Morphological and immunohistochemical features of tooth extraction sites in rats treated with alendronate, raloxifene, o
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ORIGINAL ARTICLE
Morphological and immunohistochemical features of tooth extraction sites in rats treated with alendronate, raloxifene, or strontium ranelate Valesca Sander Koth 1,2 Karen Cherubini 1,2
&
Fernanda Gonçalves Salum 1,2 & Maria Antonia Zancanaro de Figueiredo 1,2 &
Received: 15 April 2020 / Accepted: 14 September 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Objective The aim of this study was to evaluate morphological and immunohistochemical features of tooth extraction sites in rats subjected to different antiresorptive drugs. Materials and methods Wistar rats were allocated into 4 groups according to the treatment: (1) alendronate, (2) raloxifene, (3) strontium ranelate, and (4) control. The animals underwent tooth extraction (60th day of treatment) and afterwards were euthanized (90th day of treatment). Tooth extraction sites were analyzed by means of scanning electron microscopy (SEM), hematoxylin-eosin staining (H&E), and immunohistochemical staining (RANKL and OPG). Results On H&E analysis, the alendronate group showed greater amounts of non-vital bone, biofilm, inflammatory infiltrate and root fragment, and smaller amount of vital bone. The strontium ranelate group showed great amount of non-vital bone. This group also had lower levels of OPG, while the alendronate group showed lower OPG and RANKL than the other groups. On SEM analysis, the alendronate group showed a considerable number of microcracks on the alveolar bone surface and few Howship lacunae and lack of bone cells as well. The raloxifene, strontium ranelate, and control groups showed a large number of bone cells and Howship lacunae on the bone surface and few microcracks. Conclusion Alendronate therapy is associated with macro- and microscopic features of medication-related osteonecrosis of the jaw at tooth extraction sites, whereas raloxifene therapy is not, and strontium ranelate therapy is associated with non-vital bone. Clinical relevance Osteonecrosis of the jaws is a serious side effect of alendronate therapy, where tooth extraction is a major risk factor. Considering the significant number of patients undergoing antiresorptive therapies worldwide, the present study investigated whether raloxifene and strontium ranelate interfere with bone repair after tooth extraction in a similar way to bisphosphonates. Keywords Bisphosphonate-associated osteonecrosis of the jaw . Osteoporosis . Tooth extraction . Alendronate . Electron scanning microscopy . Jaws
Introduction Medication-related osteonecrosis of the jaw (MRONJ) is an important side effect of antiresorptive drugs, whose poor
* Valesca Sander Koth [email protected] 1
Post-Graduate Program, School of Health and Life Sciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil
2
Serviço de Estomatologia—Hospital São Lucas, PUCRS, Av. Ipiranga, 6690 Sala 231, Porto Alegre, RS 90610-000, Brazil
response to treatment can lead to lesion persistence for months or years [1]. When this condition is associated with o
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