Micheletti Chiara, DiCecco Liza-Anastasia, Larsson Wexell Cecilia, Binkley Dakota M, Palmquist Anders, Grandfield Kathryn, Shah Furqan A
Department of Materials Science and Engineering McMaster University Hamilton Ontario Canada.
Department of Biomaterials, Sahlgrenska Academy University of Gothenburg Gothenburg Sweden.
JBMR Plus. 2022 Nov 8;6(12):e10693. doi: 10.1002/jbm4.10693. eCollection 2022 Dec.
Medication-related osteonecrosis of the jaw (MRONJ) is a known side effect of bisphosphonates (BPs). Although bacterial infection is usually present, the etiology of MRONJ remains unknown. Here we apply a multimodal and multiscale (micro-to-nano) characterization approach to investigate the interface between necrotic bone and bacteria in MRONJ. A non-necrotic bone sample was used as control. Both necrotic and non-necrotic bone samples were collected from the jaw of a female individual affected by MRONJ after using BPs for 23 years. For the first time, resin cast etching was used to expose bacteria at the necrotic site. The bone-bacteria interface was also resolved at the nanoscale by scanning transmission electron microscopy (STEM). Nanosized particulates, likely corresponding to degraded bone mineral, were often noted in close proximity to or enclosed by the bacteria. STEM also revealed that the bone-bacteria interface is composed of a hypermineralized front fading into a highly disordered region, with decreasing content of calcium and phosphorus, as assessed by electron energy loss spectroscopy (EELS). This, combined with the variation in calcium, phosphorus, and carbon across the necrotic bone-bacteria interface evaluated by scanning electron microscopy (SEM)-energy dispersive X-ray spectroscopy (EDX) and the lower mineral-to-matrix ratio measured by micro-Raman spectroscopy in necrotic bone, indicates the absence of a mineralization front in MRONJ. It appears that the bone-bacteria interface originates not only from uncontrolled mineralization but also from the direct action of bacteria degrading the bone matrix. © 2022 The Authors. published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
药物相关性颌骨坏死（MRONJ）是双膦酸盐（BP）已知的副作用。尽管通常存在细菌感染，但MRONJ的病因仍不清楚。在此，我们应用多模态和多尺度（从微观到纳米）表征方法来研究MRONJ中坏死骨与细菌之间的界面。使用非坏死骨样本作为对照。坏死和非坏死骨样本均取自一名使用BP 23年后患MRONJ的女性个体的颌骨。首次使用树脂铸型蚀刻来暴露坏死部位的细菌。还通过扫描透射电子显微镜（STEM）在纳米尺度上解析了骨-细菌界面。经常在细菌附近或被细菌包围处发现可能对应于降解骨矿物质的纳米颗粒。STEM还显示，骨-细菌界面由一个过度矿化的前沿逐渐过渡到一个高度无序的区域，通过电子能量损失谱（EELS）评估，钙和磷的含量逐渐降低。这与通过扫描电子显微镜（SEM）-能量色散X射线光谱（EDX）评估的坏死骨-细菌界面上钙、磷和碳的变化以及通过微拉曼光谱测量的坏死骨中较低的矿物质与基质比率相结合，表明MRONJ中不存在矿化前沿。看来骨-细菌界面不仅源于不受控制的矿化，还源于细菌降解骨基质的直接作用。© 2022作者。由Wiley Periodicals LLC代表美国骨与矿物质研究学会出版。
