Treatment of hypercalcemia of malignancy with bisphosphonates

Hypercalcemia of malignancy (HCM) is a potentially life-threatening complication of cancer resulting from increased bone resorption by osteoclasts. Clinical management of HCM primarily consists of intravenous rehydration therapy combined with pharmaceutical agents that decrease osteoclast activity. Several generations of drugs designed to combat HCM have evolved, the latest being intravenous bisphosphonate therapy. Bisphosphonates safely and effectively decrease serum calcium levels by interfering with osteoclast activity and stimulating osteoclast apoptosis. Zoledronic acid is the most recent bisphosphonate approved by the US Food and Drug Administration for treatment of HCM and is significantly more effective in reducing serum calcium levels than previously used bisphosphonates. Furthermore, zoledronic acid has a safety profile similar to that of pamidronate and other intravenous bisphosphonates. Thus, zoledronic acid represents a significant therapeutic advance in the clinical management of HCM.