Influence of phosphocitrate, a potent inhibitor of hydroxyapatite crystal growth, on mineralization of cartilage and bone

An invivo bone induction system was used to study the effect of phosphocitrate, a potent inhibitor of calcium phosphate crystallization, on the initial stages of mineralization. Subcutaneous transplantation of coarse powders of demineralized rat diaphyseal bone matrix into allogenic recipients results in a well defined sequence of mineralization steps involving cartilage formation, calcification and bone formation. Phosphocitrate when administered locally or systemically had no effect on the mineralization of either cartilage or bone. Dose levels were chosen to be consistent with that of a previous study which demonstrated that ethane-1-hydroxy-1, 1-diphosphonate (EHDP), a similarly effective invitro inhibitor of hydroxyapatite crystallization, has a strong inhibitory effect on the initial mineralization steps. Since EHDP is not metabolized invivo, the lack of effect of phosphocitrate in this study is suggestive of possible enzymatic hydrolysis at the calcification site which may regulate the level of phosphocitrate.