Histologic and histomorphometric features of bisphosphonate-related osteonecrosis of the jaws: An analysis of 31 cases with confocal laser scanning microscopy
Histologic and histomorphometric features of bisphosphonate-related osteonecrosis of the jaws: An analysis of 31 cases with confocal laser scanning microscopy
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DOI：
10.1016/j.bone.2009.05.008
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发表时间：
2009-09-01
期刊：
影响因子：
4.1
通讯作者：
Maiorano, E.
中科院分区：
文献类型：
--
作者：
Favia, G.;Pilolli, G. P.;Maiorano, E.
简介：接受双膦酸盐治疗的患者可能出现颌骨病变，主要表现为骨坏死。到目前为止，还没有针对这种病变提出有效的治疗方法，对于这种实体的可能发病机制也没有统一的概念。方法：研究人群包括31例双膦酸盐相关性颌骨骨坏死患者和10例健康供体。所有患者均行颌骨活检，组织标本分为两部分，其中一部分进行固定、脱钙和常规处理。第二部分是固定的，嵌入在甲基丙烯酸酯中，切割并用亚甲基蓝和碱性品红染色。所有样本都进行了光镜和共聚焦显微镜检查，并进行了组织形态学分析，以评估两组样本之间骨结构的差异。结果：在ONJ患者中发现了三种主要的组织学模式：1 -急性炎症活动区，以软组织为主，炎症浸润，脱细胞坏死碎片，薄壁血管扩张，强烈嗜碱性骨刺呈扇形边界，骨吸收突出。2 -以骨结构为主的区域表现为广泛的脱细胞坏死隔离和含有炎症细胞的大扇形哈弗氏管。3非坏死区骨量较大，骨小梁厚度增加，骨间骨沉积，哈弗氏管更小、更少，在比较ONJ患者和对照组样本的组织形态学数据后，这些差异更为明显。此外，治疗患者的板层骨由含有较大骨细胞的较大骨块组成。在这些区域可以很容易地检测到两种不同类型的新形成的编织骨，主要表现为离心空间取向。在接受治疗的患者的炎症区检测到的破骨细胞样细胞很小且含有很少的细胞核，但在同一患者的非坏死骨中很少或没有。结论：这些特征表明，在接受双膦酸盐治疗的患者中，出现了一种特殊的骨重塑过程，即破骨细胞活性不足，随后新形成的骨沉积。后者将由更厚的骨骼结构组成，由更少的血管供应。因此，在代谢需求增加的情况下，这种改良的骨骼将得不到足够的血液供应，从而导致坏死和重复感染。(C) 2009爱思唯尔公司版权所有。
Introduction: Patients undergoing bisphosphonate therapies may develop jaw lesions, mainly consisting in bone necrosis. No effective treatment has been proposed so far for such lesions, nor is there a uniform concept on the possible pathogenesis of this entity.Methods: The study population included 31 patients with bisphosphonate-related osteonecrosis of the jaws and 10 healthy donors. All patients underwent to jaw bone biopsy and the tissue samples were divided into two parts, one of which was fixed, decalcified and routinely processed. The second part was fixed, embedded in methylmetacrylate, cut and stained with methylene blue and basic fuchsine. All samples were subjected to light and confocal microscopic examination and to histomorphometric analyses to evaluate differences in bone structure between the two samples groups.Results: Three main histological patterns were identified in ONJ patients: 1 - Areas with active acute inflammation, characterized by predominance of soft tissues, inflammatory infiltrate, acellular necrotic debris, thin-walled and dilated blood vessel, intensely basophilic bone spiculae with scalloped borders showing prominent bone resorption. 2 - Areas characterized by predominance of bony structures showing wide acellular necrotic sequestra and large, scalloped Haversian canals containing inflammatory cells. 3 Non-necrotic areas contained larger amounts of bone, showing increased trabecular thickness, inter-osteonic bone deposition and smaller and fewer Haversian canals, These differences were more evident after comparing the histomorphometrical data of samples from ONJ patients with controls. Also, lamellar bone from treated patients was composed of bigger osteones containing larger osteocytes. Two different types of newly-formed woven bone, mainly showing centrifugal spatial orientation, were easily detectable in these areas. Osteoclast-like cells detected in inflammatory areas from treated patients were small and contained few nuclei, but they were rare to absent in non-necrotic bone from the same patients.Conclusions: These features point at a peculiar process of bone remodeling in patients undergoing bisphosphonate therapy, which showed scarce osteoclastic activity and subsequent deposition of newly-formed bone. The latter would be made up of thicker bone structures supplied by fewer blood vessels. Consequently, in case of increased metabolic requests, this modified bone would not be supported by adequate blood supply, thus leading to necrosis and superinfection. (C) 2009 Elsevier Inc. All rights reserved.