Effect of bisphosphonates on the mandibular bone and gingival epithelium of rats without tooth extraction

De Ponte,Francesco  Saverio; Catalfamo,Luciano; Micali,Gregorio; Runci,Michele; Cutroneo,Giuseppina; Vermiglio,Giovanna; Centofanti,Antonio; Rizzo,Giuseppina

doi:10.3892/etm.2016.3168

Effect of bisphosphonates on the mandibular bone and gingival epithelium of rats without tooth extraction

Authors:
- Francesco Saverio De Ponte
- Luciano Catalfamo
- Gregorio Micali
- Michele Runci
- Giuseppina Cutroneo
- Giovanna Vermiglio
- Antonio Centofanti
- Giuseppina Rizzo
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Affiliations: Unit of Maxillo‑Facial Surgery, Department of Odonostomatology, University of Messina, I-98125 Messina, Italy, Department of Biomedical Sciences and Morpho‑Functional Images, University of Messina, I-98125 Messina, Italy
Published online on: March 15, 2016 https://doi.org/10.3892/etm.2016.3168
Pages: 1678-1684
Copyright: © De Ponte et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Osteonecrosis of the jaw (ONJ) is an adverse effect of bisphosphonate treatment that has become the subject of increasing investigations, in particular due to its poorly understood pathogenesis. Several experimental studies on animal models have been conducted; however, the majority of these replicate human ONJ following tooth extraction, and describe alterations in the bone and gingival epithelium when necrosis is manifested. The aim of the present study was to analyze the rat mandibular bone and gingival epithelium during 45 days of zoledronate treatment (which is a bisphosphonate agent), without tooth extraction. Intraperitoneal injections of zoledronate acid (0.1 mg/kg) were performed three times a week in normal male Wistar rats (n=20), while a control group of rats (n=20) was treated with saline solution for 45 days. After 7, 15, 30 and 45 days of drug treatment, all rats were sacrificed and hematoxilin and eosin staining, immunofluorescence and scanning electron microscopy analyses were performed. The results of the analyses after 7 and 15 days of treatment were similar in the treatment and control group. After 30 and 45 days of treatment, structural alterations were observed in the bone. No structural alterations to the gingival epithelium were observed. Based on these results, it was hypothesized that low doses of zoledronate act directly on the bone tissues to induce morphological alterations from bone to necrotic tissue following surgical procedures, although no cytotoxic effects were detected in the gingival epithelium.

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