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

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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.