FLUORIDE & BONE: An Annotated Bibliography

FLUORIDE & BONE: An Annotated Bibliography

Prepared by Michael Connett
Updated October 2003

1a) Studies reporting association between fluoridated water (< 1.2 ppm fluoride) & hip fracture
1b) Studies reporting association between fluoride levels higher than fluoridated water (2 to 5 ppm) & bone fracture
1c) Studies reporting no association between fluoridation & hip fracture

2) Clinical trials finding association between fluoride therapy and bone fracture
3) Animal studies finding fluoride reduces the strength/quality of bone
4) Fluoride & Bone Mineral Density (BMD):

4a) Fluoride, BMD, & Trabecular Bone
4b) Fluoride, BMD, & Cortical Bone

5) Fluori de & Osteoporosis:

5a) Endemic fluorosis studies
5b) Animal studies

6) Fluoride & Arthritis:

6a) Early stag es of skeletal fluorosis
6b) Combined effects of repetitive stress & fluoride
6c) Results from clinical trials

7) Kidney Disease: A factor increasing the risk for fluoride bone accumulation & damage

8) Fluo ride concentrations in bone in fluoridated & non-fluoridated areas

1) Water Fluoridation & Hip Fracture:

In the 1980s, a host of clinical trials testing the efficacy of fluoride as a treatment for osteoporosis, reported that fluoride increased the rate of bone fracture (see section 2). In light of these trials, interest began to emerge as to whether water fluoridation might also increase the rate of fracture. While the clinical trials used higher daily doses of fluoride (23 - 35 mg F/day) than are ingested in fluoridated communities, the trials lasted for relatively short periods of time (1 - 4 years). With water fluoridation, people consume lower doses of fluoride (1.6 - 6.6 mg F/day), but for much longer periods (70-100 years).

In the 1990s, a flurry of epidemiological studies were conducted to determine whether fluoridation increased fracture rates, with particular interest placed on hip fractures, the most serious type of fracture.

The majority of these studies have found that a relationship does in fact exist, with 10 studies finding increased rates of hip fracture in the fluoridated areas (see below).

The public health implications of these findings, if indeed confirmed, are huge.

According to the Centers for Disease Control, 50 percent of the elderly who fracture their hip never regain an independent existence, while, according to the Osteoporosis Centre in Australia, 12 to 40% of the elderly who fracture a hip die within a year of the operation.

1a) Studies reporting association between fluoridated water (< 1.2 ppm fluoride) & hip fracture. (Back to top)

Jacobsen SJ, et al. (1990). Regional variation in the incidence of hip fracture: US white women aged 65 years and olders. J Am Med Assoc 264(4): 500-2.

"This study examines the geographic distribution of hip fracture incidence in the United States at the county level. To this end, data are obtained from the Health Care Financing Administration (HCFA) and the Department of Veteran Affairs that identify all hospital discharges with a diagnosis of hip fracture for women aged 65 years and older for the period 1984 through 1987...After exclusions, 541,985 cases remained eligible for study... There is a weak positive association between the percent of county residents who receive fluoridated water and hip fracture incidence in the unadjusted analysis that is strengthened after adjustment."

a) Cooper C, et al. (1990). Water fluoride concentration and fracture of the proximal femur. J Epidemiol Community Health 44: 17-19.

b) Cooper C, et al. (1991). Water fluoridation and hip fracture. JAMA 266: 513-514 (letter, a reanalysis of data presented in 1990 paper).

"We found a significant positive correlation between fluoride levels and discharge rates for hip fracture. This relationship persisted for both women and men... Using an appropriately weighted regression model, there appears to be a positive ecologic association between fluoride levels of county water supplies and fracture discharge rates. This ecologic association is consistent with a recently published study and others currently in progress."

Keller C. (1991) Fluorides in drinking water. Unpublished results. Discussed in Gordon, S.L. and Corbin, S.B, (1992) Summary of Workshop on Drinking Water Fluoride Influence on Hip Fracture on Bone Health. Osteoporosis Int. 2: 109-117.

" An ecologic study compared fracture rates in 216 counties with natural fluoride levels greater than 0.7 ppm with rates in 95 counties with naturally low fluoride (less than 0.4 PPM) in the drinking water. In general, with increasing dose of fluoride in the drinking water the hip fracture ratio also increased."

Danielson C, et al. (1992). Hip fractures and fluoridation in Utah's elderly population. Journal of the American Medical Association 268(6): 746-748.

"We found a small but significant increase in the risk of hip fracture in both men and women exposed to artificial fluoridation at 1 ppm, suggesting that low levels of fluoride may increase the risk of hip fracture in the elderly."

Jacobsen SJ, et al. (1992). The association between water fluoridation and hip fracture among white women and men aged 65 years and older; a national ecologic study. Annals of Epidemiology 2: 617-626.

"In order to assess the association between water fluoridation and hip fracture, we identified 129 counties across the United States considered to be exposed to public water fluoridation and 194 counties without exposure...There was a small statistically significant positive association between fracture rates and fluoridation. The relative risk (95% confidence interval) of fracture in fluoridated counties compared to nonfluoridated counties was 1.08 (1.06 to 1.10) for women and 1.17 (1.13 to 1.22) for men."

May DS, Wilson MG. (1992). Hip fractures in relation to water fluoridation: an ecologic analysis. Unpublished data, discussed in Gordon SL, and Corbin SB. (1992). Summary of Workshop on Drinking Water Fluoride Inflruenbce on Hip Fracture on Bone Health. Osteoporosis Int. 2:109-117.

"The 1985 Fluoridation Census data were used for the 438 counties with populations over 100,000, which represents about 70% of the US population... The percentage of the population that received natural or adjusted fluoride (approximately 1 ppm) was estimated for each county. Medicare data for 1984-1987 were used to calculate the annual incidence of age adjusted hip fractures for white males and females age 65 and older. As the percentage of individuals exposed to fluoridated water increased within a county, the hip fracture rate generally rose for both sexes, but not in a smooth linear fashion... Adjustment for county latitude and longitude produced higher correlation values and significance for females and males."

Suarez-Almazor M, et al. (1993). The fluoridation of drinking water and hip fracture hospitalization rates in two Canadian communities. Am J Public Health. 83: 689-693.

The authors of this study conclude there is no association between fluoridation and hip fracture. However, their own data reveals a significant increase in hip fracture for men living in the fluoridated area. According to the study, "although a statistically significant increase in the risk of hip fracture was observed among Edmonton men, this increase was relatively small (RR=1.12)."

a) Jacqmin-Gadda H, et al. (1995). Fluorine concentration in drinking water and fractures in the elderly. JAMA. 273: 775-776 (letter).

b) Jacqmin-Gadda H, et al. (1998). Risk factors for fractures in the elderly. Epidemiology 9(4): 417-423. (An elaboration of the 1995 study referred to in the JAMA letter).

"We found a higher risk of hip fractures for subjects exposed to fluorine concentrations over 0.11 mg per liter but without a dose-effect relation."

Kurttio PN, et al. (1999). Exposure to natural fluoride in well water and hip fracture: A cohort analysis in Finland. American Journal of Epidemiology 150(8): 817-824.

"[A]mong younger women, those aged 50-64 years, higher fluoride levels increased the risk of hip fractures."

Hegmann KT, et al. (2000). The Effects of Fluoridation on Degenerative Joint Disease (DJD) and Hip Fractures. Abstract #71, of the 33rd Annual Meeting of the Society For Epidemiological research, June 15-17, 2000. Published in a Supplement of Am. J. Epid. P. S18.

This study found an age-specific, statistically-significant relationship between fluoridation and hip fracture in women 75-84 years old - RR = 1.43 (95% CI, 1.02-1.84). An increase in hip fractures was also found in women aged 85 and older - RR = 1.42 (CI, 0.98 - 1.87).

1b) Studies reporting association between fluoride levels higher than fluoridated water (2 to 5 ppm) & bone fracture. (Back to top)

Sowers M, et al. (1991). A prospective study of bone mineral content and fracture in communities with differential fluoride exposure. American Journal of Epidemiology. 133: 649-660.

"Residence in the higher-fluoride community was associated with a significantly lower radial bone mass in premenopausal and postmenopausal women, an increased rate of radial bone mass loss in premenopausal women, and significantly more fractures among postmenopausal women."

Li Y, et al. (2001). Effect of long-term exposure to fluoride in drinking water on risks of bone fractures. J Bone Miner Res.16(5):932-9.

"In general, the hip fracture prevalence was stable up to 1.06 ppm of fluoride and then appeared to rise, although it did not attain statistical significance until the water fluoride concentration reached 4.32 - 7.97 ppm... The prevalence of hip fractures was highest in the group with the highest water fluoride."

Alarcon-Herrera MT, et al. (2001). Well Water Fluoride, Dental fluorosis, Bone Fractures in the Guadiana Valley of Mexico. Fluoride 34(2): 139-149.

"A linear correlation between the Dean index of dental fluorosis and the frequency of bone fractures was also observed among both children and adults... [T]he highest fracture incidence for both groups was found in the fluoride concentration levels of 1.51 to 4.99 mg/L, which is one of lower concentration zones rather than one of the higher ones, as we expected. Plotting the incidence of fractures versus the average corresponding fluoride concentration in each zone for the adults indicated a third order polynomial correlation with R 2 = 0.9995."

1c) Studies reporting no association between fluoridation & hip fracture. (Back to top)

(Note that in 3 of these 9 studies, an association was found between fluoride and some form of fracture. See notes and quotes below.)

Madans J, et al. (1983). The relationship between hip fracture and water fluoridation: an analysis of national data. Am J Public Health 73: 296-298.

Arnala I, et al. (1986). Hip fracture incidence not affected by fluoridation. Osteofluorosis studied in Finland. Acta Orthop Scand. 57: 344-348.

While this study didn't find an association between 20 years of fluoridation and hip fracture, an earlier study by the same authors (Arnala et al 1985) found that slightly elevated levels of fluoride in water (> 1.5 ppm) caused adverse effects on bone quality. According to the study, "The upper limit for fluoride concentration in drinking water that does not increase the amount of unmineralized bone is roughly 1.5 parts per million... We should however, recognize that it is difficult to give a strict value for a safe concentration in drinking water because individual susceptibility to fluoride varies."

Jacobsen SJ, et al. (1993). Hip Fracture Incidence Before and After the Fluoridation of the Public Water Supply, Rochester, Minnesota. American Journal of Public Health. 83: 743-745.

This study looked at hip fracture rates in a community which had been fluoridated for only 10 years. It does not, therefore, address the life long cumulative effect of fluoridation.

Cauley J. et al. (1995). Effects of fluoridated drinking water on bone mass and fractures: the study of osteoporotic fractures. J Bone Min Res 10(7): 1076-86.

Karagas MR, et al. (1996). Patterns of Fracture among the United States Elderly: Geographic and Fluoride Effects. Ann. Epidemiol. 6 (3): 209-216.

This study didn't find an association between fluoridation & hip fracture, but it did find an association between fluoridation and distal forearm fracture, as well as proximal humerus fracture. "Independent of geographic effects, men in fluoridated areas had modestly higher rates of fractures of the distal forearm and proximal humerus than did men in nonfluoridated areas."

Feskanich D, et al. (1998). Use of toenail fluoride levels as an indicator for the risk of hip and forearm fractures in women. Epidemiology 9(4): 412-6.

As with Karagas (1996), this study didn't find an association between fluoridation and hip fracture, but it did find an association -- albeit non-significant 1.6 (0.8-3.1) -- between fluoride exposure and elevated rates of forearm fracture.

Lehmann R, et al. (1998). Drinking Water Fluoridation: Bone Mineral Density and Hip Fracture Incidence. Bone. 22: 273-278.

Hillier S, et al. (2000). Fluoride in drinking water and risk of hip fracture in the UK: a case control study. The Lancet 335: 265-2690.

Phipps KR, et al. (2000). Community water fluoridation, bone mineral density and fractures: prospective study of effects in older women. British Medical Journal. 321: 860-4.

This study actually found a decrease in hip fractures among those exposed to fluoridation. The average exposure to fluoridation, however, was only 20 years, and thus the study may not be relevant to life-long exposure. Also, as with Feskanich (1998) and Karagas (1996), this study did find an association between fluoridation and another type of fracture - in this case, wrist fracture. "There was a non-significant trend toward an increased risk of wrist fracture." For a critique of this study, see http://www.fluoridealert.org/phipps.htm

2) Clinical trials finding association between fluoride therapy and bone fracture. (Back to top)

Due to it's capacity to increase bone mass (see section 4), fluoride has been used since the 1960s as a treatment for osteoporosis, particularly spinal osteoporosis. However, despite approximately 40 years of use, fluoride treatment remains controversial and is no longer recommended by the US National Institutes of Health, Osteoporosis Society of Canada, and French Government among others.

The reasons for the controversy include the high rate of side effects (i.e. arthritic pains & gastrointestinal problems), the contradictory effects on bone mass (see section 4), the narrow margin of safety between beneficial and toxic effects on bone, and most importantly, the tendency for fluoride treatment to increase the fracture rate, particularly non-vertebral fractures such as hip fracture.

Included here is a listing of clinical trials reporting an increase in fracture rates among fluoride-treated patients.

Inkovaara J, et al. (1975). Phophylactic fluoride treatment and aged bones. Br Med J. 3: 73-74.

"Fractures and exacerbation of arthrosis were more frequent in the fluoride group...The many fractures in the fluoride group, 14 during treatment and the following month as against 6 among the controls, were surprising. Three or four of the fractures in the fluoride group appeared to be spontaneous hip fractures. In the past fractures have not been regarded as being caused by fluoride but as resulting from prolonged osteoporosis before treatment. We believe that the fluoride treatment here was probably partly responsible for the fractures in our cases."

Gerster JC, et al. (1983). Bilateral fractures of femoral neck in patients with moderate renal failure receiving fluoride for spinal osteoporosis. Br Med J (Clin Res Ed). 287(6394):723-5.

"Two patients with moderate renal failure sustained spontaneous bilateral hip fractures during treatment with fluoride, calcium, and vitamin D for osteoporosis....As bilateral femoral neck fractures are very rare these data suggest a causal link between fractures and fluoride in patients with renal failure. Thus fluoride should be given at a lower dosage, if at all, to patients with even mild renal failure."

Dambacher MA, et al. (1986). Long-term fluoride therapy of postmenopausal osteoporosis. Bone. 7: 199-205.

"[T]he increased number of new crush fractures of the spine during the first year of treatment raise the possibility of fluoride-induced microfractures."

O'Duffy JD, et al. (1986). Mechanism of acute lower extremity pain syndrome in fluoride-treated osteoporotic patients. Amer J Med. 80: 561-566.

"How fluoride can produce stress microfractures is unclear. That they are complications of fluoride therapy is clear, as there were no microfractures in the 101 patients in the calcium-treated group."

Orcel P, et al. (1987). [Spontaneous fissures and fractures of the legs in patients with osteoporosis treated with sodium fluoride]. Presse Med.16(12):571-5.

"Thirteen cases of spontaneous fissure or fracture of the lower limbs observed in 8 patients under treatment with sodium fluoride are reported; 7 of these patients were being treated for osteoporosis... Fluor seems to be responsible for the fissures which cannot be avoided by calcium and/or vitamin D intake. The main pathogenic hypotheses are excessive bone resorption, large amounts of poorly mineralized osteoid tissue and architectural abnormalities of the trabeculae. When such fissures occur, fluoride therapy must be discontinued and the limb put at rest..."

Hedlund LR, Gallagher JC. (1989). Increased incidence of hip fracture in osteoporotic women treated with sodium fluoride. Journal of Bone and Mineral Research. 2:223-5.

"[T]he six hip fractures occurring in patients receiving fluoride during 72.3 patient years of treatment is 10 times higher than would be expected in normal women of the same age. The probability of observing six fractures in 2 years is extremely small (0.0003). In four of the hip fracture cases, the history suggested a spontaneous fracture. These findings suggest that fluoride treatment can increase the risk of hip fracture in osteoporotic women."

Orcel P, et al. (1990). Stress fractures of the lower limbs in osteoporotic patients treated with fluoride. J Bone Miner Res. 5(Suppl 1): S191-4.

"We report clinical and bone morphometric findings in 18 osteoporotic patients who experienced stress fractures during fluoride therapy... Fluoride appears to be a key factor in the pathogenesis of stress fractures, and may be associated with increased trabecular resorption in some treated patients."

Bayley TA, et al. (1990). Fluoride-induced fractures: relation to osteogenic effect. Journal of Bone and Mineral Research. 5(Suppl 1):S217-22.

"Using all 61 fluoride-treated patients, femur fractures/patient were significantly correlated to bone fluoride (p less than 0.05) and to age (p less than 0.05)... These results suggest that fluoride therapy may be implicated in the pathogenesis of hip fractures which may occur in treated patients despite a rapid, marked increase in bone mass."

Gutteridge DH, et al. (1990). Spontaneous hip fractures in fluoride-treated patients: potential causative factors. J Bone Miner Res. 5 Suppl 1:S205-15.

"We report 11 fluoride-treated postmenopausal patients who developed spontaneous fractures of the femoral necks...In all there were 19 spontaneous fractures: 5 were asymptomatic, including 2 with deformity; 12 fractures required surgery... [W]e believe that the available evidence strongly favors an association between spontaneous femoral fractures (stress and surgical) and NaF plus Ca treatment under certain circumstances."

Riggs BL, et al. (1990). Effect of Fluoride treatment on the Fracture Rates in Postmenopausal Women with Osteoporosis. New England Journal of Medicine. 322:802-809.

Fluoride treatment was "associated with a significant three-fold increase in the incidence of nonvertebral fractures, both incomplete and complete...This increased rate of fracturing suggests that bone formed during fluoride therapy has increased fragility."

Schnitzler CM, et al. (1990). Bone fragility of the peripheral skeleton during fluoride therapy for osteoporosis. Clin Orthop (261):268-75.

"Bone fragility during fluoride therapy for osteoporosis was observed in 24 (37.5%) of 64 patients treated with sodium fluoride, calcium, and vitamin D for 2.5 years who developed episodes of lower-limb pain during treatment. Eighteen (28%) of these patients had clinical and roentgenographic features of 41 stress fractures and 12 new spinal fractures. There were 26 periarticular, six femoral neck, three pubic rami, three tibia and fibula, one greater trochanter, and two subtrochanteric fractures. Vertebral fractures appeared first, then periarticular, then femoral neck, and lastly long-bone shaft fractures. All fractures were spontaneous in onset. The peripheral fracture rate during treatment was three times that in untreated osteoporosis."

Haguenauer D, et al. (2000). Fluoride for the treatment of postmenopausal osteoporotic fractures: a meta-analysis. Osteoporosis International. 11(9):727-38.

"We conducted an effectiveness meta-analysis to determine the efficacy of fluoride therapy on bone loss, vertebral and nonvertebral fractures and side effects in postmenopausal women...[A]lthough fluoride has an ability to increase bone mineral density at the lumbar spine, it does not result in a reduction in vertebral fractures. Increasing the dose of fluoride increases the risk of nonvertebral fractures and gastrointestinal side effects without any effect on the vertebral fracture rate."

Gutteridge DH, et al. (2002). A randomized trial of sodium fluoride (60 mg) +/- estrogen in postmenopausal osteoporotic vertebral fractures: increased vertebral fractures and peripheral bone loss with sodium fluoride; concurrent estrogen prevents peripheral loss, but not vertebral fractures. Osteoporosis International. 13(2):158-70.

"Vertebral fracture rates and peripheral bone density changes were surprising - and demonstrate that NaF administration is capable of increasing vertebral fracture rates and of increasing peripheral (nonspinal) bone loss. Thus our study demonstrates the potential for an anti-osteoporosis agent, under certain circumstances, to worsen a patient's clinical state."

Reginster JY, et al. (2003). Effect of raloxifene combined with monofluorophosphate as compared with monofluorophosphate alone in postmenopausal women with low bone mass: a randomized, controlled trial. Osteoporosis International June 19.

"[I]t is possible that the fluoride administered to all patients, may have increased the risk of osteoporotic fractures, and that the raloxifene added to the MFP treatment mitigated this theoretical increase in the combination group. The relatively high proportion of the fractures in the MFP group, which were non-vertebral, supports this interpretation."

3) Animal studies finding fluoride reduces the strength/quality of bone (Back to top)

As noted recently in a critique of the Irish Government's Fluoridation Forum report, "it is now clear from numerous animal and clinical studies that fluoride decreases the strength of bone. The question is not whether fluoride reduces the strength of bone, but, at what level?"

Included below are the animal studies referred to in the Forum critique.

Roholm K. (1937). Fluoride intoxication: a clinical-hygienic study with a review of the literature and some experimental investigations. H.K. Lewis Ltd, London.

"The effects of fluorine on the osseous system are complicated, which may explain some of the apparently contradictory experimental observations. Both diffuse sclerosing processes, and a generalized condition resembling osteomalacia are observed... The osteomalacic condition to some extent varies with the species and age of the animal. Certain features are common, however... Common features are the reduced strength of the bones, the tendency to form exostoses, bone atrophy, and a deficient calcification."

Huffman WT. (1949). Effects on livestock of air contamination caused by fluoride fumes. pp. 59-63. In: Air Pollution. Proceedings of the United States Technical Conference on Air Pollution. McGraw-Hill Book Co, New York.

"High fluorine levels interfere with mineral metabolism and cause abnormal growth of bone that may be structurally weak."

Rockert H. (1963). X-ray absorption and x-ray fluorescence micro-analysis of mineralized tissue of rats which have ingested fluoridated water. Acta Pathologica et Microbiologica Scandinavica. 59: 32-38.

"At high dosages osteosclerosis is seen within a year; later, resorption cavities occur. At more moderate dosages no osteosclerosis is seen but resorption cavities sometimes occur... The resorption cavities which occur in the animals show a microradiographic picture which would be expected from increased osteosclastic activity. These pictures have a distinct resemblance to the microradiograms of bone following radium radiation..."

Gedalia I, et al. (1964). Effects of Estrogen on Bone Composition in Rats at Low and High Fluoride Intake. Endocrinology. 75: 201-205.

"[T]he decrease in the mean breaking strength was significant statistically" among the fluoride-treated rats, and "is in agreement with the known fact that the breaking strength of bone decreases with increased fluoride intake."

Daley R, et al. (1967). The Effects of Sodium Fluoride on Osteoporotic Rats. The Journal of Bone and Joint Surgery. (Abstract). 49A:796.

"[T]he heavily fluorinated bone tended to break under less stress than did bone from any other group. These findings suggest that the heavily fluorinated bone was not as strong as the bone from normal rats or from rats fed low-calcium diets without fluoride."

Beary DF. (1969). The Effects of Fluoride and Low Calcium on the Physical Properties of the Rat Femur. Anat Rec. 164: 305-316.

"In the low calcium group a similar significant increase in flexibility appeared at the 10.0 ppm dosage level as well as the 45.0 ppm, but a significant decrease in strength at the two dosage levels were observed. These were in direct relation to the amount of fluoride given."

Wolinsky I, et al. (1972). Effects of fluoride on metabolism and mechanical properties of rat bone. American Journal of Physiology. 223(1): 46-50.

"Femurs of fluoride-treated rats exhibited a decrease in mechanical strength as manifested by a decrease in ultimate stress to breaking as well as decrease in limit and modulus of elasticity."

Chan MM, et al. (1973). Effect of Fluoride on Bone Formation and Strength in Japanese Quail. Journal of Nutrition. 103: 1431-1440.

"Our observations corroborate the findings that, in general, elevated dietary fluoride results in an acceleration of bone mineralization. Uniquely, however, the increase in mineralization was accompanied by a decrease in bone strength." The authors conclude that "the changes in bone that occur with prolonged and excessive fluoride ingestion may result in a reduction of bone strength."

Riggins RS, et al. (1974). The Effects of Sodium Fluoride on Bone Breaking Strength. Calc Tiss Res. 14: 283-289.

"The administration of sodium fluoride increased bone diameter, indicating stimulation of periosteal bone formation, but bone strength was reduced or not affected by fluoride ingestion."

Riggins RS, et al. (1976). The effect of fluoride supplementation on the strength of osteopenic bone. Clin Orthop. (114):352-7.

"The strength of osteopenic bone from calcium deprived rats, quail and roosters was significantly reduced after fluoride supplementation...This detrimental effect on bone strength must be considered in any therapeutic attempt to use fluoride ion to stimulate bone formation in osteopenic bone disorders."

Robin JC, et al. (1980). Studies on osteoporosis III. Effect of estrogens and fluoride. J Med.11(1):1-14.

"In the present study high levels of fluoride in the drinking water did not prevent osteoporosis, but in some experiments, by certain criteria, tended to increase it."

Uslu B. (1983). Effect of fluoride on collagen synthesis in the rat. Res Exp Med (Berl). 182(1):7-12.

"Thirty-six young rats were used to determine the effect of the fluoride on collagen synthesis in healing of fracture... Collagen synthesis of the callus was examined histochemically and histologically. In the fluoride-treated group, collagen synthesis was found to be defective, while it was normal in the controls."

Burnell TW, et al. (1986). Effect of dietary fluorine on growth, blood and bone characteristics of growing-finishing pigs. J Anim Sci. 63(6):2053-67.

"The data reported herein suggested that levels of dietary F greater than 7 ppm are detrimental to bone integrity. Breaking stress and modulus of elasticity were reduced significantly at each level of added dietary F in both experiments. Similar observations have been made with nearly all species that have been subjected to F ingestion."

Moskilde L, et al. (1987). Compressive strength, ash weight, and volume of vertebral trabecular bone in experimental fluorosis in pigs. Calcif Tiss Res. 40: 318-322.

"[T]he mechanical parameters for the fluorotic animals were unchanged...or decreased...It is concluded that the increased bone mass during the initial stages of fluoride treatment does not necessarily indicate an improved bone quality."

Turner CH, et al. (1992). The effects of fluoridated water on bone strength. J Orthop Res. 10(4):581-7.

This study examines the effect of fluoridated water on bone strength in rats. The authors conclude that "The results demonstrate that water fluoride levels of 1 ppm may lead to increased bone strength, while water fluoride levels of 4 ppm would be expected to cause a decrease in bone strength."

Turner CH, Dunipace AJ. (1993). On fluoride and bone strength (letter). Calcified Tissue International 53: 289-290.

"[S]everal investigators - including ourselves - have shown that bone strength decreases as bone fluoride levels in the mineral phase increase to beyond about 4500 ppm."

Turner CH, et al. (1995). Fluoride reduces bone strength in older rats. Journal of Dental Research 74(8):1475-81

"In older rats receiving 50 ppm fluoride, failure stress was decreased by as much as 29%. Such dramatic losses in bone strength only have been shown previously in studies where fluoride intake was accompanied by calcium deficiency, yet, in this study, calcium intake in the older rats was no different from that in the younger rats... [I]t is possible that aging effects and fluoride incorporation in the bone act synergistically to decrease bone strength."

Sogaard CH, et al. (1995). Effects of fluoride on rat vertebral body biomechanical competence and bone mass. Bone. 16(1): 163-9.

"Load corrected for ash content, which is a measure of bone quality, decreased significantly after fluoride therapy. It is concluded that the increase in bone mass during fluoride treatment does not translate into an improved bone strength and that the bone quality declines. This investigation thereby supports the hypothesis of a possible negative effect of fluoride on bone quality."

Lafage MH, et al. (1995). Comparison of alendronate and sodium fluoride effects on cancellous and cortical bone in minipigs. A one-year study. J Clin Invest. 95(5):2127-33.

"NaF reduced the strength of cancellous bone from the L4 vertebrae, relative to the control animals, and the stiffness (resistance to deformation) of the femora."

Bone strength "did not increase with bone volume, suggesting that for bones with higher volume, there was less strength per unit volume, that is, a deterioration in bone 'quality.'"

Turner CH. (1996). Fluoride and the FDA: a curious case. (letter) Journal of Bone and Mineral Research 11(9):1369-71.

"[O]ne cannot help but be alarmed by the negative effects of fluoride on bone strength consistently demonstrated in animal models... [M]any fluoride treatment regimens have been studied in animals, and I know of only two animal studies that have shown fluoride to increase bone strength... In all other studies, fluoride has either had no effect on bone strength or significantly decreased it."

Turner CH, et al. (1996). High fluoride intakes cause osteomalacia and diminished bone strength in rats with renal deficiency. Bone. 19(6):595-601.

"Our study also demonstrated evidence of osteomalacia in rats receiving 15 ppm fluoride, or the equivalent of 3 ppm fluoridated water for humans. This finding is consistent with the case studies of Juncos and Donadio showing skeletal fluorosis in two individuals with renal insufficiency who were consuming water containing 1.7-2.6 ppm fluoride."

Turner CH, et al. (1996). Reductions in bone strength after fluoride treatment are not reflected in tissue-level acoustic measurements. Bone 19(6):603-7.

"Fluoride treatment reduced all biomechanical measurements. The reductions ranged from 5% to 25%. Several of these reductions were statistically significant: the fracture force of the femoral neck was reduced by 25%, the fracture stress of the L-5 vertebra was reduced by 19%, and the bending modulus of the femur was reduced by 21%."

Turner CH, et al. (1997). Fluoride treatment increased serum IGF-1, bone turnover, and bone mass, but not bone strength, in rabbits. Calcif Tissue Int. 61(1):77-83.

"Bone strength parameters were, in general, negatively correlated with bone fluoride content. Increases in bone mass resulting from fluoride treatment did not lead to increased bone strength. In fact, many biochemical parameters, namely, vertebral and femoral fracture stress, and femoral elastic modulus, were negatively correlated with bone mass. This seems counterintuitive, however, the bone samples with the highest bone mass also had the highest fluoride content, and the negative effect of increased fluoride content on bone strength far overwhelmed the positive effect of increased bone mass."

Chachra D, et al. (1999). The effect of fluoride treatment on bone mineral in rabbits. Calcified Tissue International 64: 345-51.

"In this study, despite the observed increase in hardness of both cancellous and cortical bone, the fracture stress and elastic modulus of vertebrae ... and femora ... were decreased by fluoride treatment. The fact that the hardness (which is dependent largely on the mineral content) increases even though the modulus (which depends on both the mineral content and the collagen) decreases suggests that there is a change in the relationship between the bone mineral and the collagen."

Bohatyrewicz A. (1999). Effects of fluoride on mechanical properties of femoral bone in growing rats. Fluoride. 32: 47-54.

"Bending strength of the femoral shaft decreased significantly after fluoride therapy. We conclude that high fluoride intake decreases bone quality of the femoral shaft and neck in young growing rats. On the other hand, sodium fluoride administered in lower concentration increases the strength of the femoral neck."

4) Fluoride & Bone Mineral Density (BMD): (Back to top)

Fluoride has been used in the treatment of osteoporosis due to its capacity to increase bone mass. However, while fluoride does in fact increase bone mass, it can also decrease bone mass.

To understand how fluoride alters bone mass it is important to understand the differences in how fluoride affects the two types of bone of the human skeleton: trabecular bone and cortical bone. While fluoride will usually increase bone mass of trabecular bone, it will rarely increase - but may decrease - bone mass of the cortical.

An important point to consider in this regard, is the fact that trabecular bone is the predominant form of bone in the axial skeleton (vertebrae, ribs, cranium) while cortical bone is the predominant form of bone in the appendicular skeleton (arms, legs, hips). Thus, one would expect fluoride to have different effects on the axial and apendicular skeleton.

Perhaps most important, however, is the fact that reductions in cortical bone density can significantly increase the risk for hip fracture. That is because one of the primary sites where hip fracture occurs is the femoral neck, a bone highly dependent on the strength of cortical bone. According to Gordon and Corbin,

"The strength of the femoral neck is due mainly to its shell of cortical bone. Computer analyses indicate 90%-95% of the strength of this region is from cortical rather than trabecular bone." - Gordon SL, Corbin SB. (1992). Summary of workshop on drinking water fluoride influence on hip fracture on bone health. (National Institutes of Health, 10 April, 1991). Osteoporos Int. 2(3):109-17.

4a) Fluoride, BMD, & Trabecular Bone (Back to top)

Riggs BL, et al. (1990). Effect of Fluoride treatment on the Fracture Rates in Postmenopausal Women with Osteoporosis. New England Journal of Medicine. 322:802-809.

"[T]he large increase in the mineral density of cancellous (trabecular) bone in the vertebrae during fluoride treatment did not result in a significant reduction in the rate of vertebral fracture..."

Lindsay R. (1990). Fluoride and Bone - Quantity Versus Quality. Editorial. New England Journal of Medicine. Vol. 322. No. 12. March 22.

"[A]lthough the risk of fractures normally rises as the bone mass declines, increases in bone mass with fluoride treatment may not reduce fracture rates."

Carter DR, Beaupre GS. (1990). Effects of fluoride treatment on bone strength. J Bone Miner Res. 5 Suppl 1:S177-84.

"Due to possible adverse influences of fluoride on the mineralized tissue physical characteristics...the increase in bone mass does not necessarily result in an increase in bone strength...[W]e wish to emphasize the fact that it can be very misleading to rely on simple measures of bone volume fracture and/or bone density as indicators of bone strength in fluoride treated patients."

Fratzl P, et al. (1994). Abnormal bone mineralization after fluoride treatment in osteoporosis: a small-angle x-ray-scattering study. J Bone Miner Res 9(10):1541-9.

"All clinical studies that have been conducted during the past 32 years indicated that NaF is effective in increasing trabecular bone mass in the spine...[T]rabecular bone after fluoride treatment consists of old bone (with normal ultrastructure) and newly formed bone with a completely different mineral ultrastructure, similar to fluorotic bone...[T]he mechanical stability of such tissue is certainly different from normal: mineral is hard but brittle...In light of the present data, very important clinical questions must be addressed. First, fluoride treatment seems to be an intriguing example, in which bone mineral density (BMD) measurements do not at all correlate with the biomechanical properties of bone. Consequently, BMD data from clinical studies without exact analysis of antifracture effectiveness are useless for assessment of the risk-benefit ratio of fluoride treatment."

Sogaard CH, et al. (1995). Effects of fluoride on rat vertebral body biomechanical competence and bone mass. Bone. 16(1): 163-9.

"It is concluded that the increase in bone mass during fluoride treatment does not translate into an improved bone strength and that the bone quality declines."

Jiang Y, et al. (1996). Effects of low-dose long-term sodium fluoride preventive treatment on rat bone mass and biomechanical properties. Calcif Tissue Int. 58(1):30-9.

Fluoride-induced new bone mass "did not increase vertebral strength nor proportionally improve femoral strength, indicating that intrinsic biomechanical properties of the bones could be changed by fluoride treatment."

Turner CH, et al. (1997). Fluoride treatment increased serum IGF-1, bone turnover, and bone mass, but not bone strength, in rabbits. Calcif Tissue Int. 61(1):77-83.

"Increases in bone mass resulting from fluoride treatment did not lead to increased bone strength. In fact, many biochemical parameters, namely, vertebral and femoral fracture stress, and femoral elastic modulus, were negatively correlated with bone mass. This seems counterintuitive, however, the bone samples with the highest bone mass also had the highest fluoride content, and the negative effect of increased fluoride content on bone strength far overwhelmed the positive effect of increased bone mass."

"Vertebral fracture rates and peripheral bone density changes were surprising - and demonstrate that NaF administration is capable of increasing vertebral fracture rates..." despite an increase in vertebral BMD.

4b) Fluoride, BMD, & Cortical Bone (Back to top)

Dambacher MA, et al. (1978). Long term effects of sodium fluoride in osteoporosis. In: Fluoride and Bone; Proceedings of the Second Symposium CEMO, Nyon, Switzerland, Oct. 9-12, 1977, pp. 238-241. Editors: B Courvoisier, A Donath, and CA Baud. Hans Huber Publishers, Bern.

"On sodium fluoride cortical bone decreased while an increase of cancellous bone, especially in the lumbar spine, was observed... A decrease of the cortical bone was found with different methods, the Soerensen-Cameron method and the measurement of the cortical aerea according to Garn. This bone loss was seen in the right radius, femora, and the metacarpalia IV-VI in both NaF dose groups."

Bang S, et al. (1978). Morphometric and biophysical study of bone tissue in industrial fluorosis. In: Fluoride and Bone; Proceedings of the Second Symposium CEMO, Nyon, Switzerland, Oct. 9-12, 1977, pp. 168-175. Editors: B Courvoisier, A Donath, and CA Baud. Hans Huber Publishers, Bern.

"[S]ignificantly higher values were obtained for TBV [Trabecular Bone Volume] (p<0.05), CP [Cortical Porosity] (p<0.0005) and PLS (p<0.00005) of fluorotic bone tissue as compared with the control samples."

Riggs BL, et al. (1980). Treatment of primary osteoporosis with fluoride and calcium: Clinical tolerance and fracture occurrence. JAMA. 243(5): 446-449.

"In this series, we found increased vertebral trabeculation in one third of the patients, but this was associated with, if anything, decreased density of the distal radius, a site containing predominantly cortical bone. The possibility that trabecular (lamellar) bone is increased at the expense of cortical (osteonal) bone cannot be excluded at the present time."

Riggs BL. (1983). Treatment of osteoporosis with sodium fluoride: An appraisal. Bone and Mineral Research. 2: 366-393.

"The dramatic increase in the predominantly trabecular bone of the axial skeleton during fluoride therapy is not accompanied by a corresponding increase in the predominantly cortical bone of the appendicular skeleton...Indeed, several investigators have reported that cortical bone decreases significantly during treatment...These reports raise the possibility that fluoride therapy may protect against fractures of the vertebral bodies (which consist of predominantly trabecular bone) but may not protect the proximal femur, and could even increase the risk for fractures of this bone, which is predominantly cortical...Since hip fracture is more catastrophic than is vertebral fracture, it will be important for future studies to evaluate the effect of sodium fluoride therapy on mineral content of the proximal femur."

Burnell TW, et al. (1986). Effect of dietary fluorine on growth, blood and bone characteristics of growing-finishing pigs. J Anim Sci. 63(6):2053-67.

"When F was fed at levels up to approximately 132 ppm in the diet, cortical bone wall thickness decreased (both experiments)...Histological evaluation of cortical bone properties provided additional evidence in support of the decreased (P<0.004) bone width (thickness) observed macroscopically."

Hodsman AB, Drost DJ. (1989). The response of vertebral bone mineral density during the treatment of osteoporosis with sodium fluoride. J Clin Endocrinol Metab. 69(5):932-8.

"We have documented a clinically relevant increase in vertebral BMD, although there was a significant reduction in cortical BMD at the radial site...The responders were classified according to their increase in vertebral BMD. However, this same group had a significant decline in forearm BMD, a predominantly cortical site in the appendicular skeleton...Most reports have found either no change in BMD at cortical sites or a decrease....Although data on femoral neck BMD were not available in this study, clearly such measurements would have been of great importance."

Kragstrup J, et al. (1989). Effects of sodium fluoride, vitamin D, and calcium on cortical bone remodeling in osteoporotic patients. Calcif Tissue Int. 45(6):337-41.

"The therapy had no effect on the thickness of cortical bone in the iliac crest but increased the porosity slightly..."

Kragstrup J, et al. (1989). Effects of fluoride on cortical bone remodeling in the growing domestic pig. Bone. 10: 421-424.

"The purpose of the experiment was to assess the effects of fluoride (F-) on the remodeling process of cortical bone...The rate of remodeling was increased in cortical bone from pigs receiving F- due to an increased activation of new remodeling...The porosity of cortical bone was slightly but significantly increased."

Riggs BL, et al. (1990). Effect of Fluoride treatment on the Fracture Rates in Postmenopausal Women with Osteoporosis. New England Journal of Medicine. 322:802-809.

"Although the large increase in the mineral density of cancellous bone in the vertebrae during fluoride treatment did not result in a significant reduction in the rate of vertebral fracture, the small increases in bone mineral density at the sites composed of mixed cortical and cancellous bone and decreases in bone mineral density at the sites containing predominantly cortical bone were associated with a significant three-fold increase in the incidence of nonvertebral fractures, both incomplete and complete."

"We conclude that fluoride therapy increases cancellous but decreases cortical bone mineral density and increases skeletal fragility."

Gutteridge DH, et al. (1990). Spontaneous hip fractures in fluoride-treated patients: potential causative factors. J Bone Miner Res. 5 Suppl 1:S205-15.

"Histological changes in transiliac cortical bone after hip fractures... consisted of thin cortices, increased porosity and tunneling resorption... While only two pretreatment biopsies are available and showed minimal tunneling, we have never seen this degree of cortical porosity and resorption in biopsies in numerous similar untreated patients. We believe these latter important structural changes to be fluoride related."

"Because of the association between hip fracture and low femoral cortical thickness, and because of the reported decrease in cortical forearm density using Ca and NaF, it seems unwise to use NaF treatment in patients with hip fracture following minor trauma. The same reasoning leads us to recommend evaluation of the femoral necks by radiography or densitometry before instituting NaF treatment, and at intervals during treatment."

Phipps KR, Burt BA. (1990). Water-borne fluoride and cortical bone mass: A comparison of two communities. Journal of Dental Research 69: 1256-1260.

"The negative association we found between fluoride exposure and [cortical] bone mass was not an anticipated result, since this study was stimulated by the hypothesis that fluoride may actually prevent skeletal osteopenia by increasing cortical bone mass... Instead of having bone mass continually increase with water fluoride content, there may be a threshold level above which increased fluoride may in fact be detrimental to cortical bone mass."

Sowers M, et al. (1991). A prospective study of bone mineral content and fracture in communities with differential fluoride exposure. American Journal of Epidemiology. 133: 649-660.

"Residence in the higher-fluoride community was associated with a significantly lower radial bone mass (a site of primarily cortical bone) in premenopausal and postmenopausal women, an increased rate of radial bone mass loss in premenopausal women, and significantly more fractures among postmenopausal women."

Patel S, et al. (1996). Fluoride pharmacokinetics and changes in lumbar spine and hip bone mineral density. Bone. 19(6):651-5.

"It is important to note that FN (Femoral Neck) BMD in some individuals decreased markedly (by as much as 19%) for a minimal increment in LS (Lumbar Spine). This does suggest that fluoride therapy can decrease FN BMD (and possibly increase fracture risk) without any potential benefit at the lumbar spine." In light of these findings, the authors suggest that "all patients treated with fluoride need to have BMD measurements at the LS and FN to allow discontinuation of fluoride if this disparity in BMD changes is observed."

Phipps KR, et al. (2000). Community water fluoridation, bone mineral density and fractures: prospective study of effects in older women. British Medical Journal. 321: 860-4.

"Compared with women with no exposure (to water fluoridation), women with continuous exposure (20 years) had significantly higher bone mineral density of the lumbar spine, femoral neck, and trochanter, but significantly lower density of the radius" (a site of primarily cortical bone).

"A surprising finding in our study was in the changes in BMD at nonspinal sites in patients in group F CaD - where significant bone loss occurred by 27 months at all nonspinal sites examined... The serial BMD changes in the present study are strongly suggestive of an anabolic action of fluoride at the spine (a chiefly trabecular site) with a catabolic action at many other sites, chiefly cortical."

5) Fluoride & Osteoporosis: (Back to top)

Fluoride is well known to cause osteosclerosis, a bone condition marked by an increase of bone mass. Fluoride's osteosclerotic properties are what prompted the medical community to begin using fluoride as a treatment for osteoporosis (see Section 2). The idea was that fluoride-induced osteosclerosis (an increase in bone mass) would serve to counteract osteoporosis, a condition marked by a loss of bone mass.

What wasn't appreciated at the time, however, was that fluoride can have very contradictory effects on bone - as illustrated in section 4. While fluoride certainly causes osteosclerosis, it can also cause osteoporosis, the very condition which fluoride was being used to treat.

That fluoride can cause osteoporosis - a fact long observed in cattle from fluoride polluted areas (see 5b) - has become evident through research conducted over the past 30 years in areas of endemic skeletal fluorosis in countries such as China and India (see 7a).

In this section, we highlight some of this research. To help clarify the relevance of skeletal fluorosis studies to fluoride therapy, it is instructive to note the comment made by Riggs (1983) in his comprehensive review of fluoride as a treatment for osteoporosis.

"[N]ew bone formed under the stimulus of fluoride administration may exhibit various degrees of osteosclerosis, osteoporosis, osteomalacia, and architectural disorganization. Of these manifestations, only osteosclerosis increases bone strength. When fluoride is used therapeutically, therefore, it is obvious that conditions must be carefully chosen so as to maximize the development of osteosclerosis and to minimize the undesirable manifestations of osteoporosis and osteomalacia." - Riggs BL. (1983). Treatment of osteoporosis with sodium fluoride: An appraisal. Bone and Mineral Research. 2: 366-393.

5a) Fluoride & Osteoporosis: Endemic Fluorosis Studies (Back to top)

Krishnamachari KA, Krishnaswamy K. (1973). Genu valgum and osteoporosis in an area of endemic fluorosis. The Lancet. 2(7834):877-879.

"Anteroposterior views of the cervicothoracic and lumbodorsal spine showed the presence of osteosclerosis in all but two patients. The most striking radiological feature, however, was severe osteoporosis of the lower end of the femur and upper ends of the tibia and fibula and rarefaction of the metacarpal bones. In some patients, rarefaction of pelvic bones, femoral neck, and lower ends of radius and ulna was also observed."

Christie DP. (1980). The spectrum of radiographic bone changes in children with fluorosis. Radiology. 136(1):85-90.

"Painful, crippling deformities in Tanzanian children from an area of endemic fluorosis reported... Combinations of osteomalacia, osteoporosis, and osteosclerosis result in a spectrum of bone changes from an early age."

Lian ZC, Wu EH. (1986). Osteoporosis--an early radiographic sign of endemic fluorosis. Skeletal Radiol. 15(5):350-3.

"Radiological investigation of skeletal fluorosis was carried out among the inhabitants from two areas where the fluoride content of water was high, using both conventional radiography and radiographic measurements of bone mineral content (BMC)... It is very interesting to observe that in the majority of our cases, osteosclerosis in the spine and pelvis was always combined with osteoporosis of the long bones. It might be an indication that the axial skeleton undergoes a quite different pathological process from the appendicular skeleton..."

Mithal A, et al. (1993). Radiological spectrum of endemic fluorosis: relationship with calcium intake. Skeletal Radiol. 22(4):257-61.

"Skeletal fluorosis continues to be endemic in many parts of India. Osteosclerosis and interosseous membrane calcification have long been regarded as hallmarks of this disease. Our study showed in addition a wide variety of radiological patterns: coarse trabecular pattern, axial osteosclerosis with distal osteopenia and diffuse osteopenia. Subjects with osteopenic changes had a significantly lower dietary intake of calcium than those groups having normal radiological findings, predominant osteosclerosis or coarse trabecular pattern."

Wang Y, et al. (1994). Endemic fluorosis of the skeleton: radiographic features in 127 patients. Am J Roentgenol. 162(1):93-8.

This study examines the radioagraphic features of 127 patients with skeletal fluorosis. It is reported that 54% of the patients have osteosclerosis, while 40% have osteopenia (osteoporosis, 22% & osteomalacia, 18%). According to the authors: "Two different osteopenic patterns were defined: an osteoporotic pattern with overall decreased bone density and an osteomalacic pattern that combines the features of osteoporosis with bone deformity." The authors note how, in the past, skeletal fluorosis was "thought to result merely in osteosclerosis" but that "later, various radiologic features were found, including osteosclerosis, osteomalacia, and osteoporosis."

Li D, et al. (1999). Epidemiological and radiological study of skeletal fluorosis in Minzhu Town, Longli County, Guizhou Province, China. Fluoride. 32: 55-59.

"66 cases with skeletal fluorosis out of 120 examined subjects were diagnosed for a total detection rate of 55%, in which osteosclerosis accounts for 44 cases (66.67%) and osteoporosis 22 (33.33%)."

Ando M, et al. (2001). Health effects of fluoride pollution caused by coal burning. Sci Total Environ. 271(1-3):107-16.

"Skeletal radiography showed that signs of both osteosclerosis and osteoporosis were observed in some skeletal fluorosis patients. Therefore, it is suggested that fluoride may stimulate both bone resorption and bone formation."

5b) Fluoride & Osteoporosis: Animal Studies (Back to top)

Roholm K. (1937). Fluoride intoxication: a clinical-hygienic study with a review of the literature and some experimental investigations. H.K. Lewis Ltd, London.

"The effects of fluorine on the osseous system are complicated, which may explain some of the apparently contradictory experimental observations. Both diffuse sclerosing processes, and a generalized condition resembling osteomalacia are observed... The osteomalacic condition to some extent varies with the species and age of the animal. Certain features are common, however. The osseous system is attacked diffusely and the changes consist of a combination of atrophic (osteoporotic) and by hyperplastic processes. The bones are often coarser than normally; the weight is reduced and also the resistance... Common features are the reduced strength of the bones, the tendency to form exostoses, bone atrophy, and a deficient calcification."

National Academy of Sciences. (1960). The fluorosis problem in livestock production. Committee on Animal Nutrition, Agricultural Board. Washington DC.

"The bones of the skeleton in fluorosis are porous, soft, and easier to penetrate than normal skeletal structures...Bones or teeth whose fluorine concentration is in excess of 6,000 ppm (fat-free dry) may become by varying degrees less compact, more porous, and softer than normal bones."

Shupe JL, et al. (1963). The effect of fluorine on dairy cattle II. Clinical and pathologic effects. American Journal of Veterinary Research. 24: 964-979.

"Characteristic roentgenographic findings previously associated with fluorosis were seen in this experiment. Sclerosis, porosis, or hyperostosis, or any combination of these, can occur."

Lillie RJ. (1970). Air Pollutants Affecting the Performance of Domestic Animals: A Literature Review. U.S. Dept. of Agriculture. Agricultural Handbook No. 380. Washington D.C.

"The clinical symptoms of sheep poisoned by F-ingestion were very similar to those of cattle: dental lesions, dental wear, exostoses, osteoporosis, ataxia, lameness, paresis, emaciation, diarrhea, and cachexia."

Shupe JL, Olson AE. (1971). Cinical aspects of fluorosis in horses. Journal of the American Veterinary Association. 158: 167-174.

"The osteofluorotic lesions may be porosis, sclerosis, hyperostosis, osteophytosis, and malacia, depending on the interacting factors influencing the degree of fluorosis."

Robin JC, et al. (1980). Studies on osteoporosis III. Effect of estrogens and fluoride. J Med.11(1):1-14.

"In the present study high levels of fluoride in the drinking water did not prevent osteoporosis, but in some experiments, by certain criteria, tended to increase it."

6) Fluoride and Arthritis: (Back to top)

Exposure to excessive amounts of fluoride causes a crippling disease called skeletal fluorosis. Skeletal fluorosis comes in various stages of severity, with the early stages marked by symptoms (joint pain & stiffness) indistinguishable from arthritis.

In his classic study on skeletal fluorosis, Singh (1963) noted that the arthritic symptoms "may be present prior to the development of definite radiological signs." In other words, they may be present before significant calcification of the ligaments, or bone damage - detectable by x-ray - appears. With this in mind, Singh suggested that "a study of the incidence of rheumatic disorders in areas where fluoridation has been in progress for a number of years would be of interest."

However, as noted by Darlene Sherrell, in a statement recently submitted to the Centers for Disease Control, the type of study suggested by Singh is still lacking, despite 50 years of water fluoridation. Sherrell also notes that,

"There is no reliable method to detect the difference between a case of arthritis caused by excess fluoride and a case of arthritis caused by something else... Virtually everyone consumes unknown quantities of fluoride on a daily basis throughout their lifetime; and sooner or later, virtually everyone complains of arthritic symptoms. We simply do not know how many cases of chronic fluoride poisoning have been diagnosed and treated as arthritis."

6a) Fluoride & Arthritis: Early Stages of Skeletal Fluorosis (Back to top)

Hileman B. (1988). Fluoridation of water.Questions about health risks and benefits remain after more than 40 years. Chemical and Engineering News. August 1, 1988, 26-42. (See article )

"Although skeletal fluorosis has been studied intensely in other countries for more than 40 years, virtually no research has been done in the U.S. to determine how many people are afflicted with the earlier stages of the disease, particularly the preclinical stages. Because some of the clinical symptoms mimic arthritis, the first two clinical phases of skeletal fluorosis could be easily misdiagnosed. Skeletal fluorosis is not even discussed in most medical texts under the effects of fluoride; indeed, a number of texts say the condition is almost nonexistent in the U.S. Even if a doctor is aware of the disease, the early stages are difficult to diagnose. "

Kilborn LG, et al. (1950). Fluorosis with report of an advanced case. Canadian Medical Association Journal. 62: 135-141.

"Apparently [skeletal fluorosis] is rare on the North American continent, but a few cases have been reported... It is quite possible that endemic centres [of skeletal fluorosis] exist but that the cause of the disabling spondylitis or other joint affections has not been determined, and a diagnosis of chronic arthritis has resulted. Few cases in Canada or the United States will be found to be as dramatic as that recorded here from Southwest China, but by calling attention to the advanced stage of this condition help may be afforded to the diagnosis of early cases."

Singh A, et al. (1963). Endemic fluorosis. Epidemiological, clinical and biochemical study of chronic fluoride intoxication in Punjab. Medicine. 42: 229-246.

In the early stages of skeletal fluorosis, the "only complaints are vague pains noted most frequently in the small joints of hands and feet, the knee joints and those of the spine. Such cases are frequent in the endemic area and may be misdiagnosed as rheumatoid or osteoarthritis. Such symptoms may be present prior to the development of definite radiological signs."

World Health Organization. (1970). Fluorides and Human Health. pp 32, 239-240.

"Whereas dental fluorosis is easily recognized, the skeletal involvement is not clinically obvious until the advanced stage of crippling fluorosis... Such early cases are usually in young adults whose only complaints are vague pains noted most frequently in the small joints of the hands and feet, in the knee joints and in the joints of the spine. These cases are frequent in the endemic area and may be misdiagnosed as rheumatoid or osteo arthritis. In later stages, there is an obvious stiffness of the spine, with limitation of movements, and, still later, the development of kyphosis (hunchback). There is difficulty in walking, due partly to stiffness and limitation of the movements of various joints and partly to the neurological lesions of advanced cases. "

Franke J, et al. (1975). Industrial fluorosis. Fluoride. 8(2): 61-83.

"In the initial stages [of skeletal fluorosis], the complaints of the patients are not remarkable. At first they experience vague rheumatic pains, then the pains become localized in the spine, especially in the lumbosacral region. Later, a sensation of stiffness in the lumbar and cervical spine develop. However, we also found patients with slight radiological changes (subtle signs or stage 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."

Teotia SPS, et al. (1976). Symposium on the Non-Skeletal Phase of Chronic Fluorosis: The Joints. Fluoride. 9(1): 19-24. (See paper)

"In early stages, fluorosis is usually associated only with stiffness, backache, and joint pains which may suggest the diagnosis of rheumatism, rheumatoid arthritis, ankylosing spondylitis and osteomalacia. At this stage the radiological findings of skeletal fluorosis may not be evident and therefore most of these cases are either misdiagnosed for other kinds of arthritis or the patients are treated symptomatically for pains of undetermined diagnosis (PUD). The majority of our patients had received treatment for rheumatoid arthritis and ankylosing spondylitis before they came under our observation."

Czerwinski E, Lankosz W. (1977). Fluoride-induced changes in 60 retired aluminum workers. Fluoride. 10(3): 125-136.

"In our material we noted degenerative changes in the lumbar spine in 95% of cases, which suggests that fluoride accelerates these changes. In addition to pain in the lower spine which is associated with radiological changes, patients with negative x-ray findings also complain of pain in the lumbar-sacral area, an indication that symptoms precede changes demonstrable by x-ray."

Waldbott GL, et al. (1977). Skeletal fluorosis near fluoride-emitting factories. Fluoride. 10: 45-47.

"During litigation of this case, muscular pains, general fatigue, and arthritis in conjunction with liver and kidney damage and with hypothyroidism were recorded. The court decision found a definite relationship between the disease and fluoride ingested from food grown in the contaminated area."

Waldbott GL, Burgstahler AW, and McKinney HL. (1978). Fluoridation: The Great Dilemma. Coronado Press, Inc., Lawrence, Kansas.

"[E]xtensive research from India has revealed severe arthritic changes and crippling neurological complications even where the fluoride concentration in water naturally is as low as 1.5 ppm...Even though extensive bone deformities may not be found on a large scale from fluoride in water at the 1 ppm concentration, some of the early signs of the disease, such as calcifications of ligaments, joint capsules, and muscle attachments, are likely to occur. Indeed these conditions are characteristic of osteoarthritis, in which the formation of microcrystals of apatite (known to be promoted by fluoride) has now been clearly demonstrated. Among the elderly, arthritis of the spine is an especially common ailment that is customarily attributed to 'aging.' Since fluoride retention in bones increases as a person grows older, how can we disregard the possibility that this 'old age' disease might be linked with fluoride intake? For example, Pinet and Pinet described in detail X-ray changes encountered in skeletal fluorosis in North Africa that are in every respect identical with those present in the arthritic spine of the elderly elsewhere."

Carnow BW, Conibear SA. (1981). Industrial fluorosis. Fluoride. 14: 172-181.

"Our findings demonstrate a highly significant relationship between the frequency of back and neck surgery, fractures, symptoms of musculoskeletal disease and a past history of diseases of the bones and joints. In the absence of so-called classic fluorosis, a disease complex was established which involves much more than merely the radiologic appearance of dense bone."

"Similar findings of musculoskeletal changes without classic x-ray signs of fluorosis in workers exposed to high levels of fluorides have appeared in a number of other studies. Of special importance is the large prospective study by Zislin and Girskaya (1971). They followed 2738 workers from the time they first came to work in an aluminum smelter and compared them with 1700 others employed in a nonfluoride producing industry. They found that nonspecific bone changes, musculoskeletal symptoms and other findings antedate the classic x-ray changes of fluorosis in the bones by five to seven years and concluded that the changes of fluorosis described by Roholm represent the late stage of the disease. "

Grandjean P. (1982). Occupational fluorosis through 50 years: clinical and epidemiological experiences. American Journal of Industrial Medicine. 3(2):227-36.

"In light cases of fluorosis, the bone changes are often associated with nonspecific joint and muscle pains..."

Smith GE. (1985). Repetitive Strain Injury, or Incipient Skeletal Fluorosis? (Letter.) New Zealand Medical Journal 98:328. (See letter)

"Early bone fluorosis is not clinically obvious; often the only complaints of young adults are vague pains in the small joints of the hands, feet, and lower back. Such cases may be misdiagnosed as rheumatoid arthritis or ankylosing spondylitis."

Zhiliang Y, et al. (1987). Industrial fluoride pollution in the metallurgical industry in China. Fluoride. 20(3): 118-125.

"According to our survey, clinical manifestations of fluoride injury were systemic. A wide variety of vague, subtle symptoms (i.e. backache, restricted joint movement, abdominal pain) occurred either prior to or simultaneously with the development of bone changes similar to those reported previously. Nonskeletal symptoms, therefore, are important for early diagnosis."

Czerwinski E, et al. (1988). Bone and joint pathology in fluoride-exposed workers. Archives of Environmental Health. 43(5): 340-343.

"Assessment of the fluoride-induced changes from x-ray results is often difficult, especially in the initial stages commonly encountered... Analysis of workers' complaints showed no specific pain or other symptom that we could refer only to fluorosis...The only characteristic feature would be multiple-joint involvement in the case of fluorosis. This would differentitate fluorosis from monoarticular osteoarthritis (OA), but unfortunately not from multiple-joint osteoarthritis or rheumatoid arthritis (RA)."

6b) Fluoride & Arthritis: The combined effects of repetitive stress and fluoride (Back to top)

Shupe JL, Olson AE. (1971). Cinical aspects of fluorosis in horses. Journal of the American Veterinary Association. 158: 167-174.

"These [fluorotic] changes first appear at sites of greatest metabolic activity and stress within a given bone and in bones that are under the greatest stress from weight bearing and locomotion."

Carnow BW, Conibear SA. (1981). Industrial fluorosis. Fluoride. 14: 172-181.

In "Indian basket weavers exposed to fluoride, it was observed that the much used left arm and wrist were particularly susceptible to fluorotic exostosis. Additionally, Ascenzi found that the pattern of F18 distribution in the skeleton is determined by the supply of blood to a bone with increased deposition in those bones receiving the most blood. If this is true, the areas suffering repeated or constant stress or trauma, and as a result requiring ongoing repair, may be areas of increased circulation and metabolism and, as a consequence, increased deposition of fluorides."

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.

"Symptoms of pain, stiffness and diffuse aches may be dismissed as functional, but may in fact be early signs of fluoride damage to tendinous insertions and ligaments as well as joint capsules... It is notable that the symptoms and radiological changes occur first in areas of greater muscular activity. Siddiqui describes the effects on the wrists, shoulders and the neck in women engaged in household work and on the lumbar spine and lower limbs of men working in the fields. Both Siddiqui and Singh et al noted... the selective effect of this halide on the joints which are most used."

Tartatovskaya LY, et al. (1995). Clinico-hygiene assessment of the combined effect on the body of vibration and fluorine. Noise and Vibration Bulletin. 263-264.

"the combined effects of vibration and calcium-fluoride in an animal experiment caused a more pronounced effect than the individual factors alone, deviations in the state of a number of systems and also changes in the kinetics of fluorine in the body."

6c) Fluoride & Arthritis: Results from Clinical Trials (Back to top)

Rich C. (1966). Osteoporosis and fluoride therapy. JAMA. 196: 149.

"Sodium fluoride in the dose used (50 to 150 mg/day) often causes anorexia or epigastric pain... Symptoms of osteoarthritis are often made worse during treatment."

Inkovaara J, et al. (1975). Phophylactic fluoride treatment and aged bones. British Medical Journal. 3: 73-74.

"Fractures and exacerbation of arthrosis were more frequent in the fluoride group."

"Osteoarticular pains in the lower extremities often combined with ankle swelling represent the major problem of NaF treatment."

Riggs BL. (1983). Treatment of osteoporosis with sodium fluoride: An appraisal. Bone and Mineral Research. 2: 366-393

"Results from several large (fluoride clinical trials) indicate that significant side effects attributable to treatment occur in about one-third to one-half of patients. Symptoms have been of two types--periarticular and gastrointestinal. Periarticular symptoms have consisted of periarticular pain, and occasionally, tenderness about the large joints of the lower extremities and a painful plantar syndrome."

Dambacher MA, et al. (1986). Long-term fluoride therapy of postmenopausal osteoporosis. Bone. 7: 199-205.

"In 47% of the treated patients, osteoarticular side effects were observed."

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(5):932-8.

In osteoporosis treatment "there have been serious concerns raised about the safety of sodium fluoride, which has a tendency to cause significant upper gastrointestinal side-effects, arthritis, fascitis, and a more recently described acute lower extremity pain syndrome."

Duell PB, Chestnut CH. (1991). Exacerbation of rheumatoid arthritis by sodium fluoride treatment of osteoporosis. Archives of Internal Medicine. 151(4):783-4.

"This report documents the repeated exacerbation of rheumatoid arthritis on three occasions after the initiation of sodium fluoride therapy...We suggest that sodium fluoride should be used cautiously in patients with rheumatoid arthritis."

Inkovaara JA. (1991). Is fluoride treatment justified today? Calcified Tissue International. 49 Suppl:S68-9.

"The use of fluoride in the prophylaxis or treatment of osteoporosis seems highly questionable for the following reasons: (a) the therapeutic window is very narrow, (b) 15%-37% of patients do not respond to fluoride, (c) there are frequent gastrointestinal disturbances and arthralgias, and especially because (d) patients receiving fluoride have experienced more fractures, especially nonvertebral and hip fractures, than control patients."

7) Kidney disease: A factor increasing the risk for fluoride bone accumulation & damage (Back to top)

A segment of the population which may be at particularly high risk from suffering fluoride-induced bone/joint damage, are those with kidney problems. People with kidney problems (i.e. renal insufficiency) are not able to excrete fluoride in their urine as efficiently as those who are healthy, and as a result they accumulate significantly more fluoride in their bones, and joints. In addition, people with kidney disorders often experience excessive thirst (polydipsia) and thus drink more water than others, which further increases their fluoride exposure.

According to a 1991 review of fluoridation by Australia's National Health and Medical Research Council:

"It would not be surprising if there were some undetected cases of skeletal fluorosis in the Australian population in individuals with pathological thirst disorders and/or impaired renal function. However, the matter has not been systematically examined. This matter should be the subject of careful and systematic review." - National Health and Medical Research Council. (1991). The effectiveness of water fluoridation. Canberra, Australia: Australian Government Publishing Service.

As an illustration of the heightened risk faced by those with kidney disorders, a study published in the Journal of the American Medical Association (Juncos & Donadio 1972), reported case studies of two teenagers (17 and 18 years of age) who developed significant skeletal fluorosis from drinking water with just 1.7 and 2.6 ppm fluoride, respectively.

Call RA, et al. (1965). Histological and chemical studies in man on effects of fluoride. Public Health Reports. 80: 529-538.

"When we correlated bone fluoride levels with the patient's disease, it soon became evident that most of the higher levels were found in patients with an advanced chronic renal disease... Possible differences in fluoride metabolism and its patterns of deposition in bones may exist in chronic renal disease."

Juncos LI, Donadio JV. (1972). Renal failure and fluorosis. Journal of the American Medical Association. 222(7):783-5.

"It is generally agreed that water fluoridation is safe for persons with normal kidneys. Systemic fluorosis in patients with diminished renal function, however, seems a reasonable possibility. In such patients, fluoride may be retained with resulting higher tissue fluoride levels than in persons with normal renal function... We describe herein two patients in whom evidence of systemic fluorosis was related to three factors: (1) diminished renal function, (2) increased quantities of fluoride in drinking water and cooking water, and (3) polydipsia secondary to polyuria."

Marier J, Rose D. (1977). Environmental Fluoride. National Research Council of Canada. Associate Committe on Scientific Criteria for Environmental Quality. NRCC No. 16081.

"In the human body, the kidneys are probably the most crucial organ during the course of low-dose long-term exposure to fluoride. Healthy kidneys excrete 50 to 60% of the ingested dose. Kidney malfunction can impede this excretion, thereby causing an increased deposition of fluoride into bone.. [I]n persons with advanced bilateral pyelonephritis, the skeletal fluoride content can be 4-fold that of similarly-exposed persons with normal kidneys. Similarly, Mernagh et al. (1977) have reported a 4-fold higher skeletal fluoride content in persons with the renal failure of osteodystrophy. It has also been shown that plasma F- levels can be 3 1/2 to 5 times higher than normal in persons with renal insufficiency. It is thus apparent that persons afflicted with some types of kidney malfunction constitute another group that is more 'at risk' than is the general population."

Spencer H, et al. (1980). Fluoride metabolism in patients with chronic renal failure. Arch Intern Med. 140: 1331-1335.

"Most investigations on the effect of fluoride in patients with chronic renal failure have been carried out in patients undergoing hemodialysis. Increased bone levels of fluoride, osteosclerosis, increased incidence of osteomalacia, and increased plasma levels of fluoride have been reported in these caases. The present study has shown that the urinary fluoride level of patients with chronic renal failure is significantly lower than that of patients with normal renal function, most likely as a result of the inability of patients with chronic renal failure to excrete fluoride."

Hefti A, Marthaler TM. (1981). Bone fluoride concentrations after 16 years of drinking water fluoridation. Caries Res. 15(1):85-9.

"4 cases with severe chronic pyelonephritis (kidney disease) had definitely elevated fluoride values... Their bone fluoride concentration was more than double the average of 'healthy' subjects of comparable age."

Gerster JC, et al. (1983). Bilateral fractures of femoral neck in patients with moderate renal failure receiving fluoride for spinal osteoporosis. Br Med J (Clin Res Ed). 287(6394):723-5.

"Two patients with moderate renal failure sustained spontaneous bilateral hip fractures during treatment with fluoride, calcium, and vitamin D for osteoporosis... These abnormalities were considered to be the consequence of excessive retention of fluoride due to renal insufficiency. As bilateral femoral neck fractures are very rare these data suggest a causal link between fractures and fluoride in patients with renal failure. Thus fluoride should be given at a lower dosage, if at all, to patients with even mild renal failure."

Kono K, et al. (1984). Urinary fluoride excretion in fluoride exposed workers with diminished renal function. Industrial Health 22(1):33-40.

"In some patients with CRF (chronic renal function failure), only 6.2 percent of the ingested fluoride was excreted in the urine during a 24 hour period compared to 48.8 percent in the comparisons."

Arnala I, et al. (1985). Effects of fluoride on bone in Finland. Histomorphometry of cadaver bone from low and high fluoride areas. Acta Orthop Scand. 56(2):161-6.

"All subjects with slightly impaired renal function had a higher content of fluoride in bone than did those with normal creatine level... Fluoridation of drinking water up to 1.2 ppm apparently does not pose a potential risk to bone provided the renal function is normal... We should, however, recognize that it is difficult to give a strict value for a safe fluoride concentration in drinking water, because individual susceptibility to fluoride varies."

Noel C, et al. (1985). [Risk of bone disease as a result of fluoride intake in chronic renal insufficiency]. (Article in French). Nephrologie. 6(4):181-5.

"Four cases of osteosclerosis were observed in patients with renal failure. All subjects presented moderate reduction in renal function which had been stabilized for several years. Osteosclerosis appeared progressively but was clinically symptomatic in only one patient.. These observations emphasize the risk of high chronic fluoride intake in patients with renal failure, even with mild reduction of glomerular filtration rate."

Spak CJ, et al. (1985). Renal clearance of fluoride in children and adolescents. Pediatrics 75(3):575-9.

"The results suggest that children have lower renal fluoride clearance rates than adults and indicate that a moderate impairment of the renal function could lead to increased retention of fluoride."

National Institute for Public Health and Environmental Protection. (1989). Integrated criteria document fluorides. Report No 758474010. The Netherlands.

"Persons with chronic renal failures constitute a possible group at-risk with respect to the occurrence of skeletal fluorosis, because of an increased fluoride retention after oral intake. Based on the results of one study, in which the difference in retention between nephritic patients and healthy persons was quantified (average retention: 65% and 20%, respectively), a total daily intake of about 1.5 mg appears to be the maximum acceptable intake for nephritic patients. In view of the limitations of this comparative study and of the individual differences in retention and sensitivity, this figure must only be regarded as an indication."

National Health and Medical Research Council. (1991). The effectiveness of water fluoridation. Canberra, Australia: Australian Government Publishing Service.

"It would not be surprising if there were some undetected cases of skeletal fluorosis in the Australian population in individuals with pathological thirst disorders and/or impaired renal function. However, the matter has not been systematically examined. This matter should be the subject of careful and systematic review."

Environment Canada. (1993). Inorganic Fluorides: Priority Substances List Assessment Report. Government of Canada, Ottawa.

"Individuals with impaired renal function (such as those with diabetes) may be more prone to developing fluoride-related toxicological effects (i.e., fluorosis) due to their diminished excretion of fluoride."

Turner CH, et al. (1996). High fluoride intakes cause osteomalacia and diminished bone strength in rats with renal deficiency. Bone. 19(6):595-601.

"Plasma fluoride... was greatly increased by renal deficiency in all animals consuming fluoridated water. There was a strong positive, nonlinear relationship between plasma fluoride and bone fluoride levels... Our study also demonstrated evidence of osteomalacia in rats receiving 15 ppm fluoride, or the equivalent of 3 ppm fluoridated water for humans. This finding is consistent with the case studies of Juncos and Donadio showing skeletal fluorosis in two individuals with renal insufficiency who were consuming water containing 1.7-2.6 ppm fluoride. As in our study, fluoride consumption was increased in these two individuals because of the polydipsia associated with their renal disease."

8) Fluoride concentrations in Bone in fluoridated & unfluoridated areas (back to top)

Approximately 50% of the fluoride that is ingested each day accumulates in the body, primarily in the bones (Riggs 1983; NAS 1993). Thus, as we age, the fluoride concentration in bone steadily increases, and provides an effective bio-marker for previous fluoride exposure.

Unfortunately, there is currently a scarcity of data concerning fluoride levels present in the bones of people living in fluoridated areas. Without such data, it is difficult to gauge the range of cumulative fluoride exposure in modern times, and likewise, how many people are close to, or above, the threshold(s) at which bone damage occurs.

Included below are some of the few studies which have gathered data on fluoride concentrations in the bones of people living in areas with 1.2 ppm fluoride, or less, in the water.

Based on the limited data, it is clear that the spectrum of fluoride concentrations now fluctuate widely and, more importantly, can reach dangerously high levels.

For instance, in a small sampling of bones from patients with osteoporosis, Sogaard (1994) found that the fluoride concentrations were as high as 4,500 and 6,500 parts per million. These levels - which were also found in another unfluoridated community by Jackson & Weidman (1958) - exceed the level of fluoride (2,000-4,500 ppm) which has been found to damage animal bone (see Chan et al, 1973; Uslu 1983; Kragstrup et al, 1989; Turner et al, 1993; Sogaard et al, 1995), and overlaps the level of fluoride (3,500-5,500 ppm) at which the first signs of skeletal fluorosis appear (Franke 1975; ATSDR 2001). As noted earlier (see Section 6), the pre-clinical stage of fluorosis may cause a host of arthritic symptoms in the absence of "definite radiological signs" of fluorosis (Singh 1963).

What's striking about Sogaard's small sample is that his patients came from an unfluoridated area. As such, the study raises questions about how many others, particularly in fluoridated areas, currently have these type of levels? And, why, after 50 years of water fluoridation, is there still a scarcity of bone data in the United States?

(Note: All of the fluoride concentrations reported below refer to the concentrations in bone ash. Whenever the original levels were given in terms of "dry fat-free" bone, I have converted the figures into their ash values based on the conversion estimate provided by Charen et al 1979 - see table 5.)

Glock GE, et al. (1941). The retention and elimination of fluoride in bones. Biochemical Journal. 35: 1235-1239.

Place: London, England
Water F Content: <0.5 ppm
No. of Samples: 25
F-Bone Concentrations (Range): 240-3100 ppm (rib)

Smith FA, et al. (1953). Age increase and fluoride content in human bone. (Abstract). Federation Proc. 12: 368.

Place: Rochester, New York, USA
Water F Content: <0.1 ppm
No. of Samples: 64
F-Bone Concentrations (Range): 200-1200 ppm (rib)

Zipkin L, et al. (1958). Fluoride deposition in human bones after prolonged ingestion of fluoride in drinking water. US Public Health Rep. 73:732-740.

Place: Grand Rapids, Michigan, USA
Water F Content: 1 ppm (11 years)
No. of Samples: 5
F-Bone Concentrations (Mean): 2,250 ppm (iliac crest); 2,410 ppm (rib); 3,230 ppm (vertebra).
F-Bone Concentrations (Maximum): 4,022 ppm (vertebra)

Jackson D, Weidman SM. (1958). Fluorine in human bone related to age and the water supply of different regions. J. Path. Bact. 76: 451-459.

Place: Leeds, England
Water F Content: <0.5 ppm
No. of Samples: 42
F-Bone Concentration (Mean): 3,211 ppm (trabecular bone, rib)
F-Bone Concentration (Maximum): 6,660 ppm (trabecular bone, rib)

Place: The South Shields, England
Water F Content: 0.8 - 1.2 ppm
No. of Samples: 27
F-Bone Concentration (Mean): 4,141 ppm (trabecular bone, rib)
F-Bone Concentration (Maximum): 4,563 ppm (trabecular bone, rib)

Call RA, et al. (1965). Histological and chemical studies in man on effects of fluoride. Public Health Reports. 80: 529-538.

Place: Utah County, USA
Water F Content: <0.5 ppm (exposure unknown)
F Bone Concentration (Mean): 909 (60-69 yr olds); 941 ppm (70-79 yr olds)
F-Bone Concentration (Maximum): 2,130 ppm

Parkins FM, et al. (1974). Relationships of human plasma fluoride and bone fluoride to age. Calcif Tiss Res. 16: 335-338. (Data based on reanalysis by Charen 1979.)

Place: Iowa City, Iowa, USA
Water F Content: 1 ppm (yrs. of exposure unknown)
No. of Samples: 20
F-Bone Concentration (Mean): 1,601 ppm (iliac crest)

Kuo HC, Stamm JW. (1974). Fluoride levels in human rib bone: a preliminary study. Can J Public Health. 65(5):359-61.

Place: Quebec, Canada
Water F Content: Estimated at 0.2 ppm
No. of Samples: 46
F Bone Concentration (Mean): 1073 ppm (60-69 yr olds); 1307 ppm (70-79 yr olds); 1624 (80+ yr olds) (rib)
F Bone Concentration (Maximum): 2,743 ppm (rib)

Charen J, et al. (1979). Bone fluoride concentrations associated with fluoridated drinking water. Calcif Tissue Int. 27(2):95-9.

Place: Rochester, New York, USA
Water F Content: 1 ppm (exposure > 7 years)
No. of Samples: 17
F Bone Concentration (Mean): 2,085 ppm (rib)

Alhava EM, et al. (1980). The Effect of Drinking Water Fluoridation on the Fluoride Content, Strength and Mineral Density of Human Bone. Acta Orthop Scand. 51: 413-420.

Place: Kuopio, Finland
Water F Content: 1 ppm (Exposure less than 20 years)
No. of Samples: 158
F Bone Concentration (Mean): 1,280 ppm (Women, total bone); 901 ppm (Men, total bone)
F Bone Concentration (Maximum): 4,140 ppm (Women, trabecular bone); 2,740 (Men, cortical bone)

Stein ID, Granik G. (1980). Human vertebral bone: Relation of strength, porosity, and mineralization to fluoride content. Calcif Tissue Int. 32: 189-194.

Place: New Jersey, USA
Water F Content: Unknown
No. of Samples: 80
F Bone Concentration (Mean): 1,070 ppm (vertebrae)
F Bone Concentration (Range): 260-3,720 ppm (vertebrae)

Wix P, Mohamedally SM. (1980). The significance of age-dependent fluoride accumulation in bone in relation to daily intake of fluoride. Fluoride. 13: 100-104.

Place: South East, England
Water F Content: unfluoridated
No. of Samples: 600
F Bone Concentration (Mean): 1,800 ppm (60 yr olds); 1,960 ppm (70 yr olds); 2,500 ppm (80 yr olds); 2,820 ppm (90 yr olds); 3,405 ppm (99 yr olds); (iliac crest bone)

Hefti A, Marthaler TM. (1981). Bone fluoride concentrations after 16 years of drinking water fluoridation. Caries Res. 15(1):85-9.

Place: Basle, Switzerland
Water F Content: 1 ppm (0.8 ppm from June-August)
No. of Samples: 147
F Bone Concentration (Mean): 1,309-1,763 ppm (Women); 1,360-1,651 ppm (Men) (vertebral, trabecular bone)
F Bone Concentration (Maximum): 4,810 ppm (Women); 3,831 ppm (Men)

Arnala I, et al. (1985). Effects of fluoride on bone in Finland. Histomorphometry of cadaver bone from low and high fluoride areas. Acta Orthop Scand. 56(2):161-6.

Place: Kuopio, Finland
Water F Content: 1.0 ppm
No. of Samples: 43
F Bone Concentration (Mean): 1,560 ppm (Women); 1,220 ppm (Men) (trabecular bone)
F Bone Concentration (Maximum): 3,890 ppm (Women); 2,750 ppm (Men)

Boivin G, et al. (1988). Fluoride content in human iliac bone: results in controls, patients with fluorosis, and osteoporotic patients treated with fluoride. J Bone Miner Res. 3(5):497-502.

Place: Geneva Switzerland & Valais Switzerland
Water F Content: unfluoridated
No. of Samples: 76
F Bone Concentration (Mean): 800 ppm (cortical bone, iliac crest)

Eble DM, et al. (1992). Fluoride concentrations in human and rat bone. Journal of Public Health Dentistry. 52: 288-291.

Place: North Carolina, USA
Water F Content: <0.2 & 1.0 ppm
No. of Samples: 24
F Bone Concentrations (Mean): 1,775 ppm (1.0 ppm group); 1,379 ppm (<0.2 ppm group)
F Bone Concentration (Maximum): 3,708 ppm

Sogaard CH, et al. (1994). Marked decrease in trabecular bone quality after five years of sodium fluoride therapy--assessed by biomechanical testing of iliac crest bone biopsies in osteoporotic patients. Bone. 15(4): 393-99.

Place: Denmark
Water F Content: Estimated to be < 0.5 ppm
No. of Samples: 26
F Bone Concentration (Range): 200 - 6,500 ppm (iliac crest)

Richards A, et al. (1994). Normal age-related changes in fluoride content of vertebral trabecular bone - Relation to bone quality. Bone. 15: 21-26.

Place: Denmark
Water F Content: Estimated to be < 0.2 ppm
No. of Samples: 73
F Bone Concentration (Mean): 1,338 ppm (Women); 1,181 ppm (Men)
F Bone Concentration (Maximum): 4,000 ppm

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