Department Applied Prosthodontics, Institute of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Department of Prosthetic Dentistry, Institute of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Gerodontology. 2019 Dec;36(4):313-324. doi: 10.1111/ger.12416. Epub 2019 Aug 2.
The aim of this comprehensive systematic review and meta-analysis was to investigate the pathology and pathogenesis of medication-related osteonecrosis of the jaw (MRONJ) in rodents.
Medication-related osteonecrosis of the jaw occurs in patients taking antiresorptive drugs, such as bisphosphonates and denosumab, and anti-angiogenesis agents. However, there is limited information about the pathology of MRONJ at the clinical level. Moreover, no information about the exact mechanisms of MRONJ is clinically available.
The PubMed, SCOPUS and Medline databases were used to search for relevant articles up to April 2018 by two independent reviewers. A systematic review and meta-analysis were performed.
Of the 1841 studies, 10 articles met the eligibility criteria. The most commonly observed pathology of MRONJ-like lesions was exposed bone without epithelial coverage, decreases in the number of osteocytes and increases in necrotic bone with more empty lacunae. No definitive pathogenesis of MRONJ-like lesions was found. Both zoledronic acid (ZA) monotherapy and ZA/chemotherapeutic and/or dexamethasone combination therapy were significant high-risk factors for developing MRONJ-like lesions (P < 0.00001 and P < 0.0001, respectively).
Based on rodent studies, common pathological findings were extracted in bisphosphonate-related ONJ (BRONJ)-like lesions, whereas no definitive pathogenesis was identified. There is no information about the pathology and pathogenesis of denosumab-related ONJ. These findings clearly suggest that accumulation of scientific evidence based on animal studies is absolutely necessary to explore the pathology and pathogenesis of MRONJ in humans. ZA administration would be a significant risk factor for developing BRONJ-like lesions.
本全面系统评价和荟萃分析旨在研究啮齿动物药物相关性颌骨坏死（MRONJ）的病理学和发病机制。
药物相关性颌骨坏死发生在服用抗吸收药物（如双磷酸盐和地舒单抗）和抗血管生成药物的患者中。然而，在临床水平上，关于 MRONJ 的病理学信息有限。此外，临床上尚无关于 MRONJ 确切发病机制的信息。
两位独立的审查员使用 PubMed、SCOPUS 和 Medline 数据库检索截至 2018 年 4 月的相关文章。进行了系统评价和荟萃分析。
在 1841 项研究中，有 10 项符合纳入标准。MRONJ 样病变最常观察到的病理学表现为暴露的无上皮覆盖的骨，骨细胞数量减少，坏死骨增多，有空腔。未发现明确的 MRONJ 样病变发病机制。唑来膦酸（ZA）单药治疗和 ZA/化疗和/或地塞米松联合治疗均为发生 MRONJ 样病变的显著高危因素（P<0.00001 和 P<0.0001）。
基于啮齿动物研究，从双磷酸盐相关性颌骨坏死（BRONJ）样病变中提取了常见的病理发现，但未确定明确的发病机制。尚无关于地舒单抗相关性颌骨坏死的病理学和发病机制的信息。这些研究结果清楚地表明，基于动物研究积累科学证据对于探索人类 MRONJ 的病理学和发病机制是绝对必要的。ZA 给药可能是发生 BRONJ 样病变的显著危险因素。
