Cardemil Carina, Thomsen Peter, Larsson Wexell Cecilia
Department of Biomaterials, Sahlgrenska Academy at University of Gothenburg, Göteborg, Sweden.
Department of Oral and Maxillofacial Surgery, Örebro University Hospital, Örebro, Sweden.
Clin Implant Dent Relat Res. 2015 Oct;17 Suppl 2:e679-91. doi: 10.1111/cid.12307. Epub 2015 Apr 27.
Osteonecrosis of the jaw (ONJ) is a severe complication of bisphosphonate treatment.
A detailed characterization of sampled peri-necrotic jawbone from bisphosphonate-treated patients was performed at tissue and cellular level (histological analyses and gene expression).
Alveolar bone samples were collected from patients with (n = 5) and without ONJ (n = 5). Healthy patients served as controls (n = 10).
The histological analysis demonstrated low to moderate inflammation, displaying areas of inflammatory infiltrate in the bone marrow. Multinuclear giant cells and osteoclasts were found in both groups. Markers of bone formation (alkaline phosphatase, Col1a1, and osteocalcin), bone resorption (receptor activator of NF-kappaB ligand [RANKL], osteoprotegerin [OPG], tartrate-resistant acid phosphatase, and cathepsin K), inflammation (tumor necrosis factor-alpha, interleukin [IL]-1β, and IL-6), angiogenesis (vascular endothelial growth factor A), and apoptosis (Casp3, Casp8, p53, and Smac) were evaluated. Nonparametric statistical tests were used to identify differences between the groups. In patients with ONJ, the expression level of the proinflammatory marker IL-1β was strongly up-regulated compared with controls (p = .040).
A down-regulated expression of Casp8 compared with controls was observed (p = .014) in patients treated with bisphosphonates. The RANKL/OPG ratios were similar in the three groups. The results indicate a need to further investigate the molecular mechanisms involved in the course of ONJ related to antiresorptive treatment.
颌骨坏死（ONJ）是双膦酸盐治疗的严重并发症。
在组织和细胞水平（组织学分析和基因表达）对双膦酸盐治疗患者的坏死周围颌骨样本进行详细表征。
从患有ONJ（n = 5）和未患有ONJ（n = 5）的患者中收集牙槽骨样本。健康患者作为对照（n = 10）。
组织学分析显示炎症程度为低至中度，骨髓中有炎症浸润区域。两组均发现多核巨细胞和破骨细胞。评估了骨形成标志物（碱性磷酸酶、Col1a1和骨钙素）、骨吸收标志物（核因子κB受体活化因子配体[RANKL]、骨保护素[OPG]、抗酒石酸酸性磷酸酶和组织蛋白酶K）、炎症标志物（肿瘤坏死因子-α、白细胞介素[IL]-1β和IL-6）、血管生成标志物（血管内皮生长因子A）和细胞凋亡标志物（Casp3、Casp8、p53和Smac）。使用非参数统计检验来确定组间差异。在患有ONJ的患者中，促炎标志物IL-1β的表达水平与对照组相比强烈上调（p = 0.040）。
在接受双膦酸盐治疗的患者中，观察到与对照组相比Casp8表达下调（p = 0.014）。三组的RANKL/OPG比值相似。结果表明需要进一步研究与抗吸收治疗相关的ONJ病程中涉及的分子机制。
