Hypercalcemia of malignancy: pathophysiology and treatment

Hypercalcemia is a relatively common terminal complication of malignancy. In the majority of the patients it is due to excessive bone resorption, secondary either to local destruction by metastases or by the activity of several paracrine and/or endocrine factors. Increased renal tubular reabsorption of calcium plays a role in the aetiology and maintenance of hypercalcemia. It is due both to factors which stimulate the renal transport of calcium and to volume depletion that is frequently present in hypercalcemic patients. This explains why the administration of large amounts of fluids intravenously is often a necessary first step in the management of malignant hypercalcemia, followed by specific inhibitors of bone resorption such as the bisphosphonates.