New advances in the biology and treatment of myeloma bone disease.

The bisphosphonates provide effective therapy for the skeletal complications of multiple myeloma (MM). Although the earliest bisphosphonates had poor bioavailability and relatively low potency, newer compounds such as pamidronate and zoledronic acid have greater potency. Bisphosphonates block the development of monocytes into osteoclasts and are thought to promote apoptosis of osteoclasts. These agents prevent osteoclasts from moving to the bone surface and seem to inhibit the production of bone-resorbing cytokines such as interleukin-6 (IL-6) by bone marrow stromal cells. In addition, bisphosphonates seem to have a direct antimyeloma effect by inducing apoptosis of malignant plasma cells. The beneficial effects of pamidronate have been demonstrated in a clinical trial setting. Patients who failed to respond to chemotherapy had a slight prolongation of survival and better performance status and quality of life. Ongoing clinical trials with ibandronate and zoledronic acid indicate the latter is 100 to 1,000 times more potent than pamidronate. Biochemical effects of zoledronic acid continue for as long as 8 weeks after a single administration. In a new trial comparing pamidronate and zoledronic acid, 90% of the patients who received zoledronic acid were normocalcemic, compared with 69% of those who received pamidronate at 10 days. In addition, the time to relapse or development of hypercalcemia was shorter for patients receiving pamidronate compared with zoledronic acid.