Lee Kyeongho, Kim Kihun, Kim June Yeon, Kim Jin-Woo, Kang Young-Hoon, Kim Yun Hak, Kim Sung-Jin
Department of Oral Histology and Developmental Biology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, Korea.
Department of Biomedical Informatics, School of Medicine, Pusan National University, Yangsan, Korea.
Oral Dis. 2025 Apr;31(4):1073-1083. doi: 10.1111/odi.15198. Epub 2024 Nov 18.
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.
A narrative review was conducted by searching databases, including PubMed, Scopus, Google Scholar, and Web of Science, to retrieve relevant reports.
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.
Our novel hypothesis will facilitate the advancement of future research and the development of more targeted approaches to managing MRONJ.
药物相关性颌骨坏死（MRONJ）是一种罕见但使人衰弱的疾病，其特征为接受抗吸收或抗血管生成治疗的患者颌骨出现进行性坏死。不幸的是，我们仍然没有经过验证的预防或药物干预措施来帮助这些患者，主要原因是我们对MRONJ发病机制的了解有限。在此，我们对近期与MRONJ发病机制相关的研究进行了全面综述。我们提出了一个关于骨吸收与血管生成耦合的假说，该假说依赖于成骨细胞衍生的、与基质结合的血管内皮生长因子，以解释为什么ONJ与抗吸收和抗血管生成药物均有关联。
通过检索包括PubMed、Scopus、谷歌学术和科学网在内的数据库进行叙述性综述，以检索相关报告。
骨吸收减少导致血管生成减少，反之亦然，从而形成恶性循环，最终导致颌骨缺血性坏死。此外，我们认为抗吸收或抗血管生成药物诱导的血管生成减少会加重细菌感染诱导的骨坏死，这解释了为什么颌骨特别容易发生坏死。
我们的新假说将促进未来研究的进展，并推动开发更具针对性的方法来管理MRONJ。
