- Article
Background/Objectives: Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse effect associated mainly with potent antiresorptive therapy. Reliable preclinical models are needed to evaluate preventive strategies for dentoalveolar surgery in patients at risk. This study aimed to establish a standardized rabbit model of MRONJ for subsequent testing of a local preventive device. Methods: Twenty-four adult male New Zealand White rabbits were randomly allocated to three groups (n = 8 each): an experimental group receiving intravenous zoledronic acid (0.05 mg/kg once weekly for 20 weeks) with extraction of the left mandibular first incisor (I1) at week 12; a zoledronic-acid control group receiving the same drug regimen without extraction; and a sham group receiving weekly intravenous saline with I1 extraction at week 12. At study termination, osteonecrosis was assessed clinically by cone-beam computed tomography (CBCT) and histopathologically. Group differences were analyzed using two-tailed Fisher’s exact tests. Results: In the experimental group, osteonecrosis was identified in 8/8 animals by histopathology and clinical examination and in 6/8 by CBCT. In the zoledronic-acid control group, histopathologic and clinical evidence was present in 1/8 animals, while CBCT was negative in all animals. No osteonecrosis was detected in the sham group. The experimental group differed significantly from both comparator groups across all three assessment modalities after Bonferroni correction (adjusted p ≤ 0.042). Conclusions: Weekly zoledronic acid combined with tooth extraction produced a high and consistent incidence of jaw osteonecrosis in rabbits, whereas zoledronic acid alone and extraction without zoledronic acid produced few or no lesions. This model may provide a practical platform for preclinical evaluation of local preventive interventions for MRONJ.
14 November 2026







