Bullock George, Miller Cheryl A, McKechnie Alasdair, Hearnden Vanessa
Department of Materials Science and Engineering, Kroto Research Institute, The University of Sheffield, Sheffield, United Kingdom.
School of Clinical Dentistry, The University of Sheffield, Sheffield, United Kingdom.
Front Oral Health. 2022 Feb 9;2:822411. doi: 10.3389/froh.2021.822411. eCollection 2021.
Medication-related osteonecrosis of the jaw (MRONJ) is a growing problem without an effective treatment, presenting as necrotic bone sections exposed via lesions in the overlying soft tissue. There is currently a lack of clarity on how the factors involved in MRONJ development and progression contribute to disease prognosis and outcomes. Bisphosphonates (BPs), the most common cause of MRONJ, affect bone remodeling, angiogenesis, infection, inflammation and soft tissue toxicity, all of which contribute to MRONJ development. This article reviews the cellular mechanisms through which BPs contribute to MRONJ pathology, with a focus on the effects on cells of the oral mucosa. BPs have been shown to reduce cell viability, reduce proliferation, and increase apoptosis in oral keratinocytes and fibroblasts. BPs have also been demonstrated to reduce epithelial thickness and prevent epithelial formation in three-dimensional tissue engineered models of the oral mucosa. This combination of factors demonstrates how BPs lead to the reduced wound healing seen in MRONJ and begins to uncover the mechanisms through which these effects occur. The evidence presented here supports identification of targets which can be used to develop novel treatment strategies to promote soft tissue wound healing and restore mucosal coverage of exposed bone in MRONJ.
药物相关性颌骨坏死（MRONJ）是一个日益严重且缺乏有效治疗方法的问题，表现为坏死骨段通过覆盖其上的软组织病变暴露出来。目前，对于MRONJ发生和发展过程中涉及的因素如何影响疾病预后和结局尚不清楚。双膦酸盐（BP）是MRONJ最常见的病因，它会影响骨重塑、血管生成、感染、炎症和软组织毒性，所有这些都与MRONJ的发生有关。本文综述了BP导致MRONJ病理改变的细胞机制，重点关注其对口腔黏膜细胞的影响。研究表明，BP可降低口腔角质形成细胞和成纤维细胞的细胞活力、减少增殖并增加凋亡。在口腔黏膜的三维组织工程模型中，BP还被证明可减少上皮厚度并阻止上皮形成。这些因素共同表明了BP如何导致MRONJ中伤口愈合能力下降，并开始揭示这些影响发生的机制。本文提供的证据支持确定可用于开发新治疗策略的靶点，以促进软组织伤口愈合并恢复MRONJ中暴露骨的黏膜覆盖。
