FLUORIDE 31(2), 1998, 119-126	International Society for Fluoride Research	Table of Contents

The following CRITICAL REVIEW, by a professor at the School of Dentistry in San Francisco, has been sent to this journal. Dr Colquhoun's response is on pages 127-128.

I find this publication informational but biased in its details. I cannot conclude that water fluoridation is ineffective or harmful based on this paper, although Colquhoun attempts to persuade the reader of the correctness of his views. I base these conclusions on the following points.

1. In New Zealand there is a national School Dental Service that provided regular six-monthly dental treatment, with strictly enforced uniform diagnostic standards, to almost all (98 percent) school children up to the age of 12 or 13 years.

Over the next few years, these treatment statistics, collected for all children, showed that when similar fluoridated or unfluoridated areas were compared, child dental health continued to be slightly better in the fluoridated areas.

These are quotes from this paper which show that New Zealand has had a school-based dental treatment program and that, at least at one period of time Colquhoun acknowledges that fluoridation appeared to be of benefit. The school-based program provides treatment and prevention services, including application of fluorides and is a model of dental services that does not exist in many parts of the world, and not in California. It appears that Colquhoun has demonstrated that the school-based dental service, in part, has provided what fluoridation can provide. Colquhoun however does not address the issue of cost-effectiveness and presumably the dental service is far more expensive than fluoridation.

2. In comparing the work by Yiamouyiannis and that by Brunelle and Carlos of the U.S. 1986-87 national study on dental caries, Colquhoun states: 'Another publication using the same data base (Brunelle and Carlos) apparently intended to counter that findings (by Yiamouyiannis) reported that when a more precise measurement of decay was used, a small benefit from fluoridation was shown (20 percent fewer decayed tooth surfaces, which is really less than one cavity per child).' Since the publication by Yiamouyiannis includes an analysis of the publication by Brunelle and Carlos, then the journal Fluoride must have published Yiamouyiannis after the Journal of Dental Research published Brunelle and Carlos. Thus Colquhoun's conclusion that Brunelle and Carlos 'apparently intended to counter that findings (by Yiamouyiannis)' is misleading.

Colquhoun appears to have implied that because he didn't receive a reply from his American colleagues about the result of the national U.S. study and because Yiamouyiannis obtained the results 'resorting to the U.S. Freedom of Information Act' that the results would otherwise have not been published. On the contrary, they were published in 1989. (JA Brunelle. Oral health of United States children, national and regional findings. DHSS Publication No. (NIH) 89-2247, U.S. Government Printing Office, Washington, DC, 1989.)

Thus it appears that Colquhoun fuels the fires of an alleged conspiracy at the highest levels of dental research in the U.S. to withhold information from the public and to bias the findings.

3. Colquhoun refers to some authors by name without title and others by name with titles, with those whose work supports that of Colquhoun with their title, for example 'Dr John Yiamouyiannis', 'Professor Steelink' and 'Professor Teotia', as if by adding their title they are afforded a higher place in Colquhoun's hierarchy. This indicates bias.

4. The work of Teotia in India concerns areas with very high fluoride beyond the recommended concentrations for water fluoridation.

5. Colquhoun suggests that the improved nutrition (without regard to sugar consumption) in most industrialized countries that has occurred since the 1930s and after World War II may be more important than fluorides in the prevention of tooth decay. However, he acknowledges that 'I do not know the answer for sure', and indeed does not refer to any epidemiologic studies that have shown that general nutrition is a greater factor than fluorides in the prevention of tooth decay in communities where people do not generally suffer from malnutrition.

Malnutrition that accompanies wartime periods and remote and isolated communities and countries such as New Zealand in the 1930's has been linked with increases and decreases in tooth decay prevalence, depending on the availability of sugar. Colquhoun rightly points to 'The increase in tooth decay in third-world countries, much of which has been attributed to worsening nutrition.

6. Colquhoun points out 'the studies showing little if any benefit from fluoridation have been published since 1980. Are there contrary findings? Yes: many more studies, published in dental professional journals, claim that there is a benefit to teeth from water fluoride.' However Colquhoun asserts that in all of the studies published in dental professional journals there is bias in population selection and examiner diagnosis and that 'most of the examiners were keen fluoridationists'.

It was my experience in recruiting and standardizing examiners for the California Oral Health Needs Assessment of Children, 1993-94, that none of the examiners could be described as 'keen fluoridationists'.

To overcome the potential of bias on the part of examiners, a study in England transported children from fluoridated and nonfluoridated communities to the examination site and had children wear a smock over their school uniforms so that the examiners would be 'blind' to where the children came from. That study found a benefit of fluoridation in the prevention of tooth decay in children who had been exposed to fluoridation for the first time after the age of 12 years. That study demonstrated that fluoridation does not have to be consumed from infancy to be of benefit. (Hardwick JL, Teasdale J, Bloodworh G. Caries increments over 4 years in children aged 12 at the start of water fluoridation. British Dental Journal 153 (6) 217-222 1982).

This, and other studies have shown that fluoridation of water supplies exerts a benefit systemically as well as topically. The salivary concentration of fluoride is higher in fluoridated areas, and the fluoride in saliva exerts a topical effect on teeth to remineralize the enamel to prevent tooth decay.

However, Colquhoun asserts that fluoridation is of 'little if any value' and 'there is negligible benefit from swallowing fluoride'.

7. Colquhoun in discussing fluorosis states: 'Some of these children with these teeth had used fluoride toothpaste and swallowed much of it. But I could not find children with this kind of fluorosis in the nonfluoridated parts of my Health District, except in children who had been given fluoride tablets at the recommended dose at the time.'

In this matter there is general consensus that recent increases in dental fluorosis are attributed to fluoride toothpaste being swallowed by very young children and by fluoride tablets being originally at too high a dose and also being inappropriately prescribed or ingested more frequently than recommended. As a consequence, recommendations have been made to limit the amount of fluoride toothpaste used to a 'pea-size' amount and a lowering of the recommended dose of fluoride supplementation in nonfluoridated communities.

However the influence of fluoride in water fluoridation as being harmful in this way is not generally accepted.

8. The evidence on the role of water fluoridation and hip fracture has been the subject of a number of reviews. 'With respect to hip fractures and bone health, there is no scientific evidence for altering current public health policy on the use of fluorides for caries prevention'. (WHO Expert Committee on Oral Health Status and Fluoride Use. Fluorides and Oral Health, WHO technical report series #846, World Health Organization. 1994).

A 1993 review for the U.S. National Research Council addressed fluoride and bone fractures. Of six epidemiological studies using geographic comparison with no actual fluoride intake data, four found a weak association. Of two additional studies examining before and after fluoridation data, one found a negative association and the other no association. One additional essentially geographic comparison found increased risk of hip fracture at 4 mg/L and another where individual exposure data were collected showed no difference in risk.

With regard to animal studies, 'the subcommittee concluded that the weight of evidence indicates that bone strength is not adversely affected in animals that are fed a nutritiously adequate diet unless there is long-term ingestion of fluoride at concentrations of at least 50 mg/L of drinking water or 50 mg/kg in diet.' (National Academy Press: Health Effects of Ingested Fluoride; Subcommittee on Health Effects of Ingested Fluoride; Committee on Toxicology, National Research Council; 1993.)

Colquhoun, in his review of fluoride and hip fractures, points to studies published in 1989-90 indicating high doses of fluoride used to treat osteoporosis 'actually caused more hip fractures.'

In recognition of the results of those studies, a lowered protocol of fluoride was used with successful results, which Colquhoun has not included in his 1997 publication. (CYC Pak et al. Slow-release sodium fluoride in the management of postmenopausal osteoporosis. Annals of Internal Medicine. April 15, 1994 Vol 120: No. 8. p 625.) These authors concluded that their regimen of 'intermittent slow-release sodium fluoride plus continuous calcium citrate, administered for about 2.5 years, inhibits new vertebral fractures, increases the mean spinal bone mass without decreasing the radial shaft bone density, and is safe to use.' No patient in either experimental or control group developed microfractures, or blood loss anemia. These patients received 25 mg slow-release NaF twice daily in repeated 14 month cycles of 12 months on and 2 months off treatment, compared to a placebo, with both groups receiving 400 mg calcium twice daily.)

In recognition of the study by Pak et al, the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIM) issued a press release stating: This regimen (CYC Pak et al. Slow-release sodium fluoride in the management of post-menopausal osteoporosis. Annals of Internal Medicine. April 15, 1994 Vol 120: No. 8. p 625.) supports the use of fluoride at high doses for this condition, but has no bearing on fluoridation of water supplies. It adds weight to the hypothesis that there is no positive association between fluoride intake and bone fracture. (National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIM): Fluoride offers hope for treating osteoporosis. Press Release. April 14, 1994.)

9. With regard to studies in Finland, the researchers who had examined autopsy samples of the anterior iliac crest in 1980 and found the highest fluoride content of bone ash from women with severe osteoporosis, also found in 1986 that hip fracture incidence was not affected by fluoridation (Arnala I, Alhava EM, Kivivuori R, Kauranen P. Hip fracture incidence not affected by fluoridation. Osteofluorosis studied in Finland. Acta Orthopaedica 57 (4) 344-349 August 1986). However, Colquhoun did not include this later study in his publication.

Abstract: Iliac crest biopsies were taken from patients with hip fracture from a low-fluoride area (less than 0.3 ppm), from an area with fluoridated drinking water (1.0-1.2 ppm), and from a high-fluoride area (greater than 1.5 ppm). Fluoride content analysis and histomorphometry of bone were performed. The hip fracture incidence during 1972-1981 was studied in the same areas. The fluoride content of the bone samples correlated with drinking water fluoride. In patients with hip fracture, both osteomalacia and osteoporosis were common. In the high-fluoride area also osteofluorosis was found in many patients. Osteofluorosis may occur if the fluoride content of trabecular bone exceeds 4,000 ppm and either the volumetric density of osteoid or osteoid-covered trabecular bone surface is abnormally increased. There was no difference in incidence of hip fracture in the three areas.

10. A 1996 review on water fluoridation and osteoporotic fractures is included here as background on this subject: Hillier S, Inskip E, Coggon D, Cooper C. Water fluoridation and osteoporotic fracture. Community Dental Health Suppl 2 63-68 September 13 1996.

Abstract: Osteoporotic fractures constitute a major public health problem. These fractures typically occur at the hip, spine and distal forearm. Their pathogenesis is heterogenous, with contributions from both bone strength and trauma. Water fluoridation has been widely proposed for its dental health benefits, but concerns have been raised about the balance of skeletal risks and benefits of this measure. Fluoride has potent effects on bone cell function, bone structure and bone strength. These effects are mediated by the incorporation of fluoride ions in bone crystals to form fluoroapatite, and through an increase in osteoblast activity. It is believed that a minimum serum fluoride level of 100 mg/ml must be achieved before osteoblasts will be stimulated. Serum levels associated with drinking water fluoridated to 1 ppm are usually several times lower than this value, but may reach this threshold at concentrations of 4 ppm in the drinking water. Animal studies suggest no effect of low-level (0-3 ppm) fluoride intake on bone strength, but a possible decrease at higher levels. Sodium fluoride has been used to treat established osteoporosis for nearly 30 years. Recent trials of this agent, prescribed at high doses, have suggested that despite a marked increase in bone mineral density, there is no concomitant reduction in vertebral fracture incidence. Furthermore, the increase in bone density at the lumbar spine may be achieved at the expense of bone mineral in the peripheral cortical skeleton. As a consequence, high dose sodium fluoride (80 mg daily) is not currently used to treat osteoporosis. At lower doses, recent trials have suggested a beneficial effect on both bone density and fracture. The majority of epidemiological evidence regarding the effects of fluoridated drinking water on hip fracture incidence is based on ecological comparisons. Although one Finnish study suggested that hip fracture rates in a town with fluoridated water were lower than those in a matching town without fluoride, a later study failed to show differences. Ecological studies from the United States and Great Britain have, if anything, revealed a weak positive association between water fluoride concentration and hip fracture incidence. Two studies examining hip fracture rates before and after fluoridation yielded discordant results, and are complicated by underlying time trends in hip fracture incidence. Only two studies have attempted to examine the relationship between water fluoride concentration and fracture risk at an individual level. In one of these, women in as high fluoride community had double the fracture risk of women in a low fluoride community. In the other, there was no relationship between years of fluoride exposure and incidence of spine and non-spine fractures. In conclusion, the epidemiological evidence relating water fluoridation to hip fracture is based upon ecological comparisons and is inconclusive. However several studies suggest the possibility of a weak adverse effect, which warrants further exploration. Data on the relationship between fluoride intake and hip fracture risk at the individual level, and data relating fluoridation to bone mineral density are required. Until these become available , the burden of evidence suggesting that fluoridation might be a risk factor for hip fracture is weak and not sufficient to retard the progress of the water fluoridation programs.

11. A 1997 review on osteoporosis, prevention, diagnosis and management is included here as background to this subject: Deal CL. Osteoporosis, prevention, diagnosis and management. American Journal of Medicine 102 (1A) 35S-39S January 27 1997.

Abstract: Osteoporosis is a public health scourge that is usually eminently preventable. Some risk factors, such as low calcium intake, vitamin D deficiency, and physical inactivity, are amenable to early interventions that will help maximize peak bone density. Other risk factors subject to modification are cigarette smoking and excessive consumption of protein, caffeine, and alcohol. Hip fractures are the most serious outcome of osteoporosis, with enormous personal and public health consequences. The ongoing Study of Osteoporotic Fractures has identified additional independent predictors of hip fracture risk, including maternal hip fractures, absence of significant weight gain since age 25, height, hyperthyroidism, use of long-acting benzodiazepines or anticonvulsants, spending < 4 hours per day on one's feet, inability to rise from a chair without using one's arms, poor visual depth perception and contrast sensitivity and tachycardia. In an individual perimenopausal woman, the risk of osteoporotic fracture and the urgency of estrogen replacement therapy can be best estimated on the basis of bone mineral density as measured by dual-energy x-ray absorptiometry, coupled with the presence or absence of existing fractures and clinical risk factors evident from the history and physical examination. Estrogen, calcitonin and bisphosphonates have all proved effective in retarding postmenopausal bone loss and therefor reducing the risk of fracture. The use of sodium fluoride is more controversial, although a recent study has suggested a possible role for slow-release fluoride combined with high-dose calcium supplementation.

12. Colquhoun used a reference to state: Five years ago, animal experiments were reported of a fluoride-related incident of a rare bone cancer, called osteosarcoma, in young male rats. However that reference did not show any link between fluoride and cancer. It appears that there must have been an error in the publication of Colquhoun's paper.

The cited reference is: Maurer JR; Chang MC; Soysen AG; Anderson RL. Two-year carcinogenicity study of sodium fluoride in rats (see comments). Journal of the National Cancer Institute 82 (13) 1118-1126 July 4 1990.

Abstract: To determine the carcinogenic potential of sodium fluoride (NaF), we fed Sprague-Dawley rats a diet containing NaF for up to 99 weeks. Rats receiving NaF at a dose of 4, 10, or 25 mg/kg per day added to a low-fluoride diet were compared with controls receiving either a low-fluoride diet or laboratory chow. Each treatment group consisted of 70 rats of each sex. A 30% decrement in weight gain occurred at an NaF dose of 25 mg/kg per day. Evidence of fluoride toxicity was seen in the teeth, bones, and stomach, and the incidence and severity of these changes were related to the dose of NaF and the duration of exposure. Despite clear evidence of toxicity, NaF did not alter the incidence of preneoplastic and neoplastic lesions at any site in rats of either sex. Results from this study indicate that NaF is not carcinogenic in Sprague-Dawley rats.

The 'equivocal' finding that Colquhoun refers to is of a different rat study by the National Toxicology Program, and the designation 'equivocal' was based on the findings and not on any potential importance to humans.

Colquhoun's interpretation that: 'But now it has been found that the same rare bone cancer has increased dramatically in young human males - teenage boys aged nine to 19 - in the fluoridated areas of America but not in the unfluoridated areas' is different from that of the authors of that study. Indeed the authors of the New Jersey study referenced by Colquhoun stated: 'Therefore, taking both studies together (with reference to the other study by Hoover RN, Devesa S, Cantor K and Fraumeni JF. Time trends for bone and joint cancers and osteosarcoma in the surveillance, epidemiology and end results (SEER) program. In: Review of Fluoride. Benefits and Risks. Appendix F. U.S. Department of Health and Human Services, Public Health Service. Washington DC. 1991.) there is insufficient basis to draw conclusions about whether osteosarcoma incidence and fluoridation are causally linked.' (FD Cohn. An epidemiologic report on drinking water and fluoridation. Environmental Health Service. New Jersey Department of Health, November 1992.)

Another reference that Colquhoun did not include, perhaps because it didn't support his thesis, is: Gelberg KH; Fitzgerald EF; Hwang SA; Dubrow R. Fluoride exposure and childhood osteosarcoma; a case control study. American Journal of Public Health 83 (12) 1678-1683 December 1995.

Abstract: OBJECTIVES. This study tests the hypothesis that fluoride exposure in a nonoccupational setting is a risk factor for childhood osteosarcoma. METHODS. A population-based case-control study was conducted among residents of New York State, excluding New York City. Case subjects (n = 130) were diagnosed with osteosarcoma between 1978 and 1988, at age 24 years or younger. Control subjects were matched to case subjects on year of birth and sex. Exposure information was obtained by a telephone interview with the subject, parent or both. RESULTS. Based on the parents responses, total lifetime total lifetime fluoride exposure was not significantly associated with osteosarcoma among all subjects combined or among females. Protective trends were observed for fluoridated toothpaste, fluoride tablets, and dental fluoride treatment among all subjects and among males. Based on the subjects responses, no significant associations between fluoride exposure and osteosarcoma were observed. CONCLUSIONS. Fluoride exposure does not increase the risk of osteosarcoma and may be protective in males. The protective effect may not be directly due to fluoride exposure but to other factors associated with good dental hygiene. There is also biologic plausibility for a protective effect.

13. Additionally, only high levels of fluoride have been associated with reductions in testosterone levels in contrast to Colquhoun's assertion that 'very low levels can interfere with the male hormone testosterone.'

14. With regard to studies from China that children with dental fluorosis have on average lower intelligence scores, Colquhoun misstates the facts of the research. In the study by Li (Li. Effect of fluoride exposure on intelligence in children. Fluoride 28 (4) pages 189-192 1995) there were four communities with a Community Fluorosis Index (CFI) of <0.4, 0.8, 2,5, and 3.2. Only in the two communities with the highest CFI were lower IQs found. This CFI index was developed by Dean (Dean HT. The investigation of physiological effects by the epidemiological method. In: Moulton FR (Ed). Fluorine and Dental Health. Am Assoc Adv Sci, Washington 1942 pp 23-31). Dean stated that a CFI below 0.4 is of little or no public health concern; that the range from 0.4 to 0.6 is borderline; and that for indexes above 0.6 removal of excess fluoride from the water is recommended. Thus the communities where Li found lower intelligence scores were in areas of exceptionally high fluoride, apparently due to high fluoride coal being burned and inhaled, rather than in the water. Thus these findings are unrelated to water fluoridation and to suggest, as Colquhoun does, that children with dental fluorosis have on average lower intelligence scores is a gross misstatement of the facts, since there are children with very mild and mild dental fluorosis, living in the low CFI communities where IQ scores were apparently normal.

15. Colquhoun supports his contention that fluoride is harmful by citing the reference by Mullenix et al. (Mullenix PJ, Denbesten PK, Schunior A, Kernan WJ. Neurotoxicity of sodium fluoride in rats. Neurotoxicology and Teratology 17 (2) 169-177 March-April 1995.) In this study pregnant rats were injected with very high doses of sodium fluoride at 0.13 mg/kg. This would be equivalent of a human dose for a pregnant woman of 6.5 mg, not to be swallowed and therefore diluted by the body, but injected subcutaneously. This would be unconscionable in humans who are never injected with sodium fluoride. Then the weanlings (baby rats) drank water with 0, 75, 100, or 125 ppm F for 6 or 20 weeks, and the 3 month-old adults received water containing 100 ppm F for 6 weeks. Therefore all rats drank water with at least 100 times the recommended concentration for water fluoridation for extended periods of time. Thus this study was never intended to determine the effects of water fluoridation.

16. Colquhoun consistently alleges harm from fluoride without stating the dose or concentration of fluoride, which is absolutely essential in a discussion of the toxicology of fluoride.

This concludes my review.

FLUORIDE 31(2) 1998, 119-126	International Society for Fluoride Research
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