Kim Soung Min, Eo Mi Young, Cho Yun Ju, Kim Yeon Sook, Lee Suk Keun
Department of Oral and Maxillofacial Surgery, School of Dentistry, Dental Research Institute, Seoul National University, Seoul, South Korea.
Department of Dental Hygiene, College of Health Sciences, Cheongju University, Cheongju, South Korea.
Eur Arch Otorhinolaryngol. 2017 Sep;274(9):3485-3495. doi: 10.1007/s00405-017-4657-x. Epub 2017 Jun 24.
Recurrent bacterial infections in cases of bisphosphonate-related osteonecrosis of jaw (BRONJ) frequently occur. Therefore, BRONJ are usually treated by radical saucerization followed by intensive antibiotic medications without bisphosphonate therapy. The postoperative exudate (POE) from BRONJ lesions may directly indicate the inflammatory status of osteomyelitis in patients, but so far, the POE has rarely been examined for its expression of various cytokines and wound healing proteins. A total of 27 cases of BRONJ, which involved the mandible, were selected and their individual POE collected 6 h, 1 day, and 2 days after surgical intervention was analyzed by immunoprecipitation high performance liquid chromatography (IP-HPLC). The different protein expressions in the BRONJ POE were compared with findings from ten cases of chronic mandibular osteomyelitis (CMO) exudate as the control group. For the protein expressions for inflammation, osteogenesis, and angiogenesis, in the 6 h POE sample, the BRONJ exudate exhibited more expression of IL-10, IL-28, OPG, and osteocalcin, but less expression of TNFα and LL-37 than the control. In the 1 day POE sample, the BRONJ exudate showed more expression of TNFα, IL-6, 8, 12, 28, α1-antitrypsin, VEGF-A, and VEGF-C, but less expression of CD68, lysozyme, bFGF, RANKL, bFGF, and ALP than the control. In the 2 day POE sample, the BRONJ exudate consistently showed more expression of LL-37, β-defensin-1, and VEGF-A than the control. The present BRONJ POE revealed the rapid progress of bony wound healing through increased molecular signaling for inflammation, angiogenesis, and osteogenesis compared to the control. Therefore, it was suggested that the POE obtained from the postoperative bony lesions should be collected and analyzed by the IP-HPLC method to predict the prognosis of seriously complicated inflammatory bony diseases such as BRONJ.
双膦酸盐相关颌骨坏死（BRONJ）病例中经常会反复发生细菌感染。因此，BRONJ通常采用根治性碟形清创术治疗，随后进行强化抗生素治疗，不进行双膦酸盐治疗。BRONJ病变的术后渗出物（POE）可能直接表明患者骨髓炎的炎症状态，但到目前为止，很少对POE进行各种细胞因子和伤口愈合蛋白表达的检测。本研究选取了27例累及下颌骨的BRONJ病例，通过免疫沉淀高效液相色谱法（IP-HPLC）分析了手术干预后6小时、1天和2天收集的个体POE。将BRONJ POE中的不同蛋白表达与作为对照组的10例慢性下颌骨骨髓炎（CMO）渗出物的检测结果进行比较。对于炎症、骨生成和血管生成的蛋白表达，在术后6小时的POE样本中，BRONJ渗出物中IL-10、IL-28、骨保护素（OPG）和骨钙素的表达高于对照组，但TNFα和LL-37的表达低于对照组。在术后1天的POE样本中，BRONJ渗出物中TNFα、IL-6、8、12、28、α1-抗胰蛋白酶、血管内皮生长因子A（VEGF-A）和血管内皮生长因子C（VEGF-C）的表达高于对照组，但CD68、溶菌酶、碱性成纤维细胞生长因子（bFGF）、核因子κB受体活化因子配体（RANKL）和碱性磷酸酶（ALP）的表达低于对照组。在术后2天的POE样本中，BRONJ渗出物中LL-37、β-防御素-1和VEGF-A的表达持续高于对照组。与对照组相比，目前的BRONJ POE显示通过增加炎症、血管生成和骨生成的分子信号，骨伤口愈合进展迅速。因此，建议通过IP-HPLC方法收集和分析术后骨病变获得的POE，以预测BRONJ等严重复杂炎症性骨疾病的预后。
