Bisphosphonates: mechanisms of action

Bisphosphonates are widely used in the treatment of diseases involving excessive bone resorption, including post-menopausal osteoporosis, Paget’s disease of bone, tumour-associated bone disease, and hypercalcaemia of malignancy. These drugs have a high affinity for bone mineral and predominantly target bone-resorbing osteoclasts in vivo. Since their discovery in the late 1960’s, bisphosphonates have been successfully used in the clinical setting for more than 3 decades. However, it is only in recent years that major advances have been made in our understanding of the cellular and molecular mechanisms of action of bisphosphonates. This chapter will cover the history of the development, chemistry, biological actions, and molecular mechanisms of action of bisphosphonates, as well as a discussion on anti-tumour activity, and adverse effects.