Incidence of atypical femoral fractures in the treatment of bone metastasis: An alert report

BACKGROUND: As the life expectancy of cancer-bearing patients has increased, more patients with bone metastasis are receiving long-term treatment with bone-modifying agents (BMAs; e.g., zoledronate and denosumab), which are a risk factor for developing atypical femoral fracture (AFF). In this study, we surveyed the risk of iatrogenic AFF using a clinical database on treatment of bone metastasis in the past 10 years. METHODS: From April 2011 through October 2019, 721 patients with bone metastasis (436 men, 285 women; mean age, 65.7 ± 12.4 years) were registered under the bone metastasis consultation system, which has been run by orthopaedic surgeons since 2011, at a university hospital in Japan. We retrospectively reviewed the database to identify patients who had received BMAs for treatment of bone metastasis, and we investigated the incidence of critical skeletal-related events (including AFF) which required surgical interventions by orthopaedic surgeons. RESULTS: BMAs were administered to 529 patients (73.4%). Orthopaedic surgery for the treatment of skeletal-related events was performed in 36 patients (5.0%): femur, 13 (1.8%); others, 23 (3.2%). Eight AFFs in 5 patients (breast cancer, n = 4; prostate cancer, n = 1), who all had prior exposure to zoledronate or denosumab before onset of AFF, were treated with internal fixation using intramedullary nailing. In 192 patients with no BMA exposure, critical (surgically treated) AFF was not detected. In summary, the incidence of critical AFF was 0.9% among 529 patients who received BMAs for treatment of bone metastasis, and the incidence was 6.6% when limited to breast cancer patients (4 of 61). CONCLUSION: In treatment of bone metastasis using BMAs, especially for breast cancer patients, attention should be paid to the risk of developing AFFs. Routine radiographic screening for AFF might be necessary in patients with prolonged BMA use for bone metastasis, even if asymptomatic. This report alerts all physicians and surgeons involved in the management of cancer patients, especially those with bone metastasis, regarding the risk of AFF following BMA use.