Zoledronate treatment exerts sex-independent effects on bone and dental physicochemical properties in mice jaw necrosis.

INTRODUCTION: Bisphosphonate (BF) therapy is strongly related to the occurrence of medication-related osteonecrosis of the jaw (ONJ). However, no previous study has evaluated if there are sex-related differences on the ONJ establishment together with bone biomechanical alterations, and if they could have a synergy with the ZA treatment. MATERIALS AND METHODS: This study aimed to analyze the physicochemical properties of mineralized tissues in a zoledronate (ZA)-related osteonecrosis mouse model, by a 2 × 2-factorial design, considering sex (female/male) and treatment (ZA/Saline) factors (n = 8/group). After three ZA (1.0 mg/kg) or saline administrations (days 0, 7, 14), the lower left second molar was extracted (day 42). Further ZA administration (day 49) and euthanasia (day 70) were conducted. After confirmation of ZA-induced jaw necrosis (histologic and microtomographic analysis), spectroscopic and mechanical parameters were assessed. RESULTS: ZA-treated groups presented lower bone density due to impaired healing of tooth extraction socket. Sex-related alterations were also observed, with lower bone density in females. Regarding biomechanical parameters, sex and treatment exerted independent influences. ZA, although decreasing flexural modulus and yield stress, increases stiffness mainly due to a higher bone volume. Females show less resistance to higher loads compared to males (considering dimension-independent parameters). Additionally, ZA increases crystallinity in bone and dental structure (p < 0.05). In summary, although strongly related to osteonecrosis occurrence, ZA modifies bone and dental mineral matrix, improving bone mechanical properties. CONCLUSION: Despite sex-dependent differences in bone biomechanics and density, osteonecrosis was established with no sex influence. No synergistic association between sex and treatment factors was observed in this study.

Selective, stepwise, or nonselective removal of carious tissue: which technique offers lower risk for the treatment of dental caries in permanent teeth? A systematic review and meta-analysis.

OBJECTIVES: This study aimed to systematically review the literature regarding the risk of selective removal-in comparison with stepwise and nonselective removal-of carious tissue in permanent teeth. MATERIALS AND METHODS: Controlled clinical trials and cohort studies involving patients with dental caries in permanent teeth were included. Databases used were PubMed, Embase, and Scopus. The test group should be composed of patients undergoing selective removal of carious tissues, and the control group should comprise patients undergoing nonselective removal and/or stepwise removal of carious tissue. Laboratory tests, studies on primary teeth, and studies that used temporary restorations were excluded, as were literature reviews. The primary outcome was overall success of maintaining pulpal health (both clinically and radiographically). Quality of the restoration, pulp exposure, dentin deposition, and microbiological examination were also assessed. A meta-analysis, using the pooled risk ratio (RR) and its 95% confidence interval (CI), was performed to assess the success of maintaining pulpal health, using the different control treatments as a subgroup analysis. RESULTS: A total of 2333 articles were retrieved, of which 10 were included in the systematic review and four in the meta-analysis. In the qualitative evaluation, the control groups presented a higher risk of pulp exposure in relation to the selective removal. In the meta-analysis, the selective carious tissue removal showed significantly higher overall success (RR, 95% CI 1.11, 1.02-1.21). CONCLUSIONS: The selective carious tissue removal presented higher success of maintaining pulpal health. CLINICAL RELEVANCE: In permanent teeth, selective carious tissue removal should be performed, as this technique results in lower numbers of pulp complications, such as pulp exposure, as compared with nonselective removal.

Polymicrobial oral conventionalization model in mice.

The aim of this study is to describe a new polymicrobial oral conventionalization protocol in mice. Oral biofilm samples were collected from wild C57 BL/6 mice (WG), which had not been previously submitted to any experimental procedure. The contents of these samples were used for inoculation in the oral cavity of specific pathogen free (SPF) animals. This inoculation was repeated 3 times. Qualitative cytological analyses were performed in the days 0, 16 and 80 of the experimental protocol, to check the presence or absence of microorganisms, their morphology and staining characteristics on the oral cavity of the animals. At the end of this study, was observed a combination of oral bacterial microbiota of SPF animals and wild animals in the conventionalized group (CONV). Samples collected from CONV mice on day 16, a period in which these animals had been previously inoculated 3 times with wild mouse microbiota, showed a greater amount of Gram-positive cocci, as seen in SPF animals. In addition, Gram-negative cocci were present, although in a much smaller proportion than previously seen in wild mice. On the 80th experimental day, CONV animals showed a predominance of Gram-positive cocci and bacilli. Filamentous bacteria were also seen in this group. The conventionalization of SPF animals using the technique with inoculum from the resident microbiota of wild mice proved to be an effective, low-cost and easily reproducible technique. The conventionalized animals showed the colonization of a microbiota similar to wild animals up to 80 days of experiment.

Abatacept treatment impairs the cell migration and wound healing of oral ulcers in rats: Role of interleukin (IL)-1ß, -6 and -10 and CD8/CD30 cells: Influence of abatacept treatment on oral wound healing: Experimental model on rats.

The present study aimed to evaluate the healing process of ulcers in the jugal mucosa of Wistar rats treated with abatacept. The rats were randomly assigned to four groups: saline-treated control (0.3 mL/kg) abatacept-treated groups at dosages of 3.2, 8.0 and 20.0 mg/kg/week. After two weeks of subcutaneous (SC) administration, ulcers were introduced into the left jugal mucosa with an 8-mm diameter punch. SC administration was continued until euthanasia (after 1, 3, 7, 14 and 21 days of ulceration), and ulcers were clinically measured and animals weighed. Histological slides were evaluated (healing scores and polymorphonuclear, mononuclear, vessel, and fibroblast/myofibroblast counts). We also performed collagenesis analysis (Picrosirius Red) and immunohistochemistry (induced nitric oxide synthase (iNOS), interleukin (IL)-1beta (1ß), -6, -10, plus the analysis of CD8 and CD30). The experiment was repeated to perform a vascular permeability assay. ANOVA 1-way or 2-way/Bonferroni and Kruskal-Wallis/Dunn tests were used for statistical analysis (GraphPad Prism 5.0®, p < 0.05). Abatacept treatment reduced the ulcer diameter and the numbers of polymorphonuclear and mononuclear cells; reduced the CD8+/CD30+ ratio and vascular permeability; and increased collagenesis and IL-10 expression at the beginning of the protocol. At the highest dose, there was a delay in repair and vascular proliferation; a reduction in the number of fibroblasts/myofibroblasts; and prolongation of iNOS, IL- and IL- expression. We conclude that abatacept accelerates the healing of oral ulcers by reducing the migration of inflammatory cells, but overdose of abatacept leads to delayed repair and prolongation of proinflammatory cytokine expression.