Systematic review of epidemiological and toxicological evidence on health effects of fluoride in drinking water.

INTRODUCTION: Fluoride is a naturally occurring substance that is also added to drinking water, dental hygiene products, and food supplements for preventing dental caries. Concerns have been raised about several other potential health risks of fluoride. OBJECTIVE: To conduct a robust synthesis of evidence regarding human health risks due to exposure to fluoride in drinking water, and to develop a point of departure (POD) for setting a health-based value (HBV) for fluoride in drinking water. METHODS: A systematic review of evidence published since recent reviews of human, animal, and in vitro data was carried out. Bradford Hill considerations were used to weigh the evidence for causality. Several key studies were considered for deriving PODs. RESULTS: The current review identified 89 human studies, 199 animal studies, and 10 major in vitro reviews. The weight of evidence on 39 health endpoints was presented. In addition to dental fluorosis, evidence was considered strong for reduction in IQ scores in children, moderate for thyroid dysfunction, weak for kidney dysfunction, and limited for sex hormone disruptions. CONCLUSION: The current review identified moderate dental fluorosis and reduction in IQ scores in children as the most relevant endpoints for establishing an HBV for fluoride in drinking water. PODs were derived for these two endpoints, although there is still some uncertainty in the causal weight of evidence for causality for reducing IQ scores in children and considerable uncertainty in the derivation of its POD. Given our evaluation of the overall weight of evidence, moderate dental fluorosis is suggested as the key endpoint until more evidence is accumulated on possible reduction of IQ scores effects. A POD of 1.56 mg fluoride/L for moderate dental fluorosis may be preferred as a starting point for setting an HBV for fluoride in drinking water to protect against moderate and severe dental fluorosis. Although outside the scope of the current review, precautionary concerns for potential neurodevelopmental cognitive effects may warrant special consideration in the derivation of the HBV for fluoride in drinking water.

Study of ZnO nanoparticle-doped dental adhesives on enamels with fluorosis: Electron microscopy, elemental composition and shear bond strength analysis.

This study aimed to evaluate dental adhesives containing different concentrations of zinc oxide nanoparticles (ZnO-NPs) for their use in the treatment of dental fluorosis, observe the interaction of the adhesive on healthy enamel surfaces and with mild and moderate fluorosis, measure the adhesive strength and fluorosis, and determine the phosphorus (P) and calcium (Ca) content on these surfaces, as a reference for the potential use of this adhesive with ZnO-NPs for dental fluorosis treatment. Transmission electron microscopy (TEM) and field emission scanning electron microscopy (FESEM) were used to characterise the ZnO-NPs and analyse the weight percentages of P and Ca in the enamel using X-ray energy dispersive spectroscopy (EDS) and the adhesive strength using a universal mechanical testing machine. FESEM characterisation revealed that the ZnO-NPs were less than 100 nm in size, with quasi-spherical and hexagonal prism shapes. The synthesis of the ZnO-NPs was confirmed by TEM, revealing their hexagonal crystalline structure. The adhesive strength by the universal mechanical testing machine showed that the adhesive with a 3% wt. concentration of ZnO-NPs was better in the three groups of teeth, showing higher adhesive strength in teeth with mild (15.15 MPa) and moderate (12.76 MPa) fluorosis surfaces, and was even higher than that in healthy teeth (9.65 MPa). EDS analysis showed that teeth with mild and moderate fluorosis had the highest weight percentages of P and Ca, but there were no statistically significant differences compared to healthy teeth and teeth treated with adhesives. Lay description: This study focused on testing a new dental adhesive containing small particles called ZnO nanoparticles (ZnO-NPs). This study aimed to demonstrate whether this adhesive with ZnO-NPs could be useful for treating dental fluorosis by improving its adhesion to teeth. One of the first objectives was to determine whether the dental adhesive could adhere better to teeth affected by mild or moderate fluorosis than to healthy teeth by measuring whether the levels of two important elements for healthy teeth, calcium (Ca) and phosphorus (P), were affected by the adhesive. The size and shape of the small particles and teeth with mild or moderate fluorosis were observed using scanning electron microscopy. The nanoparticles were small (< 100 nm) and had specific quasi-spherical and hexagonal prismatic shapes. More damage to the enamel was observed in teeth with mild or moderate fluorosis than in healthy teeth. The adhesive strength test demonstrated that the dental adhesive with 3% ZnO-NPs had the best adhesion on all healthy conditions of teeth. It was particularly effective in teeth with mild or moderate fluorosis. Finally, the evaluation of the levels of P and Ca on the enamel showed that teeth with fluorosis had higher levels of these elements, but using the dental adhesive with ZnO-NPs did not change the levels of these elements significantly because the adhesive avoided greater detachment because of greater adhesion to these surfaces. In conclusion, adding these small particles to dental adhesives could be an option for treating teeth affected by fluorosis. It stuck well and did not affect the levels of the important elements in the teeth.

MicroRNAs in fluorosis pathogenesis: impact on dental, skeletal, and soft tissues.

Fluoride-induced toxicity (fluorosis) poses a significant health concern globally, affecting millions of individuals. Understanding the molecular mechanisms underlying fluorosis, particularly the role of microRNAs (miRNAs), is crucial for developing effective preventive and therapeutic strategies. This review explores the pivotal role of miRNAs in the pathogenesis of fluorosis, particularly examining its impact on both hard (skeletal and dental) and soft (brain, liver, kidney, heart, and reproductive organs) tissues. Skeletal fluorosis manifests as abnormal bone mineralization and structure, while dental fluorosis affects enamel formation. In vitro and in vivo studies suggest a significant involvement of miRNAs in the progression of these conditions. For skeletal fluorosis, miR-124, miR-155, and miR-200c-3p have been identified as key regulators, while miR-296-5p and miR-214-3p are implicated in dental fluorosis. Moreover, soft tissue fluorosis encompasses a spectrum of adverse effects on various organs, including the brain, liver, kidneys, heart, and reproductive system. In soft tissues, miRNAs, such as miR-124, miR-200c-3p, miR-132, and miR-34b-5p, have been linked to cellular damage and dysfunction. Notably, miRNAs exert their effects through the modulation of critical pathways involved in fluorosis pathology, including Wnt signaling, apoptosis, cell cycle, and autophagy. Understanding the regulatory roles of miRNAs in fluorosis pathogenesis holds promise for identifying biomarkers and therapeutic targets. However, further research is needed to elucidate the molecular mechanisms underlying miRNA-mediated responses to fluoride exposure. Integration of miRNA research into fluorosis studies could facilitate the development of diagnostic tools and therapeutic interventions, thus mitigating the detrimental effects of fluorosis on both hard and soft tissues.

Ultrastructural evaluation of adverse effects on dentine formation from systemic fluoride application in an experimental mouse model.

AIM: Fluoride is widely used in dentistry for its caries prevention. To reduce dental caries, the optimal fluoride concentration of public water supplies in the United States is 0.7 ppm. However, excessive systemic fluoride consumption can lead to dental/enamel fluorosis. Numerous studies have explored the effects of fluoride on enamel and enamel-forming cells. However, research on systemic fluoride's impact on dentine is limited, particularly the effect of fluoride on the structure of the dentine-pulp complex. Therefore, this study aimed to identify how excessive fluoride affects dentine microstructure using an experimental mouse model. METHODOLOGY: C57BL6/J male mice (6-9 weeks old) were randomized into four groups (Fluoride at 0, 50, 100, or 125 ppm in drinking water) (n = 4/group). Mice were provided water ad libitum for 6 weeks along with fluoride-free food. Thereafter, mandibular incisors were analysed. Enamel phenotypes were evaluated using light microscopy and quantitative light-induced fluorescence (QLF) to measure fluorosis levels. Dentine morphology was evaluated using micro-CT, scanning electron microscopy (SEM), SEM-EDX (energy-dispersive X-ray), microhardness test and histological imaging. Data were analysed using one-way ANOVA with Dunnett's multiple comparisons as a post hoc test and the Kruskal-Wallis test with Dunn's multiple comparisons post hoc test (p < .05). RESULTS: Mice treated with fluoride at 50-125 ppm developed enamel hypoplasia in their erupting incisors and micro-CT imaging revealed that fluoride 125 ppm caused external resorption of the growing incisor. Dentine mineral density, dentine volume decreased compared with the 0 ppm control, while pulp volume increased compared with the 0 ppm control group. SEM showed wider predentine layer and abnormalities in calcified matrix vesicles derived from odontoblasts in fluoride 100 and 125 ppm groups. Vickers microhardness of dentine significantly decreased in the high-dose group. Fluoride-induced dentine hypoplasia in a dose-dependent manner. Histological evaluation showed excessive fluoride 125 ppm induced micro abscess formation and inflammatory cell infiltration. Fluoride induced dentine dysplasia with a dentine microstructure resembling hypophosphatasia. CONCLUSIONS: High doses of systemic fluoride can cause dentine dysplasia. Both three-dimensional and microstructural analyses showed the structural, chemical and mechanical changes in the dentine and the mineralized tissue components, along with external resorption and pulp inflammation.

Comparison of case-based and lecture-based learning in dental fluorosis diagnostic ability with visual analog scale assessment.

OBJECTIVE: This study aimed to compare the impact of case-based learning (CBL) versus lecture-based learning (LBL) on dental students' clinical decision-making regarding DF severity using Visual Analog Scale (VAS) scoring. METHODS: Eighty first-year graduate dental students were randomly assigned to either the CBL (n = 38) or LBL (n = 42) groups. Both groups received instruction on DF diagnosis, with CBL involving small group sessions analyzing real cases and LBL involving traditional lectures. Effectiveness was assessed by presenting 32 dental fluorosis cases with Thylstrup-Fejerskov Index (TSIF) scores ranging from 0 to 7 through slide presentations to both groups for VAS assessment. Five evaluators of each group randomly selected were asked to repeat the rating 2 weeks later. Statistical analysis included two-way ANOVA for group and gender differences, intra-class correlation coefficient (ICC) for reliability, and Spearman correlation coefficients for validity. RESULTS: Variations in VAS scores were observed between CBL and LBL groups, with no significant gender impact. Excellent inter- and intra-evaluator agreement was found for VAS scoring in both groups, indicating its reliability. Validation against established indices (such as DI and TSIF) demonstrated strong correlations, with CBL students exhibiting higher correlations. CONCLUSIONS: CBL enhances students' clinical decision-making and proficiency in DF diagnosis, as evidenced by more consistent and accurate VAS scoring compared to LBL. These findings highlight the importance of innovative educational strategies in dental curricula, with implications for improving training quality and clinical outcomes. TRIAL REGISTRATION: The study was registered at the Clinical Research Center, Hospital of Stomatology, Wuhan University (Registration code: HGGC-036).

Impact of dental fluorosis on the oral health-related quality of life: a systematic review.

OBJECTIVE: The aim of this systematic review is to investigate the literature to assess the effect of dental fluorosis on the Oral Health-Related Quality of Life (OHRQoL). MATERIALS AND METHODS: Included studies were epidemiological investigations, clinical trials, or human studies that directly compared the impact on OHRQoL between individuals with dental fluorosis and those without, utilizing valid OHRQoL assessment tools. The searches were conducted up to March 2024 in databases, including PubMed, Scielo, LILACS, Scopus, Web of Science, Embase, and the Virtual Health Library. Additionally, gray literature sources such as Google Scholar, OpenGrey, Ibict/BDTD, and ProQuest were searched. Reference lists were also manually reviewed for potential eligible studies. The risk of bias in cohort studies was assessed using the Newcastle-Ottawa Scale (NOS), while its modified version was employed for cross-sectional studies. A narrative synthesis of the results was conducted. RESULTS: 16 studies were included in this Systematic Review. In total, 16,314 participants, aged 8 to 18, were assessed across the studies. Most of the included studies were cross-sectional, except for one cohort study. In assessing OHRQoL across different age groups and severities of dental fluorosis, the impact varied. A negative association between dental fluorosis and OHRQoL was found in 9 of the included studies, a positive association was found in 1 study, and no significative association was identified in 6 studies. Limitations in the included studies primarily pertained to cross-sectional designs, with significant issues such as the absence of sample size calculations, lack of non-response rate reporting, limited consideration of confounding factors, and substantial heterogeneity stemming from diverse diagnostic methods and assessment tools. CONCLUSION: The findings of the systematic review demonstrate a complex and varied relationship between dental fluorosis and OHRQoL in children and adolescents. These conclusions may have limitations in scientific evidence. The findings emphasize the need for further investigations to explore the intricate aspects of this relationship and identify contributing factors to varying outcomes. CLINICAL RELEVANCE: Dental caries preventive fluoridated measures might be indicated even if there would be a risk for mild dental fluorosis as the fluoridated public water. REVIEW REGISTRATION: This systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under number: CRD42020186552.

Tooth whitening: current status and prospects.

As a safe, effective, economical, and convenient technique, tooth whitening is one of the most popular treatments for improving tooth discoloration. This review summarizes the theoretical and recent research developments in the classification and mechanisms of tooth discoloration, as well as the principles, agents, effects, and side effects of tooth whitening techniques. The aim is to provide a basis for the clinical treatment of tooth whitening techniques and to suggest possible new ideas for further research. The accepted mechanism of whitening is the redox reaction of oxides in the whitening reagent, and the whitening effect is remarkable. However, side effects such as tooth sensitivity and irritation of gum and other oral soft tissues can still occur. It is recommended that more monitoring be carried out in the clinic to monitor these side effects, and care should be taken to protect the soft tissues in the mouth during office whitening procedures. Furthermore, there is a need to develop new additives or natural whitening products to reduce the occurrence of side effects.

Does the Transillumination Technique Using a Diagnostic White Tip Influence the Degree of Conversion of the Infiltrant Resin? A Case Report With In Vitro Insights: A New Technique to Improve the Predictability During the Application of Resin Infiltration: Transillumination Using a Diagnostic White Tip.

OBJECTIVE: This study aimed to evaluate, through a case report combined with in vitro study, whether a new diagnostic white tip for the transillumination technique during resin infiltration influences the procedure and degree of conversion (DC). MATERIALS AND METHODS: A clinical case report demonstrated resin infiltration using the transillumination technique with a new white diagnostic tip (Radii Xpert LED diagnostic tip, SDI, Bayswater, VIC, AU) along with a light-curing device to enhance aesthetic results. An in vitro study assessed the DC of two diagnostic white tips (Radii Xpert LED diagnostic tip [SDI, Bayswater, VIC, AU] and Valo Grand White Light Lens [Ultradent Prod., South Jordan, UT, USA]) compared to that achieved using conventional tips of both light-curing devices. Statistical analysis was performed using two-way ANOVA and Tukey's test (α = 0.05). RESULTS: The clinical case achieved complete masking of the white spot lesion. In vitro, the diagnostic white tips exhibited significantly lower DC values compared to conventional tips (p = 0.001), regardless of the light-curing unit. CONCLUSIONS: The diagnostic white tip used in the transillumination technique improves resin infiltration visibility without compromising the degree of conversion. CLINICAL SIGNIFICANCE: The transillumination technique with the diagnostic white tip enables monitoring of resin infiltration while maintaining effective polymerization.

Fluoride Alters Gene Expression via Histone H3K27 Acetylation in Ameloblast-like LS8 Cells.

Excessive fluoride ingestion during tooth development can cause dental fluorosis. Previously, we reported that fluoride activates histone acetyltransferase (HAT) to acetylate p53, promoting fluoride toxicity in mouse ameloblast-like LS8 cells. However, the roles of HAT and histone acetylation status in fluoride-mediated gene expression remain unidentified. Here, we demonstrate that fluoride-mediated histone modification causes gene expression alterations in LS8 cells. LS8 cells were treated with or without fluoride followed by ChIP-Seq analysis of H3K27ac. Genes were identified by differential H3K27ac peaks within ±1 kb from transcription start sites. The levels of mRNA of identified genes were assessed using rea-time PCR (qPCR). Fluoride increased H3K27ac peaks associated with Bax, p21, and Mdm2 genes and upregulated their mRNA levels. Fluoride decreased H3K27ac peaks and p53, Bad, and Bcl2 had suppressed transcription. HAT inhibitors (Anacardic acid or MG149) suppressed fluoride-induced mRNA of p21 and Mdm2, while fluoride and the histone deacetylase (HDAC) inhibitor sodium butyrate increased Bad and Bcl2 expression above that of fluoride treatment alone. To our knowledge, this is the first study that demonstrates epigenetic regulation via fluoride treatment via H3 acetylation. Further investigation is required to elucidate epigenetic mechanisms of fluoride toxicity in enamel development.

Genetic polymorphisms associated with developmental defects of enamel: A systematic review.

BACKGROUND: Polymorphisms in genes related to enamel formation and mineralization may increase the risk of developmental defects of enamel (DDE). AIM: To evaluate the existing literature on genetic polymorphisms associated with DDE. DESIGN: This systematic review was registered in the PROSPERO (CRD42018115270). The literature search was performed in PubMed, Scopus, Web of Science, LILACS, BBO, Cochrane Library, and in the gray literature. Observational studies assessing the association between DDE and genetic polymorphism were included. The Newcastle-Ottawa Scale was used to assess the risk of bias. RESULTS: One thousand one hundred and forty-six articles were identified, and 28 met the inclusion criteria. Five studies presented a low risk of bias. Ninety-two genes related to enamel development, craniofacial patterning morphogenesis, immune response, and hormone transcription/reception were included. Molar-incisor hypomineralization (MIH) and/or hypomineralization of primary second molars (HPSM) were associated with 80 polymorphisms of genes responsible for enamel development, immune response, morphogenesis, and xenobiotic detoxication. A significant association was found between the different clinical manifestations of dental fluorosis (DF) with nine polymorphisms of genes responsible for enamel development, craniofacial development, hormonal transcription/reception, and oxidative stress. Hypoplasia was associated with polymorphisms located in intronic regions. CONCLUSION: MIH, HPSM, DF, and hypoplasia reported as having a complex etiology are significantly associated with genetic polymorphisms of several genes.

Prevalence and risk factors of dental fluorosis among children aged 8-12 years in Shandong province of China.

This study was to investigate the prevalence and severity of children's dental fluorosis (DF) in Shandong and identified the potential risk factors for DF. A total of 87 villages in Shandong were investigated to calculate the prevalence of DF and Community Fluorosis Index (CFI) in 2018-2019. Six hundred and seventy children were enrolled to identify the potential risk factors using univariate and multivariate logistic regressions. Goodman-Kruskal Gamma was used to explore the factors related to the severity of DF. In 87 villages, 1249 of 8700 (14.36%) children still have DF. The prevalence of DF in most villages was below 40% in 2018-2019. Water fluorine concentration when selected for the study and urinary fluorine concentration were related to the risk of DF (P < 0.001). Some eating habits, like lower frequency of eating fresh vegetables, eggs, and beans, were associated with the risk of DF (P < 0.001). The high water fluorine concentration, and lower frequency of eating fresh vegetables, eggs, and beans were also related to the severity of DF (P < 0.001). DF in children in Shandong province is still a common endemic disease. This study tries to provide a useful guide for the prevention and control of DF.

Health risk assessment in an area of dental fluorosis disease from high fluoride drinking water: a case study from southeastern Türkiye.

This study focuses on identifying fluoride (F‒) concentrations and its health risk assessment (HRA) in drinking water sources in south-eastern Türkiye. Groundwater quality was assessed using some graphical approaches such as Schoeller and Piper diagrams and GIS mapping. Average daily exposure dosages through oral and dermal contact exposure routes were considered to determine the potential health risk of F‒ in groundwater. Groundwater samples were taken from 53 points in spring, summer, autumn, and winter seasons. The results showed that the average annual F‒ concentrations in water resources in the study area were 0.26‒3.62 mg/L. According to the HRA results, the highest F‒ health risk in this region was observed in children, followed by teenagers and adults. This study indicated that there is a strong relationship between the high health risk (4.28 > 3.5) in children and dental fluorosis caused by high F‒ concentration in groundwater.

Association between fluoride intake from drinking water and severity of dental fluorosis in Northern and Western Mexico: systematic review and meta-analysis.

BACKGROUND: Dental fluorosis (DF) is caused by excessive exposure to fluoride during odontogenesis and leads to various changes in the development of tooth enamel. Some regions in Mexico are considered endemic fluorosis zones due to the high fluoride content in drinking water. The objective of this study was to perform a systematic review and meta-analysis to identify the association between the concentration of fluoride in drinking water and the severity of dental fluorosis in northern and western Mexico. METHODS: This protocol was registered in the PROSPERO database (ID: CRD42023401519). The search for information was carried out in the PubMed/Medline, Scopus, SpringerLink, and Google Scholar databases between January 2015 and October 2023. The overall relative risk was calculated using the inverse of variance approach with the random effects method. The RoB 2.0 tool was used to construct risk plots. RESULTS: Eleven articles were analyzed qualitatively, and most of the included studies presented at least one level of DF severity; six articles were analyzed quantitatively, dividing them into two regions. In North region it was observed a higher prevalence of severe TF cases, corresponding to ≥ TF 5 category (4.78) [3.55, 6.42]. In the West region, most of the included studies presented a higher prevalence of less severe cases, corresponding to ≤ TF 4, in comparison with the North region (0.01) [0.00, 0.52], interpreted as a protective effect. CONCLUSION: The concentrations of fluorides in drinking water are reportedly high in these regions and are directly related to the severity of dental fluorosis experienced by the inhabitants. In the Northern region exists a major concentration of fluoride in drinking water compared with the Western region as well as a prevalence of higher severity cases of dental fluorosis.

Knowledge Attitude and Practices Regarding Dental Fluorosis among Saudi Subpopulations: A Questionnaire-based Study.

AIM: This study aims to examine the awareness, attitudes, and perceptions towards dental fluorosis in Hail, Saudi Arabia. MATERIALS AND METHODS: It was an epidemiological study with a descriptive cross-sectional design. Participants meeting the inclusion criteria were recruited from Hail, Saudi Arabia, through a convenient non-probability sampling strategy. The study planned to recruit at least 400 participants. However, (n = 419) was obtained during the 2 months of data collection. Data for the present study was collected using a validated questionnaire via Google form by disseminating it to the targeted population using non-probability snowball sampling through various social media platforms. The questionnaire comprised three parts including demographics (6 questions), a knowledge-related section comprised of (6 questions), and attitude relation portion (14 questions). RESULTS: The majority of participants (n = 369, 88.1%) were willing to undergo treatment for dental improvement. Additionally, most respondents (n = 389, 92.8%) advocated for government participation in preventive programs and emphasized the importance of raising public awareness. Furthermore, a significant proportion (n = 401, 95.7%) expressed interest in launching mass public health campaigns to prevent dental fluorosis. Females showed significantly higher awareness levels. CONCLUSION: The study highlights significant sociodemographic influences on awareness and attitudes towards dental fluorosis. While age, nationality, and income showed no impact, gender and education were significant factors. Despite gaps in knowledge, there was strong support for preventive measures. Esthetic concerns were evident, with high rates of dental consultations and recognition of social stigma. Targeted interventions are needed to address knowledge gaps and promote preventive measures, considering sociodemographic differences and broader social implications. CLINICAL SIGNIFICANCE: The findings could be the cornerstone for promoting preventive measures and improving consultation behaviors, ultimately enhancing the overall management and prevention of dental fluorosis in the community. How to cite this article: Siddiqui AA, Alanazi YA, Almagdawy EA, et al. Knowledge Attitude and Practices Regarding Dental Fluorosis among Saudi Subpopulations: A Questionnaire-based Study. J Contemp Dent Pract 2024;25(5):405-410.

Potential risk of dental fluorosis associated with different baby formulas and water brands marketed in Spain.

Despite efforts to promote breastfeeding, many babies aged <6 months receive only baby formula reconstituted with bottled water. The intake of high levels of fluoride during amelogenesis has been associated with hypomineralization of the tooth enamel, with aesthetic and mechanical repercussions. The objective of this study was to determine the potential risk of dental fluorosis associated with baby formulas marketed in Spain. We measured 26 baby formulas frequently consumed in Spain; 17 brands for babies aged <6 months, 5 for those aged >6 months, and 4 ready-to-use brands. They were prepared with 4 types of water: distilled water and three brands of bottled water with different levels of fluoride. The fluoride concentration (mg/L or ppm F) was measured with an ion-specific electrode coupled to an ion analyzer. Each sample was prepared according to the manufacturer's instructions and analyzed in triplicate. A descriptive analysis was carried out. The minimum fluoride level found was 0.04 mg/L and the maximum was 1.02 mg/L. Considering the daily intake of these formulas, none exceeded the clinically-acceptable daily dose limit risk for fluorosis (0.07 mg F/day/kg body weight) when mixed with bottled water with a low level of fluoride (0.1 mg/L). However, when the same brands of formula were reconstituted with bottled water with a higher fluoride content (0.99 mg/L), they all exceeded the daily dose limit for the risk of fluorosis. As the potential risk of dental fluorosis associated with the formulas tested depends exclusively on the fluoride concentration of the waters used for reconstitution, formula packaging should contain a warning.

A Bibliometric Analysis of the Top 100 Most-Cited Papers Concerning Dental Fluorosis.

A high number of citations can indicate the potential of any specific paper to influence other research and generate changes in clinical practice. Analyzing the most-cited papers in a certain scientific field may assist researchers to identify the influential papers as well their main characteristics. The present study aimed to analyze the 100 most-cited papers concerning dental fluorosis (DF) through a bibliometric review. A search was performed in the Web of Science Core Collection (WoS-CC) database in November 2021. The papers were displayed in descending order according to the number of citations in WoS-CC. Two independent researchers performed the selection. Scopus and Google Scholar were used to compare the number of citations with WoS-CC. The following data were extracted from the papers: title, authors, number and density of citations, institution, country, continent, year of publication, journal title, keywords, study design, and theme. Collaborative networks were generated using the VOSviewer software. The top 100 most-cited papers were published between 1974 and 2014 and were cited 6,717 times (ranging from 35 to 417). Community Dentistry and Oral Epidemiology (24%), Journal of Dental Research (21%), Journal of Public Health Dentistry (17%), and Caries Research (13%) published the most papers. Observational studies (60%) and literature reviews (19%) were the most common study designs. The main topics were epidemiology (44%) and fluoride intake (32%). The countries with the highest number of papers were the USA (44%), Canada (10%), and Brazil (9%). The University of Iowa (USA) had the most papers (12%). Levy SM was the author with the highest number of papers (12%). The 100 most-cited papers on DF were mainly observational studies focused on epidemiology and originated in North America. There were few interventional studies and systematic reviews among the most-cited papers concerning this topic.

Integrated 16S rDNA sequencing and metabolomics to explore the intestinal changes in children and rats with dental fluorosis.

Dental fluorosis (DF) is a widely prevalent disease caused by excessive fluoride with limited awareness of its underlying pathogenesis. Here, a pilot population study was conducted to explore the pathogenesis of DF from the perspective of intestinal microbiome changes, and verified it in animal experiments combining intestinal microbiome and metabolomics. A total of 23 children were recruited in 2017 in China and divided into DF (n = 9) and control (n = 14) groups (DFG and CG, respectively). The SD rat model was established by drinking water containing sodium fluoride (NaF). Gut microbiome profiles of children and rats were analyzed by16S rDNA V3-V4 sequencing, and the intestinal metabolomics analysis of rats was performed by LC-MS methods. The 16 S rDNA sequencing revealed that the gut microbiome composition was significantly perturbed in children in DFG compared to that in CG. Acidobacteria and Thermi were specifically observed in DFG and CG, respectively. Besides, 15 fecal microbiotas were significantly altered at the genus level in DFG. Furthermore, only the expression of annotated genes for pentose and glucuronate interconversion pathway was significant lower in DFG than that in CG (P = 0.04). Notably, in NaF-treated rats, we also observed the changes of some key components of pentose and glucuronate interconversion pathway at the level of microorganisms and metabolites. Our findings suggested that the occurrence of DF is closely related to the alteration of intestinal microorganisms and metabolites annotated in the pentose and glucuronate interconversion pathway.

Excessive fluoride impairs autophagy flux in ameloblasts which is prevented by the autophagy activator rapamycin.

Excessive fluoride intake can cause dental fluorosis during teeth development and growth. However, the mechanisms underlying fluoride-induced enamel damage are still not fully elucidated. Previously, we observed fluoride-induced autophagy in ameloblasts, but the effects of fluoride on autophagy flux in ameloblasts remain unclear. Hence, this study aimed to clarify the effects of fluoride and rapamycin, an autophagy activator, on autophagy flux in ameloblasts. This in vitro study used the murine ameloblast-derived cell line LS8. Cells were treated with different concentrations of sodium fluoride (NaF) to evaluate NaF-induced cytotoxicity. Using transmission electron microscopy, we observed an increase in the number of autophagosomes with increasing fluoride concentrations. Western blot analyses showed increases in microtubule-associated protein 1 light chain 3 (LC3) and SQSTM1 (p62) expression after NaF treatment and an increase in LC3II expression after bafilomycin A1 administration. Together with changes in RFP-GFP-LC3 lentivirus expression, this demonstrated that fluoride impaired autophagy flux. Furthermore, we evaluated whether rapamycin can alleviate fluoride-induced cytotoxicity by restoring autophagy flux. Compared to the NaF-treated group, LS8 cells cotreated with NaF and rapamycin grew considerably better and had significantly decreased p62 expression. Taken together, these data suggest that fluoride-induced impaired autophagosome degradation may damage ameloblasts. This provides experimental in vitro evidence and an explanation for the observed NaF-induced toxicity of ameloblasts. Rapamycin probably alleviates this impairment by decreasing the expression of p62, thereby preventing autophagy defects.

Toothbrushing practices as risk factors for dental fluorosis in an area with varying fluoride levels in drinking water.

BACKGROUND: Despite contributing to a reduction in dental caries, improper use of fluoridated toothpaste could add to the burden of dental fluorosis in children. AIM: To assess the association between tooth-brushing practices such as the type and amount of toothpaste used, frequency of tooth brushing, parental assistance in tooth brushing, timing of tooth brushing and dental fluorosis in school children in Kurunegala district, an endemic area for dental fluorosis in Sri Lanka. METHODS: For this case-control study, a sex-matched sample of 15-year-old school children attending government schools in Kurunegala district and who were lifetime residents of the district was selected. Dental fluorosis was measured using the Thylstrup and Ferjeskov (TF) Index. Those children with a TF⟩1 were considered as cases and those with a TF score of 0 or 1 served as controls. An interview of parents/caregivers of the participants was used to assess risk factors for dental fluorosis. The fluoride concentration in drinking water was measured using spectrophotometry. Data analysis used chi-square tests and conditional logistic regression. RESULTS: Tooth brushing ≥ twice/day, brushing after breakfast and parent/care giver brushing the child's teeth reduced the likelihood of developing fluorosis. CONCLUSION: Use of fluoridated toothpaste adhering to the recommended guidelines could prevent dental fluorosis in children in this endemic area.

Extended caries prevention programme with biannual application of fluoride varnish for toddlers: prevalence of dental fluorosis at ages 7-9 years and associated factors.

OBJECTIVE: To investigate the prevalence of and factors associated with dental fluorosis in children living in areas of high caries risk in Stockholm and who had participated in a prospective, parallel, cluster-randomized, controlled caries prevention trial between ages 1 and 3 years. MATERIALS AND METHODS: The study group comprised a random sample of the children who had completed the 2-year prevention trial (n = 2536) in 2011-2014. All children were instructed to use fluoride toothpaste; the test group received fluoride varnish applications twice a year. Dental fluorosis prevalences in the reference (n = 220) and the test (n = 234) groups were compared. Presence of fluorosis was determined using the Thylsturp & Fejerskov (TF) index on photos of the permanent maxillary incisors. RESULTS: No significant difference in dental fluorosis was observed between the two groups. Nearly one-third (29.7%) of the children in the study cohort exhibited dental fluorosis (TF index ≥ 1). Associations with use of fluoride toothpaste at age 1 year and with socioeconomic status factors were found. CONCLUSIONS: Biannual applications of fluoride varnish in toddlers was not associated with dental fluorosis, which when found was rarely of aesthetic concern. Parental education in tooth-brushing routines is recommended.