Department of Oncology, Rambam Medical Center, Technion, Haifa, Israel.
Institute of Endocrinology, Diabetes & Metabolism and Department of Internal Medicine C, Rambam Medical Center & RB Rappaport Faculty of Medicine, Technion, Haifa, Israel
J Dent Res. 2015 Feb;94(2):252-60. doi: 10.1177/0022034514560768. Epub 2014 Dec 4.
Medication-related osteonecrosis of the jaw (MRONJ) is a severe devastating complication for which the exact pathogenesis is not completely understood. Multiple systemic and local factors may contribute to the development of MRONJ. A growing body of evidence supports diabetes mellitus (DM) as an important risk factor for this complication; however, the exact mechanism by which DM may promote MRONJ has yet to be determined. The current review elucidates the role of DM in the pathogenesis of MRONJ and the mechanisms by which DM may increase the risk for MRONJ. Factors related to DM pathogenesis and treatment may contribute to poor bone quality through multiple damaged pathways, including microvascular ischemia, endothelial cell dysfunction, reduced remodeling of bone, and increased apoptosis of osteoblasts and osteocytes. In addition, DM induces changes in immune cell function and promotes inflammation. This increases the risk for chronic infection in the settings of cancer and its treatment, as well as antiresorptive medication exposure, thus raising the risk of developing MRONJ. A genetic predisposition for MRONJ, coupled with CYP 450 gene alterations, has been suggested to affect the degradation of medications for DM such as thiazolidinediones and may further increase the risk for MRONJ.
药物相关性下颌骨坏死(MRONJ)是一种严重的破坏性并发症,其确切发病机制尚未完全阐明。多种全身和局部因素可能导致 MRONJ 的发生。越来越多的证据支持糖尿病(DM)是这种并发症的重要危险因素;然而,DM 促进 MRONJ 的具体机制尚未确定。目前的综述阐明了 DM 在 MRONJ 发病机制中的作用,以及 DM 可能增加 MRONJ 风险的机制。与 DM 发病机制和治疗相关的因素可能通过多种受损途径导致骨质量变差,包括微血管缺血、内皮细胞功能障碍、骨重塑减少以及成骨细胞和破骨细胞凋亡增加。此外,DM 会引起免疫细胞功能的变化并促进炎症。这增加了癌症及其治疗以及抗吸收药物暴露情况下慢性感染的风险,从而增加了发生 MRONJ 的风险。MRONJ 的遗传易感性,加上 CYP450 基因突变,被认为会影响 DM 药物如噻唑烷二酮的降解,从而进一步增加 MRONJ 的风险。