodents models