Response of 1α,25-Dihydroxyvitamin D₃ to Hypocalcemia in Human Subjects

Abstract

We determined the response of 1α,25-dihydroxyvitamin D₃ after mithramycin-induced hypocalcemia in eight subjects with polyostotic Paget's disease of bone. Thirty-six hours after infusion of mithramycin (25 μg per kilogram), the average calcium declined from 9.9±0.14 (S.E.M.) to 8.0±0.19 mg per deciliter (P<0.005). Serum parathyroid hormone increased from 122±6 to 226±36 μ eq per milliliter (P<0.05), serum phosphate decreased from 3.8±0.11 to 2.9±0.14 mg per deciliter (P<0.005), and urinary cyclic 3,5′-adenosine monophosphate increased from 4.6±0.35 to 7.5±0.80 μmol per gram of creatinine (P<0.005). Serum 1α,25-dihydroxyvitamin D₃ rose from 98±12 to 332±61 pM (P<0.05), the increase following the changes in parathyroid hormone and phosphate by 12 to 24 hours. When this lag period was taken into account, there was a significant relation (P<0.01) between the increase in 1α,25-dihydroxyvitamin D₃ and changes in parathyroid hormone (correlation coefficient, r = +0.91) and phosphate (r=-0.96). The relatively rapid response of 1α,25-dihydroxyvitamin D₃ to hypocalcemia occurs with a time course consistent with regulation by parathyroid hormone and phosphate. (N Engl J Med 299:437–441, 1978)