Therapy of hypercalcemia due to parathyroid carcinoma with intravenous dichloromethylene diphosphonate

Abstract

Dichloromethylene diphosphonate (Cl 2MDP), a potent inhibitor of osteoclast-mediated bone resorption, lowers serum calcium in hypercalcemia associated with malignancies and with primary hyperparathyroidism, and reduces excess calcium mobilization from bone in multiple myeloma and in Paget's disease. We have evaluated the effectiveness of intravenously administered Cl 2MDP in five patients with parathyroid carcinoma, a disorder characterized by severe hypercalcemia, very high parathyroid hormone (PTH) levels, and marked osteoclast-mediated bone resorption. All patients had biopsy-proved metastatic parathyroid carcinoma and hypercalcemia which persisted after multiple surgical procedures and other attempts at management. During a three-day observation period, each patient continued to demonstrate stable or progressive hypercalcemia despite infusion with saline solution and furosemide. Cl 2MDP was administered over 2 hours at 2.5 mg/kg on day 1 and 5 mg/kg on days 2 through 7. Response was noted in all five patients; there was a gradual decline in the average serum calcium from 16.0 ± 1.1 mg/dl (SEM) to 11.1 ± 0.9 mg/dl by the eighth day (p < 0.01). There were concomitant reductions in urinary calcium excretion, from 798 ± 153 mg/g creatinine to 350 ± 96 mg/g creatinine (p < 0.05) and in the urinary hydroxyproline excretion, from 155 ± 38 mg/g creatinine to 94 ± 29 mg/g creatinine (p < 0.02). Serum PTH levels remained markedly elevated (460 +- 141 μl eq/ml to 493 ± 169 μl eq/ml). In three patients, all indices returned to pretreatment levels by 10 days after the last infusion. In two of these patients there was a response to retreatment with Cl 2MDP with a fall in calcium from 16.9 ± 0.5 mg/dl to 12.4 ± 1.5 mg/dl. There was no response in one patient. No adverse reactions to Cl 2MDP were observed. The decrease in serum calcium and concomitant declines in urinary calcium and hydroxyproline suggest that Cl 2MDP can effectively inhibit the excessive bone resorption associated with parathyroid carcinoma.