双膦酸盐相关性下颌骨坏死（BRONJ）是一种严重的并发症，发生在患有骨质疏松症或转移性骨癌并接受双膦酸盐治疗的患者中。目前还没有有效的治疗和预防BRONJ的策略。绿色蔬菜中富含无机硝酸盐，据报道具有多种保护作用。为了研究膳食硝酸盐对小鼠BRONJ样病变的影响，我们利用了一个早已建立的小鼠BRONJ模型并进行牙齿拔除。具体地，通过水饮食提前组织4 mM的硝酸钠，以评估BRONJ的短期和长期效果。 zoledronate注射可以诱发牙齿拔除窝的严重愈合抑制，而预处理膳食硝酸盐的添加可以通过减少单核细胞坏死和炎性细胞因子的产生来缓解抑制作用。 机理上，硝酸盐的摄入增加了血浆一氧化氮水平，通过RIPK3依赖通路下调脂类代谢，从而减轻了单核细胞坏死。我们的研究发现膳食硝酸盐可以抑制BRONJ中的单核细胞坏死，调节骨免疫微环境，并促进骨损伤后的骨重塑。该研究有助于理解zoledronate的免疫病理机制，并支持膳食硝酸盐在临床预防BRONJ中的可行性。 © 2023年作者。由欧洲细胞增殖学会和约翰-威利公司出版的“细胞增殖”出版。

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious complication that occurs in patients with osteoporosis or metastatic bone cancer treated with bisphosphonate. There is still no effective treatment and prevention strategy for BRONJ. Inorganic nitrate, which is abundant in green vegetables, has been reported to be protective in multiple diseases. To investigate the effects of dietary nitrate on BRONJ-like lesions in mice, we utilized a well-established mouse BRONJ model, in which tooth extraction was performed. Specifically, 4 mM sodium nitrate was administered in advance through drinking water to assess the short- and long-term effects on BRONJ. Zoledronate injection could induce severe healing inhibition of the tooth extraction socket, while addition of pretreating dietary nitrate could alleviate the inhibition by reducing monocyte necrosis and inflammatory cytokines production. Mechanistically, nitrate intake increased plasma nitric oxide levels, which attenuated necroptosis of monocytes by downregulating lipid and lipid-like molecule metabolism via a RIPK3 dependent pathway. Our findings revealed that dietary nitrate could inhibit monocyte necroptosis in BRONJ, regulate the bone immune microenvironment and promote bone remodelling after injury. This study contributes to the understanding of the immunopathogenesis of zoledronate and supports the feasibility of dietary nitrate for the clinical prevention of BRONJ.© 2023 The Authors. Cell Proliferation published by European Cell Proliferation Society and John Wiley & Sons Ltd.