Effects of Zoledronic Acid in Experimental Periapical Lesions in Rats: An Imaging and Histological Analysis

Abstract The aim of this study was to assess the imaging and histological features of experimental periapical lesions, including the adjacent alveolar bone, in rats under zoledronic acid treatment. The study used 40 male Wistar rats distributed into 8 groups of 5 animals each: G1: induction of periapical lesion (PL) and weekly intraperitoneal administration (WIPA) of saline solution (0.9% NaCl) for 4 weeks; G2: PL induction and WIPA of zoledronic acid (0.15 mg/kg/week) for 4 weeks; G3: PL induction and WIPA of saline solution for 8 weeks; G4: PL induction and WIPA of zoledronic acid for 8 weeks; G5:WIPA of saline solution for 4 weeks and subsequent PL induction; G6: WIPA of zoledronic acid for 4 weeks and subsequent PL induction; G7: WIPA of saline solution for 8 weeks and subsequent PL induction; G8: WIPA of zoledronic acid for 8 weeks and subsequent PL induction. The administration of zoledronic acid or saline solution continued after PL induction until the euthanasia. Thus, cone beam computed tomography and histological analysis were performed. Statistical analyzes were performed by ANOVA and Kruskal-Wallis test. Groups treated with zoledronic acid showed significantly smaller size of PL than the groups treated with 0.9% NaCl (p<0.05). PLs were formed by chronic inflammation ranging from mild to moderate, with no difference between groups. In all specimens, no mandibular necrosis was observed. In conclusion, the presence of PLs apparently does not represent an important risk factor for the development of bisphosphonate-related osteonecrosis of the jaws.摘要 本研究旨在评估唑来膦酸（zoledronic acid）干预下大鼠实验性根尖周病变（periapical lesions，PL）及其邻近牙槽骨的影像学与组织学特征。本研究纳入40只雄性Wistar大鼠，分为8组，每组5只：G1组：诱导根尖周病变后，每周腹腔注射（weekly intraperitoneal administration，以下简称WIPA）0.9%生理盐水，持续4周；G2组：诱导根尖周病变后，WIPA唑来膦酸（0.15 mg/kg/周），持续4周；G3组：诱导根尖周病变后，WIPA生理盐水，持续8周；G4组：诱导根尖周病变后，WIPA唑来膦酸，持续8周；G5组：先以WIPA生理盐水干预4周，随后诱导根尖周病变；G6组：先以WIPA唑来膦酸干预4周，随后诱导根尖周病变；G7组：先以WIPA生理盐水干预8周，随后诱导根尖周病变；G8组：先以WIPA唑来膦酸干预8周，随后诱导根尖周病变。根尖周病变诱导完成后，唑来膦酸或生理盐水的给药将持续至动物实施安乐死。随后对所有样本开展锥形束计算机断层扫描（cone beam computed tomography）与组织学分析。统计学分析采用单因素方差分析（ANOVA）及Kruskal-Wallis检验。结果显示，与0.9%生理盐水治疗组相比，唑来膦酸治疗组的根尖周病变体积显著更小（p<0.05）。根尖周病变均表现为轻至中度慢性炎症，各组间无显著差异。所有样本均未观察到下颌骨坏死。综上，根尖周病变似乎并非双膦酸盐相关性颌骨坏死（bisphosphonate-related osteonecrosis of the jaws）发生的重要危险因素。