Bisphosphonates - Mechanisms of Action in Multiple Myeloma

Bisphosphonates are a class of anti-resorptive drugs, which are effective in the treatment of osteoclast-mediated bone disease, including the osteolytic bone disease, which is a major clinical feature of patients with multiple myeloma. Recently, increases in survival following treatment with pamidronate have been observed in some patients with multiple myeloma, raising the possibility that bisphosphonates may also have an anti-tumour effect. We have demonstrated that bisphosphonates can have an anti-tumour effect in human myeloma cell in vitro, and that these anti-tumour effects induced by potent nitrogen-containing bisphosphonates are a result of inhibition of enzymes of the mevalonate pathway. However, we and others have been unable to demonstrate an anti-tumour effect of the potent bisphosphonate ibandronate in vivo, using murine models of multiple myeloma. It is therefore likely that only by studying patients receiving bisphosphonates will we be able to determine whether these compounds have a clinically important anti-tumour effect.