Bisphosphonate-related osteonecrosis of the jaw: a mechanobiology perspective.
Bisphosphonate-related osteonecrosis of the jaw: a mechanobiology perspective.
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DOI：
10.1016/j.bonr.2018.03.003
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发表时间：
2018-06
期刊：
影响因子：
2.5
通讯作者：
Saunders MM
中科院分区：
文献类型：
--
作者：
George EL;Lin YL;Saunders MM
双膦酸盐相关性颌骨坏死 (BRONJ) 是一种严重的颌骨崩解，影响接受双膦酸盐 (BP) 治疗的以骨质流失为特征的疾病的患者。这些疾病通常是转移性癌症（如多发性骨髓瘤、乳腺癌和前列腺癌）以及骨质疏松症。 BRONJ 尚不完全清楚，尽管人们认为它是由骨重塑的缺陷引起的，骨重塑是感觉骨细胞向破骨细胞和成骨细胞发出信号以响应刺激而吸收和形成骨骼的复杂过程。此外，拔牙和感染绝大多数与 BRONJ 有关（Ikebe，2013）。由于骨细胞高度网络化，因此在这些危险因素发生期间多细胞相互作用和力传导的重要性怎么强调也不为过。因此，这一观点涉及当前关于 BP、机械负荷和炎症对骨重塑和 BRONJ 发育影响的研究。我们的研究使我们得出结论，需要改进体外系统，能够充分重现多细胞通讯，并结合骨细胞机械传感对骨吸收和形成的影响，以阐明 BRONJ 发生的机制。综述了目前 BRONJ 相关辅助因子的研究。血压、负荷和炎症协同作用，形成 BRONJ。辅助因子对口腔重塑的影响知之甚少。骨细胞感知和响应辅助因子的能力可能是 BRONJ 的核心。由于缺乏集成机械传感的多细胞系统，研究受到限制。
Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a dramatic disintegration of the jaw that affects patients treated with bisphosphonates (BPs) for diseases characterized by bone loss. These diseases are often metastasizing cancers (like multiple myeloma, breast cancer and prostate cancer) as well as osteoporosis. BRONJ is incompletely understood, although it is believed to arise from a defect in bone remodeling—the intricate process by which sensory osteocytes signal to osteoclasts and osteoblasts to resorb and form bone in response to stimuli. Further, tooth extraction and infection have been overwhelmingly linked to BRONJ (Ikebe, 2013). Because bone cells are highly networked, the importance of multicellular interactions and mechanotransduction during the onset of these risk factors cannot be overstated. As such, this perspective addresses current research on the effects of BPs, mechanical load and inflammation on bone remodeling and on development of BRONJ. Our investigation has led us to conclude that improved in vitro systems capable of adequately recapitulating multicellular communication and incorporating effects of osteocyte mechanosensing on bone resorption and formation are needed to elucidate the mechanism(s) by which BRONJ ensues. Current research on cofactors implicated in BRONJ is reviewed. BPs, load and inflammation work in tandem to contribute to BRONJ. Effects of cofactors on remodeling in the oral cavity are poorly understood. Osteocytes' ability to sense and respond to cofactors is likely central to BRONJ. Research is limited by a lack of multicellular systems integrating mechanosensing.