Morphological and immunohistochemical features of tooth extraction sites in rats treated with alendronate, raloxifene, or strontium ranelate

Clin Oral Investig. 2021 May;25(5):2705-2716. doi: 10.1007/s00784-020-03585-x. Epub 2020 Sep 23.

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: Alendronate; Bisphosphonate-associated osteonecrosis of the jaw; Electron scanning microscopy; Jaws; Osteoporosis; Tooth extraction.

MeSH terms

  • Alendronate* / pharmacology
  • Animals
  • Bone Density Conservation Agents* / pharmacology
  • Humans
  • Raloxifene Hydrochloride / pharmacology
  • Rats
  • Rats, Wistar
  • Thiophenes
  • Tooth Extraction

Substances

  • Bone Density Conservation Agents
  • Thiophenes
  • strontium ranelate
  • Raloxifene Hydrochloride
  • Alendronate