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Effect of fluoride addition on ionized calcium in salivary sediment and in saliva containing various amounts of solid calcium fluoride.

The aim of the present study was to estimate the fluoride concentrations necessary for the precipitation of calcium fluoride or calcium fluoride-like substances in saliva and salivary sediment, in the presence of various amounts of chemically pure calcium fluoride. Fluoride was added in increments to whole saliva to which solid calcium fluoride had been added. The ionized calcium concentration was determined immediately after centrifugation. In salivary sediments and saliva with no calcium fluoride added the ionized calcium concentration was nearly independent of the fluoride concentration added below 10 and 20 mmol/l, respectively, and at fluoride concentration above 15 and 25 mmol/l, respectively, nearly no ionic calcium was detected. In the presence of calcium fluoride the ionized calcium concentration decreased rapidly with increasing concentrations of fluoride. The more calcium fluoride added, the lower the ionized calcium concentration at a certain fluoride level. The results suggested that in the in vivo-situation, caries preventive measures based on frequent oral exposure to low concentrations of fluoride may provide calcium fluoride or calcium fluoride-like substances, which will serve as a reservoir for fluoride.

Calcium

Fluoride in dog parotid saliva after intravenous administration of sodium fluoride, sodium monofluorophosphate, and calcium fluoride.

Sodium fluoride, sodium monofluorophosphate, or calcium fluoride, in amounts equivalent to 0.5 mg/kg, were given intravenously to dogs and the effect on parotid saliva F was determined. Significant (P less than 0.01) differences in saliva F levels were related to the ionization of NaF, the hydrolysis of the PO3F ion, and the insolubility of CaF2.

Animals

Critical evaluation of the composition and use of topical fluorides, with emphasis on the role of calcium fluoride in caries inhibition.

There is evidence that a major part of the fluoride which is retained on teeth during topical application is calcium fluoride or calcium fluoride-like, and that this material is relatively stable in the mouth. This is due to surface adsorption of phosphate (HPO4(2-)) ions onto the calcium fluoride surface. Calcium fluoride releases fluoride during caries challenges due to reduced concentration of HPO4(2-) at acid pH. Normally, the fluoride released from calcium fluoride during caries challenges is subsequently built into hydroxyfluorapatite through dissolution/re-precipitation reactions. It appears likely that the formation of calcium fluoride from topical application agents should be increased and not reduced, as believed in the past. Increased deposition of calcium fluoride can be achieved with increased reaction time between fluoride and enamel, reduced pH of the solution, increased concentration, or pre-treatment with calcium. A reduction in pH of the agents is probably the most practical approach to increase the deposition of calcium fluoride during topical application, and clinical data support this contention. Calcium fluorides with various dissolution rates are formed during different procedures of topical application with fluoride, presumably due to incorporation of phosphate into the calcium fluoride crystals.

Animals

Review on fluoride, with special emphasis on calcium fluoride mechanisms in caries prevention.

Low concentrations of fluoride have a beneficial effect on enamel and dentin de- and remineralization. After fluoride treatments, such as topical applications, rinses or dentifrices, salivary fluoride concentrations decrease exponentially in a biphasic manner to very low concentrations within a few hours. For treatments to be effective over periods longer than the brushing and the following salivary clearance, fluoride needs to be deposited and slowly released. Calcium fluoride (or like) deposits act in such a way, owing to a surface covering of phosphate and/or proteins, which makes the CaF2 less soluble under in vivo conditions than in a pure form in inorganic solutions. Moreover, due to the phosphate groups on the surface of the calcium fluoride globules, fluoride is assumed to be released with decreasing pH when the phosphate groups are protonated in the dental plaque.

Calcium Fluoride

Protein adsorption to hydroxyapatite and to calcium fluoride in vitro and amino acid analyses of pellicle formed on normal enamel and on calcium-fluoride-covered enamel in vivo.

Fluoride treatment of enamel has been reported to result in the formation of a layer of a CaF2-like material on the enamel surface. Protein adsorption to enamel is a specific process dependent on the nature of the surface, and little is known about protein adsorption to CaF2. Albumin and lysozyme were adsorbed to hydroxyapatite (HA) and CaF2 powder in vitro, and protein adsorption patterns constructed. In vivo pellicle was collected from three volunteers from fluoride-treated enamel and from normal enamel, and the amino acid compositions analyzed separately. The results showed that CaF2 took up small amounts of proteins as compared with HA. When the CaF2 was pretreated with a phosphate buffer, pH 6.8, the protein adsorption increased markedly. The amino acid analyses showed no major differences in the amino acid compositions between pellicle collected from CaF2-covered enamel and pellicle collected from normal enamel. This lack of difference is presumably due to the adsorption of phosphate ions to the CaF2 crystals and hence changed surface properties.

Adsorption

Study on the dissolution behaviour of calcium fluoride.

The dissolution of two analytical calcium fluoride preparations was studied in aqueous solution. Dissolved calcium fluoride was determined from analysis of Ca and F in solution. Original samples of the two preparations and the residue after partial dissolution were studied by X-ray diffractometry in comparison with natural fluorite. The dissolution of calcium fluoride was found to be extremely slow. After a period of 1-15 weeks, depending on the experimental conditions, a state was reached where apparently no further dissolution occurred, although the solution was far from saturation. The dissolution rate was obviously closely related to the crystal size. On partial dissolution the mean crystal size increased, probably due to the disappearance of the finest fractions. Placing the salt in a dialysis bag before immersion in the water lowered the dissolution rate and increased the undissolved fraction considerably. The results seem to support the assertion that calcium fluoride accumulated in early carious lesions after topical applications of fluoride may persist for considerable periods of time.

Calcium Fluoride

Experiments on the initiation of calcium fluoride formation with reference to the solubility of dental enamel and brushite.

As calcium fluoride formation following topical application of fluoride may be responsible for at least some of the caries-reducing effect of fluoride, the concentration of fluoride necessary to induce its formation were examined. The aim was to determine the degree of supersaturation with respect to calcium fluoride necessary for inducing its spontaneous precipitation, with close reference to its possible formation and retention on dental hard tissue when topical fluoride solutions are used clinically. Powdered enamel or brushite were suspended for 4 h in aqueous solutions buffered at pH 7.2 and 5.0. After the equilibration, ion concentrations were determined and degrees of saturation with respect to apatite and brushite were calculated. In aqueous solutions at pH 7.2 and 5.0 with similar concentrations as those found in the equilibrated suspensions the fluoride concentration was adjusted to from 5 to 500 parts/10(6). After 2 h of gentle agitation the supernatant was analysed, the precipitate (if any) isolated and examined by X-ray diffraction. Initiation of spontaneous calcium fluoride formation required a calcium fluoride ion-activity product of 10(-7.6) or more, 300 parts/10(6) fluoride were necessary to initiate calcium fluoride formation in neutral solution saturated with enamel, and the increased solubility of enamel apatite at low pH allowed calcium fluoride formation from solutions with as low as 100 parts/10(6) fluoride. When phosphate was present in the solution a competing apatite formation could mask the calcium fluoride formation. In neutral solutions saturated with respect to brushite, spontaneous fluorapatite formation was initiated by 100 pats/10(6) fluoride. With 200 parts/10(6) fluoride a further competing formation of calcium fluoride occurred.

Calcium Fluoride

Kinetics of acquisition and loss of calcium fluoride by enamel in vivo.

Two in vivo experiments were performed, concerning (1) the kinetics of the acquisition of calcium fluoride on enamel during daily rinses with a solution of 0.023% F as sodium fluoride, and (2) the loss of calcium fluoride from enamel slabs which had been topically treated with a neutral solution containing 0.9% F as sodium fluoride. Enamel slabs were carried in the mouth by 6 volunteers for 8 days in both experiments. Sound and etched enamel were included. (1) During mouthrinses moderate amounts of fluoride were acquired by sound enamel, and more as calcium fluoride than as fluoridated apatite, whereas on etched enamel, more fluoride was deposited as fluoridated apatite. On etched enamel there was also a tendency that the deposition of calcium fluoride levelled out whereas the incorporation of firmly bound fluoride continued. This may indicate that calcium fluoride was transformed into fluoridated apatite, probably through remineralization during pH cycling in plaque covering the etched enamel. (2) After single topical application, it was found that etched enamel initially took up more calcium fluoride than sound enamel, but also lost more during the 1st day of in vivo exposure. The loss of calcium fluoride was arrested after 1-2 days, on sound enamel at 70% and on etched enamel at 40% of the original level. It is suggested that the increased amounts of firmly incorporated fluoride in enamel originated from calcium fluoride on enamel, and that calcium fluoride is an important and clinically significant source of fluoride ions on enamel.

Acid Etching, Dental

Dissolution of calcium fluoride in human saliva.

The dissolution behavior of calcium fluoride in saliva was investigated. Chemically pure calcium fluoride (200 mg) was equilibrated in 10 ml of either saliva or distilled water for 3 weeks or repeatedly exposed, at 15-min intervals, to 10 ml of fresh solutions of saliva, distilled water, or phosphate- or calcium-containing solutions. Calcium fluoride dissolved more readily in water than in saliva. The study confirmed that exposure to saliva caused formation of a dissolution-limiting layer and that this layer consists of surface-adsorbed phosphates and showed in addition that the dissolution rate was continuously reduced with time of exposure to saliva or phosphate buffer. Calcium fluoride-like material, formed on enamel by treatment with 2% NaF solution, was shown by scanning electron microscopy to have higher stability in saliva than in water after 3 weeks' incubation.

Calcium

Kinetics of dissolution and growth of calcium fluoride and effects of phosphate.

The rate of growth of pure calcium fluoride crystals is controlled by a surface polynuclear mechanism when the supersaturation is less than 4.4. The surface free energy is found to be 120 mJ/m2. The dissolution process is also controlled by a surface process. Both of these processes are very strongly inhibited by phosphate ions. Calcium fluoride-like materials contaminated with phosphate are formed when calcium fluoride is precipitated in phosphate-containing solutions or suspensions. The physical and chemical properties of these materials have been investigated and compared with the corresponding properties of pure calcium fluoride. The former dissolve much faster than pure calcium fluoride in solutions containing phosphate, but an inhibitory effect is still shown. It is suggested that the calcium fluoride-like material formed on dental enamel during treatment of enamel with acidified solutions of high fluoride content is a phosphate-containing calcium fluoride.

Calcium Fluoride

Calcium fluoride formation on enamel and its influence on uptake of fluoride in the apatitic lattice.

Human dental enamel was exposed to a pH 4 buffer containing 150 parts/10(6) fluoride. It was found that due to the arising degrees of saturation with respect to calcium fluoride and apatites, surface enamel dissolved coincident with a formation of calcium fluoride. The calcium fluoride redissolved while it kept the liquid saturated with respect to this salt. During this second period, fluorapatite was formed while hydroxyapatite dissolved. Finally, all calcium fluoride was dissolved and the unreacted fluoride was taken up in the apatitic lattice. The results are discussed with reference to the conditions of the oral cavity and enamel solubility experiments.

Apatites

Dissolution of various calcium fluoride preparations in inorganic solutions and in stimulated human saliva.

The aim of the present study was to examine the dissolution of various preparations of calcium fluoride in inorganic solutions and in human saliva. Calcium fluoride was prepared by mixing either 0.25 or 0.02 mol/l calcium chloride with 0.5 or 0.04 mol/l sodium fluoride. After preparation, the salts were washed in 1 mmol/l calcium chloride solution and in distilled water. A commercial product, calcium fluoride Suprapur (Merck), was used for comparison. The solubility of the salts was examined in distilled water, in a 2-mmol/l sodium phosphate solution, and in whole human saliva, produced by chewing paraffin. It was found that the calcium fluoride ion product after suspension for 1-3 h in distilled water ranged closely around 10(-10.7) for all salts. In the phosphate solution, the commercial product dissolved slowly, the ratio between dissolved fluoride and calcium ranged from 4 to 7, in buffered solutions approaching 2. The supernatant was not saturated by the salt. Our two calcium fluoride salts dissolved quickly and made the phosphate-containing solutions supersaturated with respect to fluorapatite, leading to fluorapatite formation, and because of compensating calcium fluoride dissolution, this led to increasing fluoride concentrations in saliva of up to around 85-95 ppm. The results of this study indicate that calcium fluoride of less than Suprapur standard may dissolve quickly in saliva, unless the dissolution is retarded by a physical barrier, like a forming pellicle.

Apatites

Alkali solubility of calcium fluoride pre-exposed to inorganic orthophosphate at pH 6.8.

The dissolution behavior in 1 M KOH solution of calcium fluoride which had been pre-exposed to inorganic orthophosphate at pH 6.8 was investigated. Chemically pure calcium fluoride (50 mg) was incubated in 5 ml of 2 mmol/l sodium phosphate buffer, pH 6.8, for 24 h or 120 h and subsequently incubated in 5 ml 1 M KOH for 24h. Control samples were incubated in distilled water before KOH exposure. Pre-treatment with phosphate caused a significantly reduced dissolution rate of calcium fluoride in alkali. Longer exposure to phosphate resulted in further reduction of the dissolution rate in alkali. Calcium fluoride formed on teeth in vitro and in vivo will always be exposed to phosphate. The alkali method thus has limitations because calcium fluoride that has been exposed to phosphate will be underestimated.

Alkalies

Determination of citric acid based on inhibition of the crystal growth of calcium fluoride.

Inhibition of the growth of calcium fluoride crystals in the presence of citrate was followed using a kinetic-potentiometric technique and a calcium ion-selective electrode, and as a consequence, a method for the determination of citrate in the range 0.5-2.4 micrograms ml-1 has been developed. The method was successfully applied to the determination of citrate contained in pharmaceutical products and urine. Urine analysis requires prior separation of phosphate, sulphate and magnesium(II). Elimination of these interferences was studied and accomplished using precipitation processes. Magnesium and phosphate were jointly eliminated in basic media by the addition of ammonium ions. Phosphate and sulphate were eliminated with barium(II). Phosphate was also eliminated as a lithium salt.

Calcium Fluoride

On the role of calcium fluoride in the cariostatic mechanism of fluoride.

The literature concerning the formation and stability of CaF2 in the oral environment is reviewed. In early work the CaF2 formed during topical application with fluoride was assumed to be beneficial. It was suggested that it could protect the enamel surface directly or provide free fluoride ions for subsequent incorporation into the hydroxyapatite lattice. However, McCann claimed, in 1968, that CaF2 is soluble in saliva (12-15 mg/l), that it would be rapidly lost in the oral cavity, and that the clinical effect of fluoride was related to formation of firmly bound fluoride only. In this period many authors reported total loss of CaF2 during 24 h after a topical application of fluoride. It has now been shown in several laboratories that calcium fluoride is stable in saliva at neutral pH owing to surface adsorption of HPO2-4 to the crystal surface and formation of a solubility-limiting phase. Extended exposure of saliva can cause formation of a fluorapatite layer on the CaF2 crystals, restricting their dissolution further. Low pH (pH less than 5) causes loss of the solubility-limiting adsorbed HPO2-4 and a slow dissolution of CaF2. The CaF2 crystals may thus serve as pH-controlled reservoirs of fluoride ions on the enamel or in plaque and release fluoride during caries challenges. It is suggested that calcium fluoride is an essential phase explaining important aspects of the mechanism of topically applied fluoride, contrary to what was assumed in the past.

Calcium Fluoride

[Calcium fluoride or not? That is the question!].

The relative cariostatic effect of fluoride as fluorapatite, calcium fluoride-like material, loosely bound fluoride or KOH-soluble fluoride is debated. The present study was carried out to investigate this further in an intraoral caries model. Pair of premolars extracted for orthodontic reasons were used. Enamel from one tooth of each pair was used as controls (untreated). Two slabs were cut from the enamel of the other contralateral premolar. These slabs were treated with 2% NaF for 24 h. One slab was then treated with 1 mol/L KOH for 24 h to remove all loosely bound fluoride. The slabs treated with 2% NaF and then 1 mol/L KOH would contain the KOH-insoluble fluoride. Those treated with only 2% NaF would, in addition, contain KOH-soluble fluoride. Each slab, control, KOH-insoluble F and KOH-soluble and insoluble F, was mounted on different upper removable appliances. The slabs were covered with orthodontic banding material, allowing space for plaque accumulation. Five individuals wore the appliances in 3 separate 4-week periods. The slabs were analyzed by quantitative microradiography. The average mineral loss (delta Z) was 1680 +/- 1000 vol% z microns in the control teeth, 620 +/- 76 vol% . microns in the KOH-soluble and insoluble F teeth and 2167 +/- 1278 vol% . microns in the KOH-insoluble F teeth. The average lesion depths were 90 +/- 41 microns in the control teeth, 35.3 +/- 5.5 microns in the KOH-soluble F teeth and 88 +/- 35 microns in the KOH-insoluble F teeth. It was concluded that only KOH-soluble fluoride reduced mineral loss and lesion depths significantly compared with the untreated teeth.

Calcium Fluoride