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Study of odontotherapy rerated-osteonecrosis of the jaw following to long-term bisphosphonate application

长期使用双膦酸盐后牙病治疗相关颌骨坏死的研究

基本信息

批准号：
18592162
负责人：
DEYAMA Yoshiaki
金额：
$ 2.49万
依托单位：
Hokkaido University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18592162/
关键词：
bisphosphonate osteonecrosis odontotherapy 顎骨壞死

项目摘要

Intravenous bisphosphonates are primarily used and effective in the treatment and management of cancer-related conditions. These include hypercalcemia of malignancy, skeletal-related events associated with bone metastases in the context of solid tumors such as breast cancer, prostate cancer, and lung cancer, and in the management of lytic lesions in the setting of multiple myeloma. Oral bisphosphonates are approved to treat osteoporosis and are frequently used to treat osteopenia as well. They are also used for a variety of less common conditions such as Paget's disease of bone, and osteogenesis imperfecta of childhood. Recently, cases of nonhealing exposed, necrotic bone in the maxillofacial region in patients treated with intraveneous bisphosphonates, pamidronate and zoledronic acid, have been recognized and reported. To date, the incidence and pathophysiology of osteonecrosis of the jaw (ONJ). In this study, we aimed to elucidate the mechanism of ONJ.ONJ typically appears as an area of exposed alveolar bone that can occur in the mandible or the maxilla. We hypothesis that pathogen in oral cavity might be involved in the etiology of ONJ, and focused to toll like receptors (TLRs), which recognize microviral antigens to provoke innate immunity and establish adaptive immunity.TLR3 stably expressed in osteoblastic MC3T3-E1 cells. Poly (I):poly (C) induced interferon-β (IFN-β) mRNA, and which enhanced TLR3 expression in autocrin manner via IFN-α/β receptor, IFNAR, following by STAT1 phosphorylation.LPS treatment decrease in cell viability in pamidronate-pretreated macrophage-like RAW 264 cells. Moreover, high concentration of pamidronate and zoledronic acid suppressed inflammatory cytokines, such as interleukin-1β and tumor necrosis factor-α. High concentration Bps might suppress innate immunity system in the osteoblasts.

静脉注射双磷酸盐主要用于治疗和管理癌症相关疾病并有效。这些包括恶性肿瘤的高钙血症、乳腺癌、前列腺癌和肺癌等实体瘤中与骨转移相关的骨骼相关事件，以及多发性骨髓瘤中溶解性病变的治疗。口服双膦酸盐被批准用于治疗骨质疏松症，并且也经常用于治疗骨质减少症。它们还用于治疗各种不太常见的疾病，例如佩吉特骨病和儿童成骨不全症。最近，已经发现并报道了接受静脉注射双膦酸盐、帕米膦酸盐和唑来膦酸治疗的患者出现颌面部骨暴露、坏死且无法愈合的病例。迄今为止，颌骨坏死（ONJ）的发病率和病理生理学。在这项研究中，我们旨在阐明 ONJ 的机制。ONJ 通常表现为下颌骨或上颌骨中暴露的牙槽骨区域。我们假设口腔中的病原体可能与ONJ的病因有关，并集中于Toll样受体（TLR），其识别微病毒抗原以激发先天免疫并建立适应性免疫。TLR3在成骨细胞MC3T3-E1细胞中稳定表达。 Poly (I):poly (C) 诱导干扰素-β (IFN-β) mRNA，并通过 IFN-α/β 受体、IFNAR 以自分泌方式增强 TLR3 表达，随后 STAT1 磷酸化。LPS 处理会降低帕米膦酸预处理的巨噬细胞样 RAW 264 细胞中的细胞活力。此外，高浓度的帕米膦酸和唑来膦酸可抑制炎症细胞因子，例如白细胞介素-1β和肿瘤坏死因子-α。高浓度的 Bps 可能会抑制成骨细胞的先天免疫系统。