Fractional urinary fluoride excretion and nail fluoride concentrations in normal, wasted and stunted 4-5 year-old children in Nepal.

INTRODUCTION: It has been suggested that undernourished children are more likely to develop dental fluorosis. We investigated the effects of nutritional status on systemic fluoride metabolism including the proportion of ingested fluoride excreted through urine (i.e. fractional urinary fluoride excretion - FUFE) and fluoride concentration in nail clippings in children, aged 4-5 years, in Nepal. METHODS: Nutritional status was evaluated using weight-for-age (wasting) and height-for-age (stunting) indices. Total daily fluoride intake (TDFI) was estimated from diet and toothpaste ingestion and 24 -h urine collected to assess daily urinary fluoride excretion (DUFE). FUFE was calculated by dividing DUFE by TDFI. Nail clippings (finger and toe) were collected and analysed for fluoride concentration. RESULTS: Of the 100 children who participated, 89 provided information to assess FUFE and 51 children provided nail samples. Overall, 86.5 % of the 89 children were wasted and 39.3 % were stunted. When the samples were pooled into binary (affected and non-affected) categories, mean TDFI and mean DUFE were statistically significantly higher in the 77 wasted children (57.7 and 29.7 µg/kgbw/d, respectively) than the 12 non-wasted children (39.4 and 17.0 µg/kgbw/d, respectively). TDFI and DUFE were also statistically significantly higher in the 35 stunted children (65.1 and 34.5 µg/kgbw/d, respectively) than in the 54 non-stunted children (48.8 and 23.7 µg/kgbw/d, respectively). However, mean FUFE was similar in all groups. There were no statistically significant differences in fluoride concentration of either fingernails or toenails among the different categories of wasting, while mean fingernail fluoride concentration was statistically significantly higher in stunted (5.4 µg/g) than in non-stunted children (3.5 µg/g). CONCLUSION: Our study found no significant effect of nutritional status on the proportion of ingested fluoride excreted in urine (and consequently the proportion retained in the body). These findings suggest that nutritional status may be less likely to be a main risk factor for the development of dental fluorosis than children's dietary habits or total fluoride intake.

Efficacy of Calcium-Containing Eggshell Powder Supplementation on Urinary Fluoride and Fluorosis Symptoms in Women in the Ethiopian Rift Valley.

Dietary calcium binds Fluoride (F), thus preventing excess F absorption. We aimed to assess the efficacy of supplementing calcium-containing Eggshell Powder (ESP) on F absorption using urine F excretion and on fluorosis symptoms. In total, 82 women (41 Intervention Group, IG; 41 Control Group, CG) were recruited; overall, 39 in each group completed the trial. Morning spot urine was collected before (baseline, BL) and after (endline, EL) the intervention that was 6-months daily supplementation with 2.4 g ESP (providing ~1000 mg of calcium). Dental, skeletal, and non-skeletal fluorosis assessments was carried out at BL and, except for dental, at EL. Relative risk (RR) and linear generalized estimating equation were used to compare outcomes between groups. At BL, urinary F excretion in the IG and CG groups was similar, ~10 mg/L. At EL, urinary F excretion in IG women was six-fold lower (ß = -6.1 (95% CI: -7.1, -5.1)) compared to CG. The risk of developing skeletal and non-skeletal fluorosis were significantly (p < 0.001) reduced in the intervention group. A significant reduction in urinary F excretion and reduction in many fluorosis symptoms were observed among women supplemented with calcium-containing ESP, thus providing evidence for using this dietary calcium source for mitigation of fluorosis. Clinical trials registration: NCT03355222.

Ossification of posterior longitudinal ligament and fluorosis.

OBJECTIVE: Ossification of posterior longitudinal ligament (OPLL) is a progressive disease that causes spinal canal compromise and serious neurological sequelae in advanced cases. The incidence of OPLL in the Asiatic population is 2%-3%, but the incidence is more in the background of fluorosis. Our aim was to study the association of OPLL with fluorosis by comparing urine fluoride levels and to study the types of OPLL. MATERIALS AND METHODS: Thirty consecutive patients with OPLL, observed on cervical skiagram, and confirmed by the computed tomography (CT) of the cervical spine, underwent a 24-h urine fluoride level assessment by the ion-selective electrode method. Due consent of all the patients was obtained and the data was collected. Thirty patients with a normal cervical radiograph were taken as a control group and their 24-h urine fluoride levels were compared with the test group. The 24-h urine fluoride level above 1.6 mg/L was taken as the diagnostic parameter of fluorosis. Imaging analysis of the study group focused on the subtype of OPLL, the mass occupying ratio, the sagittal cervical angle, the signs of dural penetration, and the spinal levels involved. Urinary fluoride levels were correlated with the presence of OPLL and different types of OPLL. RESULTS: Of the 30 patients with OPLL, 25 were males and 5 were females. The most common presentation was myelopathy. Continuous type of OPLL was seen in 11 (36.6%), segmental in 8 (26.6%), focal in 5 (16.6%), and mixed variant in 6 (20%) patients. 24-h urinary fluoride levels ranged from 0.26 mg/L to 12.2 mg/L. 18 (60%) of the patients in the study group were found to have urinary fluoride levels above 1.6 mg/L and only 1 patient (4%) of the control group had the urine fluoride level >1.6 mg/L. This difference was statistically significant. Patients with continuous and mixed types of OPLL had a higher mean urine fluoride level than those with a segmental and focal type of OPLL. The continuous variant of OPLL had a statistically significant occupancy ratio when compared to the other three variants, and the high mass occupancy ratio of the OPLL was directly associated with the presence of dural penetration. CONCLUSION: Fluorosis is associated with a higher incidence of OPLL. Higher urinary fluoride levels correlate with the severe forms of OPLL.

Dental fluorosis, nutritional status, kidney damage, and thyroid function along with bone metabolic indicators in school-going children living in fluoride-affected hilly areas of Doda district, Jammu and Kashmir, India.

A case-control study was undertaken among the school children aged 8-15 years to know the presence and severity of dental fluorosis, nutrition and kidney status, and thyroid function along with bone metabolic indicators in Doda district situated at high altitude where drinking water was contaminated and heat stress. This study included 824 participants with an age of 8-15 years. The results of the study reviled that dental fluorosis was significantly higher in affected than control area children. Urinary fluoride was significantly higher (p < 0.05) in affected children as compared to the control area school children. Nutritional status of affected children was lower than control area children. The chronic kidney damage (CKD) was higher in affected than control school children. Thyroid function was affected more in affected than control area schools. Serum creatinine, total alkaline phosphatase, parathyroid hormone, 1, 25(OH)2 vitamin D, and osteocalcin were significantly higher in affected school children (p < 0.05) as compared to control school children, whereas there was no significant difference in triiodothyronine (T3), thyroxine (T4), and 25-OH vitamin D among the two groups. There was a significant decrease in thyroid-stimulating hormone (TSH) in the affected area school children compared to control. In conclusion, fluorotic area school children were more affected with dental fluorosis, kidney damage, along and some bone indicators as compared to control school children.

Groundwater fluoride contamination and its possible health implications in Indi taluk of Vijayapura District (Karnataka State), India.

Groundwater fluoride concentration and fluoride-related health problems were studied in twenty-two villages of Indi taluk of Vijayapura district, Karnataka, India. Present study (2015) was also used to compare groundwater fluoride concentration in same 22 villages with previous government report (2000). Groundwater fluoride concentrations of 62 bore wells of 22 villages were analyzed by using an ion-sensitive electrode. A total of 660 adults and 600 children were screened for fluorosis symptoms and signs. Sixty clinically suspected fluorosis patients' urine samples were further analyzed for fluoride. The mean value (1.22 ± 0.75 mg/L) of fluoride concentration of 62 bore wells and 54.83 % bore wells with ≥1.0 mg/L of fluoride concentrations in Indi taluk indicates higher than the permissible limit of drinking water fluoride concentration recommended for India. Clinical symptoms like arthritis, joint pains, gastrointestinal discomfort and lower limb deformities with high urinary fluoride concentrations in some subjects suggest fluorosis. Results also showed an increase in groundwater fluoride concentration of the same 22 villages between previous and present study. Preliminary arthritis symptom of the villagers could be due to drinking fluoride-contaminated water. Increase in fluoride concentration with time to the bore wells definitely indicates future danger.

High prevalence of dental fluorosis among schoolchildren in three villages in Vavuniya District: an observational study

Background: Studies of groundwater sources in Sri Lanka show that in the entire Northern, North Central, Uva and Eastern Provinces, and also in a large area of the North Western Province, groundwater fluoride content is within the range 1.0 mg/l and 3.0 mg/l. The WHO recommended safe upper limit of fluoride for drinking water is 1.5 mg/l. Objective: Our objective was to determine the prevalence and degree of dental fluorosis in a cohort of schoolchildren in Sinnasippikulam in Vavuniya District, the fluoride content in their serum and urine, and fluoride levels in drinking water in dug wells of the area. Methods: Invitations in Tamil and Sinhala were sent to all households by courier. Demographic information and oral hygiene practices of 307 responsive children were recorded by interviewing children and their mothers. Detailed clinical examinations were performed according to WHO basic methods, with some modifications. Assessment of dental fluorosis in the children was done according to Dean's Index codes and criteria. Results: We found drinking water sources (dug wells) in Sinnasippikulam (n= 82) to have a high mean concentration of fluoride ( x̄ 1.58+ 0.69 mg/l). Of 307 children examined, 224 (72.9%) had clinical evidence of dental fluorosis of varying degrees of severity. The mean fluoride level in serum of schoolchildren was 0.198 mg/l (SD + 0.074; S.E.M. 0.013), and in their urine, 1.44 mg/l (SD + 0.59; SEM 0.11). Conclusions: Our results show that harmful levels of fluoride are extremely common in groundwater sources in the study area, and consequently, dental fluorosis is highly endemic (72.9%) among resident schoolchildren.

The decreased expression of mitofusin-1 and increased fission-1 together with alterations in mitochondrial morphology in the kidney of rats with chronic fluorosis may involve elevated oxidative stress.

This study was designed to characterize changes in the expression of mitofusin-1 (Mfn1) and fission-1 (Fis1), as well as in mitochondrial morphology in the kidney of rats subjected to chronic fluorosis and to elucidate whether any mitochondrial injury observed is associated with increased oxidative stress. Sixty Sprague-Dawley (SD) rats were divided randomly into 3 groups of 20 each, i.e., the untreated control group (natural drinking water containing <0.5mg fluoride/L), the low-fluoride group (drinking water supplemented with 10mg fluoride/L, prepared with NaF) and the high-fluoride group (50mg fluoride/L), and treated for 6 months. Thereafter, renal expression of Mfn1 and Fis1 at both the protein and mRNA levels was determined by immunohistochemistry and real-time PCR, respectively. In addition, the malondiadehyde (MDA) was quantitated by the thiobarbituric acid procedure and the total antioxidative capability (T-AOC) by a colorimetric method. The morphology of renal mitochondria was observed under the transmission electron microscope. In the renal tissues of rats with chronic fluorosis, expression of both Mfn1 protein and mRNA was clearly reduced, whereas that of Fis1 was elevated. The level of MDA was increased and the T-AOC lowered. Swollen or fragmented mitochondria in renal cells were observed under the electronic microscope. These findings indicate that chronic fluorosis can lead to the abnormal mitochondrial dynamics and changed morphology in the rat kidney, which in mechanism might be induced by a high level of oxidative stress in the disease.

Impaired heart rate recovery in patients with endemic fluorosis.

The objective of the present study was to determine the heart rate recovery index (HRRI), a marker of autonomic nervous system function in patients with endemic fluorosis. Forty patients with endemic fluorosis (16 men/24 women) and 40 age-, sex-, and body mass index-matched healthy controls (16 men/24 women) with normal fluoride intake were enrolled in this study. HRRI was calculated by subtracting the heart rate values at the first, second, and third minutes of the recovery phase from the peak heart rate (HRRI 1, HRRI 2, HRRI 3). Urine fluoride levels of fluorosis patients were significantly (P < 0.001) higher than control subjects as expected. HRRI 2 was significantly lower in fluorosis patients than in the controls. The incidence of abnormal HRRI 1 was significantly higher in fluorosis patients than in the controls (P < 0.05). We observed that HRRI, a marker of autonomic nervous system function, is impaired in patients with chronic fluorosis.

The relationship of PTH Bst BI polymorphism, calciotropic hormone levels, and dental fluorosis of children in China.

The aim of this study was to explore the association of parathyroid hormone (PTH) gene Bst BI polymorphism, calciotropic hormone levels, and dental fluorosis of children. A case-control study was conducted in two counties (Kaifeng and Tongxu) in Henan Province, China in 2005-2006. Two hundred and twenty-five children were recruited and divided into three groups including dental fluorosis group (DFG), non-dental fluorosis group (NDFG) from high fluoride areas, and control group (CG). Urine fluoride content was determined using fluoride ion selective electrode; PTH Bst BI were genotyped using PCR-RFLP; osteocalcin (OC) and calcitonin (CT) levels in serum were detected using radioimmunoassay. Genotype distributions were BB 85.3% (58/68), Bb 14.7% (10/68) for DFG; BB 77.6% (52/67), Bb 22.4% (15/67) for NDFG; and BB 73.3% (66/90), Bb 27.7% (24/90) for CG. No significant difference of Bst BI genotypes was observed among three groups (P > 0.05). Serum OC and urine fluoride of children were both significantly higher in DFG and NDFG than in CG (P < 0.05, respectively), while a similar situation was not observed between DFG and NDFG in high fluoride areas (P > 0.05). Serum OC level of children with BB genotype was significantly higher compared to those with Bb genotype in high fluoride areas (P < 0.05). However, no significant difference of serum CT or calcium (Ca) was observed. In conclusion, there is no correlation between dental fluorosis and PTH Bst BI polymorphism. Serum OC might be a more sensitive biomarker for detecting early stages of dental fluorosis, and further studies are needed.

Fluoride consumption and its impact on oral health.

OBJECTIVE: The purpose of this study was to evaluate caries and dental fluorosis among Mexican preschoolers and school-aged children in a non-endemic zone for fluorosis and to measure its biological indicators. METHODS: DMFT, DMFS, dmft, dmfs, and CDI indexes were applied. Fluoride urinary excretion and fluoride concentrations in home water, table salt, bottled water, bottled drinks, and toothpaste were determined. RESULTS: Schoolchildren presented fluorosis (CDI = 0.96) and dental caries (DMFT = 2.64 and DMFS = 3.97). Preschoolers presented dmft = 4.85 and dmfs = 8.80. DMFT and DMFS were lower in children with mild to moderate dental fluorosis (DF). Variable fluoride concentrations were found in the analyzed products (home water = 0.18-0.44 ppm F, table salt = 0-485 ppm F, bottled water = 0.18-0.47 ppm F, juices = 0.08-1.42 ppm F, nectars = 0.07-1.30 ppm F, bottled drinks = 0.10-1.70 ppm F, toothpaste = 0-2,053 ppm F). Mean daily fluoride excretion was 422 ± 176 µg/24 h for schoolchildren and 367 ± 150 µg/24 h for preschoolers. CONCLUSIONS: Data from our study show that, despite values of excretion within an optimal fluoride intake range, the prevalence of caries was significant in both groups, and 60% of the 11- to 12-year-old children presented with dental fluorosis. In addition, variable fluoride concentrations in products frequently consumed by children were found.

Proteomic analysis of urine in rats chronically exposed to fluoride.

Urine is an ideal source of materials to search for potential disease-related biomarkers as it is produced by the affected tissues and can be easily obtained by noninvasive methods. 2-DE-based proteomic approach was used to better understand the molecular mechanisms of injury induced by fluoride (F(-)) and define potential biomarkers of dental fluorosis. Three groups of weanling male Wistar rats were treated with drinking water containing 0 (control), 5, or 50 ppm F(-) for 60 days (n = 15/group). During the experimental period, the animals were kept individually in metabolic cages, to analyze the water and food consumption, as well as fecal and urinary F(-) excretion. Urinary proteome profiles were examined using 2-DE and Colloidal Coomassie Brilliant Blue staining. A dose-response regarding F(-) intake and excretion was detected. Quantitative intensity analysis revealed 8, 11, and 8 significantly altered proteins between control vs. 5 ppm F(-), control vs. 50 ppm F(-) and 5 ppm F(-) vs. 50 ppm F(-) groups, respectively. Two proteins regulated by androgens (androgen-regulated 20-KDa protein and α-2µ-globulin) and one related to detoxification (aflatoxin-B1-aldehyde-reductase) were identified by MALDI-TOF-TOF MS/MS. Thus, proteomic analysis can help to better understand the mechanisms underlying F(-) toxicity, even in low doses.

Effect of endemic fluorosis on hematological parameters.

Although so many studies exist on effect of fluoride on hematological parameters in experimental animals, a few studies have been conducted to investigate the effects of chronic fluorosis on hematological parameters in humans' subjects with endemic fluorosis. So we aimed to determine the hematological parameters in patients with endemic fluorosis. The study group consisted of 60 patients with endemic fluorosis (27 females, 33 males, and mean age 33.4 ± 9.6 years). An age-, gender-, and body mass index-matched control group was composed of 34 healthy volunteers (11 females, 23 males with a mean age 32.6 ± 5.6 years). Urine fluoride levels of fluorosis patients were significantly higher than control subjects as expected (0.42 ± 0.09 vs 1.92 ± 0.14 mg/l, respectively; P < 0.001). There were no statistically significant differences between the fluorosis group and control group with respect to hematological parameters (complete blood count and ferritin). We concluded that chronic fluorosis has no effect on hematological parameters in patients with endemic fluorosis.

[Survey on children's dental fluorosis and fluoride content in urine after defluridation to improve drinking water].

The authors surveyed the dental fluorosis and fluoride content in urine of 8-12 years old children's in 1993 to 1999 for the evaluation of the efficiency to prevent endemic fluorosis after defluoridation to change drinking water source in Guangdong Province. Three villages: slight fluorosis area in Dazhai village, middle fluorosis area in Hupi village and severe fluorosis area in Anquan village in Fengshun County were surveyed. The results showed that the fluoride contents in drinking water were 1 mg/L (or less) in Anquan village, at the same time the prevalence of dental fluorosis and indexes of dental fluorosis were decreasing as changing water time. Fluoride contents in urine were normal. But in other two villages, the fluoride contents in drinking water exceeded 1 mg/L, therefore the children's prevalence rates and indexes of dental fluorosis were higher than the national standards. It is important to keep fluoride contents in drinking water under 1 mg/L for preventing endemic fluorosis by defluoridation to improve drinking water.

Urinary fluoride levels and prevalence of dental fluorosis in three Brazilian cities with different fluoride concentrations in the drinking water.

Urine samples from three daytime periods were collected from 545 5-50-year-old residents of three different Brazilian cities: Garça had fluoridated drinking water since 1973, Bauru since 1975 and Itápolis was not fluoridated. Dental fluorosis was examined in 985 5-24-year-olds using the Thylstrup-Fejerskov index (TF). The subjects were asked to estimate their daily intake of liquids and frequency of beverage consumption. The analysis of 94 water samples showed high variations in the fluoride content of the drinking water. The mean fluoride concentration of the water samples in Garça was 0.9 mg/L (range 0.75-1.2), in Bauru 0.64 mg/L (range 0.01-1.3), and in Itápolis 0.02 mg/L. Mean urinary fluoride concentration was 1.31 mg/L (s 0.61) in Garça, 0.88 mg/L (s 0.49) in Bauru, and 0.39 mg/L (s 0.21) in Itápolis. Self-reported daily liquid intake was not related to urinary fluoride concentration. The mean prevalence of fluorosis was 13.3% in Garça, 6.8% in Bauru, and 1.7% in Itápolis, with mainly categories TF 1 and TF 2 being recorded. Subjects with dental fluorosis tended to show a higher mean urinary fluoride concentration but the difference was not statistically significant. The study showed that fluoride exposure measured by urinary fluoride excretion was within the range expected for the level of fluoride concentration in the drinking water. However, enamel fluorosis tended to be markedly lower than expected. This study revealed that fluoride levels in the two cities with fluoridated drinking water were variable. To optimise anticaries benefits and minimise the risk of fluorosis greater control of the fluoride dosing of the drinking water is required.

Determinants and mechanisms of enamel fluorosis.

Enamel fluorosis occurs when fluoride concentrations in or in the vicinity of the forming enamel are excessive during its pre-eruptive development. Fluoride concentrations in plasma, enamel and other tissues reflect the difference between intake and excretion, i.e. fluoride balance. In addition to the diet, modern sources of ingested fluoride include a variety of dental products, some of which have been identified as risk factors for fluorosis. Fluoride absorption is inversely related to dietary calcium which, at high concentrations, may cause net fluoride secretion into the gastrointestinal tract. The excretion of absorbed fluoride occurs almost exclusively via the kidneys, a process which is directly related to urinary pH. Thus, fluoride balance and tissue concentrations and the risk of fluorosis are increased by factors such as high protein diets, residence at high altitude, and certain metabolic and respiratory disorders that decrease pH. Factors that increase urinary pH and decrease the balance of fluoride include vegetarian diets, certain drugs and some other medical conditions. Although several other fluoride-induced effects might be involved in the aetiology of fluorosis, it now appears that inhibition of enzymatic degradation of amelogenins, which may delay their removal from the developing enamel and impair crystal growth, may be of critical importance. In addition to the effects of fluoride, disturbances in enamel formation that can be confused with fluorosis are caused by chronic acidosis and hypoxia independently of the level of fluoride exposure.