Studies of the mechanism by which phosphate infusion lowers serum calcium concentration.

It has long been known that oral or intravenous administration of phosphate salts lowers the serum calcium concentration in normal animals (1, 2) and in hypercalcemic human subjects (3-5). Recently , interest has been renewed in the clinical use of phosphate therapy to control life-threatening hypercalcemia because of the relative in-effectiveness or toxicity of other modes of therapy (6, 7). In 1962, Dent (5) reported dramatic lowering of the serum calcium concentration in a patient with hyperparathyroidism during the intravenous infusion of sodium phosphate and sustained lowering of serum calcium by continuing oral doses of phosphate in another patient with hyperpara-thyroidism. Since then, Goldsmith and Ingbar (8) have demonstrated the clinical effectiveness and apparent safety of both oral and intravenous phosphate therapy in the management of hyper-calcemia accompanying a variety of diseases. Most of the investigators who have shown that phosphate administration lowers serum calcium concentration have suggested that this effect is the result of the precipitation of calcium phosphate salts in the body. The present studies were carried out to further test this hypothesis. If phosphate infusion lowers serum calcium concentration by causing calcium phosphate salt precipitation, then. a) phosphate infusion should * tend to lower serum calcium concentration in all subjects, regardless of the presence or absence of those endocrine organs normally involved in the regulation of the serum calcium; b) a simultaneous increase in calcium excretion should not account for the fall in serum calcium occurring during phosphate infusion; and c) the degree by which serum calcium concentrations fall should be a function of the extent to which the solubility product of some calcium phosphate salt is exceeded during the infusion of phosphate. The results of the present experiments satisfy all of these postulates and strongly support the hypothesis that phosphate infusion lowers serum calcium concentration as a result of CaHPO4 precipitation. Methods Studies were carried out in 22 patients divided into four groups: 1) eight control subjects without disorders of calcium homeostasis, 2) three patients with hypopara-thyroidism on adequate calcium and vitamin D therapy, 3) four patients with primary hyperparathyroidism, and 4) seven patients with hypercalcemia in association with malignant tumors of the breast or lung or with multiple myeloma. All were hospitalized in the Marquette University Clinical Research Center, where they received constant diets. Calcium and phosphorus intakes were constant for each subject but varied from subject to subject, ranging from 10 to 26 mmoles …