FLUORIDE 30 (2)
 1997, p 110
International Society for Fluoride Research Table of Contents
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ISFR -- XXIst Conference Abstracts

FLUORIDATED WATER AND DOWN’S SYNDROME

Albert W Burgstahler
Lawrence, Kansas, USA

Reports appearing between 1956 and 1963 indicated a positive association between the congenital malformation known as Down’s syndrome (DS, trisomy 21 or mongolism) and the fluoride content of drinking water in north central regions of the United States. Although widely disputed or ignored, these findings are supported by results of later investigations that, after further analysis, also confirm the additional important observation of higher rates of DS births among younger mothers living in fluoridated areas.

Here, in this paper, related findings on the occurrence of DS in Lower Michigan during the period 1951-1964 are presented. The data, based on over 2,000 recorded cases, indicate a 10 to 30 percent higher rate of DS births by maternal residence in urban areas with, or after, fluoridation of the municipal water supply. Overall, with all cities of 2,500 or more residents included (1950 census), the rate was 1.06 DS births per 1,000 live births in fluoridated communities compared to 0.94 in non-fluoridated communities (0.88 if the very large city of Detroit is excluded). For all cities of 25,000 to 200,000 population, the rates were 1.04 vs. 0.73. These differences, by the Chi-square test, have P < 0.065, 0.008, and 0.001, respectively. Besides this agreement with results of previous investigations by others, the present work also revealed a higher frequency of DS births among younger mothers in the fluoridated communities.

Key words: Down’s Syndrome; Fluoridation.
Address: Department of Chemistry, The University of Kansas, Lawrence, Kansas 66045-0046, USA.


EXPERIMENTAL OSTEOFLUOROSIS AND ARTHROFLUOROSIS IN RATS

M Bély, G Ferencz, K ltai* and H Tsunoda*
Budapest, Hungary and Morioka, Japan*

OBJECTIVE: to study qualitative and quantitative changes of bone tissue and articular cartilage in rats exposed to sodium fluoride.

MATERIALS AND METHODS: 75 female Wistar rats, each weighing about 200 g, were divided equally into three groups. Animals in Groups 1 and 2 received daily doses of 0.5 mg and 5 mg of NaF, respectively, through intraperitoneal administration, whereas those in Group 3 (controls) received physiological saline solution only. The experiments were run for a period of 3 months.1 Histological and histochemical studies were carried out on adjoining bones, femur and tibia, and lumbar vertebrae III-V of the animals. The materials used for histological studies were fixed in a 10% formaldehyde solution, decalcified at room temperature in a solution composed of 24 ml 85% formic acid, 50 mL 55% HCl, and 126 mL distilled water. Sections were stained with haematoxylin and eosin (H-E), picrosirius red F3BA,2,3 and exposed to toluidine-blue at pH 6 and pH 3.5.4 The ultrastructural changes of bone tissue and articular cartilage were investigated by polarization optical methods.5,6 The fluoride content of bone tissue was determined by ion selective analysis. The fluorapatite crystals were identified by electron diffraction.

RESULTS: The bone tissue mass, the osteoid surface and osteoid volume increased, the enchondral ossification and the mineralisation of osteoid were delayed, and the proportion of newly formed woven bone increased in correlation with the administered dose of fluoride. A sporadic, scattered necrosis of osteocytes and chondrocytes, and a progressive disorientation in the bone and articular cartilage, were shown in rats exposed to NaF. Compared with the controls, the specimens obtained from NaF-treated animals showed marked decreases in orientation of capsular and intercapsular collagen fibers and glycosaminoglycans in the preexisting bone tissue and articular cartilage.

The structural changes were correlated with the dose of administered NaF, and with the fluoride content of bone tissue (in Group 1: 1.10 mgF/g, in Group 2: 1.44 mgF/g, and in Group 3 (control): 0.423 mgF/g). The fluorapatite crystals, in spite of decalcification, could still be identified in the animals of Group 2.

CONCLUSIONS AND INTERPRETATION: The quantity of bone tissue increased and the quality diminished with increase in NaF levels administered. The enlarged bone mass may be caused by increased bone formation and/or by decreased bone resorption. The augmented bone (osteoid) formation can be caused by either the relatively or absolutely greater number, increased activity, or longer life span, of osteoblasts. The cause of diminished bone resorption may be due to absolutely or relatively reduced number, decreased activity or shorter life span of osteoclasts. The reduced solubility of fluorapatite may play an important role also. According to our interpretation the increased bone and osteoid volume is caused by decreased bone resorption. The ultrastructural disorientation of bone tissue and articular cartilage are connected to the necrosis of osteocytes and chondrocytes, and may be accepted as a toxic effect of fluoride.

REFERENCES

  1. Bély M. Experimental fluorosis in rats: NaF induced change in bone and bone marrow. Fluoride 16 (2) 106-111 1983.
  2. Sweat F, Puchtler H, Rosenthal SI. Sirius red F3BA as stain for connective tissue. Archives of Pathology 78 69-72 1954.
  3. Constantine VS, Mowry RW. Selective staining of human dermal collagen. II. The use of Picrosirius red F3BA with polarization microscopy. Journal of Investigations in Dermatology 50 419-423 1968.
  4. Bély M. The orientation of capsular and intercapsular collagen fibres and glycosaminoglycans in experimental osteofluorosis. Fluoride 23 (4) 171-174 1990.
  5. Frig J, RAF C, Dominic GW. The orientation of glycosaminoglycans in osteocyte capsules of fluoride treated rats. Fluoride 23 (1) 27-30 1990.
  6. Bély M. Changes of polysaccharides and collagen in bone and articular cartilage of rats exposed to fluoride. Environmental Sciences 4 193-198 1995.

Key words: Arthrofluorosis; Bone; Osteofluorosis; Rat.
Addresses: National Institute of Rheumatology and Physiotherapy, Department of Pathology, Budapest 114, PO Box 54 H-1525, Hungary, and Iwate Medical University, Department of Hygiene and Public Health, Iwate 020,19-1 Uchimaru, Morioka, Japan.


A STUDY ON THE CHANGES OF ORGANIC ACIDS,
FLUORIDE AND OTHER IONS IN DENTAL PLAQUE

T Yasui and S Nakao
Sakado, Saitama, Japan

By using l00 ppm F solution of sodium fluoride and sodium monofluorophosphate, the concentrations of some selected organic acids, fluoride ion, phosphorus ion, and calcium ion were measured before and after the application of 10% glucose solution. The relationship between the organic acid production in dental plaque and fluoride was analysed and discussed. The results obtained were as follows: 1) In the control group without fluoride application, distinct production of lactate in the surface solution of dental plaque was recognized after the application of 10% glucose solution. 2) In the group for sodium fluoride application, production of lactate in surface solution of dental plaque was clearly inhibited after the application of 10% glucose solution. Fluoride ion increased with statistical significance, and calcium ion decreased significantly. 3) In the group for monofluorophosphate application, production of lactate in the surface solution of dental plaque was inhibited clearly after the application of 10% glucose solution. Although fluoride ion showed a tendency to increase and calcium ion showed a tendency to decrease, these amounts of change were less than those in the case of sodium fluoride. 4) As a result of topical application of l00 ppm fluoride, it was demonstrated that the acid production in plaque was inhibited, fluoride ion increased and calcium ion decreased in the surface solution.

Key words: Dental plaque; Organic acids; Monofluorophosphate; Sodium fluoride.
Reprints: Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 35002 Japan.


THE CONTROVERSY OVER WATER FLUORIDATION

Zan-Dao Wei
Guiyang, China

On looking back at past international conferences on fluoride research, we realize that the controversy over water fluoridation has been a key background influence for a long time.

With progress in fluoride research, it has become evident that the toxic effects of excess fluoride involve all body systems. These health problems occur with water fluoridation. However, some scholars still support fluoridation and assert it is a safe and reasonable method to control tooth decay. This controversy has continued for half a century, ever since water fluoridation was proposed by Dean in 1942, and initiated in the United States in 1945. Actually, the relevant research was started by Black in 1916, so the story goes back 80 years.

The purpose of fluoride research should be to improve the health of human beings. Yet scientists working on fluoride still have differing viewpoints on water fluoridation. Up to now, our people in China have experienced many benefits from fluoride research. So what is the problem, internationally?

In China, we tried water fluoridation in Guangzhou in 1965. My colleagues and I carried out research which revealed high prevalences of fluorosis, and established that multiple sources of fluoride contributed to total fluoride intake. The results showed that the water fluoridation program had provided little benefit, but a lot of harm. The total F intake for adults was up to 4 mg/day, well above the permissible 3 mg/day now set as the standard. The water fluoridation program in Guangzhou was ended in 1983.

Key words: Fluoridation controversy; Guangzhou; Total fluoride intake.
Address: Guiyang Medical College, Guizhou 550004, China


WATER FLUORIDATION RESULTING IN HIGH PREVALENCE
OF DENTAL FLUOROSIS IN GUANGZHOU

Y Guo, H Zhang, W Lim and R Yi
Guangzhou, China

In the city of Guangzhou, water was fluoridated at the level of 0.8 ppm for prevention of dental caries. Unfortunately it resulted in a high prevalence of dental fluorosis. Based on the fact that this affliction develops mainly between birth and the age of 5 years, the authors made a study of the particular environment of infants and young children - their common habits, fluid and food intakes, as well as the water fluoride concentration of the tap water. The results of extensive surveys and statistical analysis showed that fluoride intake comes not only from the water supply but also from various other sources. In recent years, many authors have reported the "halo" effect. It is recognized that dental fluorosis occurs not only in districts with fluoridated water but also in non-fluoridated areas. This is compatible with the first author’s theory of the multiple origin of dental fluorosis. However, water fluoride is the main cause of the high prevalence of dental fluorosis. We feel that the discontinuance of water fluoridation in this city was justified as a proper public health measure to eliminate harmful effects.

Key words: Dental caries; Dental fluorosis; Water fluoridation.
Address: Sun Yat-Sen University of Medical Sciences, Guangzhou, China.


MILK FLUORIDATION: AN ALTERNATIVE METHOD
FOR CARIES PREVENTION

J Bánóczy
Budapest, Hungary

Dental caries is still one of the most common diseases affecting a considerable number of children and adults in many countries.

Milk fluoridation, as an alternative to water or salt fluoridation, was first introduced in Switzerland in the mid 1950s. Since then, fluoridated milk projects have been carried out in the USA, Scotland and Hungary, while the International Milk Fluoridation Program, implemented by the World Health Organization and the Borrow Dental Milk Foundation, brought good results at the national level in Bulgaria. The aim of this report is to present the results of the Hungarian milk fluoridation project.

Milk fluoridation in Hungary was initiated in 1979. Started with institutionalized, healthy children, with standardized living conditions, of kindergarten age (2-5 years), the program was extended one year later to children aged 6-14 years. The children consumed 200 mL of milk daily, supplemented with 0.4-0.75 mg F, according to age. Mean DMF (decayed, missing and filled) values were evaluated after 2, 3, 5 and 10 years of consumption, and the data were compared with those of a group of similar institutionalized children without preventive measures. The five-year evaluation, comparing 165 test and 122 control children, showed statistically significant reductions in both the primary and permanent dentitions - in the latter between 60 and 67%. After 10 years consumption, the ratio of caries-free children was 10% higher in the test than in the control group; the reduction of DMFT(teeth) was 36.78% and the reduction of DMFS(surfaces) 40.02%. The milk fluoridation programs were accompanied by monitoring urinary fluoride, plaque fluoride, and enamel fluoride content (Kertész et al. 1992, Tóth et al. 1989).

In conclusion, milk fluoridation proved to be effective in home children. Early starting age increased the protective effect considerably. Similarly the results of the large-scale scheme in Bulgaria after five years give evidence to recommend milk fluoridation on a community level.

Key words: Dental caries; Hungary; Milk fluoridation.
Address: Professor J Bánóczy, Department of Conservative Dentistry,
Semmelweis University of Medicine,
Mikszáth Kálmán tér 5, H-1088, Budapest, Hungary.


FLUORIDE IN THE TREATMENT OF OSTEOPOROSIS
AN OVERVIEW: 35 YEARS OF CLINICAL RESEARCH

J Franke
Bad Liebenstein, Germany

It has long been known that fluoride ingestion through drinking water in areas naturally rich in fluoride, or ingestion or inhalation of fluoride containing gases or dusts, leads to osteosclerosis, known as endemic or industrial fluorosis.

We studied over 100 cases of industrial fluorosis developing after 10 to 20 years of fluoride exposure, and we found hypermineralization, hyperossification also in the peripheral bones, and an increase in the bone strength.

The first suggestion that fluoride be used in the treatment of osteoporosis was made by Rich and Ensinck in 1961. Despite 35 years of research, fluoride treatment for osteoporosis still remains controversial.

Fluoride has a dual effect on osteoblasts. On the one hand, it causes proliferation and differentiation of osteoblasts, while on the other hand it has a toxic effect on the osteoblasts with alteration of the composition of the bone matrix and impairment of mineralization with higher doses.

In Europe in the late sixties some research groups successfully started sodium fluoride (NaF) therapy for osteoporosis. We also started in 1969. Since that time we have carried out four prospective studies together on 263 patients. We used pure NaF powder (20-60 mg/d) at the beginning or some slow release NaF preparations (60 to 80 mg/d or 1 mg NaF/kg body weight and day) in the later studies for 2 to 5 years of treatment.

Clinically about 80% of the patients recovered distinctly or became symptom-free. In 64% we detected radiologically a distinct reossification of the spine, and in a further 20% this reossification was questionable. In summary, we found about 20% were fast-responders (reossification after 11 to 16 months), 60% were responders and 20% were non-responders.

The vertebral fracture rate decreased from 750 fractures per thousand patient years in the first year of treatment to 96.2 fractures in the second year and to zero in the third and fourth year. There was no increase of proximal femur fracture rate.

These fractures should not be confused with the stress fractures, observed in 3.7% peripherally and in 4.9% at the femoral neck, which do not cause serious problems, because they heal quickly with discontinuation of the fluoride intake. In the last study with a dose of 1 mg NaF/kg and day a careful monitoring of the fasting morning serum fluoride level (7.5-12 µmol/L) we could reduce this stress fracture rate to 0.95%.

These results are in agreement with other studies from Europe and the USA, except the studies of Riggs et al. (1990) and Kleerekoper et al. (1991) who found, in spite of a distinct increase of the bone mineral content in the spine (15%), no significant decrease of the vertebral fracture rate.

The cause of this disagreement was: both study groups used too high doses (60 to 90 mg NaF) and fast release sodium fluoride preparations. In 1995 Pak et al. confirmed our results in a randomized controlled trial with slow release sodium fluoride.

Side effects of the fluoride therapy are gastrointestinal intolerance and the painful lower extremity syndrome.

Five years ago we started using more and more disodium monofluorophosphate (MFP) preparations. MFP remains soluble in the presence of calcium, is better absorbed in the duodenum, and there are fewer gastric and intestinal side effects.

Because we very often observed a vitamin-D-hypovitaminosis in our patients with osteoporosis, and because the possibility that fluoride could cause a calcium deficiency osteomalacia, we also give our patients an adequate calcium supply (1 g/d) and low doses of vitamin D (1000 IU/d).

According to Marx et al. (1992) the combination of estrogen and fluoride together is additive. Therefore we also use this combination in severe cases of osteoporosis.

In conclusion, the therapeutic window of fluoride is narrow, but by careful monitoring of the treatment (determination of the morning fasting serum fluoride level and of alkaline phosphatase every 4 months, and control of the spine X-rays and the spinal bone mineral content every year) fluoride therapy for osteoporosis is beneficial and safe.

Key words: Fluoride therapy; Osteoporosis.
Address: Department of Orthopædic Rehabilitation, Heinrich Mann Hospital, D-36448 Bad Liebenstein, Germany.


FLUORIDE 30 (2)
 1997, pp
International Society for Fluoride Research
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