Separation of the Hypocalcemic and Hypophosphatemic Actions of Calcitonin with Disodium Ethane-l-hydroxy-l,l-diphosphonate1

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Abstract
The present studies were designed t o determine the effects of ethane-1,1-diphos-phonic acid (EHDPTM), an analog of pyrophos-phate, on the hypocalcemic and hypophosphatemic actions of salmon calcitonin (SCT). Rats were pretreated for 3 or 4 days with daily subcutaneous (sc) injections of EHDP (40 mg/kg body wt). 45Ca was administered (intraperitoneally) 10 days prior to EHDP treatment and 32P (intravenously) the day following the last injection of the drug. SCT (0.4 MRC mU/g body wt) was injected sc 1 hr after 32-P administration. Preliminary tests with thfS drug had confirmed that the dosage used at least partially inhibited the 45Ca removal from bone stimulated by low-calcium diet or parathyroid hormone administration; and at least partially reduced the uptake of both 45Ca and 32P by bone, during the first 5 hr after intravenous administration of isotopes. Following SCT injection plasma calcium concentrations fell only 5% in EHDP-treated rats compared to 25% in rats not treated with EHDP. Plasma phosphate concentrations and 32P plasma values, however, fell markedly and similarly in rats given SCT regardless of whether or not they had been pretreated with EHDP. These studies demonstrate that the hypophosphatemic effect of SCT was produced independently of the hypo-calcemic action of the hormone and the hypophos-phatemia did not result solely from a reduction of phosphate release from bone but rather was due to an increased exit of phosphate out of the plasma. (Endocrinology94: 413, 1974)

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