Hypercalcemia of malignancy: pathophysiology and implications for treatment.

As the most common metabolic consequence of cancer, hypercalcemia of malignancy is often encountered in patients with solid tumors, most often lung, head and neck, and breast carcinomas. Since the clinical consequences of hypercalcemia of malignancy may be fatal, an understanding of its pathogenesis and skeletal-related factors that may lead to hypercalcemia is important in directing therapy. It is also important to have reasonable expectations and goals outlined before initiating therapy in an individual patient. Interventions aimed specifically at osteoclast inhibition normalize serum calcium levels while treating the final common pathway responsible for the disorder; these include calcitonin, plicamycin, gallium nitrate, and the bisphosphonates. An important consequence of the advent of antiresorptive therapy has been the initiation of clinical trials aimed at preventing skeletal-related morbid events from bone metastases. These trials may ultimately prove to be the most significant benefit of osteoclast inhibitor therapy for patients.