George Estee L, Lin Yi-Ling, Saunders Marnie M
The University of Akron, Olson Research Center 319, 302 E. Buchtel Ave., Akron, OH 44325, USA.
University of California, Los Angeles School of Dentistry, 10833 Le Conte Ave., Los Angeles, CA 90095, USA.
Bone Rep. 2018 Mar 15;8:104-109. doi: 10.1016/j.bonr.2018.03.003. eCollection 2018 Jun.
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 (Aragon-Ching et al., 2009)) 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.
双膦酸盐相关颌骨坏死（BRONJ）是颌骨的一种严重崩解，影响因骨量丢失疾病而接受双膦酸盐（BP）治疗的患者。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（阿拉贡 - 钦等人，2009年））以及骨质疏松症。尽管BRONJ被认为源于骨重塑缺陷——即感觉骨细胞向破骨细胞和成骨细胞发出信号以响应刺激进行骨吸收和形成的复杂过程，但目前对其了解并不完全。此外，拔牙和感染与BRONJ的关联极为密切（池部，2013年）。由于骨细胞高度网络化，在这些危险因素发生过程中多细胞相互作用和机械转导的重要性再怎么强调也不为过。因此，本观点阐述了目前关于BP、机械负荷和炎症对骨重塑以及BRONJ发生影响的研究。我们的研究使我们得出结论，需要改进体外系统，能够充分模拟多细胞通讯并纳入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。
