Table 3 Summary of findings in context of research questions

From: A systematic review of the efficacy and safety of fluoridation

Benefit/ risk Question Findings
Dental caries
 Water fluoridation Is intentional water fluoridation more effective than no water fluoridation in prevention of dental caries? Existing evidence strongly suggests water fluoridation is beneficial at reducing dental caries. After adjustment for potential confounding variables, it was shown2 that introducing water fluoridation into an area significantly increased proportion of caries-free children, and decreased mean dmft/DMFT scores vs areas that were non-fluoridated over the same time period. These findings2 also suggest cessation of fluoridation resulted in the difference in caries prevalence narrowing between fluoridated and nonfluoridated populations. Only one additional relevant original study was identified in the current review, which did not change the conclusion.
 Milk fluoridation Is intentional milk fluoridation more effective than no milk fluoridation in prevention of dental caries? Results of the SR suggest milk fluoridation is beneficial in preventing/ reducing caries but there is less good quality evidence than for water fluoridation. Results of two original studies included represent low levels of evidence but results are consistent with milk fluoridation being associated with caries prevention and cessation of milk fluoridation with worsening dental health.
 Salt fluoridation Is intentional salt fluoridation more effective than no salt fluoridation in prevention of dental caries? No studies were identified that met criteria for inclusion in review. Results of three before-and-after cross-sectional studies suggest salt fluoridation reduces caries in populations of children of age 6–15 years. Note that these studies were considered of poor methodological quality because of lack of assessment of and adjustment for potential confounding factors.
 Topical fluoride supplementation Is use of topical fluoride supplementation more efficacious than no topical fluoride supplementation in prevention of dental caries? There is consistent level I evidence from existing SR and a review of additional original studies that topical fluoride agents reduce caries in children vs no topical fluoride supplementation. Compared with placebo/ no treatment, magnitude of the effect achieved with varnish is greater than other topical agents but when compared directly there is no significant difference between agents.
 Combination of topical fluoride supplementation Is a combination of topical fluoride supplementation products more efficacious than a single topical fluoride supplement product in prevention of dental caries? There is level I evidence that some combinations of topical agents may be more effective at preventing/ reducing caries than single agents.
Dental fluorosis
 Water fluoridation Does intentional water fluoridation result in dental fluorosis over and above no intentional water fluoridation? There is consistent level III/IV evidence from existing SR that water fluoridation results in development of dental fluorosis but most of it is mild and not considered to be of aesthetic concern. The NNH with water fluoridation at an optimal level vs no fluoridation to get one additional person with any fluorosis is approx. 6. The corresponding NNH to get one additional person with fluorosis of aesthetic concern is approx. 22. Meta-analysis of additional original studies provides results consistent with those seen in the existing SR.
 Milk fluoridation Does intentional milk fluoridation result in dental fluorosis over and above no intentional milk fluoridation? One study provided level IV evidence that milk fluoridation is not associated with significant levels of fluorosis. A statistically significant increase in fluorosis was seen in a number of age groups following introduction of milk fluoridation but the majority of this fluorosis was mild and not considered to be of aesthetic concern.
 Salt fluoridation Does intentional salt fluoridation result in dental fluorosis over and above no intentional salt fluoridation? One level IV study provided evidence of a significantly increased risk of “any fluorosis” associated with salt fluoridation. Two additional supportive studies (not strictly meeting inclusion criteria) agreed with the included study. There were no data relating to risk of fluorosis of aesthetic concern.
 Topical fluoride supplementation Does topical fluoride supplementation result in dental fluorosis over and above no topical fluoride supplementation? Two level IV studies provide evidence regarding impact of use of topical fluorides on dental fluorosis. One study showed fluoridated toothpaste may be associated with “any fluorosis” but when “fluorosis of aesthetic concern” was examined, no statistically significant difference between higher fluoride dose and control groups was found, and prevalence of fluorosis in higher dose toothpaste group was low (<2%). One poor quality study in which fluorosis was measured after a campaign was implemented to reduce the amount of topical fluoride use in children suggested that a decrease in fluorosis was seen.
 Combination of topical fluoride supplementation Does a combination of topical fluoride supplementation products result in dental fluorosis over and above a single topical fluoride supplementation product? There is currently no evidence comparing combinations of topical agents with a single topical agent.
Fracture or osteoporosis
 Water fluoridation Does intentional water fluoridation result in fracture over and above no intentional water fluoridation? Authors of three existing SR concur that water fluoridation at levels aimed at preventing dental caries has little effect on fracture risk, either protective or deleterious. Results of subsequent original studies support this, but do suggest optimal fluoridation levels of 1 ppm may result in a lower risk of fracture vs excessively high levels (well beyond those experienced in Australia). One study also indicated optimal fluoridation levels may lower overall fracture risk vs no fluoridation (the latter was not the case when hip fractures were considered in isolation).
 Milk fluoridation Does intentional milk fluoridation result in osteoporosis or fracture over and above no intentional milk fluoridation? There is currently no evidence available to determine impact of milk fluoridation upon fracture risk.
 Salt fluoridation Does intentional salt fluoridation result in osteoporosis or fracture over and above no intentional salt fluoridation? There is currently no evidence available to determine impact of salt fluoridation upon fracture risk.
 Topical fluoride supplementation Does topical fluoride supplementation result in osteoporosis or fracture over and above no topical fluoride supplementation? There is currently no evidence available to determine impact of topical fluoride supplementation upon fracture risk.
 Combination of topical fluoride supplementation Does a combination of topical fluoride supplementation products result in osteoporosis or fracture over and above a single topical fluoride supplementation product? There is currently no evidence available to determine impact of combination topical fluoride supplementation upon fracture risk.
Cancer
 Water fluoridation Does intentional water fluoridation increase risk of cancer over and above no intentional water fluoridation? The existing SR2 concluded there is no clear association between water fluoridation and overall cancer incidence or mortality (for “all cause” cancer, and specifically for bone cancer and osteosarcoma). The authors state that evidence relating fluoridation to cancer incidence or mortality is mixed, with small variations on either side of the effect. The current literature review identified four additional studies investigating relationship between water fluoridation and cancer incidence or mortality, including three level IV ecological studies and one level II-3 matched case–control study.3 The latter study compares fluoride exposure of histologically-confirmed osteosarcoma cases with that of matched controls (subset of patients from larger case–control study by Harvard School of Dental Medicine yet to report its findings). After adjusting for significant differences at baseline between cases and controls, results3 suggest an increased risk of osteosarcoma in young males (not females) with water fluoridation but note the letter from co-investigators which points out that they have not been able to replicate these findings in the broader Harvard study which included prospective cases from the same 11 hospitals. The bone samples taken in the broader study also corroborate a lack of association between fluoride content in drinking water and osteosarcoma in new cases. The full study is not yet published and the letter's authors caution readers not to over-interpret results3 in the interim.
 Milk fluoridation Does intentional milk fluoridation increase risk of cancer over and above no intentional milk fluoridation? There is currently no evidence available to determine impact of milk fluoridation upon cancer risk.
 Salt fluoridation Does intentional salt fluoridation increase risk of cancer over and above no intentional salt fluoridation? There is currently no evidence available to determine impact of salt fluoridation upon cancer risk.
 Topical fluoride supplementation Does topical fluoride supplementation increase risk of cancer over and above no topical fluoride supplementation? There is currently no evidence available to determine impact of topical fluoride supplementation upon cancer risk.
 Combination of topical fluoride supplementation Does a combination of topical fluoride supplementation products increase risk of cancer over and above a single topical fluoride supplementation product? There is currently no evidence available to determine impact of combination topical fluoride supplementation upon cancer risk.
Other adverse effects
 Water fluoridation Is intentional water fluoridation associated with other adverse effects over and above no intentional water fluoridation? Authors of previous SR concluded that studies examining other possible negative effects of water fluoridation provide insufficient evidence to reach a conclusion.
 Milk fluoridation Is intentional milk fluoridation associated with other adverse effect over and above no intentional milk fluoridation? There is currently no evidence available to determine impact of milk fluoridation upon other harms.
 Salt fluoridation Is intentional salt fluoridation associated with other adverse effects over and above no intentional salt fluoridation? There is currently no evidence available to determine impact of salt fluoridation upon other harms.
 Topical fluoride supplementation Is topical fluoride supplementation associated with other adverse effects over and above no topical fluoride supplementation? There is currently no evidence available to determine impact of topical fluorides upon other harms.
 Combination of topical fluoride supplementation Is a combination of topical fluoride supplementation products associated with other adverse effects over and above a single topical fluoride supplementation product There is currently no evidence available to determine impact of combination topical fluorides upon other harms.
  1. dmft/DMFT, Decayed, missing or filled teeth of the primary or permanent dentition; SR, systematic review; NNH, number needed to harm.