Treatment of the hypercalcaemia of malignancy with intravenous clodronate

We studied the effects of intravenous clodronate (100-300 mg daily for 3-10 days) in 27 episodes of hypercalcaemia due to malignancy. Comparisons were also made between responses in patients with haematological malignancies and those with solid tumours. Following extracellular volume expansion, clodronate induced a significant decrease in serum calcium within 2 days of the start of treatment which was maximal at 7 days. This was associated with a decrease in bone resorption as judged by decreases in urinary excretion of hydroxyproline and calcium. Hypercalcaemia recurred 5-7 days after stopping treatment. Patients with solid tumours had higher pretreatment serum calcium values than those with haematological malignancies despite comparable values for fasting urinary excretion of calcium suggesting that renal tubular reabsorption of calcium was more markedly increased in patients with solid tumours. No difference was observed in the final calcium values between patients with solid tumours and haematological malignancies except in those patients in whom renal tubular reabsorption of calcium was markedly increased before treatment. We conclude that intravenous clodronate provides a safe and effective treatment of hypercalcaemia due to a wide range of tumour types provided that increased bone resorption contributes significantly to the hypercalcaemia. When increased renal reabsorption of calcium is the predominant mechanism for the maintenance of hypercalcaemia, the response to clodronate is incomplete.