Plasma Fluoride Level and Bone Mineral Density

Plasma Fluoride Level and Femoral Bone Mineral Density in Post-Menopausal Women

The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA

Correspondence to
Prasanna Santhanam, MBBS, MD, The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Baltimore, MD, 21287, USA


Received: Dec 9, 2016

Accepted: Dec 20, 2016

Online First: Dec 21, 2016

Fluoride content in water and levels in blood have been an important epidemiological and environmental concern. Recently, water fluoride levels have been reported to influence bone mineral density in post-menopausal women through stimulation of gamma-interferons (γ-IFN) that increase osteoclastic bone resorption—an effect that is counteracted by estrogen.1 On the other hand, skeletal fluorosis may elevate bone mineral density (BMD, often reported in mg/dL) and has been reported to occur due to environmental exposure to cleaning agents.2 We performed an analysis on the National Health and Nutrition Examination Survey (NHANES) cross-sectional data3 (2013–2014) to determine the association between plasma fluoride level and BMD as well as bone mineral concentration (BMC) at different areas of the femoral bone.

Demographic data on age and ethnicity was compiled. BMC/BMD using dual x-ray absorptiometry (DXA) measured values for women aged over 50 years (defined as post-menopausal) was tabulated for the following sites: total femur, femoral neck, inter-trochanteric area, and Ward's triangle. To improve the lower limit of detection, the hexamethyldisiloxane (HMDS) facilitated diffusion method has been employed in NHANES sample collection to quantitatively transfer fluoride from the plasma sample into a small amount of alkaline trapping solution.3 A plasma fluoride level of <0.5 µmol/L was considered “low” (low-F group) and ≥0.5 µmol/L “high” (high-F group). Since there might be effects of degenerative joint disease (DJD) on the lumbar vertebrae, we only included the above femoral sites in our study, which are remote from the degenerative changes that occur at the hip joint. NHANES data also has World Health Organization fracture risk assessment tool (WHO-FRAX) scores giving a 10-year risk for major osteoporotic (MOF) as well as hip fracture. A 10-year risk of ≥10% for a MOF was considered “high” and <10% was considered “low” for statistical comparison. Continuous variables were compared by the non-parametric tests (Wilcoxon rank-sum and Spearman's ρ). Statistical analyses were done with IBM SPSS Statistics for Windows®, ver 21.0 (IBM, Armonk, NY, USA).

The mean post-menopausal age was not different between the low-F (n=238) and high-F groups (n=74) (64.7 [SD 9.4] vs 64.5 [SD 9.2] years, p=0.85). Plasma fluoride level did not correlate with water fluoride level (p=0.53). Plasma fluoride level did not correlate with BMD or BMC at various sites of the femoral bone (Spearman's ρ), total femur BMC 0.10 (p=0.1), femoral neck BMD -0.05 (p=0.4), Ward's triangle BMD -0.03 (p=0.55), Ward's triangle BMC -0.01 (p=0.93), and femoral neck BMC -0.06 (p=0.3). The median plasma fluoride level was not significantly different between women with low-risk for fracture (<10%) compared to those with high-risk (≥10%) (0.39 [IQR 0.86] vs 0.36 [IQR 0.48] μmol/L, p=0.3). The median BMC and BMD at femoral neck (most important for fracture assessment) was not different between low-F and high-F groups (4.02 [IQR 0.78] vs 4.06 [IQR 0.79] mg/dL for BMC, p=0.22; and 4.94 [IQR 0.76] vs 3.57 [IQR 0.69] mg/dL for BMD, p=0.59).

The cross-sectional data from NHANES showed that plasma fluoride level did not affect BMD/BMC at the femoral neck and other regions (cancellous bony areas of femur) in post-menopausal women from the normal population. Fluoride appears to have a level dependent action on osteoclastic activity (levels between 0.5 and 8 mg/dL have no effect; at 0.5, it appears to have some osteoclastic inhibitory effect)4.

Our study is limited by the cross-sectional nature of the design and lack of sufficient population with higher fluoride values. Further studies are need to examine the role of fluoride levels on bone health with epidemiological and environmental considerations.

Conflicts of Interest: None declared.

Financial Support: None.


  1. Lv YG, Kang L, Wu G. Fluorosis increases the risk of postmenopausal osteoporosis by stimulating interferon gamma. Biochem Biophys Res Commun 2016;479:372-9.
  2. Tucci JR, Whitford GM, McAlister WH, et al. Skeletal fluorosis due to inhalation abuse of a difluoroethane-containing computer cleaner. J Bone Miner Res 2016. doi:10.1002/jbmr.2923.
  3. Centers for Disease Control and Prevention (CDC). National Center for Health Statistics (NCHS). National Health and Nutrition Examination Survey Data. Hyattsville MUSDoH. Available from (Accessed December 2, 2016).
  4. Junrui P, Bingyun L, Yanhui G, et al. Relationship between fluoride exposure and osteoclast markers during RANKL-induced osteoclast differentiation. Environ Toxicol Pharmacol 2016;46:241-5.

Cite this article as: Santhanam P, Rowe SP, Solnes LB, Javadi MS. Plasma fluoride level and femoral bone mineral density in post-menopausal women. Int J Occup Environ Med 2017;8:-57.

 pISSN: 2008-6520
 eISSN: 2008-6814

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