Chemotherapeutic and antiresorptive combination therapy suppressed lymphangiogenesis and induced osteonecrosis of the jaw-like lesions in mice

摘要: Osteonecrosis of the jaw (ONJ) is a serious adverse event that occurs predominantly in patients on both antiresorptive and antineoplastic therapies. However, how these combination therapies are connected to high frequency ONJ this particular patient population unclear. This study's aim was determine mechanism associated with therapy antiresorptives chemotherapeutics. Mice received zoledronic acid (ZA) conjunction melphalan or dexamethasone. The maxillary first molars were extracted 3 weeks after initiation treatment wound healing assessed at 4 post-extractions using microcomputed tomography immunohistochemistry. receiving ZA developed ONJ-like lesions, while lesions not found mice monotherapy, characterized by lack epithelium, exposed necrotic bone, severe inflammatory cell infiltration, minimal bone formation. Fluorescent immunohistochemistry showed lymphatic vessel formation significantly suppressed concomitant decrease F4/80(+) macrophages expressing vascular endothelial growth factor C (VEGFC). Interestingly, lymphatics also draining lymph nodes melphalan. Thus, lymphangiogenesis strongly development current study. Since critical resolution inflammation during healing, control may serve as potential strategy prevent ONJ.