Octacalcium Phosphate as a Precursor in Biomineral Formation

Abstract

What are biominerals and how are they formed? It is usually assumed: (i) that the prototype for most apatitic biominerals is hydroxyapatite (OHAp), Ca₅(PO₄) ₃OH; and (ii) that the OHAp structure has been modified by the presence of impurity ions and vacancy defects in specific OHAp lattice sites. The usual answer, at least implicitly, to the second question is that the apatitic mineral is formed directly by the precipitation of ions from the surrounding solution. Our answers are: (i) that apatitic biominerals are formed through a precursor mechanism in which octacalcium phosphate (OCP), Ca₈H ₂(PO₄)₆·5H₂O, precipitates first and then hydrolyzes ireversibly in situ to a transition product intermediate to OCP and OHAp; and (ii) that this product, "octacalcium phosphate hydrolyzate" (OCPH), may contain (a) OHAp-like and OCP-like domains in varying amounts, (b) vacancy defects and impurity ions in lattice sites in these domains, and (c) various kinds of one-, two-, and three-dimensional defects which are not present in either the OHAp or the OCP lattice, these defects being formed during the in situ hydrolysis step. A calcification model of this type was first proposed in 1957, but full acceptance was delayed because most of the evidence was circumstantial and in vitro in nature. The situation has changed radically because of three unrelated studies that are in vivo in nature but lead to the same conclusion: I. ³²P-pyrolysis studies of rat enamel: The results clearly demonstrated that an acidic calcium phosphate precursor was involved. II. Precipitation of calcium phosphates in serum. Ultrafiltered serum was equilibrated with brushite. Subsequent changes in the ionic concentrations revealed that OCP was formed at first and then hydrolyzed to a more basic form, OCPH, but never reached the solubility of OHAp. III. Physicochemical properties of cardiovascular biominerals: We recently characterized biominerals in cardiovascular deposits in an encompassing variety of ways. As an overall conclusion, OCPH was the prototype most compatible with the data [including indices of refraction, solubility, P₂O₇^4- formation on pyrolysis, thermogravimetric analysis (TGA) measurements, presence of water, and incorporation of CO₃^2-, Na+, and Mg²⁺]. This calcification model has important consequences relative to all kinds of calcification and decalcification processes, including those of enamel.