Advances in Dental Research最新文献

Since the classical epidemiological studies by Dean, it has been known that there should be an optimum level of exposure to fluoride that would be able to provide the maximum protection against caries, with minimum dental fluorosis. The "optimal" daily intake of fluoride for children (0.05-0.07 mg per kilogram bodyweight) that is still accepted worldwide was empirically determined. In the present review, we discuss the appropriateness of the current guidance for fluoride intake, in light of the windows of susceptibility to caries and fluorosis, the modern trends of fluoride intake from multiple sources, individual variations in fluoride metabolism, and recent epidemiological data. The main conclusion is that it is very difficult to think about a strict recommendation for an "optimal" range of fluoride intake at the individual level in light of existing knowledge of 1) the mechanisms of action of fluoride to control caries, 2) the mechanisms involved in dental fluorosis development, 3) the distinct factors that interfere in the metabolism of fluoride, and 4) the windows of susceptibility to both dental caries and fluorosis development. An "optimal" range of fluoride intake is, however, desirable at the population level to guide programs of community fluoridation, but further research is necessary to provide additional support for future decisions on guidance in this area. This list includes the effect of factors affecting fluoride metabolism, clinical trials on the effectiveness of low-fluoride dentifrices to prevent caries in the primary dentition, and validation of biomarkers of exposure to fluoride.

Policy on fluoride intake involves balancing caries against dental fluorosis in populations. The origin of this balance lies with Dean's research on fluoride concentration in water supplies, caries, and fluorosis. Dean identified cut points in the Index of Dental Fluorosis of 0.4 and 0.6 as critical. These equate to 1.3 and 1.6 mg fluoride (F)/L. However, 1.0 mg F/L, initially called a permissible level, was adopted for fluoridation programs. McClure, in 1943, derived an "optimum" fluoride intake based on this permissible concentration. It was not until 1944 that Dean referred to this concentration as the "optimal" concentration. These were critical steps that have informed health authorities through to today. Several countries have derived toxicological estimates of an adequate and an upper level of intake of fluoride as an important nutrient. The US Institute of Medicine (IOM) in 1997 estimated an Adequate Intake (AI) of 0.05 mg F/kg bodyweight (bw)/d and a Tolerable Upper Intake Level (UL) of 0.10 mg F/kg bw/d. These have been widely promulgated. However, a conundrum has existed with estimates of actual fluoride intake that exceed the UL without the expected adverse fluorosis effects being observed. Both the AI and UL need review. Fluoride intake at an individual level should be interpreted to inform more nuanced guidelines for individual behavior. An "optimum" intake should be based on community perceptions of caries and fluorosis, while the ultimate test for fluoride intake is monitoring caries and fluorosis in populations.

The purpose of this report is to examine critically the appropriateness of the current guidance for fluoride intake in the population (0.05-0.07 mg F/kg bodyweight/d), consider whether changes to the current guidance are desirable, and suggest further research that will strengthen the evidence base for future decisions on guidance/advice in this area. The benefits and the risks of using fluoride particularly concern preschool children because it is at this age that excessive fluoride intake may result in dental fluorosis. Data from mostly cross-sectional studies show a wide variation in exposure and a considerable variation in the amount of fluoride ingested. Fluorosis, mostly mild, is commonly observed. For considering changes in current guidance, there is a need for more knowledge on the relationship between exposure to fluoride at an early age and the development of fluorosis. For that, prospective epidemiological studies with sufficiently large and representative samples of children are required. It is also important to study children in communities both with and without water fluoridation and to include populations where salt or milk fluoridation is used. There is also a need for professional agreement on acceptable levels of mild and moderate/severe fluorosis and a more comprehensive knowledge on the appreciation of mild fluorosis among the public.

Cariogenic biofilms are highly structured microbial communities embedded in an extracellular matrix, a multifunctional scaffold that is essential for the existence of the biofilm lifestyle and full expression of virulence. The extracellular matrix provides the physical and biological properties that enhance biofilm adhesion and cohesion, as well as create a diffusion-modulating milieu, protecting the resident microbes and facilitating the formation of localized acidic pH niches. These biochemical properties pose significant challenges for the development of effective antibiofilm therapeutics to control dental caries. Conventional approaches focusing solely on antimicrobial activity or enhancing remineralization may not achieve maximal efficacy within the complex biofilm microenvironment. Recent approaches disrupting the biofilm microbial community and the microenvironment have emerged, including specific targeting of cariogenic pathogens, modulation of biofilm pH, and synergistic combination of bacterial killing and matrix degradation. Furthermore, new "smart" nanotechnologies that trigger drug release or activation in response to acidic pH are being developed that could enhance the efficacy of current and prospective chemical modalities. Therapeutic strategies that can locally disrupt the pathogenic niche by targeting the biofilm structure and its microenvironment to eliminate the embedded microorganism and facilitate the action of remineralizing agents may lead to enhanced and precise anticaries approaches.

Remineralization of caries lesions is naturally achieved by salivary ions, and it can be enhanced by external factors or elements such as fluoride. Numerous studies have demonstrated the remineralizing efficacy of fluoride therapies as well as the limitations with some groups of the population. Consequently, developing new remineralization therapies to close this gap in efficacy has been a priority for the last 2 decades. In this review, we summarize and briefly discuss some of the latest advances in remineralization therapies. Most new therapies try to enhance the effect of fluoride by adding other potentially active ingredients to the formulation, such as calcium, phosphate, stannous, xylitol, and arginine. Other remineralization strategies have focused on creating remineralizing scaffolds within the lesions (e.g., self-assembling peptides). While several of the new remineralization strategies have progressed significantly in recent years, for most of them, the evidence is still insufficient to assess their true clinical potential.

Medical management of caries is a distinct treatment philosophy that employs topical minimally invasive therapies that treat the disease and is not merely prevention. This strategy is justified as an alternative or supplement to traditional care by significant disease recurrence rates following comprehensive operative treatment under general anesthesia. Silver diamine fluoride (SDF) is one agent to enable effective noninvasive treatment. The announcement of breakthrough therapy designation by the Food and Drug Administration (FDA) suggests that SDF may become the first FDA-approved drug for treating caries. Since our systematic review performed in April 2015, 4 clinical trials have been completed, which inform an update to the application protocol and frequency regimen. Suggestions from these studies are to skip the rinsing step due to demonstration of safety in young children, start patients with high disease severity on an intensive regimen of multiple applications over the first few weeks, and continue with semiannual maintenance doses as previously suggested. Breakthroughs in elucidating the impact of SDF on the dental plaque microbiome inform potential opportunities for understanding caries arrest. SDF can be added to the set of evidence-based noninvasive methods to treat caries lesions in primary teeth, such as the Hall crown technique and sealing lesions with accessible margins.