What is the treatment of hypercalcemia of malignancy?
The primary goal in the management of hypercalcemia is to enhance the urinary excretion of calcium and to decrease the osteoclast-mediated bone resorption.
The first goal is achieved by aggressive volume repletion with a goal urine output of 100 to 150 mL/hour. Furosemide should only be used once the patient is made adequately volume replete.
Calcitonin inhibits bone resorption and osteoclast maturation and acts quickly within 4 to 6 hours of administration. Tachyphylaxis prevents its long-term use. In volume overloaded or anuric patients, dialysis with a low dialysate calcium may be needed.
Bisphosphonates, namely zoledronate and pamidronate, have become the cornerstone of treatment of hypercalcemia of malignancy.
Bisphosphonates reduce the osteoclast activity by preventing the osteoclasts from adhering to the bone surface, and preventing the production of their proteins, which are responsible for continued bone resorption.
They also result in decreased osteoclast progenitor development and promote their apoptosis. RANKL inhibitors, such as denosumab, play a role in the management of bisphosphonate-resistant hypercalcemia of malignancy even though it does not yet have U.S. Food and Drug Administration approval.
