Myeloma--the therapeutic challenge

Bone loss--the major clinical manifestation of multiple myeloma--often leads to pathologic fractures, spinal cord compression, hypercalcemia and bone pain.

Analgesics, surgery and radiotherapy may effectively palliate patients with complications from myeloma bone disease, but cannot slow the progressive bone loss. Chemotherapy may reduce tumor burden but has little impact on the underlying bone disease. A dramatic change was the demonstration that intravenous pamidronate could reduce skeletal complications. Importantly, because bisphosphonates lack significant bone marrow suppressive effects they can be administered to other cytotoxic therapy. Laboratory studies show the improved potency of the 3rd-generation bisphosphonate zoledronic acid in its anti-bone resorptive as well as anti-myeloma effects. Phase-I and -II studies evaluating zoledronic acid in myeloma patients show marked and sustained inhibition of bone resorption markers.

The randomized studies evaluating zoledronic acid have demonstrated its superiority to pamidronate in overcoming tumor-induced hypercalcemia. Results of ongoing phase-III studies will determine its relative safety and efficacy compared to pamidronate.