Key Findings - High Individual Variability in Skeletal Response to Fluoride:

1) People exposed to the same dose, and duration, of fluoride can exhibit markedly different effects, in both type and severity. This has been observed in areas with endemic skeletal fluorosis and in clinical trials where fluoride has used as an experimental drug to treat osteoporosis.

2) The duration of exposure necessary to produce fluorosis varies widely, even among people exposed to the same dose of fluoride.

3) In the advanced stages of skeletal fluorosis, some people can remain symptom-free, while in the early stages, some people can be mired with symptoms.

4) The concentration of fluoride in bone producing skeletal fluorosis in one individual can exist without any apparent effect in another.

Excerpts from Scientific Literature - Variable Prevalence/Type of Skeletal Fluorosis at Same Exposure to Fluoride: (back to top)

"It has been a consistent observation in epidemiologic studies that the clinical severity of fluoride-induced toxic effects is highly variable among persons living in the same environment and exposed to the same risk of fluoride ingestion."
SOURCE: Wang Y, et al. (1994). Endemic fluorosis of the skeleton: radiographic features in 127 patients. American Journal of Roentgenology 162: 93-8.

"In our study... this spectrum (of radiological features in fluorosis) was present in subjects living in the same village and sharing a water source. Obviously factors other than the amount of fluoride ingested are important in determining the type of skeletal change that occurs in fluorosis."
SOURCE: Mithal A, et al. (1993). Radiological spectrum of endemic fluorosis: relationship with calcium intake. Skeletal Radiology 22: 257-61.

"Skeletal fluorosis is highly variable in its clinical severity among individuals living in the same environment and exposed to the same risk of fluoride ingestion... A number of factors govern the amount of fluoride deposited in the skeleton. Important factors include: 1) age of exposure; 2) the duration of exposure; 3) the dose of fluoride (as reflected in the blood concentration); 4) nutritional status; 5) renal status; and 6) individual biological variation."
SOURCE: Department of Health & Human Services. (U.S. DHHS) (1991). Review of Fluoride: Benefits and Risks. Report of the Ad Hoc Committee on Fluoride, Committee to Coordinate Environmental Health and Related Programs. Department of Health and Human Services, USA.

"We suggest that predisposition to fluorosis (chronic toxicity) is biochemically mediated and genetically determined. This would explain the marked variation in fluorosis prevalence in areas with comparable levels of fluoride intake and the selectivity of the disease within the same area. Further studies are necessary to elucidate the complex interaction between calcium, iodine, sex hormones, vitamins and fluoride ions."
SOURCE: Anand JK, Roberts JT. (1990). Chronic fluorine poisoning in man: a review of literature in English (1946-1989) and indications for research. Biomedicine & Pharmacotherapy 44: 417-420.

"Individual differences in sensitivity to noxious fluoride seems to be important... [I]t is quite possible to be an aluminum smelter worker for 30 years or longer without showing fluoride-caused bone changes, whereas others develop symptoms of fluorosis after only 10 years..."
SOURCE: Runge H, Franke J. (1989). Radiological modifications of the skeletal system among aluminum smelter workers: A 15 year retrospective study. Fluoride 22: 157-164.

"[M]any problems remain unclear. For instance, the disease in many people in highly endemic areas may be very severe whereas approximately half of the local population have no obvious fluorotic symptoms or signs. Patients live in the same village and drink the same high fluorine content water but their presentations differ. In some, osteoporosis and osteomalacia are predominant while in others osteosclerosis is predominant."
SOURCE: Xu JC, et al. (1987). X-ray findings and pathological basis of bone fluorosis. Chinese Medical Journal 100:8-16.

"The considerable individual variability of skeletal response to excessive fluoride ingestion implies that causative factors other than total daily ingestion of fluoride exist."
SOURCE: Christie DP. (1980). The spectrum of radiographic bone changes in children with fluorosis. Radiology 136:85-90.

"it is an enigma that people from the same area, drinking water from the same source, have considerable variability in the degree of sclerosis, and indeed may have no roentgenographic changes at all.... The individual response to the fluorides must, for some reason, be greatly variable."
SOURCE: Morris JW. (1965). Skeletal fluorosis among indians of the American Southwest. American Journal of Roentgenology, Radium Therapy & Nuclear Medicine 94: 608-615.

Excerpts from Scientific Literature - Variable Response to Fluoride Treatment for Osteoporosis: (back to top)

"the bioavailability may be markedly different from one patient to another."
SOURCE: Boivin G, et al. (1993). Relationship between bone fluoride content and histological evidence of calcification defects in osteoporotic women treated long term with sodium fluoride. Osteoporosis International 3:204-208.

"the osteogenic response (to fluroide) shows marked interpatient variation."
SOURCE: Dure-Smith BA, et al. (1991). Fluoride therapy for osteoporosis: A review of dose response, duration of treatment, and skeletal sites of action. Calcified Tissue International 49(Suppl): S64-S67.

"It is still not possible to determine what factors determine those patients who ultimately respond (with higher BMD) to fluoride therapy."
SOURCE: Hodsman AB, Drost DJ. (1989). The response of vertebral bone mineral density during the treatment of osteoporosis with sodium fluoride. Journal of Clinical Endocrinology and Metabolism 69:932-8.

"Recent data strongly suggest that individual skeletal responsiveness to fluoride therapy varies... The cause or causes of the individual variability in response are unknown."
SOURCE: Riggs BL. (1983). Treatment of osteoporosis with sodium fluoride: An appraisal. Bone and Mineral Research 2: 366-393.

"An increase in the width of osteoid seams was noted in all the present cases of osteoporosis who were treated with NaF. Since this effect was quite variable, however, the question can be raised whether a relationship to the dose and duration of the therapy exists. Of particular interest in this respect are patients 1, 6, and 7: Despite the smallest total dose of NaF (25 to 50 mg/day NaF) for only short periods of time, an extensive effect on the bone was apparent, whereas in case number 3, who received (94.3 mg/day of NaF) within 350 days, an only minute effect was noted. This applies to case number 4, as well."
SOURCE: Kuhlencordt F, et al. (1970). The histological evaluation of bone in fluoride treated osteoorosis. In: TL Vischer, ed. (1970). Fluoride in Medicine. Hans Huber, Bern. pp. 169-174.

Excerpts from Scientific Literature - Variable Duration of Exposure Capable of Producing Fluorosis: (back to top)

"Individual differences in sensitivity to noxious fluoride seems to be important... [I]t is quite possible to be an aluminum smelter worker for 30 years or longer without showing fluoride-caused bone changes, whereas others develop symptoms of fluorosis after only 10 years; the varying effect of fluoride has been demonstrated by therapy tests for osteoporosis."
SOURCE: Runge H, Franke J. (1989). Radiological modifications of the skeletal system among aluminum smelter workers: A 15 year retrospective study. Fluoride 22: 157-164.

"Cases of the 1st phase were observed after 2 5/12 years work, of the 2nd phase after 4 10/12 years, of the 3rd phase after 11 2/12 years. On the other hand the changes were slight in a certain number of the workers, even after long employment...One female worker had no bone changes, though she had been employed for 24 years with one interruption."
SOURCE: Roholm K. (1937). Fluoride intoxication: a clinical-hygienic study with a review of the literature and some experimental investigations. London: H.K. Lewis Ltd.

"As regards the bone changes... they were pronounced in one male worker who had only been in the factory 5 years, and rather severe also in two female workers who had only been there 6 years."
SOURCE: Moller P, Gudjonsson SV. (1932). Massive fluorosis of bones and ligaments. Acta Radiologica 12: 269-294

Excerpts from Scientific Literature - Variable Symptoms at Same Phase of Skeletal Fluorosis: (back to top)

"[W]e found patients with slight radiological changes (subtle signs or O-I) who complained of intense pains in the spine and in the large joints. On the other hand, some patients whose fluorosis was radiologically distinct were almost without complaints."
SOURCE: Franke J, et al. (1975). Industrial fluorosis. Fluoride 8: 61-83.

Excerpts from Scientific Literature - Variable Degree of Skeletal Fluorosis at Same Bone Fluoride Levels: (back to top)

"[A]vailable data suggest that there is wide variability in individual tolerance to toxic effects of skeletal accumulation of fluoride." "Fluoride concentrations of 200 to 6500 ppm have been reported in bones which were 'normal'... But bones from patients with severe chronic fluorosis have been found to contain 700-7000 ppm, 905-13,580 ppm, 1120-6050 ppm, and 2040-11,500 ppm. This overlap with the 'normal' range is indicative of wide variability in individual sensitivity to harm."
SOURCE: Groth, E. (1973), Two Issues of Science and Public Policy: Air Pollution Control in the San Francisco Bay Area, and Fluoridation of Community Water Supplies. Ph.D. Dissertation, Department of Biological Sciences, Stanford University, May 1973.

"Singh et al (1961) described skeletal fluorosis in individuals with F levels in bones in the 700 to 1600 ppm range. This F level in bones is far below that at which many claim fluorosis cannot occur. Data published by Call demonstrated that F content of bones does not parallel the F content in soft tissue organs. Therefore the presence or absence of ill-effect due to fluoride cannot be established on the basis of the F content of bones."
SOURCE: Waldbott GL. (1968). Hydrofluorosis in the U.S.A. Fluoride 1: 94-102.

"From tabulations of the present study, it is apparent that the degree of bone change does not correlate well with the amount of fluoride present in the bone."
SOURCE: Morris JW. (1965). Skeletal fluorosis among indians of the American Southwest. American Journal of Roentgenology, Radium Therapy & Nuclear Medicine 94: 608-615

"The fluoride content of bone does not appear to be the only factor contributing to the onset of fluorosis. Other metabolic factors must be considered. Concentrations of fluoride from 0.50% to 0.75% (dry, fat-free basis) have been found in ribs, sternum, and vertebrae during postmortem studies of persons with endemic fluorosis, whereas McClure et al reported fluoride values as high as 0.51% to 0.65% in various regions of the skeleton with no associated malfunction or microscopically detectable bone changes."
SOURCE: Marier JR, et al. (1963). Accumulation of skeletal fluoride and its implications. Archives of Environmental Health 6: 664-671.

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