These bone changes can result in patients having evidence of osteolytic skeletal destruction leading to severe bone pain that requires either radiation therapy or narcotic analgesics (or both) for symptomatic relief. These changes also cause pathologic fractures of bone in both the axial and appendicular skeleton. Axial skeletal fractures of the vertebral bodies may lead to spinal cord compression or vertebral body collapse with significant neurologic complications. Also, patients may experience episode(s) of hypercalcemia.

Clinical Trials
In a double-blind, randomized, placebo-controlled trial, 392 patients with advanced multiple myeloma were enrolled to receive pamidronate disodium or placebo in addition to their underlying antimyeloma therapy to determine the effect of pamidronate disodium on the occurrence of skeletal-related events (SREs). SREs were defined as episodes of pathologic fractures, radiation therapy to bone, surgery to bone, and spinal cord compression. Patients received either 90 mg of pamidronate disodium or placebo as a monthly 4 hour intravenous infusion for 9 months. Of the 392 patients, 377 were eva luable for efficacy (196 pamidronate disodium, 181 placebo). The proportion of patients developing any SRE was significantly smaller in the pamidronate disodium group (24% vs 41%, P<0.001), and the mean skeletal morbidity rate (#SRE/year) was significantly smaller for pamidronate disodium patients than for placebo patients (mean: 1.1 vs 2.1, P<0.02). The times to the first SRE occurrence, pathologic fracture, and radiation to bone were significantly longer in the pamidronate disodium group (P=0.001, 0.006, and 0.046, respectively). Moreover, fewer pamidronate disodium patients suffered any pathologic fracture (17% vs 30%, P=0.004) or needed radiation to bone (14% vs 22%, P=0.049).

In addition, decreases in pain scores from baseline occurred at the last measurement for those pamidronate disodium patients with pain at baseline (P=0.026) but not in the placebo group. At the last measurement, a worsening from baseline was observed in the placebo group for the Spitzer quality of life variable (P<0.001) and ECOG performance status (P<0.011) while there was no significant deterioration from baseline in these parameters observed in pamidronate disodium-treated patients.*

After 21 months, the proportion of patients experiencing any skeletal event remained significantly smaller in the pamidronate disodium group than the placebo group (P=0.015). In addition, the mean skeletal morbidity rate (#SRE/year) was 1.3 vs 2.2 for pamidronate disodium patients vs placebo patients (P=0.008), and time to first SRE was significantly longer in the pamidronate disodium group compared to placebo (P=0.016). Fewer pamidronate disodium patients suffered vertebral pathologic fractures (16% vs 27%, P=0.005). Survival of all patients was not different between treatment groups.

Two double-blind, randomized, placebo-controlled trials compared the safety and efficacy of 90 mg of pamidronate disodium infused over 2 hours every 3 to 4 weeks for 24 months to that of placebo in preventing SREs in breast cancer patients with osteolytic bone metastases who had one or more predominantly lytic metastases of at least 1 cm in diameter: one in patients being treated with antineoplastic chemotherapy and the second in patients being treated wi