Increased prevalence of bisphosphonate-related osteonecrosis of the jaw with vitamin D deficiency in rats.
Increased prevalence of bisphosphonate-related osteonecrosis of the jaw with vitamin D deficiency in rats.
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DOI：
10.1002/jbmr.23
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发表时间：
2010-06
影响因子：
6.2
通讯作者：
Nishimura, Ichiro
中科院分区：
文献类型：
--
作者：
Hokugo, Akishige;Christensen, Russell;Chung, Evelyn M.;Sung, Eric C.;Felsenfeld, Alan L.;Sayre, James W.;Garrett, Neal;Adams, John S.;Nishimura, Ichiro
最近有报告称，在接受含氮双膦酸盐治疗的患者中，口腔中的坏死骨暴露是多发性骨髓瘤或骨转移癌治疗方案的一部分。据推测，与癌症患者相关的全身性疾病与拔牙相结合可能会增加颌骨骨坏死（ONJ）的风险。本研究的目的是通过检测这些危险因素的组合来建立双膦酸盐相关ONJ的动物模型。在静脉注射唑来膦酸盐（ZOL; 35 µg/kg，每2周一次）、拔除上颌磨牙和维生素D缺乏[VitD（−）]的共同作用下，大鼠中产生了类似于人类疾病的ONJ病变。维生素D（-）/ZOL组ONJ的患病率为66.7%，显著高于对照组（0%）、维生素D（-）组（0%）和ZOL单药组（14.3%）（p <0.05，Fisher精确检验）。与人类患者相似，大鼠ONJ病变延长了坏死骨死骨的口腔暴露，并且与假上皮瘤样增生独特相关。VitD（−）/ZOL组拔牙后牙槽骨表面的末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸-生物素缺口末端标记阳性（TUNEL+）破骨细胞数量显著增加，[18 F]氟脱氧葡萄糖微正电子发射断层扫描（µPET）显示持续炎症。发现ONJ病变与混合炎性/免疫细胞的密集积聚相关。这些细胞，由中性粒细胞和淋巴细胞组成，出现并列凋亡破骨细胞。提示ONJ的病理生理机制可能涉及双膦酸盐与骨骼稳态和先天免疫领域中受损维生素D功能之间的相互作用。© 2010美国骨与矿物质研究学会。
Necrotic bone exposure in the oral cavity has recently been reported in patients treated with nitrogen-containing bisphosphonates as part of their therapeutic regimen for multiple myeloma or metastatic cancers to bone. It has been postulated that systemic conditions associated with cancer patients combined with tooth extraction may increase the risk of osteonecrosis of the jaw (ONJ). The objective of this study was to establish an animal model of bisphosphonate-related ONJ by testing the combination of these risk factors. The generation of ONJ lesions in rats resembling human disease was achieved under the confluence of intravenous injection of zoledronate (ZOL; 35 µg/kg every 2 weeks), maxillary molar extraction, and vitamin D deficiency [VitD(−)]. The prevalence of ONJ in the VitD(−)/ZOL group was 66.7%, which was significantly higher (p < .05, Fisher exact test) than the control (0%), VitD(−) (0%), and ZOL alone (14.3%) groups. Similar to human patients, rat ONJ lesions prolonged the oral exposure of necrotic bone sequestra and were uniquely associated with pseudoepitheliomatous hyperplasia. The number of terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate–biotin nick-end label–positive (TUNEL+) osteoclasts significantly increased on the surface of post–tooth extraction alveolar bone of the VitD(−)/ZOL group, where sustained inflammation was depicted by [18F]fluorodeoxyglucose micro-positron emission tomography (µPET). ONJ lesions were found to be associated with dense accumulation of mixed inflammatory/immune cells. These cells, composed of neutrophils and lymphocytes, appeared to juxtapose apoptotic osteoclasts. It is suggested that the pathophysiologic mechanism(s) underpinning ONJ may involve the interaction between bisphosphonates and compromised vitamin D functions in the realm of skeletal homeostasis and innate immunity. © 2010 American Society for Bone and Mineral Research.
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影响因子：
4.8
作者：
Gombart, AF;Borregaard, N;Koeffler, HP
通讯作者：
Koeffler, HP
影响因子：
56.9
作者：
Liu, PT;Stenger, S;Modlin, RL
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Modlin, RL
影响因子：
45.3
作者：
Bamias, A;Kastritis, E;Dimopoulos, MA
通讯作者：
Dimopoulos, MA
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作者：
Diaz-Curiel, M.;de la Piedra, C.;Phipps, R. J.
通讯作者：
Phipps, R. J.
影响因子：
22.4
作者：
HABER, M
通讯作者：
HABER, M