Influence of zoledronic acid in physicochemical and morphostructural parameters of bone and dental tissue of mice submitted to a jaw osteonecrosis model

Abstract

Zoledronic acid (ZA) leads to structural and physicochemical changes in mineralized tissues. The aim was to an- alyze physicochemical and morphostructural properties of bone and dental tissue of mice submitted to a model of ZA-related osteonecrosis of the jaws (OJ). This is a 2 × 2 factorial design experimental study, considering sex (male/female) and treatment (ZA/Saline). Lower left 2nd molar (day 42) extraction was performed after three ad- ministrations (days 0, 7, 14) of ZA 1.0 mg / kg or saline (n=8/group), with another administration on 49^th and eu- thanasia on 70^th day. Histological analysis, computerized microtomography, three-point bending test and Raman spectroscopy were performed. ANOVA 2-way/Bonferroni test was applied (p<0.05). Treatment with ZA promoted histological alterations in femoral epiphysis and increased bone necrosis signs (p <0.05) at sites of exodontia. Be- sides, ZA groups presented a lower number and greater separation of bone trabeculae, and smaller ratio bone/tissue volume in alveolar trabecular bone. Females presented a lower value of these parameters. In femoral bone, sex and treatment factors exerted an independent influence in mechanical parameters, on the cross-sectional area, maximum load, moment of inertia and work to fracture (p <0.05), being lower in females and increased in treated animals, which also presented higher flexural stiffness. Yield stress and flexural modulus were higher in females and lower with ZA treatment (p <0.05). Spectroscopic analysis showed increased crystallinity with ZA in cortical and medullar of right and left hemimandible, respectively, as well as femoral cortical. There was an increase of crys- tallinity in dental enamel and dentin with treatment. It is concluded that treatment with ZA, although associated with occurrence of OJ, modifies bone and dental mineral matrix, contributing to tissue biomechanics' improvement. Females present differences in femoral biomechanical properties and have a lower density of trabecular bone in the post-dental extraction socket, when compared to males.