Human parathyroid hormone 1-34-mediated hypercalcemia in a rat model, and its inhibition by dichloromethane diphosphonate.

Abstract

The purpose of these experiments was twofold: (a) to see if a continuous hPTH-(1-34) infusion could sustain hypercalcemia for 1–2 weeks; and (b) to test the efficacy of dichloromethane diphosphonate (Cl2MDP) in controlling the hypercalcemia of bone origin. First, 150-g Sprague-Dawley rats underwent parathyroid transplant-thyroidectomy and were equilibrated on a calcium-free diet prior to treatment. To evaluate the model, animals received either the hPTH-(1-34) infusion (12 units/rat/h), or 0.1 cc 0.9% NaCl per 100 g body weight (b.w.) per day. Thereafter, similar animals received 1 of 4 treatments: (a) hPTH-(1-34); (b) Cl2MDP (10 mg drug per kg b.w. per day); (c) hPTH-(1-34) plus Cl2MDP; or (d) saline (controls). The peptide was administered by subcutaneously implanted osmotic minipumps; the Cl2MDP and saline by once-daily subcutaneous injections. Plasma calcium and inorganic phosphate were measured for up to 15.5 days.