Bisphosphonate Mechanisms of Action

The nitrogen-containing bisphosphonates are potent and highly effective non-hormonal anti-osteoporotic agents for clinical use in the treatment of post menopausal or glucocorticoid-induced osteoporosis, Paget’s disease, metastatic bone disease and hypercalcemia of malignancy, among others. The Potency of the nitrogen-containing bisphosphonates can partially be attributed to their specific targeting to bone-associated osteoclasts with intermittent dosing at monthly or yearly intervals, the nitrogen-containing bisphosphonates may also label the osteoblast surface, where they remain insert, awaiting the next resorption cycles that will eventually initials at these sites. Through current or future resorption cycles these bisphosphonates can be liberated from the bone surface and taken into the osteoclast interior, where they exert their pharmacological effects as inhibitors of the isoprenoid biosynthetic enzyme, farnesyl diphosphate synthase. This chapter will discuss the utility of this class of drug as effective antifracture agents with a focus on their intriguing mechanism of action.