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Abstract

Highlights

  • A novel ultrasonic bone quality biomarker was tested in a population with low to high exposure to F.–
  • Negative associations were found between F– exposure and bone quality
  • Decreased bone quality reflects net bone loss, abnormal mineralization and altered collagen.
  • The finding highlights that F– exposure has complex effects on bone quality that go beyond changes in bone density alone.

Background: Various studies, mostly with animals, have provided evidence of adverse impacts of fluoride (F–) on bone density, collagen and microstructure, yet its effects on overall bone quality (strength) has not been clearly or extensively characterized in human populations.

Objective: In this observational study, we assessed variation in an integrated measures of bone quality in a population exposed to wide-ranging F– levels (0.3 to 15.5 mg/L) in drinking water, using a novel application of non-ionizing ultrasonic method.

Method: We collected 871 speed of sound (SOS) measurements from 341 subjects residing in 25 communities, aged 10-70 years (188 males and 153 females). All subjects received scans of the cortical radius and tibia, and adults over the age of 19 received an additional scan of the phalanx. Associations between F– in drinking water and 24-h urine samples, and SOS as a measure of bone quality, were evaluated in bivariate and multivariable regressions adjusting for age, sex, BMI, smoking, and toothpaste use.

Results: We found negative associations between F– exposure and bone quality at all three bones. Adult tibial SOS showed the strongest inverse association with F– exposure, which accounted for 20% of the variance in SOS measures (r = 0.45; n = 199; p < 0.0001). In adjusted analysis, a 1 mg/L increase in F– in drinking water was related to a reduction of 15.8 m/s (95% CI: -21.3 to -10.3), whereas a 1 mg/L increase in 24-h urinary F– (range: 0.04-39.5 mg/L) was linked to a reduction of 8.4 m/s (95% CI: -12.7, -4.12) of adult tibial SOS. Among adolescents, in contrast, weaker and non-significant inverse associations between F– exposure and SOS were found, while age, gender, and BMI were more significant predictors than in adults.

Conclusions: These results are indicative of a fluoride-induced deterioration of bone quality in humans, likely reflecting a combination of factors related to SOS: net bone loss, abnormal mineralization and collagen formation, or altered microarchitecture. The portable and low-cost ultrasound technique appears potentially useful for assessment of bone quality, and should be tested in other locations and for other bone-related disorders, to assess the feasibility of its more extensive diagnostic use in hard-to-reach rural regions.

Acknowledgements and funding

This work was initiated through the NIH K99/R00 grant support that has a goal of understanding F– related mineralized tissue disorders and other potential health consequences in the Ethiopian Rift Valley population. We are immensely grateful for the NIEHS‘s career development grant (K99/R00 ES023472). We thank all the children and parents who participated in this study, and the local water bureaus for their help in recruiting them as well as guiding us during the field work. The content expressed in this paper is the responsibility of the authors and does not necessarily reflect the official views of the NIH.

*Original abstract online at https://www.sciencedirect.com/science/article/pii/S2352187219300415