Research Paper
Clinical Pathology
High-dose zoledronic acid narrows the periodontal space in rats

https://doi.org/10.1016/j.ijom.2012.11.011Get rights and content

Abstract

The aim of this experiment was to evaluate the histological effects of zoledronic acid on the periodontal space in rats. 40 male Wistar rats were divided into three zoledronic acid groups and a control group. Zoledronic acid was injected subcutaneously at doses of 10, 50, or 500 μg/kg once a week for 3 weeks. The rats were killed 1 or 9 weeks after the last injection. Histological examination of the periodontal space around the incisor tooth revealed that zoledronic acid did not inhibit tooth development. In the rats killed 1 week after treatment discontinuation, the periodontal space gradually narrowed in response to increasing zoledronic acid doses, and the changes were statistically significant according to ANOVA but not according to ANOVA with post hoc tests. The changes persisted in the high-dose zoledronic acid group despite zoledronic acid discontinuation, with significant differences identified by ANOVA and ANOVA with post hoc tests. Therefore, although zoledronic acid had an insignificant effect on tooth development, it had a significant effect on the periodontal space when high doses were administered. The results of this experiment may provide useful information for future investigations on the role of zoledronic acid in the osteonecrosis of the jaw.

Section snippets

Materials and methods

40 male Wistar rats (Nihon SLC, Shizuoka, Japan: body weight 300–350 g; 10–12 weeks old) were used in the experiment. All rats were housed in cages with free access to food and water, and a 12 h light/dark cycle was maintained. All experiments were approved and performed in accordance with the guidelines for Animal Experiments Ethic Committee of Yokohama City University.

The 40 rats were randomly divided into four groups. Groups A, B, and C received ZA at doses of 10, 50, and 500 μg/kg,

Results

The experiment was performed without any complications, and no infection was observed in any of the rats. Histological examination revealed that neither spontaneous soft tissue necrosis nor spontaneous ONJ was observed in any of the rats.

The cross-sectional area of the incisor tended to narrow in a ZA dose-dependent manner. The narrowest and widest mean values and the standard deviations in the short-term groups were 2.340 ± 0.067 (group Cs) and 2.384 ± 0.117 mm2 (group Ctls), respectively, whereas

Discussion

Local inflammation and connective soft tissue reactions to infection are observed in most cases of ONJ.14, 18 Stephen et al. reported that the administration of ZA with dexamethasone prior to dental extractions in rats resulted in the development of histopathological changes that were similar to ONJ in humans.13 These findings indicate that ONJ occurs in the presence of any factor associated with bacterial infection of an intraoral wound. In the present study, the authors examined the effects

Funding

This study was supported by Novartis Pharma AG and in part by a Grant-in-Aid for Young Scientists (B) (No. 23792366) from the Japan Society for the Promotion of Science.

Competing interests

None declared.

Ethical approval

Animal experiments were approved by the ethics committee at Yokohama City University (No. 10-027).

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