Mesenchymal stem cell therapy for treatment of medication related osteonecrosis of the jaw (MRONJ): A systematic review

Abstract

Background: Medication-related osteonecrosis of the jaw (MRONJ) is a significant adverse effect associated with antiresorptive and antiangiogenic therapies. Therapies utilizing mesenchymal stem cells (MSCs) represent a promising regenerative strategy; however, conventional management methods have shown limited effectiveness. This systematic review aimed to evaluate the effectiveness of MSC-based interventions in preventing and treating MRONJ. Method: A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science to identify studies published from 2011 to 2024. Studies examining MSCs therapy in the context of MRONJ were incorporated according to predefined inclusion and exclusion criteria. Results: Seventeen studies (6 clinical, 11 preclinical) met inclusion criteria. Preclinical models demonstrated that MSCs enhance angiogenesis and bone regeneration, providing mechanistic support for human application. Clinically, 80-90 of patients achieved complete mucosal healing with radiographic evidence of bone regeneration. However, due to species differences in oral microbiome and immunity, animal findings require confirmation in human trials. Conclusion: This review integrates human clinical data with mechanistic insights from preclinical studies. Human evidence shows promising mucosal and bone regeneration, while animal studies elucidate underlying mechanisms-particularly angiogenesis and immunomodulation. Given that animal models cannot replicate the human oral immune environment, these findings should be interpreted as hypothesis-generating. MSC therapy represents a biologically sound but experimental strategy, warranting confirmation through randomized controlled trials.