Osteonecrosis of the jaw--do bisphosphonates pose a risk?

n engl j med 355;22 www.nejm.org november 30, 2006 2278 N bisphosphonates are used widely for the management of metastatic cancer in bone (intravenous zoledronic acid or pamidronate), for the prevention and treatment of osteoporosis (oral alendronate, risedronate, and ibandronate and intravenous ibandronate), for the treatment of Paget’s disease of bone (intravenous pamidronate and oral alendronate and risedronate), and for the short-term management of acute hypercalcemia (intravenous zoledronic acid and pamidronate). The nitrogen moiety attached to the side chain of the middle carbon of the phosphorus–carbon–phosphorus bisphosphonate backbone renders these drugs much more potent as inhibitors of bone resorption than the bisphosphonates that do not contain nitrogen (etidronate and clodronate). Bisphosphonates reduce the survival and function of osteoclasts, the bone-resorbing cells. These antiresorptive actions largely account for the drugs’ efficacy in conditions in which the rate of bone resorption exceeds the rate of bone formation. Until recently, the only adverse events of substantial consequence