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Published on: June 8, 2014
Mechanisms Underlying Medication-Related Osteonecrosis of the Jaw
Kyeongho Lee1, Kihun Kim2,3, June Yeon Kim1
1Department of Oral Histology and Developmental Biology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, Korea.
Objective:
Medication-related osteonecrosis of the jaw (MRONJ) is a rare but debilitating disease characterized by a progressive necrosis of jaw bones in patients who have received anti-resorptive or anti-angiogenic therapies. Unfortunately, we still have no validated preventive or pharmaceutical interventions to help these patients, primarily due to our limited understanding of MRONJ pathogenesis. Here, we offer an extensive review of recent studies relevant to MRONJ pathogenesis. We present a hypothesis regarding the coupling of bone resorption and angiogenesis that relies on osteoblast-derived, matrix-bound vascular endothelial growth factors to explain why ONJ is associated with both anti-resorptive and anti-angiogenic agents.
Methods:
A narrative review was conducted by searching databases, including PubMed, Scopus, Google Scholar, and Web of Science, to retrieve relevant reports.
Results:
Reduced bone resorption leads to reduced angiogenesis, and vice versa, creating a vicious cycle that ultimately results in ischemic necrosis of the jaw. Additionally, we suggest that reduced angiogenesis, induced by anti-resorptive or anti-angiogenic agents, aggravates bacterial infection-induced bone necrosis, explaining why the jaw bone is particularly susceptible to necrosis.
Conclusion:
Our novel hypothesis will facilitate the advancement of future research and the development of more targeted approaches to managing MRONJ.
Insights
Medication-related osteonecrosis of the jaw (MRONJ) pathogenesis involves a cycle of reduced bone resorption and angiogenesis. This vicious cycle, exacerbated by certain therapies, leads to jaw bone necrosis.
Area of Science:
- Oral and Maxillofacial Surgery
- Oncology
- Pharmacology
Background:
- Medication-related osteonecrosis of the jaw (MRONJ) is a severe condition affecting patients on anti-resorptive or anti-angiogenic therapies.
- Current understanding of MRONJ pathogenesis is limited, hindering the development of effective preventive and therapeutic strategies.
- Jaw bone necrosis is a significant complication associated with these medical treatments.
Purpose of the Study:
- To review recent research on MRONJ pathogenesis.
- To propose a novel hypothesis explaining the link between anti-resorptive/anti-angiogenic therapies and MRONJ.
- To elucidate the role of coupled bone resorption and angiogenesis in MRONJ development.
Main Methods:
- A comprehensive narrative review of scientific literature was performed.
- Databases searched include PubMed, Scopus, Google Scholar, and Web of Science.
- Relevant studies focusing on MRONJ pathogenesis were systematically retrieved.
Main Results:
- A proposed hypothesis links reduced bone resorption and angiogenesis, creating a detrimental cycle.
- This cycle, driven by osteoblast-derived vascular endothelial growth factors, explains MRONJ development.
- Reduced angiogenesis potentiates bacterial infection-induced necrosis, particularly in the jaw bone.
Conclusions:
- The novel hypothesis provides a framework for understanding MRONJ pathogenesis.
- This understanding is crucial for developing targeted preventive and pharmaceutical interventions for MRONJ.
- Future research can build upon this hypothesis to advance MRONJ management.
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