Osteonecrosis of the Jaw and Atypical Femoral Fractures

Bisphosphonates reduce the risk of spine and nonspine fractures, including hip fractures. However, they are associated with osteonecrosis of the jaw (ONJ) and atypical femoral fractures. The incidence of ONJ is highest in patients with malignancy receiving high doses of intravenous bisphosphonates and denosumab, and is considerably lower in patients receiving lower doses of bisphosphonates for osteoporosis and Paget disease, with estimates ranging from 1 in 10,000 to 1 in 250,000. Major risk factors for ONJ are antiresorptive drug potency, longer duration of use, periodontal disease, dental extractions, or trauma. The pathogenesis is likely related to suppression of bone remodeling, common to both bisphosphonates and denosumab, and infection and inflammation. Atypical subtrochanteric and femoral shaft fractures are associated with long-term bisphosphonate, and more recently with denosumab use, but also occur in patients who have never been exposed to these drugs. Although the estimated relative risks of atypical femoral fractures range from xx to xx in patients on bisphosphonates, their absolute risk is low, ranging from 3.2 to 50 cases per 100,000 person-years. Given the very low incidence of ONJ and atypical femur fractures in patients treated with bisphosphonates for osteoporosis versus the marked reduction in fracture risk associated with these drugs, the risk to benefit ratio for the use of bisphosphonates and denosumab clearly favors treating patients with a prior fragility fracture, a spine or femur neck T-score below -2.5, or at high risk of fractures.