Mineral trioxide aggregate (MTA) and Portland cement are being used in dentistry as root end-filling materials. However, biocompatibility data concerning genotoxicity and cytotoxicity are needed for complete risk assessment of these compounds. In the present study, genotoxic and cytotoxic effects of MTA and Portland cements were evaluated in vitro using the alkaline single cell gel (comet) assay and trypan blue exclusion test, respectively, on mouse lymphoma cells. The results demonstrated that the single cell gel (comet) assay failed to detect DNA damage after a treatment of cells by MTA and Portland cements for concentrations up to 1000 μg/ml. Similarly, results showed that none of the compounds tested were cytotoxic. Taken together, these results seem to indicate that MTA and Portland cements are not genotoxins and do not induce cellular death.

Treatment with cumulative dosages of zoledronic acid (ZA) in elderly patients is a risk factor for the development of medication-related osteonecrosis of the jaws (MRONJ), mainly related to surgical triggers such as tooth extraction. However, animal models for the investigation and understanding of MRONJ pathophysiology in senescent and postmenopausal stages remains to be developed and characterized. The aim of this study was to analyze MRONJ development in senescent female mice treated with cumulative dosages of ZA. For this purpose, twenty 129/Sv female mice, 64 weeks old, were treated with 0.9% saline solution as control group (n = 10), and with ZA at 250μg/Kg (n = 10), once a week, starting 4 weeks before the upper right incisor extraction and until the end of the experimental time points (7 days and 21 days). At 7 and 21 days post-surgery, specimens were harvested for microCT, histological, birefringence and immunohistochemical analysis. Clinically, an incomplete epithelialization was observed in ZA group at 7 days and a delayed bone matrix mineralization and collagen maturation at 7 and 21 days compared to the controls. Controls revealed sockets filled with mature bone at 21 days as observed by microCT and birefringence, while ZA group presented delayed bone deposition at 7 and 21 days, as well increased leukocyte infiltration and blood clot at 7 days, and increased bone sequestrum and empty osteocyte lacunae at 21 days (p<0.05). Also, ZA group presented decreased quantity of TGFb+ and Runx-2+ cells at 7 days, and decreased quantity of TRAP+ osteoclasts compared to the control at 21 days (p<0.05). Altogether, these data demonstrate the usefulness of this model to understanding the pathophysiology of MRONJ.