Hypercalcemia of Malignancy: Treatment with Intravenous Dichloromethylene Diphosphonate

Abstract

Patients [12] with hypercalcemia associated with various malignancies were treated with i.v. dichloromethylene diphosphonate (Cl2MDP), a potent inhibitor of osteoclastic bone resorption, in doses of 2.5 mg/kg of body wt initially and 5.0 mg/kg thereafter for up to 7 days. Mean serum Ca concentration fell from 13.8 .+-. 0.6 mg/dl (SEM [standard error of mean]) before Cl2MDP to 9.8 .+-. 0.7 mg/dl (SEM) (P < 0.001) after 7 days. Urine Ca 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 2 patients. The ability of Cl2MDP to correct hypercalcemia and reduce urine Ca 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.