Fluoridated apatites fluoridation effects

Fluoride is tenaciously held by the inorganic phase of enamel. In solution at concentrations of less than 100 ppm it replaces hydroxyl ions in the apatite lattice, which is partially converted to fluorapatite. Above this level a second phase of calcium fluoride is formed. These substances have been demonstrated, both in vitro and on the enamel surface where the concentration of fluoride is highest, to be for practical purposes less soluble in slightly acid solutions than is unsubstituted hydroxyapatite. Fluoride likewise becomes concentrated in regions of local demineralization such as enamel defects and areas of incipient caries. Here it replaces hydroxyl ions on the surface of damaged hydroxyapatite crystals, the fluorapatite surface so formed being less vulnerable to further acid attack than if it had remained as hydroxyapatite. Thus in both healthy and carious enamel, fluoride effectively decreases solubility and promotes remineralization of the inorganic phase. 

In conclusion, the solubility data indicate that upon precipitation from aqueous solutions which have a F/OH molar ratio less than a certain value, slightly fluoridated hydroxyapatites will be formed (x .0.15), and above that ratio nearly pure fluor-apatite will be formed. Usually the F/OH ratio varies so that intimate mixtures of hydroxyapatite and fluorapatite will result (64). The effect of fluoride on teeth and bones are discussed elsewhere (52, 57). 

There are multiple applications of fluoridated bioceramics, essentially as bone and tooth substitutes (Table 1), involving bulk ceramics, glasses, composite materials and coatings for medical devices and surface treatments. In some cases, fluoride ions can leach out of the material inducing a direct biological effect in a soluble form. However, considering the affinity of fluoride ions for apatite... 

Several effects of fluoride ions have been claimed (Table 1) concerning the stability of the biomaterials, the implant-tissue interface, or the tissue itself. The incorporation of fluoride ions in apatitic materials is generally aimed at increasing their stability and decreasing their solubility. 

Banes and Hailer [81] studied the effect of fluoride addition on the size and morphology of apatite crystals in close-to-physiological conditions. These authors in particular reported that fluoride uptake was accompanied by some anisotropic growth of the apatite crystals the width and/or thickness of the crystals increased with F uptake while no noticeable change in length was observed. In addition, LeGeros et al. [66] pointed out the decrease in calcium deficiency linked to a progressive fluoride incorporation. 

Finally, other effects of fluoride addition to HA have been investigated. In particular, the electrical conductivity of HA was found to be modified with fluoride substitution, as an increase in conductivity was observed [82] for OH-F apatites where up to 50% of OH ions were replaced by F. Beyond this proportion, however, a sharp drop in conductivity was pointed out. It seems, however, difficult to... 

The effect of fluoride on odontoblast seems to follow similar pathways however, fluoride does not seem to show any effect on the proliferation of ameloblast cells. In addition to direct biological effects, fluoride ions may also exhibit indirect effects related to the decrease in Calcium concentration they can involve, and the change in the surface properties of biological apatites. 

Osteoclast cells generally require an apatitic substrate (dentine, enamel, bone slices or synthetic apatite coatings) to attach to and act on and the effect of fluoride ions in solution cannot be readily distinguished from the effect of fluoride on... 

The data concerning the effect of fluoride-containing apatites on cell adhesion, proliferation and expression seem rather disparate, probably because of the variation of other surface characteristics and the use of different cell strains. No real negative effect of fluoride-containing substrates has been reported so far and the osteoblast cells seem to behave similarly [184,185] or better [183,186,187] on fluoridated apatites than on HA surfaces. Some reports mention weaker attachment and proliferation, compensated for by improved collagen matrix production [188]. The shape of cells appeared different on fluoridated apatites than on HA. Other authors have found an improvement in cell attachment [183] which has been attributed to the change in surface charge of FA compared to HA. 

T. Tanabe, T. Aoba, E.C. Moreno, M. Fukae, Effect of fluoride in the apatitic lattice on adsorption of enamel proteins onto calcium apatites, J. Dent. Res. 67 (1988) 536-542. C. Robinson, S. Connell, J. Kirkham, S.J. Brookes, R.C. Shore, A.M. Smith, The effect of fluoride on the developing tooth. Caries Res. 38 (2004) 268-276. 

C. Robinson, K. Yamamoto, S.D. Connell, J. Kirkham, H. Nakagaki, A.D. Smith, The effect of fluoride on the nanostructure and surface pK of enamel crystals An atomic force microscopy study of human and rat enamel, Eur. J. Oral Sci. 114 (2006) 99-104. E.D. Eanes, A.W. Mailer, The effect of fluoride on the size and morphology of apatite crystals grown from physiological solutions, Calcif. Tissue Int. 63 (1998) 250-257. 

A. Barry, H. Zhuang, A.A. Baig, W.l. Higuchi, Effect of fluoride pretreatment on the solibility of synthetic carbonated apatite, Calcif. Tissue Int. 72 (2003) 236-242. 

Nevertheless, fluoride does lead to a reduction in the solubility of hydroxyapatite in aqueous solution, even in the absence of trace levels of fluoride in solution, and hence can be seen to have an effect in the solid state as well [57], Apatites are complex and diverse materials which have the general formula Caio(P04)eX2 (X = F, Cl, OH) and they represent a crystallographic system, in which there can be considerable replacement of species. Thus, with little or no change in the dimensions of the crystal lattice, there can be exchanges of OH for F, Ca + for Sr +, and PO4 for CO and all of these are known to occur in biological systems. Natural hydroxyapatite, for example, is often partially carbonate substituted [58]. 

In the presence of fluoride, calcium ions have been found to be more firmly anchored than in pure hydroxyapatite [67]. This enhances the overall resistance to dissolution. Thus, the presence of a thin stable film of fluorapatite on the surface of hydroxyapatite crystals has two effects, namely (i) resistance to diffusion and dissolution of the anion and (ii) firmer binding of calcium ions into the surface. Both of these make the resulting apatite structure more resistant to dissolution, regardless of the pH of the external medium, and they thereby increase the resistance of the mineral phase to the onset of caries. 

The role of fluoride in this mineralisation process seems to be in promoting the conversion of OCP to hydroxypatite, and producing plate-like crystals of the more thermodynamically stable mineral. Fluoride is effective at promoting the formation of an apatite lattice through a solid-state transformation of OCP at levels between 0.05 and 0.4 ppm [72]. 

Posner, A. S., Eanes, E. D., Harper, R. A., Zipkin, I. X-ray diffraction analysis of the effect of fluoride on human bone apatite. Arch. Oral Biol. 8, 549 (1963)... 

Fluoride has certain physiological properties [31,32] of great importance to human health. The role of fluoride in the process of mineralization of certain tissues is important. At low concentrations fluoride stabilizes the skeletal system by increasing the size of apatite crystals and reducing their solubility [12]. Although beneficial effects can be demonstrated at low concentrations, it has detrimental effects when concentrations exceed the threshold [33],... 

The fluoride ion can exchange for hydroxyl in the crystal structure of apatite, a main component of skeletal bone and teeth. This stabilizes the regenerating tooth surface. Fluoride is available from saliva and may also be released from dental plaque at low pH. Initially, benefit was considered solely to be for the erupting teeth of children, but topical effects on adult teeth are now also thought to reduce decay. There is some initial evidence from small studies that pharmacological doses of fluoride may reduce the incidence of bone fracture in patients with osteoporosis. However, a metaanalysis of fluoride therapy from 11 controlled studies on 1429 subjects found that although this increased lumbar bone density, the incidence of vertebral fractures was not significantly decreased. ... 

Bone ash, and synthetic apatite, which are essentially calcium phosphate (Ca3(P04)2), or a synthetic apatite, calcium hydroxide mixture, are also effective methods for fluoride removal because of their affinity for these phosphate salts. 

This chapter describes how individuals with severe enamel fluorosis (mottled tooth enamel) became associated with fluoride in the public water supply and protection from dental caries. A comparison of caries experience with the fluoride content of public water supplies and enamel fluorosis in adolescents indicated that 1 pg fluoride/mL (1 part/million) in the water provides caries protection with minimal enamel fluorosis (sect. 1). One mechanism is the spontaneous isomorphic replacement of apatite s hydroxide anions with fluoride, which reduces enamel solubility. A second is fluoride-mediated inhibition of enolase, which retards bacterial acid production at teeth surfaces. These findings led to the use of fluoride in toothpastes, which provides better protection from caries at tooth surfaces than water fluoridation alone (sect. 2). The chapter concludes with a discussion of potentially harmful effects of fluoride ingestion (sect. 3). 

The first and primary protective effect of fluoride is due to its strong, spontaneous reaction with metal ions. Biologically, the most important of these ions is the calcium ion, large amounts of which interact with phosphate to form bones and teeth. Studies show that fluoride reduces apatite solubility in acids by an isomorphic replacement of hydroxide ions with fluoride ions to form fluoro-hydroxyapatite and difluoro-apatite (Fig. 16.6a). 

Apatites must undergo a solid-state transition to amorphous calcium phosphate before they can dissolve and the spontaneous replacement of hydroxide with fluoride ions slows the rate at which this transition occurs (Fig. 16.6b). Conversely, as an acid environment becomes more alkaline, fluoride ions promote the precipitation and crystallization of amorphous calcium monohydrogen phosphate/calcium fluoride into fluoro- and difluoro-apatites faster than amorphous calcium phosphate would crystallize into hydroxyapatite. Thus, fluoride ions have two effects on enamel that protect from caries they slow enamel dissolution in lactic acid and promote its re-precipitation and crystallization when the lactic acid is neutralized. 

Deutsch Y, Sarig S (1977) The effect of fluoride ion concentration on apatite formation and on its crystal habit. J Cryst Growth 42 234-237... 

The reduction in dental caries as a result of fluoridation of water supplies and use of fluoride containing toothpastes is well known (Shell s and Duckworth 1994). This is clearly linked in part to the fact that the solubility product of fluorapatite is less than that of HAP (Moreno et al. 1977). For a partial replacement of OIT by F ions, the solubility product for Ca5(P04)3(0H)i.xFx is a minimum for x = 0.56 (Moreno et al. 1977). Chow and Banes (2001) and LeGeros (1991) discuss further the effects of F ions on the solubility, rate of dissolution and formation of apatites. Fluoride has also been used in attempts to rebuild bone lost as a result of osteoporosis (see Grynpas and Cheng 1988 and Baud et al. 1988 for references). Fluoride has effects on both bone mineral and cellular activity (Baylink et al. 1970, Banes and Reddi 1979). For example, F ions reduce the rate of dissolution of the mineral in acidic buffers (Grynpas and Cheng 1988). Other effects on the mineral will be mentioned later. 

Driessens FCM, Verbeeck RMH (1990) Biominerals. CRC Press, Boca Raton, Florida Eanes ED, Hailer AW (1998) The effect of fluoride on the size and morphology of apatite crystals grown from physiologic solutions. Calcif Tissue Inti 63 250-257 Eanes ED, Reddi AH (1979) The effect of fluoride on bone mineral apatite. Metabohc Bone Disease Related Res 2 3-10... 

Substitutions in the HA structure are possible. Substitutions for Ca, PO4, and OH groups result in changes in the lattice parameter as well as changes in some of the properties of the crystal, such as solubility. If the OH" groups in HA are replaced by F" the anions are closer to the neighboring Ca " ions. This substitution helps to further stabilize the structure and is proposed as one of the reasons that fluoridation helps reduce tooth decay as shown by the study of the incorporation of F into HA and its effect on solubility. Biological apatites, which are the mineral phases of bone, enamel, and dentin, are usually referred to as HA. Actually, they differ from pme HA in stoichiometry, composition, and crystallinity, as well as in other physical and mechanical properties, as shown in Table 35.7. Biological apatites are usually Ca deficient and are always carbonate substituted (COs) " for (P04). For... 

Until recently it was thought that when the apatite lattice contains fluoride, it is more stable in the presence of acid than when fluoride is not present. However, experiments showed that enamel initially dissolves in acid at the same rate, whether it contains fluoride or not. When fluoride is present in enamel, however, the rate of solution of enamel falls very rapidly with time compared with the rate for enamel which does not contain fluoride. It therefore appears that fluoride ions are only effective in reducing enamel solubility when in solution. The uptake of fluoride by the enamel surface and by carious enamel is especially important in protecting these vulnerable areas by forming a local immobilized store some of which will be released in the presence of acid and will protect the enamel in its immediate neighbourhood from further attack by the acid. 

Evidence exists that certain trace elements can reduce the incidence of caries. Systemically administered fluoride appears to favour the deposition of apatite with a reduced solubility in acid (page 429) and also to be essential for maturation of the enamel and the remineralization of an early carious lesion (page 511). Even after the teeth are fully developed, the presence of fluoride in the oral fluids is beneficial because fluoride ions are adsorbed on the enamel surface and have an adverse effect on bacterial metabolism (page 500). 

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