Mandible matrix necrosis in beagle dogs after 3 years of daily oral bisphosphonate treatment
Mandible matrix necrosis in beagle dogs after 3 years of daily oral bisphosphonate treatment
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DOI：
10.1016/j.joms.2008.01.038
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发表时间：
2008-05-01
影响因子：
1.9
通讯作者：
Burr, David B.
中科院分区：
文献类型：
--
作者：
Allen, Matthew R.;Burr, David B.
目的：越来越多的报告表明双膦酸盐可导致颌骨骨坏死。本研究的目的是评估口服阿仑膦酸钠（ALN）治疗3年的比格犬下颌骨坏死的情况。材料和方法：成年雌性比格犬每天口服剂量的赋形剂（VEH）或ALN（0.20或1.0 mg/kg/天），持续3年。以mg/kg计，这些剂量分别接近用于绝经后骨质疏松症和佩吉特病的剂量。尸检时，切除下颌骨的第二磨牙区域，用碱性品红整体染色，并使用组织学评估基质坏死和皮质内骨转换率。基质坏死的定义是一个区域大于500 μ m（2），没有碱性品红染色，使用明视野和共聚焦显微镜进行评估。结果：在3年的研究中，没有动物在口腔中出现暴露的骨病变。在25%的ALN0.2动物、33%的ALN1.0动物中观察到基质坏死，并且在所有媒介物动物中明显不存在（P <0.05合并的ALN剂量vs VEH）。这些坏死区域主要发生在牙槽骨中，并且明显没有开放的小管。ALN治疗动物的下颌骨牙槽骨区域的皮质内骨转换率显著低于VEH.Conclusions：每日口服双磷酸盐治疗三年可显著降低骨转换率，并增加犬下颌骨内基质坏死的发生率。(c)2008年美国口腔颌面外科医师协会。
Purpose: An increasing number of reports have implicated bisphosphonates as contributing to osteonecrosis of the jaw. The goal of this study was to evaluate mandible necrosis in beagle dogs treated for 3 years with oral alendronate (ALN).Materials and Methods: Skeletally mature female beagles were treated daily for 3 years with oral doses of vehicle (VEH) or ALN (0.20 or 1.0 mg/kg/day). These doses approximate, on a mg/kg basis, those used for postmenopausal osteoporosis and Paget's disease, respectively. At necropsy, the second molar region of the mandible was excised, stained en bloc with basic fuchsin, and assessed for matrix necrosis and intracortical bone turnover rate using histology. Matrix necrosis was defined as a region greater than 500 mu m(2) that was void of basic fuchsin stain, assessed using both bright-field and confocal microscopy.Results: No animals developed exposed bone lesions in the oral cavity during the 3-year study. Matrix necrosis was observed in 25% of ALN0.2 animals, 33% of ALN1.0 animals, and was noticeably absent from all vehicle animals (P < .05 pooled ALN doses vs VEH). These necrotic regions occurred predominately in the alveolar bone and were clearly void of patent canaliculi. Intracortical bone turnover rate of the alveolar mandible bone region was significantly lower (-75%, P < .05) in ALN-treated animals compared with VEH.Conclusions: Three years of daily oral bisphosphonate treatment reduces bone turnover significantly and increases the incidence of matrix necrosis within the mandible of dogs. (c) 2008 American Association of Oral and Maxillofacial Surgeons.