Recent Advances in Physiology of Calcification

Abstract

The biochemistry and physiology of the local mechanism of calcification is one of the most important unsolved problems in orthopaedics and medicine. Current studies suggest that the calcifying substrate of matrix consists of a mixture of fibrous and globular proteins, protein-protein complexes, mucoproteins, lipoproteins, and other substances in the form of complexes with calcium. This mixture is referred to as elastoid. Beginning with this material, the chemical reactions leading to deposition of calcium phosphate salts in the living tissues occur in a definite sequence: first, between elastoid-protein and calcium; second, between protein-bound calcium and phosphate, possibly as ion pairs or as a chelate in solution in the connective-tissue gel; and third, between protein-calcium-phosphate complexes in the tissue and A_Ca⁺⁺ and A_HPOHPO4^– in the extracellular fluid to produce a transitional solid phase which hydrolyzes to form hydroxyapatite. The composition of the transitional solid phase is not known, but octacalcium phosphate, calcium-deficient apatite, hydrated α-tricalcium phosphate, and other substances are under consideration. After the deposition and hydrolysis of the transitional solid phase, crystal growth proceeds by homogeneous nucleation. Further investigations are necessary to improve basic knowledge and develop practical applications for prevention, diagnosis, and treatment of dystrophic calcifications in tendon, heart valves, muscle, skin, eye, and other vital organs in man.