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

静脉注射双膦酸盐主要用于治疗和管理癌症相关疾病，并且有效。这些包括恶性高钙血症、实体瘤（如乳腺癌、前列腺癌和肺癌）背景下与骨转移相关的肿瘤相关事件，以及多发性骨髓瘤背景下溶解性病变的管理。口服双膦酸盐被批准用于治疗骨质疏松症，也经常用于治疗骨质减少症。它们也用于各种不太常见的疾病，如佩吉特骨疾病和儿童骨生成障碍。最近，已经认识到并报道了静脉注射双膦酸盐、帕米膦酸盐和唑来膦酸治疗的患者中颌面部区域的不愈合暴露、坏死骨的病例。到目前为止，颌骨骨坏死（ONJ）的发病率和病理生理学。在这项研究中，我们的目的是阐明ONJ的机制。ONJ通常表现为暴露的牙槽骨区域，可以发生在下颌骨或上颌骨。我们推测口腔病原体可能参与ONJ的发病过程，并将研究重点放在Toll样受体（TLRs）上，TLR3在成骨细胞MC3T3-E1中稳定表达。Poly（I）：poly（C）诱导IFN-β mRNA的表达，并通过IFN-α/β受体（IFNAR）和STAT1磷酸化以自分泌方式增强TLR3的表达。高浓度的帕米膦酸二钠和唑来膦酸可抑制IL-1 β和TNF-α等炎性细胞因子的表达。高浓度Bps可抑制成骨细胞的天然免疫系统。

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.