- RUNX2 promotor methylation is positively related to excessive fluoride (F) exposure.
- Bone mineral density (BMD) is negatively related to excessive F exposure in women.
- BMD is negatively associated with RUNX2 promotor methylation in women.
- RUNX2 methylation mediates the association of excessive F exposure and BMD in women.
Bone mineral density (BMD) changes were reported to be associated with excessive fluoride exposure and abnormal expression of RUNX2. However, whether the alteration of methylation status, a most commonly used marker for the alteration of gene expression in epidemiological investigation, of RUNX2 is associated with low-to-moderate fluoride exposure and BMD changes has not been reported. Our study aims to explore the role of RUNX2 promoter methylation in BMD changes induced by low-to-moderate fluoride exposure. A total of 1124 adults (413 men and 711 women) were recruited from Kaifeng City in 2017. We measured BMD using ultrasound bone densitometer. Concentrations of urinary fluoride (UF) were measured using ion-selective electrode, and the participants were grouped into control group (CG) and excessive fluoride group (EFG) according to the concentration of UF. We extracted DNA from fasting peripheral blood samples and then detected the promoter methylation levels of RUNX2 using quantitative methylation-specific PCR. Relationships between UF concentration, RUNX2 promoter methylation and BMD changes were analyzed using generalized linear model and logistic regression. Results showed in EFG (UF concentration > 1.6 mg/L), BMD was negatively correlated with UF concentration B: -0.14; 95%CI: -0.26, -0.01) and RUNX2 promoter methylation (B: -0.13; 95%CI: -0.22, -0.03) in women. The methylation rate of RUNX2 promoter increased by 2.16% for each 1 mg/L increment in UF concentration of women in EFG (95%CI: 0.37, 3.96). No any significant associations between UF concentration, RUNX2 promoter methylation, and BMD were observed in the individuals in CG. Mediation analysis showed that RUNX2 promoter methylation mediated 18.2% (95% CI: 4.2%, 53.2%) of the association between UF concentration and BMD of women in EFG. In conclusion, excessive fluoride exposure (>1.6 mg/L) is associated with changes of BMD in women, and this association is mediated by RUNX2 promoter methylation.
*Original abstract online at https://www.sciencedirect.com/science/article/abs/pii/S0147651320308708
Fluoride in Drinking Water, Diet, and Urine in Relation to Bone Mineral Density and Fracture Incidence in Postmenopausal Women.
Background: Although randomized controlled trials (RCTs) have demonstrated that high fluoride increases bone mineral density (BMD) and skeletal fragility, observational studies of low-dose chronic exposure through drinking water (<1.5mg/L, the maximum recommended by the World Health Organization) have been inconclusive. Objective: We assessed associations of fluoride in urine, and intake via
Fluoride exposure and CALCA methylation is associated with the bone mineral density of Chinese women.
Highlights Excessive fluoride exposure is positively related to CALCA methylation in women. CALCA methylation in Chinese women is negatively associated with BMD. Long-term excessive fluoride exposure is negatively related to BMD in women. BMD in women with CALCA hypermethylated is more susceptible to fluoride. The statistical associations are age-specific
Effects of water improvement and defluoridation on fluorosis-endemic areas in China: A meta-analysis.
Highlights The first analysis of the effect of improving water quality and reducing fluoride in China over 40 years. Analysis of the effect of water improvement and fluoride reduction in different provinces of China. We analyzed the effect of water improvement on dental fluorosis, skeletal fluorosis, and fluoride content
Early diagnosis and classification of professional fluorosis
On the basis of evaluating the clinical course and supplementary method of examination carried out in 132 patients suffering of professional fluorosis and in 200 workers in the premorbid state the author proposes criteria of early diagnosis. Considering Zislin's classification of professional fluorosis, literature data and own findings the author
[Osteofluorosis caused by excess use of toothpaste].
BACKGROUND: Osteofluorosis is caused by chronic fluoride intoxication. Fluoride is used in toothpaste for the prevention of dental caries, and dental fluorosis has often been reported among children and attributed to ingestion of fluoride toothpaste. We report a case of chronic fluoride intoxication caused by excess use of toothpaste in
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Skeletal Fluorosis: The Misdiagnosis Problem
It is a virtual certainty that there are individuals in the general population unknowingly suffering from some form of skeletal fluorosis as a result of a doctor's failure to consider fluoride as a cause of their symptoms. Proof that this is the case can be found in the following case reports of skeletal fluorosis written by doctors in the U.S. and other western countries. As can be seen, a consistent feature of these reports is that fluorosis patients--even those with crippling skeletal fluorosis--are misdiagnosed for years by multiple teams of doctors who routinely fail to consider fluoride as a possible cause of their disease.
As demonstrated by the studies below, skeletal fluorosis may produce adverse symptoms, including arthritic pains, clinical osteoarthritis, gastrointestinal disturbances, and bone fragility, before the classic bone change of fluorosis (i.e., osteosclerosis in the spine and pelvis) is detectable by x-ray. Relying on x-rays, therefore, to diagnosis skeletal fluorosis will invariably fail to protect those individuals who are suffering from the pre-skeletal phase of the disease. Moreover, some individuals with clinical skeletal fluorosis will not develop an increase in bone density, let alone osteosclerosis, of the spine. Thus, relying on unusual increases in spinal bone density will under-detect the rate of skeletal fluoride poisoning in a population.
Fluoride & Osteoarthritis
While the osteoarthritic effects that occurred from fluoride exposure were once considered to be limited to those with skeletal fluorosis, recent research shows that fluoride can cause osteoarthritis in the absence of traditionally defined fluorosis. Conventional methods used for detecting skeletal fluorosis, therefore, will fail to detect the full range of people suffering from fluoride-induced osteoarthritis.
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