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The associations between plasma fluoride and bone mass in children and adolescents.
| Pediatric Research | Park JY, Choi Y, Park S. |
National Health and Nutrition Examination Survey Sex-related difference U.S. Age Bones/Joints Human Study

Abstract

Background

Peak bone mass is attained during childhood and adolescence and is a key determinant of osteoporosis risk later in life. This study investigated the associations between plasma fluoride levels and bone mineral density (BMD) and bone mineral content (BMC) in children and adolescents.

Methods

We analyzed data from 2851 children and adolescents (8–18 years), collected through the National Health and Nutrition Examination Survey 2013–2016. We performed multivariable linear regression analyses to examine the relationships between plasma fluoride levels and bone mass, adjusting for sociodemographic factors, calcium and vitamin D intake, and physical activity.

Results

Plasma fluoride levels among children and adolescents aged 8–18 were not significantly associated with BMD or BMC, except in girls aged 12–18. In this group, higher fluoride levels were associated with higher BMD in the total body (B = 0.025, P = 0.031) and legs (B = 0.031, P = 0.037). However, no association was found between plasma fluoride levels and BMC in girls aged 12–18.

Conclusion

Higher fluoride levels were statistically significantly associated with higher BMD in girls aged 12–18. However, in other age groups and sexes, fluoride levels were not significantly associated with BMD or BMC levels.

Impact

  • Except for girls aged 12–18, plasma fluoride levels among children and adolescents aged 8–18 were not statistically significantly associated with bone mineral density (BMD) or bone mineral content (BMC).
  • Higher fluoride levels in girls aged 12–18 were associated with higher BMD in the total body and legs.
  • Our findings indicated that higher fluoride exposure may not be associated with lower BMD or BMC.
  • Further investigation is warranted to clarify the effects of fluoride exposure on bone health and the underlying mechanisms in young populations.

References

  1. Oweis, R. R. et al. Fluoride intake and cortical and trabecular bone characteristics in adolescents at age 17: a prospective cohort study. Community Dent. Oral. Epidemiol. 46, 527–534 (2018).

    Article  PubMed  PubMed Central  Google Scholar

  2. Pouresmaeili, F., Kamalidehghan, B., Kamarehei, M. & Goh, Y. M. A comprehensive overview on osteoporosis and its risk factors. Ther. Clin. Risk Manag 14, 2029–2049 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar

  3. Griffin, S. O., Regnier, E., Griffin, P. M. & Huntley, V. Effectiveness of fluoride in preventing caries in adults. J. Dent. Res. 86, 410–415 (2007).

    Article  CAS  PubMed  Google Scholar

  4. Dean, H. Fluoridation of drinking water to prevent dental caries. Morb. Mortal. Wkly. Rep. 48, 933–940 (1999).

    Google Scholar

  5. Haguenauer, D. et al. Fluoride for the treatment of postmenopausal osteoporotic fractures: a meta-analysis. Osteoporos. Int. 11, 727–738 (2000).

    Article  CAS  PubMed  Google Scholar

  6. Schamschula, R. G. et al. Daily fluoride intake from the diet of Hungarian children in fluoride deficient and naturally fluoridated areas. Acta Physiol. Hung. 72, 229–235 (1988).

    CAS  PubMed  Google Scholar

  7. Riggs, B. L. et al. Effect of fluoride treatment on the fracture rate in postmenopausal women with osteoporosis. N. Engl. J. Med. 322, 802–809 (1990).

    Article  CAS  PubMed  Google Scholar

  8. Dure-Smith, B. A. et al. Fluoride therapy for osteoporosis: a review of dose response, duration of treatment, and skeletal sites of action. Calcif. Tissue Int 49, S64–S72 (1991).

    Article  PubMed  Google Scholar

  9. Sowers, M. R., Wallace, R. B. & Lemke, J. H. The relationship of bone mass and fracture history to fluoride and calcium intake: a study of three communities. Am. J. Clin. Nutr. 44, 889–898 (1986).

    Article  CAS  PubMed  Google Scholar

  10. Phipps, K. R. & Burt, B. A. Water-borne fluoride and cortical bone mass: a comparison of two communities. J. Dent. Res. 69, 1256–1260 (1990).

    Article  CAS  PubMed  Google Scholar

  11. Sowers, M. F., Clark, M. K., Jannausch, M. L. & Wallace, R. B. A prospective study of bone mineral content and fracture in communities with differential fluoride exposure. Am. J. Epidemiol. 133, 649–660 (1991).

    Article  CAS  PubMed  Google Scholar

  12. Cooper, C., Wickham, C. A., Barker, D. J. & Jacobsen, S. J. Water Fluoridation and Hip Fracture. JAMA 266, 513–514 (1991).

    Article  CAS  PubMed  Google Scholar

  13. Gruber, H. E. & Baylink, D. J. The effects of fluoride on bone. Clin. Orthop. Relat. Res. 264–277 (1991).

  14. Farley, J. R., Wergedal, J. E. & Baylink, D. J. Fluoride directly stimulates proliferation and alkaline phosphatase activity of bone-forming cells. Science 222, 330–332 (1983).

    Article  CAS  PubMed  Google Scholar

  15. Tylenda, C. A. Toxicological Profile for Fluorides, Hydrogen Fluoride, and Fluorine (Agency for Toxic Substances and Disease Registry, 2003).

  16. Gutteridge, D. H., Price, R. I., Kent, G. N., Prince, R. L. & Michell, P. A. Spontaneous hip fractures in fluoride-treated patients: potential causative factors. J. Bone Min. Res. 5, S205–S215 (1990).

    Google Scholar

  17. Riggs, B. L. et al. Clinical trial of fluoride therapy in postmenopausal osteoporotic women: extended observations and additional analysis. J. Bone Min. Res. 9, 265–275 (1994).

    Article  CAS  Google Scholar

  18. Lin, S. Y. et al. Efficacy and safety of postmenopausal osteoporosis treatments: a systematic review and network meta-analysis of randomized controlled trials. J. Clin. Med. 10, 3043 (2021).

  19. Phipps, K. R., Orwoll, E. S., Mason, J. D. & Cauley, J. A. Community water fluoridation, bone mineral density, and fractures: prospective study of effects in older women. BMJ 321, 860–864 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar

  20. Levy, S. M. et al. Associations of fluoride intake with children’s bone measures at age 11. Community Dent. Oral. Epidemiol. 37, 416–426 (2009).

    Article  PubMed  PubMed Central  Google Scholar

  21. Levy, S. M. et al. Effects of life-long fluoride intake on bone measures of adolescents: a prospective cohort study. J. Dent. Res. 93, 353–359 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar

  22. Levy, S. M. et al. Associations of fluoride intake with children’s cortical bone mineral and strength measures at age 11. J. Public Health Dent. 78, 352–359 (2018).

    Article  PubMed  PubMed Central  Google Scholar

  23. Saha, P. K. et al. Effects of fluoride intake on cortical and trabecular bone microstructure at early adulthood using multi-row detector computed tomography (MDCT). Bone 146, 115882 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar

  24. World Health Organization (WHO). Recognizing Adolescence https://apps.who.int/adolescent/second-decade/section2/page1/recognizing-adolescence.html (2020).

  25. Centers for Disease Control and Prevention (CDC). Plasma Fluoride Analysis: NHANES 2015-2016 Laboratory Procedures Manual (2017).

  26. Mehta, A. Biomarkers of fluoride exposure in human body. Indian J. Dent. 4, 207–210 (2013).

    Article  Google Scholar

  27. Centers for Disease Control and Prevention (CDC), National Center for Health Statistics (NCHS), National Health and Nutrition Examination Survey laboratory protocol: 2013-2014: US Department of Health and Human Services, Centers for Disease Control and Prevention (2014).

  28. Laskey, M. A. Dual-energy X-ray absorptiometry and body composition. Nutrition 12, 45–51 (1996).

    Article  CAS  PubMed  Google Scholar

  29. Jain, R. K. & Vokes, T. Dual-energy X-ray absorptiometry. J. Clin. Densitom. 20, 291–303 (2017).

    Article  PubMed  Google Scholar

  30. Ogden, C. L. et al. Centers for Disease Control and Prevention 2000 growth charts for the United States: improvements to the 1977 National Center For Health Statistics Version. Pediatrics 109, 45–60 (2002).

    Article  PubMed  Google Scholar

  31. Bull, F. C. et al. World Health Organization 2020 guidelines on physical activity and sedentary behaviour. Br. J. Sports Med. 54, 1451–1462 (2020).

    Article  PubMed  Google Scholar

  32. Centers for Disease Control and Prevention (CDC). NHANES Tutorials: Dietary Analyses Module (2024).

  33. Everett, E. T. Fluoride’s effects on the formation of teeth and bones, and the influence of genetics. J. Dent. Res. 90, 552–560 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar

  34. Teotia, M., Teotia, S. P. & Singh, K. P. Endemic chronic fluoride toxicity and dietary calcium deficiency interaction syndromes of metabolic bone disease and deformities in India: year 2000. Indian J. Pediatr. 65, 371–381 (1998).

    Article  CAS  PubMed  Google Scholar

  35. Cadogan, J., Blumsohn, A., Barker, M. E. & Eastell, R. A longitudinal study of bone gain in pubertal girls: anthropometric and biochemical correlates. J. Bone Min. Res. 13, 1602–1612 (1998).

    Article  CAS  Google Scholar

  36. Theintz, G. et al. Longitudinal monitoring of bone mass accumulation in healthy adolescents: evidence for a marked reduction after 16 years of age at the levels of lumbar spine and femoral neck in female subjects. J. Clin. Endocrinol. Metab. 75, 1060–1065 (1992).

    CAS  PubMed  Google Scholar

  37. Davies, J. H., Evans, B. A. & Gregory, J. W. Bone mass acquisition in healthy children. Arch. Dis. Child 90, 373–378 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar

  38. Walsh, J. S., Henry, Y. M., Fatayerji, D. & Eastell, R. Lumbar spine peak bone mass and bone turnover in men and women: a longitudinal study. Osteoporos. Int. 20, 355–362 (2009).

    Article  CAS  PubMed  Google Scholar

  39. Faulkner, R. A. et al. Bone densitometry in canadian children 8-17 years of age. Calcif. Tissue Int. 59, 344–351 (1996).

    Article  CAS  PubMed  Google Scholar

  40. From the Centers for Disease Control and Prevention. Achievements in public health, 1900-1999: fluoridation of drinking water to prevent dental caries. JAMA 283, 1283–1286 (2000).

    Article  Google Scholar

  41. Ott, S. M. Attainment of peak bone mass. J. Clin. Endocrinol. Metab. 71, 1082A–1082C (1990).

    Article  CAS  PubMed  Google Scholar

  42. Hansen, M. A., Overgaard, K., Riis, B. J. & Christiansen, C. Role of peak bone mass and bone loss in postmenopausal osteoporosis: 12 year study. BMJ 303, 961–964 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar

  43. Levy, S. M. & Guha-Chowdhury, N. Total fluoride intake and implications for dietary fluoride supplementation. J. Public Health Dent. 59, 211–223 (1999).

    Article  CAS  PubMed  Google Scholar

ABSTRACT ONLINE AT https://www.nature.com/articles/s41390-025-04069-y