Bisphosphonates - Mechanisms of action in multiple myeloma

Bisphosphonates are a class of anti-resorptive drugs, which are effective i n the treatment of osteoclast-mediated bone disease, including the osteolyt ic bone disease, which is a major clinical feature of patients with multipl e myeloma. Recently, increases in survival following treatment with pamidro nate have been observed in some patients with multiple myeloma, raising the possibility that bisphosphonates may also have an anti-tumour effect. We h ave demonstrated that bisphosphonates can have an anti-tumour effect in hum an myeloma cell in vitro, and that these anti-tumour effects induced by pot ent nitrogen-containing bisphosphonates are a result of inhibition of enzym es of the mevalonate pathway. However, we and others have been unable to de monstrate 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 det ermine whether these compounds have a clinically important anti-tumour effe ct.