Oncologic doses of zoledronic acid induce osteonecrosis of the jaw-like lesions in rice rats (Oryzomys palustris) with periodontitis.
Oncologic doses of zoledronic acid induce osteonecrosis of the jaw-like lesions in rice rats (Oryzomys palustris) with periodontitis.
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DOI：
10.1002/jbmr.1669
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发表时间：
2012-10
期刊：
影响因子：
--
通讯作者：
Wronski TJ
中科院分区：
文献类型：
--
作者：
Aguirre JI;Akhter MP;Kimmel DB;Pingel JE;Williams A;Jorgensen M;Kesavalu L;Wronski TJ
虽然颌骨骨坏死（ONJ）与含氮双膦酸盐（N-BP）的使用暂时相关，但因果关系尚未确定。我们假设ONJ是一个两阶段的过程，其中：a）风险因素在口腔中启动病理过程，导致硬组织坏死的超正常率，和B）强效抗吸收剂降低坏死骨的清除率，足以使其在颌骨中净积累。为了验证这一假设，我们使用了大鼠牙周炎模型。在28日龄时，将大鼠（n=15/组）置于高蔗糖和酪蛋白饮食中以加剧牙周炎的发展。动物每两周SC注射一次溶媒或阿仑膦酸钠（ALN，15μg/kg），或每月一次IV给予载体、低剂量（LD）或高剂量（HD）唑来膦酸（ZOL），并在6、12、18和24周后处死。a）牙周炎的进展，B）牙槽骨的完整性，c）骨吸收和形成的状态，d）血管分布，和e）骨细胞活力。我们发现，只有HD-ZOL诱导ONJ样病变的水稻大鼠下颌骨后18和24周的治疗。这些病变的特征在于暴露的坏死牙槽骨区域、骨质溶解、牙槽骨的蜂窝状外观、细菌菌落的存在和牙周组织破坏。此外，骨形成的抑制，一个矛盾的取消的抗吸收作用，只有HD-ZOL，增加骨细胞坏死/凋亡，减少血管数目后发现18和/或24 wks. Our研究表明，只有HD-ZOL加剧炎症反应和牙周组织损伤的大米大鼠，诱导骨病变，类似ONJ。
Though osteonecrosis of the jaw (ONJ) is temporally-associated with the use of nitrogen-containing bisphosphonates (N-BPs), a cause/effect relationship has not yet been established. We hypothesize that ONJ is a two-stage process in which: a) risk factors initiate pathologic processes in the oral cavity that lead to a supranormal rate of hard tissue necrosis, and b) powerful anti-resorptives reduce the rate of removal of necrotic bone sufficiently to allow its net accumulation in the jaw. To test this hypothesis, we used the rice rat model of periodontitis. At age 28 days, rats (n=15/group) were placed on a high sucrose and casein diet to exacerbate the development of periodontitis. Animals were injected SC biweekly with vehicle or alendronate (ALN, 15μg/kg), or IV once monthly with vehicle, a low dose (LD), or a high dose (HD) of zoledronic acid (ZOL) and sacrificed after 6, 12, 18, and 24 wks. Mandibles and maxillae were analyzed to determine the effects on the: a) progression of periodontitis, b) integrity of alveolar bone, c) status of bone resorption and formation, d) vascularity, and e) osteocyte viability. We found that only HD-ZOL induced ONJ-like lesions in mandibles of rice rats after 18 and 24 wks of treatment. These lesions were characterized by areas of exposed necrotic alveolar bone, osteolysis, a honey comb-like appearance of the alveolar bone, presence of bacterial colonies, and periodontal tissue destruction. In addition, inhibition of bone formation, a paradoxical abolition of the antiresorptive effect of only HD-ZOL, increased osteocyte necrosis/apoptosis, and decreased blood vessel number were found after 18 and/or 24 wks. Our study suggests that only HD-ZOL exacerbates the inflammatory response and periodontal tissue damage in rice rats, inducing bone lesions that resemble ONJ.
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影响因子：
3.8
作者：
Belibasakis, Georgios N.;Meier, Andre;Bostanci, Nagihan
通讯作者：
Bostanci, Nagihan
DOI：
10.1016/0030-4220(56)90249-3
发表时间：
1956-01-01
期刊：
ORAL SURG ORAL MED AND ORAL PATHOL
影响因子：
--
作者：
GUPTA, O. P.;SHAW, J. H.
通讯作者：
SHAW, J. H.
DOI：
10.1016/j.tripleo.2007.08.040
发表时间：
2008-03-01
期刊：
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTOLOGY
影响因子：
--
作者：
Bedogni, Alberto;Blandamura, Stella;Nocini, Pier Francesco
通讯作者：
Nocini, Pier Francesco
影响因子：
6.2
作者：
Hoff, Ana O.;Toth, Bela B.;Hortobagyi, Gabriel N.
通讯作者：
Hortobagyi, Gabriel N.
影响因子：
3.3
作者：
Hansen, T;Kunkel, M;Kirkpatrick, CJ
通讯作者：
Kirkpatrick, CJ