Fluoride

BACKGROUND:
A review of the literature of the element fluorine and its bonded-form, fluoride, was undertaken. Generally regarded as safe, an expanding body of literature reveals that fluoride’s toxicity has been unappreciated, un-scrutinized, and hidden for over 70 years. The context for the literature search and review was an environmental climate-change study, which demonstrated widespread fluoride contamination by smokestack emissions from coal-fired electricity-generating plants. The objective of this review is to educate and inform regarding the ubiquitous presence and harmful nature of this now ever-present corrosive and reactive toxin.

METHODS:
Methods include examination of national health agency reviews, primarily the National Research Council (NRC), Agency for Toxic Substances & Disease Registry (ATSDR), standard medical toxicology references, text books, as well as reports and documents from both private and public research as well as consumer-based NGOs. Study criteria were chosen for relevancy to the subject of the toxicity of fluoride.

RESULTS:
Fluoride is the extreme electron scavenger, the most corrosive of all elements, as well as the most-reactive. Fluoride appears to attack living tissues, via several mechanisms. Fluoride renders strong evidence that it is a non-biological chemical, demonstrating no observed beneficial function or role in organic chemistry, beyond use as a pesticide or insecticide. Fluorine has a strong role to play in industry, having been utilized extensively in metals, plastics, paints, aluminium, steel, and uranium production.

CONCLUSION:
Due to its insatiable appetite for calcium, fluorine and fluorides likely represent a form of chemistry that is incompatible with biological tissues and organ system functions. Based on an analysis of the affects of fluoride demonstrated consistently in the literature, safe levels have not been determined nor standardized. Mounting evidence presents conflicting value to its presence in biological settings and applications. Evidence examined in this review of the literature, and specifically the recent report by the National Research Council (NRC), offer strong support for an immediate reconsideration concerning risk vs benefit. Consensus recommendations from several sources are presented.

“Excessive systemic exposure to fluoride (F) can lead to disturbances in bone homeostasis and dental enamel development. We have previously shown strain-specific responses to F in the development of dental fluorosis (DF) and in bone formation/mineralization. The current study was undertaken to further investigate F responsive variations in bone metabolism and to determine possible relationships with DF susceptibility. Seven-week-old male mice from FVB/NJ, C57BL/6J, C3H/HeJ, A/J, 129S1/SvImJ, AKR/J, DBA/2J, and BALB/cByJ inbred strains were exposed to NaF (0 or 50 ppm as F–) in drinking water for 60 days. Sera were collected for F, Ca, Mg, PO4, iPTH, sRANKL, and ALP levels. Bone marrow cells were subjected to ex vivo cell culture for osteoclast potential and CFU colony assays (CFU-fibroblast, CFU-osteoblast, CFU-erythrocyte/granulocyte/macrophage/megakaryocyte, CFU-granulocyte/macrophage, CFU-macrophage, and CFU-granulocyte). Femurs and vertebrae were subjected to micro-CT analyses, biomechanical testing, and F, Mg, and Ca content assays. DF was evaluated using quantitative fluorescence and clinical criteria. Strain-specific responses to F were observed for DF, serum studies, ex vivo cell culture studies, and bone quality. Among the strains, there were no patterns or significant correlations between DF severity and the actions of F on bone homeostasis (serum studies, ex vivo assays, or bone quality parameters). The genetic background continues to play a role in the actions of F on tooth enamel development and bone homeostasis. F exposure led to variable phenotypic responses between strains involving dental enamel development and bone metabolism. “

“Aim: Our aim was to test the hypothesis that co-exposure to lead and fluoride alter the severity of enamel fluorosis. Materials and methods: Wistar rats were allocated in four groups: control, and 3 groups that received water containing 100 ppm of fluoride (F), 30 ppm of lead (Pb), or 100 ppm of F and 30 ppm of Pb (F + Pb) from the beginning of gestation. Enamel analysis and F and Pb determinations in enamel, dentine, and bone were performed in 81-day-old animals. Fluorosis was quantified using a new fluorosis index based on the identification of incisor enamel defects (white bands and white islets, representing hypomineralization, and cavities) weighted according to their severity and quantity. Hypomineralization was validated histopathologically by polarizing microscopy and microradiography. Scores were given by two blinded calibrated examiners (intra and interexaminer kappa values were 0.8 and 0.86, respectively). Results: The control and the Pb groups presented normal enamel. The F + Pb group presented more severe enamel defects compared with the F group (P < 0.0001). Conclusions: This study shows that lead exacerbates dental fluorosis in rodents, suggesting that co-exposure to lead may affect the degree of fluorosis.”

“The association between fluoride and risk for osteosarcoma is controversial. The purpose of this study was to determine if bone fluoride levels are higher in individuals with osteosarcoma. Incident cases of osteosarcoma (N = 137) and tumor controls (N = 51) were identified by orthopedic physicians, and segments of tumor-adjacent bone and iliac crest bone were analyzed for fluoride content. Logistic regression adjusted for age and sex and potential confounders of osteosarcoma was used to estimate odds ratios (OR) and 95% confidence intervals (CI). There was no significant difference in bone fluoride levels between cases and controls. The OR adjusted for age, gender, and a history of broken bones was 1.33 (95% CI: 0.56-3.15). No significant association between bone fluoride levels and osteosarcoma risk was detected in our case-control study, based on controls with other tumor diagnoses. “

“Lesions of skeletal and dental fluorosis have been described recently in eastern grey kangaroos (Macropus giganteus). The present study further examined the epidemiology of skeletal fluorosis in this species. Bone fluoride concentrations were obtained from a range of skeletal sites of animals from a high (Portland Aluminium) and a low (Cape Bridgewater) fluoride environment in Victoria, Australia. Age, but not sex, affected the mean bone fluoride concentration of kangaroos. For a given age, bone fluoride concentrations were significantly higher in kangaroos from Portland than Cape Bridgewater. Concentrations varied between skeletal sites examined, with samples containing cancellous bone having higher fluoride concentrations than those containing only cortical bone. “

“Objectives: Amoxicillin use has been reported to be associated with developmental defects on enamel surfaces. This analysis assessed the association between amoxicillin use and fluorosis on late-erupting permanent teeth.

Methods: As part of the Iowa Fluoride Study, subjects were followed from birth to 32 months with questionnaires every 3-4 months to gather information on fluoride intake and amoxicillin use (n = 357 subjects for this analysis). Permanent tooth fluorosis on late-erupting zones was assessed by three trained dentists using the fluorosis risk index (FRI) at approximately age 13. A case was defined as fluorosis if a subject had at least two FRI classification II zone scores of 2 or 3. Chi-square tests and logistic regression were used, and relative risks (RRs) and odds ratios (ORs) were calculated.

Results: There were 113 cases and 244 controls. In bivariate analyses, amoxicillin use from 20 to 24 months significantly increased the risk of fluorosis on FRI classification II zones [44.2 percent versus 30.4 percent, [RR = 1.45, 95 percent confidence interval (CI) 1.05-2.04], but other individual time periods did not.  Multivariable logistic regression confirmed the increased risk of fluorosis for amoxicillin use from 20 to 24 months (OR = 2.92, 95 percent CI = 1.34-6.40), after controlling for otitis media, breast-feeding, and fluoride intake.

Conclusions: Amoxicillin use during early childhood could be a risk factor in the etiology of fluorosis on late-erupting permanent tooth zones, but further research is needed.”

“Objectives: Multiple systematic reviews have evaluated fluorides for caries prevention in children, but a need to review the literature regarding supplemental fluoride use in adults still remains. The purpose of this systematic review is to evaluate the research regarding professional and/or supplemental self-applied fluoride for preventing and remineralizing caries in moderate and high caries risk adults.

Methods: Utilizing multiple databases, a comprehensive search was undertaken in both foreign and English languages. Studies included were randomized control trials (RCT) or clinical trials conducted in moderate or high caries risk adult populations, evaluating self- or professionally applied fluoride with the outcomes of caries reduction/remineralization. Studies were excluded if they were in situ, in vitro, split mouth design, or with unclear outcomes specific to fluorides. A quality evaluation of the studies used a checklist of critical domains and elements for an RCT.

Results: Seventeen studies were included in the systematic review. Findings were categorized into the following groups: sodium fluoride (NaF) and amine/potassium fluoride mouthrinses of varying strengths, NaF gels and pastes, NaF varnish, and stannous fluoride. Quality evaluation scores varied from 50.2 percent to 88.9 percent.

Conclusions: The strongest studies demonstrated the following modalities as moderately effective in higher caries risk adults: low strength NaF rinses [relative risk reduction (RRR) for carious lesions: 50-148 percent]; 1.1 percent NaF pastes/gels (RRR for root lesion remineralization: 35-122 percent); fluoride varnishes [RRR for RC remineralization: 63 percent; RRR for decrease in decayed, missing, and filled surfaces: 50 percent]. Evidence regarding 1.1 percent NaF and 5 percent NaF varnishes related primarily to root caries and older adults.”

“Knowledge of all aspects of fluoride metabolism is essential for comprehending the biological effects of this ion in humans as well as to drive the prevention (and treatment) of fluoride toxicity. Several aspects of fluoride metabolism – including gastric absorption, distribution and renal excretion – are pH-dependent because the coefficient of permeability of lipid bilayer membranes to hydrogen fluoride (HF) is 1 million times higher than that of F(-). This means that fluoride readily crosses cell membranes as HF, in response to a pH gradient between adjacent body fluid compartments. After ingestion, plasma fluoride levels increase rapidly due to the rapid absorption from the stomach, an event that is pH-dependent and distinguishes fluoride from other halogens and most other substances. The majority of fluoride not absorbed from the stomach will be absorbed from the small intestine. In this case, absorption is not pH-dependent. Fluoride not absorbed will be excreted in feces. Peak plasma fluoride concentrations are reached within 20-60 min following ingestion. The levels start declining thereafter due to two main reasons: uptake in calcified tissues and excretion in urine. Plasma fluoride levels are not homeostatically regulated and vary according to the levels of intake, deposition in hard tissues and excretion of fluoride. Many factors can modify the metabolism and effects of fluoride in the organism, such as chronic and acute acid-base disturbances, hematocrit, altitude, physical activity, circadian rhythm and hormones, nutritional status, diet, and genetic predisposition. These will be discussed in detail in this review.”

BACKGROUND:

Dietary fluoride supplements were first introduced to provide systemic fluoride in areas where water fluoridation is not available. Since 1990, the use of fluoride supplements in caries prevention has been re-evaluated in several countries.

OBJECTIVES:

To evaluate the efficacy of fluoride supplements for preventing dental caries in children.

SEARCH METHODS:

We searched the Cochrane Oral Health Group’s Trials Register (to 12 October 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 3), MEDLINE via OVID (1950 to 12 October 2011), EMBASE via OVID (1980 to 12 October 2011), WHOLIS/PAHO/MEDCARIB/LILACS/BBO via BIREME (1982 to 12 October 2011), and Current Controlled Trials (to 12 October 2011). We handsearched reference lists of articles and contacted selected authors.

SELECTION CRITERIA:

We included randomised or quasi-randomised controlled trials comparing, with minimum follow-up of 2 years, fluoride supplements (tablets, drops, lozenges) with no fluoride supplement or with other preventive measures such as topical fluorides in children less than 16 years of age at the start. The main outcome was caries increment measured by the change in decayed, missing and filled tooth surfaces (DMFS).

DATA COLLECTION AND ANALYSIS:

Two review authors, independently and in duplicate, assessed the eligibility of studies for inclusion, and carried out risk of bias assessment and data extraction. In the event of disagreement, we sought consensus and consulted a third review author. We contacted trial authors for missing information. We used the prevented fraction (PF) as a metric for evaluating the efficacy of the intervention. The PF is defined as the mean caries increment in controls minus mean caries increment in the treated group divided by mean caries increment in controls. We conducted random-effects meta-analyses when data could be pooled. We assessed heterogeneity in the results of the studies by examining forest plots and by using formal tests for homogeneity. We recorded adverse effects (fluorosis) when the studies provided relevant data.

MAIN RESULTS:

We included 11 studies in the review involving 7196 children.In permanent teeth, when fluoride supplements were compared with no fluoride supplement (three studies), the use of fluoride supplements was associated with a 24% (95% confidence interval (CI) 16 to 33%) reduction in decayed, missing and filled surfaces (D(M)FS). The effect of fluoride supplements was unclear on deciduous or primary teeth. In one study, no caries-inhibiting effect was observed on deciduous teeth while in another study, the use of fluoride supplements was associated with a substantial reduction in caries increment.When fluoride supplements were compared with topical fluorides or with other preventive measures, there was no differential effect on permanent or deciduous teeth.The review found limited information on the adverse effects associated with the use of fluoride supplements.

AUTHORS’ CONCLUSIONS:

This review suggests that the use of fluoride supplements is associated with a reduction in caries increment when compared with no fluoride supplement in permanent teeth. The effect of fluoride supplements was unclear on deciduous teeth. When compared with the administration of topical fluorides, no differential effect was observed. We rated 10 trials as being at unclear risk of bias and one at high risk of bias, and therefore […]

In spite of decades of research on fluoride and the recognition of its role as the cornerstone of dental caries reduction in the last fifty years, questions still arise on its use at community, self-applied and professional application levels. Which method of fluoride delivery should be used? How and when should it be used? How can its benefits be maximized and still reduce the risks associated with its use? These are only some of the challenging questions facing us daily. The aim of this paper is to present scientific background to understand the importance of each method of fluoride use considering the current caries epidemiological scenario, and to discuss how individual or combined methods can be used based on the best evidence available.