Análise comparativa do efeito das drogas alendronato de sódio, raloxifeno e ranelato de estrôncio sobre a cicatrização alveolar pós-exodontia : estudo in vivo

Abstract

Osteoporosis is a silent disorder that affects a great number of people worldwide, and is characterized by loss of bone mass and architectural deterioration of bone, which increases the risk of fractures. This condition requires medical treatment, where bisphosphonates are the most used antiresorptive drugs. Medication-related osteonecrosis of the jaw (MRONJ) is an adverse effect of antiresorptive therapy and, even though the literature associates this disorder with bisphosphonates and denosumab, it is not known if other antiresorptive drugs would also be involved. This study aimed to analyze macro- and microscopic features of tooth extraction sites in rats undergoing sodium alendronate, raloxifene or strontium ranelate therapies. Forty eight Wistar rats were allocated into four groups according to the treatment: (1) alendronate, (2) raloxifene, (3) strontium ranelate and (4) control. All animals underwent tooth extraction of the upper right molars at the 60th day of treatment. At the 90th day, the animals were euthanized and the maxillae were dissected for macroscopic analysis and histomorphometry with hematoxylin and eosin (H&E); immunohistochemistry with RANKL and OPG; and scanning electron microscopy analysis (SEM). Macroscopic examination showed greater frequency and syze of mucosal lesion in the alendronate group. On H&E analysis, the proportion of non-vital bone was greater in the alendronate and strontium ranelate groups. Alendronate also showed more biofilm than raloxifene and strontium groups, higher inflammatory infiltrate than all the other groups and less vital bone than the control. The alendronate group had lower expression of RANKL and OPG, while the strontium ranelate group had lower levels of OPG 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 raloxifen, strontium ranelate and control groups showed a large number of bone cells and Howship lacunae on the bone surface and few microcracks. Conclusion: Sodium alendronate determines, in tooth extraction sites, greater histologic and structural features compatible with MRONJ and reduced bone metabolism as well. Strontium ranelate is associated with non-vital bone, whereas raloxifen is not associated with MRONJ features.