Bisphosphonate treatment of lytic bone metastases

Tumour-induced osteolysis or lytic bone disease is mediated by osteoclast a ctivation. Osteoclasts can be activated directly by tumour products or indi rectly through an influence on other cells. By reducing osteoclastic activi ty, bisphosphonates inhibit bone resorption. Pamidronate is a second-genera tion aminobisphosphonate that is a potent inhibitor of osteoclastic activit y. In multiple myeloma, a phase III study has shown that the proportion of patients at the end of 21 months who had any skeletal event was significant ly lower in the pamidronate group (38%) than in the placebo group (58%). Th e therapeutic benefit was independent of the type of antimyeloma chemothera py. Patients who received pamidronate had significant decrease in bone pain and delayed deterioration in performance status and quality of life. Overa ll there was no survival advantage in patients who received pamidronate. In similar fashion, in 2 phase III breast cancer trials, patients who receive d pamidronate had fewer skeletal events, decrease in bone pain and analgesi c use, and slower deterioration of performance status that in those patient s receiving placebo. Again, there was no survival advantage in these patien ts. Recent studies suggest that the bisphosphonates clodronate can prevent the development of bone metastases in patients with breast cancer.