Division of Periodontology, Department of Diagnosis and Surgery, School of Dentistry, UNESP- Univ. Estadual Paulista, Araraquara, SP, Brazil.
Int J Exp Pathol. 2013 Feb;94(1):65-73. doi: 10.1111/iep.12007.
Osteonecrosis of the jaw (ONJ) following the use of bisphosphonates has become of increased interest in the scientific community, due in particular to its as-yet-unsolved pathogenesis. An experimental model of ONJ was induced in normal male rats [alendronate (ALN); 1 mg/Kg/day; n = 10] and matched controls (saline solution; n = 10). After 60 days of drug treatment, all animals were subjected to extractions of the left first lower molars and were euthanized at 3 and 28 days postsurgery. The following analyses were performed: (i) descriptive and quantitative (scores) histological evaluation, (ii) stereometry of distal sockets and (iii) biochemical measurement of C-telopeptide cross-linked collagen type I (CTX) and bone-specific alkaline phosphatase (BALP). The results showed that 28 days postsurgery the animals treated with ALN had areas of exposed and necrotic bone, associated with significant infection, especially in the interalveolar septum area and crestal regions, compared with controls. The levels of CTX, BALP and bone volume, as well as the degrees of inflammation and vascularization, were significantly reduced in these animals. Therefore, analysis of the data presented suggests that ALN therapy is associated with the development of osteonecrosis in the jaws of rodents after tooth extraction.
双膦酸盐相关颌骨坏死（ONJ）由于其尚未阐明的发病机制，引起了科学界的广泛关注。本研究建立了正常雄性大鼠颌骨 ONJ 实验模型[阿仑膦酸钠（ALN），1mg/Kg/天；n=10]并设置了对照组（生理盐水；n=10）。药物治疗 60 天后，所有动物均接受左侧下颌第一磨牙拔除术，并于术后 3 天和 28 天处死。进行了以下分析：（i）描述性和定量（评分）组织学评估，（ii）远心腔体积的体视学分析，（iii）I 型胶原交联 C-末端肽（CTX）和骨碱性磷酸酶（BALP）的生化测定。结果显示，与对照组相比，术后 28 天时，ALN 治疗组动物出现暴露性和坏死性骨区域，伴有明显感染，尤其是在牙槽间隔区和牙槽嵴区域。这些动物的 CTX、BALP 和骨体积水平，以及炎症和血管化程度均显著降低。因此，数据分析表明，ALN 治疗与拔牙后啮齿动物颌骨发生 ONJ 有关。
