Hypercalcemia of Malignancy: Treatment with Intravenous Dichloromethylene Diphosphonate

Abstract

Twelve patients with hypercalcemia associated with various malignancies were treated with intravenous dichloromethylene diphosphonate (Cl₂MDP), a potent inhibitor of osteoclastic bone resorption, in doses of 2.5 mg/kg of body weight initially and 5.0 mg/kg thereafter for up to 7 days. Mean serum calcium concentration fell from 13.8 ± 0.6 mg/dL (SEM) before Cl₂MDP to 9.8 ± 0.7 mg/dL (SEM) (p < 0.001) after 7 days. Urine calcium excretion fell from 775 ± 95 mg/g creatinine (SEM) to 272 ± 70 mg/g creatinine (SEM) (p < 0.005), and urine hydroxyproline excretion fell from 144 ± 28 mg/g creatinine (SEM) to 78 ± 18 mg/g creatinine (SEM) (p < 0.05) after treatment with Cl₂MDP. The Cl₂MDP was well tolerated, and adverse effects were limited to asymptomatic hypocalcemia in two patients. The ability of Cl₂MDP to correct hypercalcemia and reduce urine calcium and hydroxyproline excretion in these patients is consistent with the hypothesis that increased bone resorption is primarily responsible for this complication of malignancy and suggests that Cl₂MDP may be highly useful in managing this condition.