Journal of Dental Research

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On the Dissolution of Hydroxyapatite in Acid Solutions

E.I.F. Pearce
J DENT RES 1988 67: 1056
DOI: 10.1177/00220345880670070801

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 Letters to the Editor
On the Dissolution of Hydroxyapatite in Acid Solutions
The Journal of Dental Research has published many papers
describing the dissolution of hydroxyapatite and biological
mineral in acid solutions. Consequently, we know much about
dissolution rates, quantities dissolved, and what happens under
various conditions. Authors are, however, less than clear when
it comes to the question of why hydroxyapatite dissolves read-
ily in dilute aqueous acid solutions, i.e., why there is an in-
creased tendency for the crystal lattice to disintegrate when the
pH is low-a subject surely of fundamental importance in car-
ies and other hard-tissue research. Perhaps it is assumed that
the answer is obvious, but a reading of the literature reveals
two separate and seemingly conflicting threads of argument on
this point. In order to promote discussion, I have attempted to
formalise these two ideas, and present them here as two dif-
ferent mechanisms. The question centres on the dissolution of
the individual crystal, and I have excluded from consideration
additional processes found in an aggregate or pellet of apatite
or a block of enamel, e.g., surface layer formation. It is as-
sumed that hydroxyapatite is a crystal where the bonds have a
predominantly ionic character and that by "dissolution" it is
meant that the ions lose their ordered arrangement character-
istic of the solid mineral phase and become free in aqueous
solution.
One mechanism is based on the solubility product principle.
According to this theory, water molecules are responsible for
disrupting the crystal lattice bonds. Because of its high dielec-
tric constant, water can reduce the attractive forces between
ions at the crystal surface, increasing their inherent tendency
to escape by thermal agitation. Moreover, hydration of the ions
in solution aids the process energetically (Holden and Singer,
1961; Masterton and Slowinski, 1977). Water is, in fact, al-
most unique in its ability to dissolve ionic compounds (Barker,
1971). Ions in solution tend to regroup, however, so that an
equilibrium is set up, for hydroxyapatite:
(Ca2+10 (P043)6 (OH-)2) solid ; 1OCa2+ sq+ 6P043 -aq 201H-
Application of the law of mass action then leads to the solu-
bility product principle. In acid dissolution, H+ ions react with
P043- or OH- ions already in the bulk solution, reducing their
concentration. More solid apatite then dissolves until the sol-
ubility product is re-established (Brown, 1973). Thus, accord-
ing to this mechanism, hydroxyapatite is not attacked directly
by H+ ions but merely responds to a shift in relevant solution
ion concentrations. Brushite or other surface phases coating
the crystal at low pH should not affect whether or not this
mechanism operates, but only which solubility product is per-
tinent. The mechanism is poorly defined in the dental litera-
ture, but the fact that several authors have found hydroxyapatite
to obey the solubility product principle over a wide range of
ionic strengths, pH, and solid/solution ratios suggests that it is
widely accepted (Clark, 1955; Hagen, 1965; Moreno et al.,
1968; Bell et al., 1978; Robertson, 1982). Larsen and Bruun
(1986), however, writing in a recent textbook of cariology,
are more explicit in the use of the mechanism to explain the
increasing solubility of enamel apatite with decreasing pH. A
modification of the concept proposes that the reaction of H+
and basic phosphate ions takes place in a diffusion layer sur-
rounding the crystal, rather than in the bulk solution (Higuchi
1056 Downloaded from jdr.sagepub.com at Bobst Library, New York University on October 6, 2014 For personal use only. No other uses without permission.
et al., 1965). In this case, too, it is presumably water mole-
cules that cause the release of phosphate ions into the diffusion
layer.
This mechanism explains certain well-known phenomena such
as the "common ion" effect. It has been used, perhaps less
adequately, to explain the rate of dissolution of hydroxyapatite
in acid solution. At the turn of the century, Noyes and Whitney
(1897) showed that the rate of solution of a salt was simply a
function of the saturation deficit. The more highly saturated
the solution, the less rapidly the salt dissolved until a net zero
rate was achieved at full saturation. This did not exclude the
possibility of simultaneous dissolution and regrowth (turnover)
at saturation. The idea has been applied to hydroxyapatite by
Hagen (1975) and others. Margolis and co-workers (1985), for
example, state that "..... the driving force for enamel demin-
eralization is best described by the degree of saturation of the
demineralization medium with respect to enamel and not by
simpler parameters such as pH".
The other mechanism may be called "Chemical Reaction"
and is quite different, in that here, H+ ions, not water mole-
cules, are identified as the primary crystal lattice-disrupting
agent. According to this theory, H+ ions in solution approach
the apatite crystal and react with P043- and OH- ions at the
surface of the solid. Conversion to HPO42- and H20 causes a
disruption of lattice bonds and release of the ions into solution.
Inclusions such as CO2 and Mg in the crystal give rise to
particularly acid-reactive sites, whereas inclusion of F gives
rise to less-reactive sites. Recombination of ions (the reverse
reaction) increases as the solution reaches saturation with hy-
droxyapatite, so that net dissolution is finally terminated. Thus,
the mineral still displays normal equilibrium solubility product
characteristics. An early reference to this idea is found in the
paper by Gray (1962), where it is stated that "dissolution oc-
curs as a result of the reaction of enamel with H+', and the
equation:
Ca1O(PO4)6(OH)2 + 8H+ -l 1OCa2+ + 6HP042- + 2H20
is used in support. The concept has appeared frequently in the
literature since, and can be identified by phrases such as "acid
reactivity", "acid attack", and "chemical reactivity". For
example, Arends (1982) states that, "During caries, enamel
crystallites are attacked by the penetrating acid" and Feath-
erstone (1984) ". . to produce H- ions to attack the carbon-
ated-apatite crystals". Christoffersen (1981) and Nelson et al.
(1983) express similar ideas. Modern textbooks also allude to
this mechanism as an explanation for the acid solubility of
enamel (e.g., Mellberg and Ripa, 1983). The most recently-
published papers that cite this mechanism are those of Patel
and co-workers (1987). In a related concept, it is proposed that
H+ ions may bond to surface OH-, CO32 , or P043 ions,
lowering the energy barrier for dissolution (D.G.A. Nelson,
personal communication).
The principal evidence for the chemical reaction mechanism
comes from dissolution rate studies. Because the solubility
product mechanism implies that solution rate is governed by
the relationship between ionic product and solubility product
(Hagen, 1975), the initial rate of dissolution of hydroxyapatite
Vol. 67 No. 7
in a solution containing no Ca or P should be independent of
pH. However, several studies suggest that this is not so (Gray,
1962; Higuchi et al., 1965; Higuchi et al., 1969). Dissolution
is apparently much more rapid at pH 4 than at pH 6 initially,
i.e., before the solution has accumulated significant amounts
of Ca and P. This suggests that the He ion per se is playing
an additional and direct role in dissolution. Nevertheless, I can
find no study where the rate of dissolution of hydroxyapatite
at a low and fixed degree of saturation, say 5%, has been
compared at pH 4 and at pH 6. If such rates were found to be
different, support for the mechanism would be strengthened.
Other evidence for the chemical reaction mechanism derives
from mathematical manipulation of dissolution data. For ex-
ample, Chen and Nancollas (1986) have, from such an analy-
sis, concluded that a surface reaction is involved.
Whether only one of these mechanisms explains the acid
dissolution of biological mineral crystals, or whether both (or
neither) are involved, is the question I raise. The facts that
apatite will dissolve at neutral pH if Ca2+ is removed from
bulk solution by ion exchange (R0lla et al., 1980) and, con-
versely, that addition of Ca2+ ions can restrict the amount of
apatite that dissolves in acid solution (the common ion effect)
(Higuchi et al., 1969; Crommelin et al., 1983) suggest that
the solubility product mechanism plays an important role. On
the other hand, I see some difficulties with chemical reaction
as an explanation for acid solubility. First, it is difficult to
imagine how sufficient H+ ions can penetrate the hydration
layer surrounding an apatite crystal to reach the surface. This
layer contains concentrations of calcium and phosphate that
are much higher than those in the bulk solution (Neuman and
Neuman, 1958) and has, presumably, a higher concentration
of OH- and P043- ions able to neutralise H+ ions before they
can reach and react with crystal lattice ions. Second, the chem-
ical reaction theory has difficulty in explaining the lack of
dissolution in saturated solution at low pH, where the H+ con-
centration is high (Hills and Sullivan, 1958). As mentioned,
proponents of this theory imply that crystal regrowth compen-
sates for acid reactivity under these conditions, i.e., rapid crys-
tal turnover occurs. However, crystal growth is usually regarded
as a relatively slow process, and when it does occur rapidly,
small imperfect crystals often result. The speed of regrowth
required to balance dissolution at pH 4 would surely result in
an obvious morphological effect on apatite crystals, but I am
unaware of any paper describing such a rapid change in acidic
saturated solution. If the pH is low enough, a slower change
to a more stable phase, e.g., brushite, can be predicted on
theoretical grounds and does occur in practice (Chow and Brown,
1975), but this is a different phenomenon. Third, because in
certain crystal planes a higher proportion of acid-susceptible
P043- and OH- ions will be "exposed" at the crystal surface,
chemical reaction in dilute acid might be expected to produce
etched crystals having a shape different from those exposed to
slightly alkaline EDTA solutions. However, this is not so.
While the rate of dissolution is certainly faster in the direction
of the c axis when apatite is treated with dilute acid (Jonge-
bloed et al., 1973; Daculsi et al., 1979), leading to a hollowing
out of the crystal core, EDTA apparently produces the very
same effect (Johnson, 1966; Simmelink et al., 1974). Fourth,
if the small but distinct solubility of hydroxyapatite at neutral
and slightly alkaline pH is not regarded as due to a chemical
reaction, is it necessary to invoke such a mechanism at a low
pH? I HILLS, J. E. and SULLIVAN, H. R. (1958): Studies on the Acid Decalcifi-
Early workers in heterogeneous systems were concerned with
diffusion of reactants to, and products away from, a surface,
in relation to the reaction at the surface, as rate-controlling
factors. However, although this analysis has been applied to
apatite and other ionic crystalline solids dissolving in water
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LETTERS TO THE EDITOR 1057
(Barton and McConnel, 1979), it may be that it is more ap-
plicable to the dissolution of, for example, metallic zinc in
HCl, where a definite surface chemical reaction must be in-
volved.
In caries research, we are interested in discovering how to
maintain the integrity of the apatite crystal lattice, and it is
thus crucial that we have a clear idea what causes its break-
down. Perhaps phrases used in various papers and cited above
are not intended to imply one or another mechanism. If, how-
ever, "acid attack" or "chemical reactivity" does not refer to
the chemical reaction mechanism, then authors should explain
their meaning more precisely. I can find no clear exposition
of hydroxyapatite acid dissolution mechanism in the dental
literature and hope that this note might lead to a clarification
of the issue.
I am indebted to Dr. D. G. A. Nelson for helpful discussions
and to Prof. J. A. Hargreaves for pointing out the electron
microscopic evidence.
-E.I.F. Pearce
Dental Research Unit
MRC of NZ
P. 0. Box 27007
Wellington
New Zealand
REFERENCES
ARENDS, J. (1982): Mechanism of Dental Caries. In: Biological Mineraliza-
tion and Demineralization, G. H. Nancollas, Ed., Berlin: Springer Ver-
lag, pp. 303-324.
BARKER, R. (1971): Organic Chemistry of Biological Compounds, Engle-
wood Cliffs: Prentice-Hall, Inc., p. 19.
BARTON, A. F. M. and McCONNEL, S. R. (1979): Dissolution Behaviour
of Solids: The Rotating Disc Method, Chem Aust 46:427-433.
BELL, L. C.; MIKA, H.; and KRUGER, B. J. (1978): Synthetic Hydroxy-
apatite Solubility Product and Stoichiometry of Dissolution, Arch Oral Biol
23:329-336.
BROWN, W. E. (1973): Solubilities of Phosphates and Other Sparingly Sol-
uble Compounds. In: Environmental Phosphorus Handbook, E. J. Grif-
fith, A. Beeton, J. M. Spencer, and D. T. Mitchell, Eds., New York:
Wiley and Sons, pp. 203-239.
CHOW, L. C. and BROWN, W. E. (1975): Formation of CaHPO4 2H20 in
Tooth Enamel as an Intermediate Product in Topical Fluoride Treatments,
J Dent Res 54:65-76.
CHRISTOFFERSEN, J. (1981): Dissolution of Calcium Hydroxyapatite, Calcif
Tissue Int 33:557-560.
CLARK, J. S. (1955): Solubility Criteria for the Existence of Hydroxyapatite,
Can J Chem 33:1696-1700.
CROMMELIN, D. J.; HIGUCHI, W. I.; FOX, J. L.; SPOONER, P. J.; and
KATDARE, A. V. (1983): Dissolution Rate Behaviour of Hydroxyapatite-
Fluorapatite Mixtures, Caries Res 17:289-296.
DACULSI, G.; KEREBEL, B.; and KEREBEL, L. M. (1979): Mechanisms
of Acid Dissolution of Biological and Synthetic Apatite Crystals at the
Lattice Pattern Level, Caries Res 13:277-289.
FEATHERSTONE, J. D. B. (1984): Diffusion Phenomena and Enamel Caries
Development. In: Cariology Today, B. Guggenheim, Ed., Basel: Karger,
pp. 259-268.
GRAY, J. A. (1962): Kinetics of the Dissolution of Human Dental Enamel in
Acid, J Dent Res 41:633-645.
HAGEN, A. R. (1965): Dental Enamel in Inorganic Salt Solutions, Oslo:
Universitetsforlaget.
HAGEN, A. R. (1975): The Calcium Orthophosphate Solubilities as Rep-
resented by a Model in Three Dimensions, Acta Odontol Scand 33:67-83.
HIGUCHI, W. I.; GRAY, J. A.; HEFFERREN, J. J.; and PATEL, P. R.
(1965): Mechanisms of Enamel Dissolution in Acid Buffers, J Dent Res
44:330-341.
HIGUCHI, W. I.; MIR, N.A.; PATEL, P. R.; BECKER, J. W.; and HEF-
FERREN, J. J. (1969): Quantitation of Enamel Demineralization Mecha-
nisms: III. A Critical Examination of the Hydroxyapatite Model, J Dent
Res 48:396-409.
cation of Human Dental Enamel, Aust Dent J 3:6-18.
HOLDEN, A. and SINGER, P. (1961): Crystals and Crystal Growing, Lon-
don: Heinemann.
JOHNSON, N. W. (1966): Differences in the Shape of Human Enamel Crys-
tallites after Partial Destruction by Caries, EDTA and Various Acids, Arch
Oral Biol 11:1421-1424.
1058
JONGEBLOED, W. L.; MOLENAAR, I.; and ARENDS, J. (1973): Orien-
tation-dependent Etchpit Penetration and Dissolution of Fluorapatite, Canes
Res 7:154-165.
LARSEN, M. J. and BRUUN, C. (1986): Enamel/Saliva - Inorganic Chem-
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Eds., Copenhagen: Munksgaard, Chapt. 10, p. 186.
MARGOLIS, H. C.; MURPHY, B. J.; and MORENO, E. C. (1985): Devel-
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MASTERTON, W. L. and SLOWINSKI, E. J. (1977): Chemical Principles,
Auckland: Holt-Saunders, p. 306.
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tistry. Theory and Clinical Applications, Chicago: Quintessence Pub-
lishing Co., Inc., p. 42.
MORENO, E. C.; GREGORY, T. M.; and BROWN, W. E. (1968): Prepa-
ration and Solubility of Hydroxyapatite, JRes NatlBur Sids 72A:773-782.
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of Bone Mineral, Chicago: University of Chicago Press.
Response to Dr. E.I.F. Pearce's Letter to the Editor
Although the questions raised in Dr. Pearce's letter do illustrate
that the dissolution properties of hydroxyapatite (OHAp) are
complex and sometimes perplexing, there are no real contra-
dictions in the findings reported by the various investigators
and the dissolution mechanisms they proposed. Much of the
confusion arises when we try to treat the solubility and the rate
of dissolution of OHAp as two aspects of the same property.
The fact is, however, that solubility is an equilibrium property
and rate of dissolution is a kinetic property. While the two are
often related, they are influenced by quite different sets of
parameters.
The solubility of OHAp is governed by the well-established
principle of solubility product, the first mechanism mentioned
in Dr. Pearce's letter. In this regard, OHAp behaves no dif-
ferently than do other ionic solids in that the solubility product
constant is a true thermodynamic constant. An important con-
cept of solubility not clearly expressed in the letter is that
solubility is a thermodynamic state function related to the Gibb's
free energy of the solid. It is a property that neither addresses
nor is determined by the dissolution mechanism. Thus, whether
the dissolution process takes place through mechanism 1 or 2,
as cited in Dr. Pearce's letter, is of no consequence to the
solubility of OHAp.
As Dr. Pearce pointed out, the greater "solubility" (refer-
ring here to the amount soluble and not to the true thermo-
dynamic solubility) of OHAp in an acidic solution is simply a
result of the ability of the H+ ions in the solution to consume
larger amounts of the P043- and OH- ions released from the
dissolving OHAp. This in turn allows more OHAp to dissolve
until the ion activity product reaches the solubility product
constant of OHAp. The terms "acid reactivity", "acid at-
tack", ". . to produce H+ ions to attack carbonated-apatite
crystals. . .", etc., found in the dental literature were used
primarily to emphasize the fact that acid solutions can effect
a greater amount of OHAp dissolution. It would appear that
these terms by themselves do not necessarily imply that either
H+ ions or water molecules are the "attacking force" of dis-
solution. It should also be noted that the "acid solubility" is
not a property unique to OHAp. Generally, all sparingly sol-
uble salts of weak acids are more soluble in acidic solutions
than in neutral or alkaline solutions. Dr. Pearce cited instances
in which inclusion of carbonate or magnesium in the apatite
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J Dent Res July 1988
NOYES, A. A. and WHITNEY, W. R. (1897): The Rate of Solution of Solid
Substances in their Own Solutions, JAm Chem Soc 19:930-934.
PATEL, M. V.; FOX, J. L.; and HIGUCHI, W. I. (1987): Physical Model
for Non-steady-state Dissolution of Dental Enamel, J Dent Res 66:1418-
1424.
PATEL, M. V.; FOX, J. L.; and HIGUCHI, W. I. (1987): Effect of Acid
Type on Kinetics and Mechanism of Dental Enamel Demineralization, J
Dent Res 66:1425-1430.
ROBERTSON, W. G. (1982): The Solubility Concept. In: Biological Min-
eralization and Demineralization, G. H. Nancollas, Ed., Berlin: Springer
Verlag, pp. 5-21.
R0LLA, G.; BERGSETH, H.; and SVATUN, B. (1980): Solubilization of
Hydroxyapatite at Neutral pH by an Anionic Ionic Exchange Resin, Acta
Odontol Scand 38:209-211.
SIMMELINK, J. W.; NYGAARD, V. K.; and SCOTT, D. B. (1974): Theory
for the Sequence of Human and Rat Enamel Dissolution by Acid and by
EDTA: A Correlated Scanning and Transmission Electron Microscope Study,
Arch Oral Biol 19:183-197.
would give rise to more acid-reactive sites, and these in turn
increase the solubility. One may again stress the fact that the
effects of impurities on the thermodynamic solubility of OHAp
can best be understood through the use of the solubility product
principle. On the other hand, to describe the effects of impur-
ities on the rate of dissolution may require the use of a specific
mechanistic model for dissolution, as discussed below.
Most of the questions raised in Dr. Pearce's letter pertain to
the rate of dissolution, a kinetic property which cannot be
adequately described by thermodynamic terms alone. The ki-
netics of OHAp dissolution has been studied extensively by
means of various experimental techniques, and the results were
often interpreted through the use of a number of dissolution
models. The dissolution process can generally be thought of
as consisting of two steps: (1) disengagement of ions from the
crystal surface, and (2) transport by diffusion of the released
ions from the solution immediately next to the crystal surface
into the bulk liquid phase. There is good consensus among
investigators that the rate of dissolution is controlled (limited)
by step 1 in systems where microscopic-size crystals dissolve
into a rapidly stirred solution. In contrast, the rate is controlled
by step 2 in systems where larger crystals dissolve into an
unstirred solution, such as is the case in dental caries and in
many other biologically related processes. An important con-
sequence of the two types of rate-controlling mechanism is
that the solution immediately next to the crystal surface is
undersaturated with respect to OHAp in the surface-controlled
process, and that this solution is saturated in the diffusion-
controlled process. It is clear from this analysis that the pH of
the solution would be an important factor in determining the
rate of dissolution if step 1 is rate-controlling and if the dis-
engagement of ions from the crystal lattice does involve attack
by H+ ions. On the other hand, the degree of undersaturation
would play an important role if step 2 is rate-controlling, be-
cause a greater degree of undersaturation would allow for faster
transport of ions from the saturated solution at the crystal sur-
face to the bulk liquid. In many experimental systems, the
situation is complicated by the fact that a lower pH often results
in a more undersaturated solution, thus making it difficult to
separate the two effects.
Dr. Pearce raised a question regarding the lack of data on
the rate of dissolution at a low and fixed degree of undersa-