Fluoride and Bone Fractures
Ingested fluoride that is not excreted in urine resides within calcified tissues such as bone and teeth, being incorporated into their mineral crystals.1 Once deposited in calcified tissues, fluoride tends to remain and is accumulated over time.2 The developing bone removes far more fluoride from plasma than mature bone due almost entirely to the greater surface area provided by the numerous and loosely organized crystallites in the developing skeleton.1 The data from the Iowa Bone Development Study and the Iowa Fluoride Study (IFS), a longitudinal study collecting data on individual’s dietary and non-dietary fluoride exposures from birth, indicated that life-long fluoride exposure did not have statistically significant effects on bone mineral measures, such as Bone Mineral Content (BMC) and Bone Mineral Density (BMD), in 15 year olds residing in fluoridated areas after controlling for potential confounders.3 It is unlikely, therefore, that chronic fluoride exposure that typically occurs in fluoridated communities in the US has a significant effect on bone mineral/osteoblastic activity beyond adolescence.
At a high dose, fluoride is known to stimulate new bone (i.e. the effect on osteoblast)4-6 thus had been used for the treatment of osteoporosis in the past with the hope of increasing bone mass to the level sufficient to decrease the occurrence of new fractures.7 Data from clinical trials of the use of therapeutic doses of fluoride (i.e. sodium fluoride 10-75 mg/day) on individuals with osteoporosis showed its effect to stimulate bone mineral density but did not unequivocally prove its effect for preventing new fractures.5,8,9
Accumulated evidence from epidemiological studies comparing fracture rates in communities with and without artificial or natural fluoride in drinking water is mixed but overall indicates no difference.4,10-12 The following points are worth noting however:
1) More than half of available observational studies use an ecological approach of measuring exposures5,10 thus incur the potential risk for misclassification of exposures. In addition, restricted individual information in these studies often hampers the control of known confounders such as menopausal status of women, body mass index, physical activities, calcium intake, the use of certain drugs, smoking, non-water fluoride exposure, as well as demographic confounders such as age, gender, and ethnicity in the risk assessment.11,12
2) the National Research Council report (2006) concluded that the scientific evidence is suggestive of increased risk for bone fractures with a lifetime exposure to drinking water containing high natural fluoride (>2 mg/L, especially 4 mg/L or higher) relative to 1 mg/L.5 Meanwhile, the report gave attention to the interesting and potentially important findings from one retrospective cohort study conducted in China which showed U-shaped exposure-response curve with the minimum fractures in the reference group of 1mg/L.5,13
3) The effect of long-term exposure to fluoride on bone fractures among potentially sensitive populations such as those with altered renal function, estrogen level, and or acid balance is not well understood and deserves well-designed investigations using an improved measure of fluoride exposure (i.e. bone fluoride concentrations).5
In summary, the role of fluoride at levels found in drinking water in the US does not convey risk for bone fractures.
Selected systematic reviews on this topic
McDonagh et al. 20006
The authors examined 29 studies of bone fracture or problems with bone development and water fluoride. In all calculations made by the review team, the area with water fluoride level closest to 1.0 mg/L was chosen and compared to the area with the lowest water fluoride level reported. The meta-regression showed that the pooled estimate of the association of bone fracture with water fluoridation was 1.00 (0.94, 1.06), and there was no patterns that linked fluoride to higher risk of hip fractures or fractures of other sites. However, the authors found a great deal of heterogeneity among the studies and recommended to interpret these findings with caution. The authors noted that studies that lasted for longer than 10 years showed a statistically significant protective effect of fluoridation on bone fractures (fewer fractures in fluoridated areas compared to non-fluoridated areas).
NRC Report 20062
The committee conducted an exhaustive evaluation of the safety of fluoride in drinking water to assess the adequacy of the current maximum-contaminant level goal (MCLG) of 4 mg/L as well as secondary maximum contaminant level (SMCL). Bone fracture, and bone health in general, were reviewed. Overall, there was consensus among the committee members that there is scientific evidence that under certain conditions fluoride can weaken bone and increase the risk of fractures. The majority of the committee found that lifetime exposure to fluoride at drinking water concentrations of 4 mg/L or higher is likely to increase fracture rates in the population, particularly in some demographic subgroups that are prone to accumulate fluoride into their bones (e.g., people with renal disease) than fluoride levels of 1 mg/L. However, one fourth of committee members judged the need of more evidence showing that bone fractures occur at an appreciable frequency in human populations exposed to fluoride at 4 mg/L before drawing a conclusion that the MCLG is likely to not be protective. The committee also found that the available epidemiologic data for assessing bone fracture risk in relation to fluoride exposure around 2mg/L are inadequate for drawing firm conclusions about the risk or safety of exposures at the concentration.
Yin et al. 20157
Fourteen observational studies (13 cohort studies and one case-control study) published prior to March 2014 were included in a meta-analysis to assess the relationship between fluoride exposure and hip fracture risk. The authors found that exposure to fluoride in drinking water does not significantly increase the incidence of hip fracture (RRs=1.05, 95%CIs=0.96-1.15) and concluded that chronic fluoride exposure from drinking water does not significantly increase the risk of hip fracture.
- Whitford GM. Fluoride metabolism and excretion in children. J Public Health Dent. 1999;59(4):224-8
- Shambaugh GE, Petrovic A. Effects of sodium fluoride on bone. Application to otosclerosis and other decalcifying bone diseases. JAMA. 1968;204(11):969-73
- Levy SM, Warren JJ, Phipps K et al. Effects of life-long fluoride intake on bone measures of adolescents: a prospective cohort study. J Dent Res. 2014;93(4):353-9
- Burt BA, Eklund SA. Dentistry, Dental Practice, and the Community. 6th ed. St Louis: Elsevier Saunders. 2005
- National Research Council. Fluoride in Drinking Water: A Scientific Review of EPA’s Standards. Washington, DC. The National Academies Press. 2006.
- National Research Council. Health effects of ingested fluoride. Washington, DC. The National Academies Press. 1993.
- Riggs BL, Hodgson SF, O’Fallon WM et al. Effect of fluoride treatment on the fracture rate in postmenopausal women with osteoporosis. N Engl J Med. 1990;322(12):802-9
- Vestergaard P, Jorqensen NP, Schwarz P, Mosekilde L. Effects of treatment with fluoride on bone mineral density and fracture risk- a meta analysis. Osteoporos. Int. 2008;19(3):257-68
- Haguenauer D, Shea B, Tugwell P et al. Fluoride for treating postmenopausal osteoporosis. Cochrane Database of Syst Rev. 2000;(4):CD002825.
- Sutton M, Kiersey R, Farragher L, Long J. Health effects of water fluoridation: An evidence review 2015. Available at http://www.hrb.ie/uploads/tx_hrbpublications/Health_Effects_of_Water_Fluoridation.pdf
- McDonagh M, Whiting P, Bradley M et al. A systematic review of water fluoridation. September 2000. The University of York. Report 18.
- Yin XH, Huang GL, Lin DR et al. Exposure to fluoride in drinking water and hip fracture risk: a meta-analysis of observational studies. PLoS One. 2015;10(5):e0126488
- Li Y, Liang C, Slemenda CW et al. Effect of long-term exposure to fluoride in drinking water on risks of bone fractures. J Bone Miner Res. 2001;16(5):932-9
- Exposure to fluoridated water and attention deficit hyperactivity disorder prevalence among children and adolescents in the United States: an ecological association
- Are fluoride levels in drinking water associated with hypothyroidism prevalence in England? A large observational study of GP practice data and fluoride levels in drinking water
- Age-specific fluoride exposure in drinking water and osteosarcoma (United States)