Bisphosphonate therapeutics in bone disease: The hard and soft data on osteoclast inhibition

With annual sales well over three billion dollars, bisphosphonate drugs have been widely prescribed to maintain bone density in patients who are at risk for fractures, such as those afflicted with osteoporosis. Paradoxically, bisphosphonate treatment has in the past few years been linked to rare adverse events, such as osteonecrosis of the jaw, marked by bone deterioration. Such side effects tend to occur within particular clinical contexts, such as cancer and dental surgery, but they have raised concern in light of the widespread use of bisphosphonate therapeutics. The mechanisms of bisphosphonate action and the dynamics of bone turnover are intricately related, and the interplay between drug and bone explains, at least in part, the paradoxical effects of bisphosphonate drugs on bone development. An understanding of this interplay may also provide routes to potential new therapeutics to ward off bone loss associated with disease.