Treatment of Experimental Hypercalcemia with Oral Phosphate1

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Abstract
Inorganic phosphate has been proposed as an agent for the treatment of hypercalcemia, but reports of side-effects have brought its use into question. In this experiment, rats were given vitamin D in daily doses ranging from 5 to 50 thousand units for 4–7 doses. Animals on each dose level were divided into 2 groups, one receiving 0.75 mmole/kg of neutral sodium and potassium orthophosphates by mouth with the last 3 doses of vitamin D, and the other sodium and potassium chloride. Calcium was measured in plasma and dry-ashed heart and kidneys by atomic absorption spectrophotometry. Plasma calcium rose from a control mean of 2.56 mm to a maximum of 4 mm with the largest doses of vitamin D. Phosphate treatment lowered plasma calcium significantly only in rats receiving more than 4 doses of vitamin D. Kidney and heart calcium rose from control means of 1.3 and 0.6 mmoles/kg, respectively, to means of 45 and 36 mmoles/kg on the largest dose of vitamin D. Following phosphate therapy, there was an over-all mean increase in calcium concentration of 37% in kidney (p <0.01) and 47% in heart (p =0.025). In those groups receiving the largest doses of vitamin D, more than half died within 48 hr after oral phosphate therapy was begun; no rats died on vitamin D alone. Higher tissue calcium concentrations were found in the dead animals. The results indicate that, under the conditions of this experiment, one mechanism by which oral phosphate lowers plasma calcium in rats is by accelerating its deposition in soft tissue, and that mortality can result from its use.

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