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OBJECTIVE: To map the current scientific landscape regarding the association/causality of medication-related osteonecrosis of the jaw (MRONJ) after tooth extraction under bisphosphonate (BF) therapy to identify knowledge gaps and guide future research. DATA: This review used the PCC strategy (P = Patient; C = Concept; C = Context). SOURCES: The MEDLINE/PubMed, Scopus, Web of Science/Clarivate Analytics, and gray literature databases were used. STUDY SELECTION: Searches were conducted by two independent reviewers until April 2024. Studies involving prior BF use and tooth extraction in humans or animals were included. Among the 176 studies, 73 (41.4 %) were in animals, and 103 (58.5 %) were in humans. Brazil led in animal studies (n = 14; 19.1 %), while Italy led in human studies (n = 14; 13.6 %). Zoledronic acid was the most cited BF (79.4 % in animals; 34.9 % in humans), with intravenous administration being most frequent (38.3 % in animals; 35.9 % in humans). The mandible was the main extraction site (n = 36 in animals; n = 41 in humans). In 91.7 % of the animal studies, sequelae compatible with osteonecrosis signs and symptoms were observed, with bone necrosis being most common (n = 39; 53.4 %). In humans, 93.2 % of studies presented 239 sequelae, with bone necrosis (n = 53; 22.1 %) being the most cited. The main location of sequelae was the mandible (n = 36 in animals; n = 41 in humans). CONCLUSIONS: Animal studies highlighted bone exposure, notably using murine models, with a significant Brazilian contribution. In human studies, bone necrosis was the main sequela of MRONJ, which has been reported by researchers in the Italy. CLINICAL SIGNIFICANCE: These findings underscore the importance of careful consideration and monitoring of patients who have a history of bisphosphonate use and who are undergoing tooth extraction, highlighting the potential risk of MRONJ.

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OBJECTIVE: To assess the in-vitro effect of single applications of CPP-ACP pastes and different fluoridated solutions on the prevention of dental caries around orthodontic brackets. MATERIAL AND METHODS: Tooth/bracket sets (n=65) were immersed in artificial saliva (1h at 37ºC) and randomly subjected to single applications (100µL; 1min) of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP emulsion), CPP-ACP with fluoride (CPP-ACPF emulsion), solutions of titanium tetrafluoride (TiF4) or sodium fluoride (NaF), or no treatment (CG). Multispecies biofilm (5 x 105 CFU/mL) was formed in the presence of 2% sucrose. After 24 h, the pH and the concentration of total soluble fluoride (TSF) were analyzed by culture medium. The presence of active white spot lesions (WSL) evaluated by macroscopic examination and the percent surface mineral loss (%SML) were analyzed. Also, the topography of enamel was detected by analysis of scanning electron microscopy (SEM). The data was assessed by chi-square, Kruskal-Wallis, and Mann-Whitney tests (p < 0.05). RESULTS: Fluoride-containing compounds led to a smaller pH reduction than did CPP-ACP and CG (p<0.05). There was difference in TSF between the groups (p<0.05), denoted as TiF4> NaF > CPP-ACPF > CPP-ACP > CG. Regarding the presence of WSL and %SML, the NaF group obtained lower values (p<0.05), while TiF4 and CPP-ACPF were similar (p>0.05). SEM demonstrated that fluoride-free groups had a larger surface dissolution. CONCLUSION: Fluoridated groups including solutions and CPP-ACPF were more effective than CPP-ACP in reducing enamel demineralization around orthodontic brackets after a single application.

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To assess the in vitro and in situ effect of experimental combined fluoride and calcium nanocomposite solutions on dental caries prevention. Nanocompound mesoporous silica (MS) with calcium (Ca) and sodium fluoride (NaF) - (MSCaNaF); MS with NaF (MSNaF), NaF solution (positive control), and deionized water (negative control - CG) were studied. The specimens (n=130) were submitted in vitro to a multispecies biofilm in the presence of 2% sucrose. After 24 h and 48 h, the culture medium pH, the percent of surface mineral loss (%SML), and lesion depth (ΔZ) were analyzed. In the in situ study, 10 volunteers participated in four phases of 7-days each. The products were applied on the specimens (n=240) before 20% sucrose solution drips. The polysaccharides (SEPS and IEPS), %SML and roughness (Sa) were evaluated. There was an in vitro decrease in pH values in 24h and 48h, compared to baseline. The MSCaNaF and MSNaF groups obtained lower values of %SML and ΔZ (p < 0.05) than CG and NaF after 24h and were similar to NaF after 48h (p<0.05). In situ results showed similar SEPS and IEPS among all groups after 48h. An after 7-days, the nanocomposites had similar values (p>0.05), while NaF was similar to CG (p>0.05). After 48h, the MSCaNaF and MSNaF reduced the %SML (p<0.05). After 7-days, both experimental nanocomposites were similar to NaF (p>0.05). Regarding Sa, MSCaNaF was better than NaF for both periods (p<0.05). The nanocomposites controlled the in vitro and in situ enamel demineralization, mainly in the initial periods.

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Abstract To assess the in vitro and in situ effect of experimental combined fluoride and calcium nanocomposite solutions on dental caries prevention. Nanocompound mesoporous silica (MS) with calcium (Ca) and sodium fluoride (NaF) - (MSCaNaF); MS with NaF (MSNaF), NaF solution (positive control), and deionized water (negative control - CG) were studied. The specimens (n=130) were submitted in vitro to a multispecies biofilm in the presence of 2% sucrose. After 24 h and 48 h, the culture medium pH, the percent of surface mineral loss (%SML), and lesion depth (ΔZ) were analyzed. In the in situ study, 10 volunteers participated in four phases of 7-days each. The products were applied on the specimens (n=240) before 20% sucrose solution drips. The polysaccharides (SEPS and IEPS), %SML and roughness (Sa) were evaluated. There was an in vitro decrease in pH values in 24h and 48h, compared to baseline. The MSCaNaF and MSNaF groups obtained lower values of %SML and ΔZ (p < 0.05) than CG and NaF after 24h and were similar to NaF after 48h (p<0.05). In situ results showed similar SEPS and IEPS among all groups after 48h. An after 7-days, the nanocomposites had similar values (p>0.05), while NaF was similar to CG (p>0.05). After 48h, the MSCaNaF and MSNaF reduced the %SML (p<0.05). After 7-days, both experimental nanocomposites were similar to NaF (p>0.05). Regarding Sa, MSCaNaF was better than NaF for both periods (p<0.05). The nanocomposites controlled the in vitro and in situ enamel demineralization, mainly in the initial periods.

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INTRODUCTION: Titanium tetrafluoride (TiF4) is a fluoride compound that, when is applied over enamel, promotes a protection against demineralization through a titanium dioxide (TiO2) acid-resistant coat. OBJECTIVES: This study sought to verify the hypothesis that a single application of 4% TiF4 increases the resistance of enamel to dental demineralization in orthodontic patients. MATERIALS AND METHODS: This controlled clinical trial followed CONSORT guidelines and investigated the prevention of enamel demineralization, fluoride retention, and the presence of a Ti layer after TiF4 application on banded teeth exposed to clinical cariogenic biofilm. Forty premolars were divided into a control group (CG; n = 20) and a test group (TG; n = 20). Teeth from both groups received prophylaxis and orthodontic bands with a cariogenic locus. In the TG, all teeth additionally underwent aqueous 4% TiF4 solution application after prophylaxis before being banded. After one month, teeth from both groups were extracted and prepared to assess the microhardness, fluoride retention, and evaluation of the Ti coating over the enamel surface. All data were analyzed with a paired Student's t-test (p<0.05). RESULTS: Enamel microhardness and fluoride uptake were higher in TG than in CG, while the Ti layer could be seen over TG teeth that received TiF4 application. CONCLUSION: Under clinical circumstances, the 4% aqueous TiF4 solution was effective in preventing enamel mineral loss through increasing the enamel resistance to dental demineralization, enhancing its microhardness and fluoride uptake, and forming a Ti coat.

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ABSTRACT Introduction: Titanium tetrafluoride (TiF4) is a fluoride compound that, when is applied over enamel, promotes a protection against demineralization through a titanium dioxide (TiO2) acid-resistant coat. Objectives: This study sought to verify the hypothesis that a single application of 4% TiF4 increases the resistance of enamel to dental demineralization in orthodontic patients. Materials and Methods: This controlled clinical trial followed CONSORT guidelines and investigated the prevention of enamel demineralization, fluoride retention, and the presence of a Ti layer after TiF4 application on banded teeth exposed to clinical cariogenic biofilm. Forty premolars were divided into a control group (CG; n = 20) and a test group (TG; n = 20). Teeth from both groups received prophylaxis and orthodontic bands with a cariogenic locus. In the TG, all teeth additionally underwent aqueous 4% TiF4 solution application after prophylaxis before being banded. After one month, teeth from both groups were extracted and prepared to assess the microhardness, fluoride retention, and evaluation of the Ti coating over the enamel surface. All data were analyzed with a paired Student's t-test (p<0.05). Results: Enamel microhardness and fluoride uptake were higher in TG than in CG, while the Ti layer could be seen over TG teeth that received TiF4 application. Conclusion: Under clinical circumstances, the 4% aqueous TiF4 solution was effective in preventing enamel mineral loss through increasing the enamel resistance to dental demineralization, enhancing its microhardness and fluoride uptake, and forming a Ti coat.

RESUMO Introdução: O tetrafluoreto de titânio (TiF4) é um composto fluoretado que, quando aplicado sobre o esmalte dentário, promove uma proteção contra desmineralização, por meio da formação de uma camada ácido-resistente de dióxido de titânio (TiO2). Objetivos: O presente estudo buscou verificar a hipótese de que uma única aplicação de TiF4 a 4% aumenta a resistência do esmalte dentário à desmineralização, em pacientes ortodônticos. Material e Métodos: Esse ensaio clínico controlado seguiu as diretrizes do CONSORT e investigou a prevenção da desmineralização do esmalte, retenção de flúor e a presença de uma camada de titânio após a aplicação do TiF4 em dentes bandados expostos ao biofilme cariogênico clínico. Quarenta pré-molares foram divididos em dois grupos: controle (GC; n = 20) e teste (GT; n = 20). Dentes de ambos os grupos receberam profilaxia e bandas ortodônticas com nicho cariogênico. No GT, todos os dentes também foram submetidos a aplicação de solução aquosa de TiF4 4 após profilaxia, antes de serem bandados. Após um mês, os dentes de ambos os grupos foram extraídos e preparados para avaliar a microdureza, retenção de flúor e avaliação da camada de titânio sobre a superfície do esmalte. Todos os dados foram analisados pelo teste t pareado (p<0,05). Resultados: A microdureza do esmalte e a absorção de flúor foram mais elevadas no GT do que no GC, enquanto uma camada de titânio pôde ser observada sobre os dentes do GT, que receberam aplicação TiF4. Conclusão: Em circunstâncias clínicas, a solução de TiF4 a 4% foi eficaz na prevenção da perda mineral do esmalte, por meio do aumento da resistência à desmineralização dentária, aumentando sua microdureza e absorção de flúor, e formando uma camada protetora de titânio.

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ABSTRACT Objective: To assess the in-vitro effect of single applications of CPP-ACP pastes and different fluoridated solutions on the prevention of dental caries around orthodontic brackets. Material and Methods: Tooth/bracket sets (n=65) were immersed in artificial saliva (1h at 37ºC) and randomly subjected to single applications (100µL; 1min) of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP emulsion), CPP-ACP with fluoride (CPP-ACPF emulsion), solutions of titanium tetrafluoride (TiF4) or sodium fluoride (NaF), or no treatment (CG). Multispecies biofilm (5 x 105 CFU/mL) was formed in the presence of 2% sucrose. After 24 h, the pH and the concentration of total soluble fluoride (TSF) were analyzed by culture medium. The presence of active white spot lesions (WSL) evaluated by macroscopic examination and the percent surface mineral loss (%SML) were analyzed. Also, the topography of enamel was detected by analysis of scanning electron microscopy (SEM). The data was assessed by chi-square, Kruskal-Wallis, and Mann-Whitney tests (p < 0.05). Results: Fluoride-containing compounds led to a smaller pH reduction than did CPP-ACP and CG (p<0.05). There was difference in TSF between the groups (p<0.05), denoted as TiF4> NaF > CPP-ACPF > CPP-ACP > CG. Regarding the presence of WSL and %SML, the NaF group obtained lower values (p<0.05), while TiF4 and CPP-ACPF were similar (p>0.05). SEM demonstrated that fluoride-free groups had a larger surface dissolution. Conclusion: Fluoridated groups including solutions and CPP-ACPF were more effective than CPP-ACP in reducing enamel demineralization around orthodontic brackets after a single application.

RESUMO Objetivo: Avaliar in-vitro o efeito de uma aplicação única de cremes dentais de CPP-ACP e diferentes soluções fluoretadas na prevenção da cárie dentária ao redor de braquetes ortodônticos Material e Métodos: O conjunto dentes/braquetes (n=65) foi imerso em saliva artificial (1h em 37°C) randomizado e submetido a tratamento único (100µL; 1 min) de emulsão de fosfopeptídeo de caseína-fosfato de cálcio amorfo (CPP-ACP) e CPP-ACP associado ao flúor (CPP-ACPF); soluções de tetrafluoreto de titânio (TiF4) e fluoreto de sódio (NaF); e ausência de tratamento (GC). Biofilmes multiespécie (5 x 105 CFU/mL) foram formados na presença de sacarose a 2%. Após 24h, o pH e a concentração de fluoreto solúvel total (FST) foram analisados pelo meio de cultura. Foram avaliadas a presença de lesões de mancha branca (LMB), por meio da análise de macroscopia visual, e a porcentagem de perda de dureza (%PD). Também foi verificada a topografia do esmalte, usando microscopia eletrônica de varredura (MEV). Os dados foram analisados pelos testes Qui-quadrado, Kruskal-Wallis e Mann-Whitney (p < 0,05). Resultados: Os compostos contendo flúor levaram a uma redução do pH menor do que o CPP-ACP e GC (p<0,05). Houve diferença no FST entre os grupos (p <0,05), sendo TiF4> NaF > CPP-ACPF > CPP-ACP > GC. Quanto à presença de LMB e à %PD, o grupo NaF obteve os menores valores (p<0,05), enquanto TiF4 e CPP-ACPF foram semelhantes (p> 0,05). A MEV demonstrou que os grupos sem flúor tiveram uma dissolução superficial maior. Conclusão: Os grupos fluoretados, incluindo soluções e CPP-ACPF, foram mais eficazes do que o CPP-ACP sem flúor na redução da desmineralização do esmalte ao redor dos braquetes ortodônticos após uma única aplicação.

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Abstract Objective: To evaluate TIF4 preventive and therapeutic use in caries and erosive lesions. Material and Methods: Searches were performed in six databases. Studies evaluating TiF4 use in vitro, in situ, and in vivo in caries and erosive lesions were included and imported into VantagePoint™ (VP). Data about publication year, authors, country, journal, study design, outcomes, TIF4 vehicles, application and intervention time, cariogenic challenge, erosive cycles, effects (positive/ negative /null) and approach (preventive/therapeutic) were analyzed through VP and Excel. Results: 93 published studies were included and an increase in publications was observed between 2010 and 2021. Forty-three authors published three or more articles, of which 67.4% were developed in Brazil and published in Caries Research (22.6%). 69.9% were in vitro studies with erosion assays (59.1%) and with preventive approaches (67.4%). The principal vehicle was a solution (69.9%) with a 1-min single application (58.0%) and with an intervention time of 5-7 days (22.6%). The principal cariogenic challenge in vitro was pH cycling (11.8%); in situ was sucrose + biofilm (6.2%); and in vivo, biofilm (6.2%). The most used erosive cycle was 4× per day in in vitro studies (20.4%) and 1× in vivo (2.1%). A positive effect was observed in prevention (41.9%) and treatment (24.7%) studies. Conclusion: TIF4 has shown a positive effect in prevention and therapeutic treatments for dental caries and erosion (AU).

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ABSTRACT Objective To describe and evaluate the xylitol products' applicability and its effects in the health area worldwide utilizing a bibliometric analysis from randomized controlled trials (RCT) with humans. Material and Methods Electronic searches were carried out in Medline/PubMed, Scopus, Cochrane Library, Web of Science, and VHL databases. The main data extracted were: year, area of applicability, type of treatment, country, journal, xylitol posology and concentration, presentation form, outcomes, and effects. Results From 1476 studies, 257 were included. These studies were published between 1973-2021. The majority was carried out in dentistry (73.9%) and under preventive treatment (67.4%). These studies were developed in the USA (15.4%) and published in Caries Research (6.6%). The posology and concentration ranged between 0.004-67 g/day and 0.002-100%, respectively. The xylitol is usually used in the chewing gum form (44.0%), and for antimicrobial activity evaluation (38.5%). A positive effect was observed in 204 studies (79.3%) and was associated with xylitol concentration ≥ 15(p=0.007). Side effects were reported in 8.2and were associated with posology ≥ 5 g/day (p=0.03). Conclusion Most studies with xylitol were conducted to prevent diseases in the dentistry field. The chewing gum form and antimicrobial activity evaluation were more frequent. Most xylitol products have a positive effect, and few studies report side effects.

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This study aimed to evaluate the in vitro effect of a single application of experimental nanocomposite solutions on the prevention of dental caries around orthodontic brackets. The specimens were exposed to mesoporous silica (MS) nanocomposites containing fluoride by association with titanium tetrafluoride (TiF4) or sodium fluoride (NaF). Nanocomposites also could contain calcium and groups were described as MSCaTiF4, MSTiF4, MSCaNaF, MSNaF, and controls (TiF4, and NaF). Specimens were subjected to the formation of a multispecies biofilm to generate a cariogenic challenge. After 24h, both pH and total soluble fluoride concentration of the culture medium were assessed. Mineral loss was evaluated by percentage of surface mineral loss (%SML), mineral volume variation (ΔZ) of inner enamel and polarized light microscopy (PL). Linear (Ra) and volumetric (Sa) surface roughness and scanning electronic microscopy (SEM) were used to assess enamel topography. Statistical analyses were conducted considering p<0.05. MSNaF had the highest value of culture medium pH after cariogenic challenge, similarly to MSTiF4. All nanocomposite solutions released less fluoride than their controls NaF and TiF4 (p<0.05). All nanocomposite solutions presented lower %SML compared to their respective control groups (p<0.05). Lower Ra, Sa and ΔZ were observed for experimental groups compared to TiF4 (p<0.05). The results were confirmed by PL and SEM analysis. The experimental nanocomposite solutions contributed for lower enamel demineralization around orthodontic brackets.

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