Pathologic calcium phosphate deposition in model systems

Pathologic calcium phosphate deposition occurs mainly in tissues exposed to highly supersaturated body fluids such as urine and saliva. In vitro models employed to study pathologic calcification include aqueous solutions and hydrogels. Results from studies on de novo formation of various biologic calcium phosphates in aqueous solutions resembling various body fluids have been rewarding. Among others, the de novo results have shown that the formation conditions for each calcium phosphate crystal phase are quite different and are pH dependent, and yet all phases including brushite can form in neutral solutions. This is an important finding because when coupled to the facts that all calcium phosphates including brushite are more soluble in acidic solutions than in neutral ones and that, except in extreme cases of hypercalciuria and/or hyperphosphaturia, body fluid Ca and Pi are not very high, it suggests that in most cases pathologic calcification occurs in alkaline or near neutral milieus. HAP is ubiquitous because it is the most insoluble calcium phosphate crystal phase in alkaline or slightly acidic fluids. In fluids close to neutrality, whitlockite is the next favored, provided that the fluid Mg:Ca ration is neither too low nor too high. Although OCP is only slightly more soluble than whitlockite in near neutral milieus, it is favored only by low fluid Ca:Pi and Mg:Ca ratios and transforms easily to HAP. Except in very acidic milieus, brushite is the most soluble biologic calcium phosphate. Its formation is favored by acidic body fluids with high Ca x Pi or by neutral or slightly alkaline ones with very low Ca:Pi ratio or high Mg:Ca ratio.