Atypical Femoral Fracture in Patients With Metastatic Bone Tumors: An Analysis Based on the Japanese Adverse Drug Event Reaction Database (JADER).

Objective Denosumab (DEN)-related atypical femoral fracture (AFF) is a rare entity, and hence not feasible to examine with a single institution-based study. In light of this, we performed a retrospective analysis of the clinical characteristics of patients with metastatic bone tumors treated with DEN and developed AFF. Methods The Japanese Adverse Drug Event Report (JADER) database (2023.8 public version) from the second quarter of 2004 to the second quarter of 2023 was used to investigate the backgrounds of patients with metastatic bone tumors who developed AFF while receiving DEN. The time of AFF onset was defined as the number of days from the start of treatment to the onset of AFF. We also aimed to identify drugs associated with the development of AFF. Cut-off values for signal detection were χ2 ≥4 and number of reports ≥3. Results The JADER database contained 2,012 cases of metastatic bone tumors for which DEN was the suspect drug or administered concomitantly with the suspect drug. Of these cases, 106 (5.3%) had AFF, with 91 (85.8%) being women and 61 (57.5%) patients receiving drugs for osteoporosis. The duration from administration to the onset of AFF by DEN was known in 36 cases, and the median value was 926 [interquartile range (IQR): 534-1,552] days. Furthermore, among the drugs suspected of involvement other than DEN, a signal was detected for ZOL, with a reporting odds ratio (OR) of 6.93 and a 95% confidence interval (CI) of 4.39-10.93. Conclusions In JADER, AFF in patients with metastatic bone tumors receiving DEN was more common in women and patients receiving osteoporosis drugs, and the time of onset of AFF was approximately 2.5 years.