Atypical femur fracture following romosozumab and bisphosphonate treatment

Romosozumab, a monoclonal antibody against sclerostin, is a newly licensed dual-acting osteoporosis treatment for patients at very high risk of fracture. Sclerostin inhibition leads to stimulation of bone formation and simultaneous inhibition of bone resorption. Only three cases of atypical femur fractures were reported out of 5,621 patients who received romosozumab in the pivotal randomised controlled trials FRAME and ARCH; however, most enrolled clinical trial patients were osteoporosis treatment-naïve or had a prolonged washout period. We report a case of an atypical femur fracture that occurred after the completion of romosozumab treatment which was followed by one dose of 5 mg intravenous zoledronic acid. The patient had previously received a 2-year course of subcutaneous teriparatide and subsequent three consecutive yearly intravenous zoledronic acid infusions, followed by a 2-year treatment break. This case highlights the risks of prolonged suppression of bone resorption, which includes romosozumab due to its dual action and the need for further research on how to minimise such deleterious medication effects. Patients who are switched from prolonged antiresorptive treatment to romosozumab, should be risk-assessed and counselled for the risk of atypical femur fracture.