Phosphocitrate, A Potential Therapeutic Agent for Calcium Crystal Deposition Diseases

The deposition of calcium-containing crystals in articular tissues is probably an under-recognized event. Clinical observations indicate that exaggerated and uniquely distributed cartilage degeneration is associated with these deposits. Perhaps the most compelling argument favoring a role for crystals in Osteoarthritis (OA) stems from their in vitro effects on articular tissues. Therapeutic options are limited and of compromised value for controlling and/or eliminating calcium crystal salt diseases. This review highlights past and present studies related to phosphocitrate (PC), a relatively unheralded compound with an ability to inhibit crystal nucleation, growth and aggregation of calcium salts, including basic calcium phosphate (a term including carbonate-substitute apatite, octacalcium phosphate, and tricalcium phosphate) and calcium pyrophosphate dihydrate. In addition, cell culture studies reveal that specific calcium phosphateinduced cellular events associated with osteoarthritis also are retarded by PC. Interest in the tetra-sodium PC form and the new Calcium/Sodium/PC (CaNaPC) salt has stemmed from their chemical characteristics and biological actions. In two instances, the CaNaPC has displayed superior inhibitory properties to that of the tetra-sodium salt. Using a calcergy animal model, a chemically-induced calcifying skin plaque in rats has been ameliorated while in cell culture studies, strong inhibition of calcium phosphate-DNA co-precipitates induced cell death has been noted. The assessed data indicate that either of the PC salts through their modes of action, could be useful as adjunct therapeutic treatment of crystal associated OA.