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The effect of fluoride on bone histology in postmenopausal osteoporosis depends on adequate fluoride absorption and retention.

Forty-one women with idiopathic postmenopausal osteoporosis have been followed for 2 years after initiation of sodium fluoride at 40-50 mg/day, given together with a daily calcium supplement of 1 gram and vitamin D2, at 50,000 IU weekly. Histological and histomorphometric analyses were done on bone biopsies taken prior to and after 1 year of treatment (mean 1.25 +/- 0.35 years). Thirty patients (74%) developed the histological fluoride effect of hyperosteoidosis, while the remaining 11 patients (26%) had no change from pretreatment biopsies. Hyperosteoidosis was based on increased values for osteoid volume and/or thickened osteoid with greater than 3 lamellar bands. Based on previously reported findings, this histological evidence of hypersoteoidosis within 12-18 months of initiation of therapy provides a useful predictor of ultimate satisfactory fluoride response in terms of bone mineral accretion. No increases in bone mass (measured by neutron activation analysis) were observed at the time of the posttreatment biopsy but, according to this previous work, increases are anticipated over a further 2-3 years of treatment. Factors affecting the development of hyperosteoidosis were analyzed. Hyperosteoidosis was associated with a significantly higher dose of sodium fluoride and a significantly higher level of bone fluoride retention but without significant increase in fasting serum fluoride. Results suggest that fluoride retention depends not only on fluoride dose but also on body size, renal function, and intestinal absorptions of calcium and fluoride. There were no differences in the initial investigations between patients with and without hyperosteoidosis, with respect to age, years of postmenopause, estrogen use, initial biochemistry, or initial bone histology.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗

X-ray microanalysis of fluoride distribution in microfracture calluses in cancellous iliac bone from osteoporotic patients treated with fluoride and untreated.

Fluoride is able to augment cancellous bone mass in vertebral osteoporosis but is responsible for osteoarticular side effects in which microfractures are thought to be involved. During healing of these microfractures, a callus is formed all around the cancellous fracture line. Our hypothesis is that in fluoride-treated osteoporotic patients, calluses are bone sites where fluoride is focally deposited at a high concentration, and this could induce a local defect of calcification with a poor healing of microfractures. Our aim was to validate this hypothesis on several calluses following microfractures in undecalcified iliac cancellous bone from six women with osteoporosis (four fluoride treated and two untreated). Histologically normal iliac cancellous bone tissue, taken from a subject having neither fluoride treatment nor microfracture, was also examined. Selected areas, including new woven bone (calluses) and old lamellar bone, were carbon-coated and analyzed using an electron microprobe. Fluoride K alpha and calcium K alpha radiations were detected with wavelength and energy-dispersive spectrometers, respectively. In old lamellar bone at a distance from microfractures, the fluoride level was similar in normal and untreated osteoporotic patients but was slightly increased in treated osteoporotic patients. In untreated osteoporotic patients, the fluoride level was slightly higher (about 1.2 times) at the site of microfractures (lamellar and woven bone) than in lamellar bone far from such fractures, but fluoride was homogeneously distributed in lamellar and woven bone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Relationship between bone fluoride content and histological evidence of calcification defects in osteoporotic women treated long term with sodium fluoride.

Fluoride treatment is used to increase bone formation and cancellous bone mass in patients suffering from postmenopausal osteoporosis with vertebral fractures. Patients submitted to similar therapeutic protocols have shown various histological responses to the treatment, some developing calcification defects and others not. In fact, the bone histological response to fluoride salts depends on the cumulative uptake of fluoride by bone. To clarify the relationship between the presence of calcification defects (identified by the presence of mottled bone and linear formation defects) and the bone fluoride content, a retrospective study was performed on 29 women with type 1 osteoporosis and treated for several months (11-24) with sodium fluoride (50 mg/day), calcium and vitamin D. Bone fluoride content always significantly increased after treatment, but it was significantly higher in patients showing calcification defects than in those having no defects. These differences between the two groups of patients were not due to differences in clinical details (no significant differences concerning age, duration of treatment, total amount of fluoride ingested, renal function) or in their bone remodelling activity. Thus, it may be hypothesized that the high bone fluoride uptake is due to different individual responses from one patient to another concerning the bioavailability of the same dose of fluoride. This is difficult to predict, except by testing the individual bioavailability of the compound to be used in each patient before starting long-term treatment.

Aged↗

Assessing regional variation of environmental fluoride concentrations in western Germany by analysis of antler fluoride content in roe deer (Capreolus capreolus).

To assess regional variation in ambient fluoride levels, we analyzed the fluoride content of 188 antlers of roe deer (Capreolus capreolus) killed between 1990 and 1999 in 14 areas of the federal state of North Rhine-Westphalia, Germany. Individual antler fluoride concentrations ranged between 113 and 11,995 mg x F-/kg bone ash, and sample means differed significantly (p < 0.0001) among the study areas. Low average concentrations (geometric means of 262 and 277 mg x F-/kg bone ash, respectively) were found in antler samples from two control areas, located quite remote to major fluoride emission sources. The highest geometric mean fluoride content (1,677 mg x F-/kg bone ash) was recorded for an antler sample from a study area exposed to fluoride emissions from an aluminium smelter and two mineral coal-fired power stations. In eight antlers obtained from roe deer living in the direct vicinity of the aluminium smelter, fluoride values ranged between 2,067 and 11,995 mg x F-/kg bone ash, thereby demonstrating the strong impact of this emission source on its surroundings. The study showed that by analyzing antler fluoride concentrations, large-scale surveys of environmental contamination by fluoride can be performed in a standardized and cost-effective way in areas inhabited by deer. Due to its rather narrow home range, abundance, and high adaptability, the roe deer is particularly suited for such studies.

Animals↗

The relative distribution of fluoride in erupted and unerupted enamel of human third molars from a low fluoride area.

Acid-etch biopsies were taken from the centre of the mesio-lingual, disto-lingual, disto-buccal and mesio-buccal cusps of non-carious erupted (n = 16, aged 18-28 years) and unerupted (n = 21, aged 18-28 years) teeth. The donor subjects had lived continuously in a low fluoride area (F water less than 0.1 parts/10(6] from birth, and had had no systemic fluoride supplementation. Tooth brushing, mouth rinsing and the application of sealers were the only fluoride-containing anti-caries programmes practised singly or in combination. Six successive acid-etchings were taken from each of the four cusps, and the fluoride levels in the etching solution were measured with an adapted, fluoride ion-selective electrode. Up to a depth of about 10 microns, unerupted enamel was etched significantly (p less than 0.05) more deeply than erupted enamel, which might be explained by changes in its composition. Up to a depth of approximately 10 microns, significantly more fluoride was found in erupted than in unerupted enamel. This difference may mainly be attributed to the effect of fluoride from the oral environment on erupted enamel. Fluoride concentrations, up to a depth of approximately 3 microns, were (p = 0.07) higher in the buccal cusps than in the lingual cusps of erupted molars, but not at the other etch depths. There were no significant differences (p greater than 0.10) between the buccal and lingual cusps of the unerupted molars at any depth. No significant correlations between enamel fluoride concentrations and age could be found either for erupted or unerupted third molars.

Adult↗

Influence of flow rate, pH and plasma fluoride concentrations on fluoride concentration in human parotid saliva.

In two separate studies the influence of some physiological factors on salivary fluoride excretion was investigated. In the first study, parotid saliva, at two predetermined flow rates, and capillary blood were sampled after ingestion of 1 mg fluoride. In the second study, parotid saliva was collected at five different flow rates, starting 1 h after ingestion of 5 mg fluoride. Capillary blood was sampled throughout the experiment. The first study showed that parotid saliva and plasma fluoride concentrations were closely correlated (r = 0.81). The mean parotid salivary and plasma fluoride concentration ratio (S/P ratio) +/- SD ranged from 0.29 +/- 0.11 to 0.65 +/- 0.15. The fractions of the ingested fluoride dose excreted from one parotid gland were 0.08 and 0.18% at flow rates of 0.25 +/- 0.02 and 0.49 +/- 0.06 ml/min, respectively. The second study showed that at the mean basal plasma fluoride concentration of 0.65 +/- 0.18 mumol/l the mean S/P ratio was 0.55 +/- 0.24. At a plasma fluoride concentration ranging from 3.5 to 11.6 mumol/l the S/P ratio was 0.73 +/- 0.15. Thus the S/P ratio was influenced by the plasma fluoride concentration, but not by variations in parotid salivary flow rate or pH.

Adult↗

Fluoride inhibition of bovine spleen purple acid phosphatase: characterization of a ternary enzyme-phosphate-fluoride complex as a model for the active enzyme-substrate-hydroxide complex.

Purple acid phosphatases (PAPs) employ a dinuclear Fe(3+)Fe(2+) or Fe(3+)Zn(2+) center to catalyze the hydrolysis of phosphate monoesters. The interaction of fluoride with bovine spleen purple acid phosphatase (BSPAP) has been studied using a combination of steady-state kinetics and spectroscopic methods. For FeZn-BSPAP, the nature of the inhibition changes from noncompetitive at pH 6.5 (K(i(comp)) approximately K(i(uncomp)) approximately 2 mM) to uncompetitive at pH 5.0 (K(i(uncomp)) = 0.2 mM). The inhibition constant for AlZn-BSPAP at pH 5.0 (K(i) = 3 microM) is approximately 50-70-fold lower than that observed for both FeZn-BSAP and GaZn-BSPAP, suggesting that fluoride binds to the trivalent metal. Fluoride binding to the enzyme-substrate complex was found to be remarkably slow; hence, the kinetics of fluoride binding were studied in some detail for FeZn-, AlZn-, and FeFe-BSPAP at pH 5.0 and for FeZn-BSPAP at pH 6.5. Since the enzyme kinetics studies indicated the formation of a ternary enzyme-substrate-fluoride complex, the binding of fluoride to FeZn-BSPAP was studied using optical and EPR spectroscopies, both in the presence and absence of phosphate. The characteristic optical and EPR spectra of FeZn-BSPAP. F and FeZn-BSPAP.PO(4).F are similar at pH 5.0 and pH 6.5, indicating the formation of similar fluoride complexes at both pHs. A structural model for the ternary enzyme-(substrate/phosphate)-fluoride complexes is proposed that can explain the results from both the spectroscopic and the enzyme kinetics experiments. In this model, fluoride binds to the trivalent metal replacing the water/hydroxide ligand that is essential for the hydrolysis reaction to take place, while phosphate or the phosphate ester coordinates to the divalent metal ion.

Acid Phosphatase↗

General dental practitioner advice regarding the use of fluoride toothpaste in two areas with a school-based milk fluoridation programme and one without such a programme.

OBJECTIVE: To describe the knowledge and practice of general denta practitioners (GDPs) working in Liverpool (where there is no milk fluoridation programme) and St Helens and Knowsley, and the Wirral (where children have fluoridated milk in schools and pre-schools) relating to the advice given for child patients regarding the use of fluoridated toothpaste. DESIGN: Data were collected via a postal questionnaire sent to all 329 GDPs working within the three areas. GDPs working in more than one of the areas and those working in specialist orthodontic or oral surgery practices were excluded. RESULTS: Two hundred and thirty-four (71%) questionnaires were completed and returned. Only 3% of dentists said that no-one in their practice gave advice on the concentration of fluoride toothpaste to be used. For caries free children under 7 years of age only 64% of GDPs gave advice concerning the concentration of toothpaste which coincided with the available clinical guidelines. Twenty eight per cent of GDPs also contradicted the guidelines by advising children under 7 with high caries to use a low fluoride toothpaste. Although 59% of GDPs in the fluoridated milk areas asked the child whether they had fluoridated milk at school, they did not appear to alter the advice given regarding the use of fluoridated toothpaste. CONCLUSION: The study showed that a significant number of GDPs did not adhere to clinical guidelines relating to the use of fluoride toothpaste when giving advice to their child patients. For evidence-based dentistry to become a reality in this area, ways must be found to disseminate the available guidelines more fully and increase their acceptance and use by practitioners.

Animals↗

Fluoride intake in children living in a high-fluoride area in Ethiopia - intake through beverages.

INTRODUCTION: The present study was conducted in Wonji Shoa, a sugar estate in the Ethiopian Rift Valley. Drinking water in the area is provided either by the Awash River or by high-fluoride ground water wells. Defluoridation plants have been installed, but are not in regular use, and fluorosis, dental as well as skeletal, is endemic. The aim of this study was to assess daily fluoride intake from drinking water and beverages in children from neighbouring villages with varying fluoride concentration in the drinking water. SUBJECTS AND METHODS: Thirty families were selected from two of the plantation villages (A and K). The criterion for being included in the project was the presence in the household of at least one child, fully weaned and below the age of 5 years. For sampling of beverages, the duplicate portion technique was used. The fluoride concentration in the beverage samples was determined using standard methods, using a fluoride ion-selective electrode. RESULTS: Ten of the selected households in Village A fetched water from the Awash River (1.8 mg F-/L) while five relied upon water from a local well (2.1 mg F-/L). All 15 households in Village K used water from a local well with fluoride concentration of 14.4 mg/L. The mean daily fluoride intake from drinking water and beverages during the four days, varied from 1.2 to 1.5 mg and 5.9 to 8.8 mg in Village A and K, respectively. Low variety in types of beverages consumed was reported both during the study period and through the questionnaire. Only local water was used for beverage preparation. Children who consumed milk had a reduced fluoride intake. Tea, which was part of the children's diet, was not found to be a main source of fluoride. CONCLUSION: A2n effective defluoridation of the drinking water or a change of water source would seem to be the only options for avoidance of dental and possibly skeletal fluorosis.

Beverages↗

Fluoride release and uptake by four new fluoride releasing restorative materials.

The present study compared the initial fluoride release and release following refluoridation of a conventional glass-ionomer Ketac-Molar (ESPE), a resin-modified glass-ionomer, Vitremer (3M), and two compomers F-2000 (3M) and Hytac (ESPE). Fifteen test specimens were prepared for each brand and immersed in deionized water. The fluoride released was measured every 2 days for 22 days. Refluoridation of the test specimens was done with solutions of 0.02, 0.04 and 0.2% NaF for 5 min on days 22, 30, 38 and 46. The fluoride released from recharged specimens was measured every 2 days until day 54. The fluoride release was highest during the first days after preparation, after which it decreased sharply and then more slowly. The four materials became 'recharged' with fluoride following repeated fluoride exposure in solution, the 0.2% solution being the most effective. From a clinical point of view, the results from this study imply that all the restorative materials tested may act as intra-oral devices for the controlled slow release of fluoride at sites at risk of recurrent caries. Fluoride release and uptake by four new fluoride releasing restorative materials.

Cariostatic Agents↗

Intestinal absorption of fluoride at high luminal concentration of fluoride.

The paper reports that high fluoride concentrations in the intestinal lumen hinders the absorption of this anion. This conclusion was verified with three different experimental models. Pharmacokinetic experiments done in human volunteers revealed that the bioavailability of fluoride from sodium fluoride (NaF, CAS 7681-49-4) enteric coated tablets was 33% of that of plain (immediate release) tablets. The latter findings were confirmed in rats receiving 1 ml of NaF solutions (40, 80 or 160 mmol/l) by gavage. The greatest AUC (area under the curve of fluoremia as a function of time) was obtained with an oral dose of 80 mumol of NaF. This parameter was significantly greater (p < 0.01) with 80 mumol than with 40 mumol NaF, but similar to that observed with 160 mumol. Fecal fluoride excretions (in the 24 h following a single dose of NaF) and the bone fluoride contents (found at the end of 30 days of treatment with 40, 80 or 160 mumol NaF/day), agreed with the AUC values. The rate of fluoride absorption (v, mumol/10 min) through the intestinal wall was investigated with perfused, isolated rat duodenum in vivo. Fluoride absorption increased between 0 and 10 mmol/l luminal fluoride and decreased with higher concentrations. Oxygen consumption of duodenal-tissue decreased exponentially between zero (1.12 mumol O2 min-1 g-1) and 10 mmol/l fluoride (0.45 mumol O2 min-1 g-1).

Adult↗

Mortality in selected cities with fluoridated and non-fluoridated water supplies.

Mortality rates (for blacks and whites only) in 24 cities with fluoridated and 22 with non-fluoridated water supplies in the United States were compared for the years 1969-1971. During these three years 570,671 deaths occurred in the cities with fluoridated water; the 1970 reference population in those cities was 15,972,817. The figures for the cities with non-fluoridated water were 351,053 and 11,106,746 respectively, so that the crude death rates for all causes were 1190.9 (fluoridated) and 1053.6 (non-fluoridated) per 100,000 person-years. Adjustments for age, sex and race reduced differences for some causes and removed them for others. Further correction, using analyses of covariance for city characteristics that influence mortality, gave adjusted death rates for all causes of 1123.9 and 1137.1, and for malignant neoplasms 195.3 and 196.9, in the cities with fluoridated and non-fluoridated water respectively. I found no evidence of a harmful effect of fluoridation.

Age Factors↗

Changes in plaque fluoride levels by school-based fluoride rinsing and tablet programs in Bangladesh.

The aim of this study was to evaluate the effects of school-based fluoride rinsing and tablet programs on plaque fluoride levels. A total of 42 children (8-9 years) were selected from two neighboring schools in Dhaka, Bangladesh. After caries recordings, vestibular plaque samples from the maxillary central incisors and mandibular first molars were collected and frozen on day 0 (baseline). The subjects of one school (rinsing group, n = 15) rinsed with 0.05% NaF, while those from the other school (tablet group, n = 16) used a 0.5 mg F tablet on the 5 school days during a 3-week period. The surfaces were sampled on the first and last school day every week. The fluoride and protein contents of each sample were analyzed using micro-techniques. The median plaque fluoride levels were 9.1 ppm at baseline in the rinsing group and 2.5 ppm in the tablet group (P < 0.05). This difference could in part be related to reported fluoride toothpaste usage. After 4 days on the fluoride programs, plaque fluoride levels in the rinsing group increased to 27.3, 24.5 and 14.2 ppm in the 3 consecutive weeks. The corresponding values after tablet usage were 8.0, 6.5 and 7.1 ppm, respectively. After 3 days without fluoride during the weekends, levels declined towards baseline values in both groups. Hence, the plaque fluoride levels in 8 to 9-year-old Bangladeshi children were increased by both rinsing and tablet programs, but the effect was not detectable 3 days later.

Bangladesh↗

Fluoride, calcium and magnesium intake in children living in a high-fluoride area in Ethiopia. Intake through food.

OBJECTIVE: The aim of this study was to assess the daily dietary fluoride intake in children living in two neighbouring villages in the Wonji Shoa Sugar Estate, a rural part of the Ethiopian Rift Valley. METHODS: The villages depended on water from different sources: Village A used either river water (Awash River, with 1.8 mg F(-)/L) or ground water (2.1 mg F(-)/L), while village K was served ground water with 14 mg F(-)/L. Fifteen fully weaned children below the age of 5 years were selected in each of the villages. Over a four-day period the total food intake for these children was assessed by using a duplicate portion technique. The food was analysed for fluoride by using a fluoride ion-selective electrode after the dry ashing. Furthermore, the energy of the food was measured, as well as the calcium and magnesium contents (atomic absorption spectrometry after microwave digestion with nitric acid and hydrogen peroxide). The mothers gave a description of the ingredients used for preparing the food. Relevant background information concerning food habits, etc. was collected through a food frequency questionnaire. RESULTS: This study shows that considerable amounts of fluoride may be retained in food prepared on high-fluoride water. In village A, food contributed 2.3 mg F(-)/day, while a dietary fluoride intake of 4.8 mg/day was found in children in village K. Interestingly, the sevenfold higher fluoride concentration of the water used for food preparation in village K compared to village A, gave only a doubling in fluoride intake through food. Calcium intake was relatively low while magnesium intake was above the recommended level. CONCLUSION: As the energy intake by both groups was low, some systematic underreporting might be suspected. Thus, the fluoride intake in the group may be even higher than what was actually found in this study.

Calcium, Dietary↗

Magnesium-fluoride interrelationships in man II. Effect of magnesium on fluoride metabolism.

The effect of magnesium on the fluoride balance was investigated in man by determining metabolic balances of fluoride and magnesium in control studies and during magnesium supplementation. The magnesium intake averaged 264 mg/day in the control studies and 825 in the experimental studies. The studies were carried out during four calcium intakes that ranged from 200 to 2,200 mg/day and during phosphorus intakes ranging from 800 to 2,000 mg/day. The studies were carried out during a fluoride intake of about 4 mg/day that was due to the dietary fluoride content and the intake of water and during a high fluoride intake of 25 mg/day that was due to the addition of sodium fluoride. During the high magnesium intake, both the urinary and fecal magnesium excretions increased and the magnesium balances became more positive. These changes were not associated with any significant changes of either the urinary or fecal fluoride excretions or of the fluoride balances during the different intakes of calcium phosphorus, or fluoride.

Adult↗

Fluoride concentration in whole saliva and separate gland secretions in schoolchildren after intake of fluoridated milk.

Fluoride concentration in whole saliva and in separate gland secretions was studied after a 7-day fluoridated milk regimen (1mg F per day) in 12 healthy schoolchildren aged 10-13 years. A 2-week fluoride-free run-in period preceded the tests in order to establish the endogenous baseline levels. Unstimulated and stimulated whole saliva and stimulated parotid and submandibular-sublingual saliva were collected at 1, 3, 6, 12 and 24h after F-milk ingestion, and fluoride concentrations were determined with an ion-selective electrode. Typical time-dependent excretion curves were obtained in all collected secretions. The fluoride levels were significantly elevated 1 and 3h in whole saliva and up to 6h in the gland secretions after intake of fluoridated milk when compared to baseline values. When acid-stimulated, the submandibular-sublingual glands were the major contributors of fluoride in the oral cavity. In conclusion, the results of this study demonstrate that fluoride ingested with milk is excreted through the salivary glands, indicating that the bioavailability of fluoride from milk equals that of other vehicles.

Adolescent↗

Fluoride profiles in dental plaque in vivo formed on fluoride pre-treated human enamel.

Using a novel device capable of generating plaque in vivo on a natural enamel substrate, it has been possible to determine fluoride profiles from the saliva-plaque interface towards the enamel surface. Fluoride profiles in dental plaques tended to fall from the saliva-plaque interface towards the enamel. The device also offered the possibility of examining fluoride distributions after pre-treatment of the enamel with fluoride in vitro. Fluoride profiles were determined in plaque generated in vivo on enamel surfaces, which had been previously treated with a 900-ppm fluoride solution. The results showed the previously reported fall from the plaque surface, but in addition, a further rise towards the enamel surface was seen. The data imply that enamel loaded with fluoride can release some of this fluoride back into the plaque and may act as a fluoride reservoir.

Calcium↗

Interactions of fluoride and non-fluoride agents with the caries process.

Fundamental to the caries process and its inhibition is an understanding of the composition and structural relationships of dental mineral. These have received greater study in recent years, leading to a better understanding of the processes involved. Fluoride has been the most successful of the anti-caries agents to date, and many studies have concentrated on this ion. The anti-caries action of fluoride has been only partially explained by the early finding that fluoride-treated mineral was less soluble, and this criterion is now less widely accepted. The dissolutive process of caries is inhibited by fluoride, monofluorophosphate, trimetaphosphate, and zinc. However, only the first three of these show anti-caries activity. The presence of fluoride during in vivo and in vitro caries is conducive to the formation of an apparently intact surface zone. Current evidence is that this zone reforms during the caries process, thus acquiring fluoride and having larger crystallites compared with sound enamel. Trimetaphosphate also favors the formation of a surface zone. There is a clear beneficial involvement of fluoride, even at low levels, in the process of lesion remineralization. It is highly probable that this process results from re-growth of residual enamel crystallites rather than de novo precipitation of calcium phosphates. Levels of fluoride found in saliva can interact with dental mineral. Although zinc has been shown to adsorb upon apatite mineral and to restrict subsequent crystal growth, it does not appear to affect the action of fluoride, including remineralization, adversely. This may be due to the fact that the uptake of zinc is reversible.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗