Medication-related osteonecrosis of the jaw (MRONJ) is primarily associated with administering antiresorptive or antiangiogenic drugs. Despite significant research on MRONJ, its pathogenesis and effective treatments are still not fully understood. Animal models can be used to simulate the pathophysiological features of MRONJ, serving as standardized in vivo experimental platforms to explore the pathogenesis and therapies of MRONJ. Rodent models exhibit excellent effectiveness and high reproducibility in mimicking human MRONJ, but classical methods cannot achieve a complete replica of the pathogenesis of MRONJ. Modified rodent models have been reported with improvements for better mimicking of MRONJ onset in clinic. This review summarizes representative classical and modified rodent models of MRONJ created through various combinations of systemic drug induction and local stimulation and discusses their effectiveness and efficiency. Currently, there is a lack of a unified assessment system for MRONJ models, which hinders a standard definition of MRONJ-like lesions in rodents. Therefore, this review comprehensively summarizes assessment systems based on published peer-review articles, including new approaches in gross observation, histological assessments, radiographic assessments, and serological assessments. This review can serve as a reference for model establishment and evaluation in future preclinical studies on MRONJ.
Animals ; Bisphosphonate-Associated Osteonecrosis of the Jaw/drug therapy* ; Bone Density Conservation Agents/adverse effects* ; Diphosphonates/therapeutic use* ; Humans ; Reproducibility of Results ; Rodentia

[Abstract] Objective: To investigate the short-term clinical efficacy and safety of intraperitoneal perfusion of natural killer (NK) cells in the treatment of ovarian cancer with ascites. Methods: The clinical data of 15 ovarian cancer patients with ascites effusion, who received NK cell perfusion in the Qinhuai Medical District of the General Hospital of Eastern Theater Command from November 2016 to January 2019, were analyzed. The peripheral blood was collected to isolate the peripheral blood mononuclear cells, and to further obtain the NK cells after culture. NK cell suspension was intraperitoneally perfused into the abdominal cavity (no less than 2×109 cells/ time). The volume of peritoneal effusion, the level of serum tumor marker CA-125, the level of serum cytokines IL-2, INF-γ and TNF-α as well as the changes in peripheral blood lymphocyte subsets were detected before and after the treatment; Moreover, the clinical efficacy and adverse reactions were observed. Results: The effective rate of intraperitoneal perfusion of NK cells was 66.7%, and there were no obvious treatment-related adverse reactions. Compared with before treatment, the serum tumor marker CA-125 level significantly decreased after treatment (P<0.05), and the levels of IL-15, IFN-γ and TNF-α increased significantly (P<0.05 or P<0.01), while there was no significant changes in peripheral blood lymphocyte subsets (all P>0.05). Conclusion: Intraperitoneal infusion of NK cells in the treatment of ovarian cancer associated peritoneal effusion has a good short-term clinical efficacy with little adverse reactions, which is a promising method for the treatment of cancerous peritoneal effusion.