# Effectiveness and Safety of Mechanical Debridement for Treating Experimental Peri-Implantitis in Elderly Rats Receiving Oncological Dosages of Zoledronate

**Authors:** Luan Felipe Toro, Eduardo Quintão Manhanini Souza, Vinícius Franzão Ganzaroli, Jéssica de Oliveira Alvarenga Freire, Leandro Lemes da Costa, Estevão Lopes Pereira, Beatriz Alexandrelli Machado, João Martins de Mello-Neto, Mariza Akemi Matsumoto, Cláudio Aparecido Casatti, Luciano Tavares Ângelo Cintra, Letícia Helena Theodoro, Valdir Gouveia Garcia, Edilson Ervolino

PMC · DOI: 10.3390/ijms27031355 · International Journal of Molecular Sciences · 2026-01-29

## TL;DR

This study found that mechanical debridement was not effective or safe for treating peri-implantitis in elderly rats given high doses of zoledronate.

## Contribution

The study is the first to evaluate mechanical debridement for peri-implantitis in zoledronate-treated elderly rats.

## Key findings

- Mechanical debridement showed no significant improvement in bone tissue or inflammation in zoledronate-treated rats.
- Zoledronate treatment was associated with increased non-vital bone tissue and reduced OCN immunolabeling.
- The ZOL-EPI-MD group had the highest levels of non-vital bone tissue compared to other groups.

## Abstract

This study evaluated the effectiveness and safety of mechanical debridement (MD) in treating experimental peri-implantitis (EPI) in rats with osseointegrated implants, specifically those treated with high-dose zoledronate. Senescent Wistar rats underwent the extraction of their upper incisor, followed by immediate implant placement. After 8 weeks, the implants were exposed, and a transmucosal component was placed. The animals were divided into four groups: Control (C), ZOL, ZOL-EPI, and ZOL-EPI-MD. In the 9th week, drug treatment commenced, consisting of the administration of 0.45 mL of a vehicle (for group C) or zoledronate (for groups ZOL, ZOL-EPI, and ZOL-EPI-MD) every 4 days over 10 weeks. After 5 weeks of drug treatment, a cotton bandage was placed around the implants to induce EPI in the ZOL-EPI and ZOL-EPI-MD groups. In the ZOL-EPI-MD group, the ligature was removed at week 16, and local treatment was performed using MD. Euthanasia was conducted at week 19. Histological sections were obtained and stained with hematoxylin–eosin for histopathological and histometric analyses, such as the percentage of total bone tissue (B.Ar/T.Ar) and the percentage of non-vital bone tissue (NVB.Ar/B.Ar). Immunohistochemical reactions were performed to detect TNFα, IL-1β, VEGF, OCN, and TRAP. In the peri-implant connective tissue, mild, intense, and moderate inflammatory infiltrates were observed in the ZOL, ZOL-EPI, and ZOL-EPI-MD groups, respectively. Immunolabeling for TNFα and IL-1β correlated with these histopathological findings. The ZOL and ZOL-EPI-MD groups showed lower immunolabeling for VEGF compared to the control group. There was a reduction in TRAP-positive cells and lower immunolabeling for OCN in the groups treated with zoledronate, with the ZOL-EPI-MD group displaying even lower levels of OCN compared to the ZOL group. While there was no significant difference in B.Ar/T.Ar across the groups, both the ZOL, ZOL-EPI, and ZOL-EPI-MD groups exhibited higher levels of NVB.Ar/B.Ar, with the ZOL-EPI-MD group showing the highest NVB.Ar/B.Ar compared to ZOL and the other groups. In conclusion, MD, as a standalone treatment, showed neither effectiveness nor safety in the management of EPI in rats that received high doses of zoledronate.

## Linked entities

- **Proteins:** TNF (tumor necrosis factor), IL1B (interleukin 1 beta), VEGFA (vascular endothelial growth factor A), BGLAP (bone gamma-carboxyglutamate protein), ACP5 (acid phosphatase 5, tartrate resistant)
- **Chemicals:** zoledronate (PubChem CID 68740)

## Full-text entities

- **Genes:** Il1b (interleukin 1 beta) [NCBI Gene 24494] {aka IL-1F2}, Tdrd7 (tudor domain containing 7) [NCBI Gene 85425] {aka Pctaire2bp}, Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, Vegfa (vascular endothelial growth factor A) [NCBI Gene 83785] {aka VEGF-A, VEGF111, VEGF164, VPF, Vegf}
- **Diseases:** EPI (MESH:D057873), inflammatory (MESH:D007249)
- **Chemicals:** ZOL (MESH:D000077211), hematoxylin (MESH:D006416), ZOL-EPI (-)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116]

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12898286/full.md

## References

64 references — full list in the complete paper: https://tomesphere.com/paper/PMC12898286/full.md

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Source: https://tomesphere.com/paper/PMC12898286