An evidence-guided review of preclinical strategies to counteract medication-related osteonecrosis of the jaw. What do rodent studies tell us?

Abstract

Abstract Medication-related osteonecrosis of the jaw (MRONJ) is an uncommon but potentially serious complication associated with antiresorptive and antiangiogenic therapies, such as bisphosphonates and denosumab. Despite increasing clinical awareness, the pathophysiology of MRONJ remains poorly understood, and no universally accepted preventive strategies are currently available. Preclinical animal studies have served as a cornerstone for investigating potential preventive and therapeutic approaches, offering valuable insights into disease onset, progression, and intervention timing. This narrative, scoping-style review critically examines and maps the available preclinical evidence on preventive and therapeutic strategies aimed at mitigating MRONJ risk, with an emphasis on animal models that simulate clinical conditions. We methodologically explore and compare a wide range of proposed interventions, including laser and photobiomodulation therapies, ozone application, antibiotics, anti-inflammatory agents, natural compounds, and biologics such as bone morphogenetic proteins, mesenchymal stem cells, and platelet-rich plasma. The efficacy of these interventions is discussed in relation to their impact on inflammation, angiogenesis, bone remodeling, microbial control, and soft tissue healing. Among the most promising strategies, low-level laser therapy and the use of mesenchymal stem cells consistently demonstrated improved healing outcomes and reduced necrotic bone exposure in rodent models. Anti-inflammatory medications and natural compounds, such as resveratrol, showed favorable modulation of the inflammatory microenvironment, while some antibiotics were effective in reducing bacterial burden when administered at appropriate doses and timings. However, discrepancies in study design, animal species, drug administration protocols, and outcome measures often limit direct comparisons and translational conclusions. Taken together, the animal literature supports the potential of multimodal preventive strategies, particularly when interventions are applied before or immediately after dentoalveolar trauma. Nonetheless, further standardization of experimental models and validation in clinical settings are urgently needed. This review highlights the strengths and limitations of current preclinical evidence and proposes directions for future research to bridge the gap between bench and bedside in the management of MRONJ.