Hydroxyapatite fluoridation

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. 

Fluorid ions stimulate bone formation by a direct mitogenic effect on osteoblasts mediated via protein kinase activation and other pathways. Further to these cellular effects, fluorides alter hydroxyapatite crystals in the bone matrix. In low doses, fluorides induce lamellar bone, while at higher doses abnormal woven bone with inferior quality is formed. The effect of fluorides on normal and abnormal (e.g. osteoporotic) bone therefore depends on the dose administered. 

Aluminium ions released from the dental silicate cement are also absorbed by hydroxyapatite and have a similar beneficial effect to that of fluoride (Halse Hals, 1976 Putt Kleber, 1985). Thus, the dental silicate cement confers protection against caries (dental decay) on surrounding tooth material. 

Bone is a porous tissue composite material containing a fluid phase, a calcified bone mineral, hydroxyapatite (HA), and organic components (mainly, collagen type). The variety of cellular and noncellular components consist of approximately 69% organic and 22% inorganic material and 9% water. The principal constiments of bone tissue are calcium (Ca ), phosphate (PO ), and hydroxyl (OH ) ions and calcium carbonate. There are smaller quantities of sodium, magnesium, and fluoride. The major compound, HA, has the formula Caio(P04)g(OH)2 in its unit cell. The porosity of bone includes membrane-lined capillary blood vessels, which function to transport nutrients and ions in bone, canaliculi, and the lacunae occupied in vivo by bone cells (osteoblasts), and the micropores present in the matrix. 

Once fluoride ions react with bone, they are not easily dissolved out or exchanged by other elements. If bone is buried for long periods of time, the relative amount of fluorine in the bone gradually increases as a function of time the "fluoridation" process continues until the maximum amount of fluorine (necessary to convert all the hydroxyapatite to fluorapatite) is reached. The total concentration of fluor in carbonated fluorapatite can reach levels as high as above 3%. There is ample room, therefore, for an increase in the relative amount of fluorine in buried bone. Determining the relative amount of fluorine in buried bone may thus serve as a tool for dating bone. 

CCP in milk is mentioned in connection with casein above (Section VI.C). Fluorapatite is a major constituent of phosphate rocks, and a constituent, probably important, of human tooth enamel for those whose drinking water contains significant amounts of naturally occurring or added fluoride. Fluorapatite is significantly less soluble than hydroxyapatite - the relationship between the solubilities of fluorapatite and hydroxyapatite parallels (but is much less extreme than) that between calcium fluoride (Ksp — 3.9 x 10 11 mol3 dm-9) and calcium hydroxide (Ksp = 7.9 x 10 6 mol3 dm 9). Calcium diphosphate, Ca2P207, is believed to be the least soluble of the calcium phosphates. 

Most foods and drinking waters contain enough fluoride to result in the incorporation of significant amounts of fluoride into this mineral whereby the solubility decreases. Therefore, the system hydroxyapatite-fluorapatite is primarily of importance for the prevention of dental caries. However, in this context its theoretical treatment is important for geochemists who may be confronted with so-called subregular solid solutions. 

The logarithm of the solubility product for hydroxyapatite is -58.6 and that of fluorapatite (CajtPO jF) is -60.6 (57), and thus, D = 0.01 in favour of fluoride incorporation into the solid apatite precipitate. Accordingly, it should be difficult to prepare solid solutions of these compounds by precipitation from aqueous solution and if prepared batchwise, they are expected to contain logarithmic gradients in their internal composition. Yet, Moreno et al.(M3) report linear changes in the lattice parameters of such solid solutions. They also determined their solubility behavior. 

On the other hand, Wier et al (59) have shown that fluoride ions react with the surface of hydroxyapatite particles so that a state of equilibrium is reached as if the aqueous solution is in equilibrium with pure fluorapatite, provided that enough fluoride ions occur in the aqueous solution. Therefore, one should expect, that particles of solid solutions of hydroxyapatite and fluorapatite will react similarly with fluoride ions from an aqueous solution, and that a surface layer is formed which has a composition closer to that of pure fluorapatite than that of the original solid solution. 

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). 

Fig. 10. Scanning electron microscope (SEM) micrograph of the surface of vacuum plasma sprayed hydroxyapatite (HA) coating after treatment in the fluoridating solution (KF 0.05 M KH2PO4 0.15 M pH 7, temperature 100 C). A layer of thin needle-like fluorhydroxyapatite crystals (0.5-3 m long, 0.1-0.3 m width) can be observed. (With kind permission of Springer Science and Business Media).

Y. Pan, P- F rotational-echo double resonance nuclear magnetic resonance experiment on fluoridated hydroxyapatite. Solid State Nucl. Magn. Reson. 5 (1995) 263-268. L. Wu, W. Forsling, P.W. Schindler, Surface complexation of calcium mineral in aqueous solution, surface protonation at fluorapatite surface, J. Colloid Interface Sci. 147 (1991) 178-185. 

E.C. Moreno, M. Kresak, R.T. Zahradnik, Fluoridated hydroxyapatite solubility and caries formation, Nature 247 (1974) 64-65. 

M. Okazaki, Fluoridated hydroxyapatites synthesized with organic phosphate ester. Biomaterials 12 (1991) 46-49. 

J. Lin, S. Raghavan, D.W. Fuerstenau, The adsorption of fluoride ions by hydroxyapatite from aqueous solution. Colloids Surf. 3 (1981) 357-370. 

M.R. Christoffersen, J. Christoffersen, J. Arends, Kinetics of dissolution of calcium hydroxyapatite. VII. The effect of fluoride, J. Cryst. Growth 67 (1984) 107-114. 

K. Cheng, W. Weng, H. Wang, S. Zhang, In vitro behavior of osteoblast-like cells on fluoridated hydroxyapatite coatings. Biomaterials 26 (2005) 6288-6295. 

A.J.S. Peaker, K.A. Hing, I.R. Gibson, L. DiSilvio, S.M. Best, L.L. Hench, W. Bonfield, Activity of human osteoblast-like cells on bioglass, hydroxyapatite and fluoride-sus-btituted hydroxyapatite. Bioceramics 11 (1998) 285-288. 

H. Qu, M. Wei, The effect of fluoride content in fluoridated hydroxyapatite on osteoblast behavior, Acta Biomateials. 2 (2006) 113-119. 

Useful insights can undoubtedly be obtained by consideration of the likely chemical species present, and their behaviour at varying pH. Saliva is known to be metastable and supersaturated with respect to hydroxyapatite [35], which is further evidence that the purely thermodynamic approach is suspect. It does mean though that there is a significant driving force for remineralisation, as the supersaturated saliva approaches equilibrium with the consequent precipitation of hydroxyapatite. The development or arrest of a carious lesion is therefore dependent on the frequency and duration of the remineralisation and demineralisation processes, and also on their respective rates. These in turn depend on factors such as sucrose consumption, salivary flow, oral hygiene [36] and, of course, fluoride exposure [37]. It is the latter that is of greatest interest in the present chapter, and its role will be considered in detail in the next section. 

In addition, the presence of low concentrations of fluoride in saliva also has the effect of preventing dissolution of hydroxyapatite from enamel at low pH, an effect that has been shown to apply at values of pH as a low as 4.2 [54,55], Thus, it is the fluoride in solution that has the effect of reducing solubility, rather than the fluoride in the mineral phase [51], This effect requires extremely small amounts of fluoride, typically in the sub-ppm range [51,56], and has the effect of shifting the balance between demineralisation and remineralisation so that loss of the hard tissue is inhibited. 

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]. 

The incorporation of fluoride in place of hydroxyl groups is chemically straightforward [59,60] and, as we have seen, results in a substance of greater resistance to acid attack. This is partly due to the greater electronegativity of fluorine, which means that the electrostatic attraction between Ca + and F is greater than that between Ca + and OH. As a result, the fluoridated apatite lattice is more stable than hydroxyapatite [61-63]. It is also more crystalline [64]. 

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