Anti-tumour activity of bisphosphonates in human myeloma cells

Multiple myeloma is a haematological malignancy characterized by an expansi on of malignant plasma cells within the bone marrow and is frequently assoc iated with bone disease involving the development of osteolytic bone lesion s, pathological fractures, osteoporosis and hypercalcaemia. A class of anti -resorptive drugs known as bisphosphonates have been in use to treat osteoc last-mediated bone diseases for the past 3 decades, and are currently provi ng effective in the treatment of the bone disease associated with multiple myeloma. Recent studies have suggested that bisphosphonate treatment may al so result in an improvement in survival in some patients with multiple myel oma. These effects on survival may reflect an indirect effect of the bispho sphonates on tumour growth, via inhibition of osteoclast activity and hence a reduction in the release of tumour growth factors. However, it is also p ossible that bisphosphonates may have a direct effect on myeloma cells. In support of this we have demonstrated that bisphosphonates can decrease cell proliferation and induce apoptosis in human myeloma cells in vitro, and th is review discusses the possibility that bisphosphonates may have not only an anti-resorptive action, but may also have a direct anti-tumour activity.