Effect of Phosphate, Calcium and Magnesium on Bone Resorption and Hormonal Responses in Tissue Culture

Abstract

The effects of changing the concentration of phosphate, calcium and magnesium on the resorption of fetal rat bone, and the responses to parathyroid hormone and calcitonin were tested in organ cultures using a chemically defined medium. Resorption was measured by the release of previously incorporated 46Ca into the medium and by changes in total bone calcium content. To differentiate effects on active resorption and passive dissolution, calcium losses from living and heat-killed bones were compared. Increasing the phosphate concentration of the medium over the range of 0.25 to 4M produced a decreased release of calcium from bone, particularly in response to parathyroid hormone. The effect was greater in living than in dead bone, demonstrating that active resorption was inhibited. Inhibition by phosphate could be observed even when the Ca×PO4 product was kept constant. The effects of calcitonin and phosphate appeared to be additive. Increasing concentrations of calcium also decreased mineral loss. This was seen in both dead and living bone and appeared to be largely a decrease in the dissolution of bone mineral, although an effect on active resorption could not be ruled out. Changing calcium concentration had little effect on the response to parathyroid hormone or calcitonin. Increasing magnesium concentration had no effect on bone resorption. However, reducing magnesium concentration to 0.3–0.4 mM decreased resorption particularly in PTH-treated bones without altering losses from dead bones. It appears that changes in ion concentration can alter bone resorption and its regulation byhormones. The results could explain some of the changes in PTH responsiveness seen experimentaly and clinically. (Endocrinology85: 446, 1969)