Atypical fractures and bisphosphonate therapy: A cohort study of patients with femoral fracture with radiographic adjudication of fracture site and features

Atypical subtrochanteric/femoral shaft (ST/FS) fractures are increasingly reported in patients on long-term treatment with bisphosphonates (BPs). We estimated the frequency of atypical fractures and their association to BP use in patients aged ≥ 50 years consecutively admitted to a single center with a new femoral fracture. All individual radiographs were examined and fracture site confirmed. A case-control study of patients with low-energy ST/FS fractures, age- and sex-matched with patients with hip fractures (1:2 ratio), was performed. Patients with atypical ST/FS fractures were further compared with those with ordinary ST/FS fractures. Cortical thickness (CT) was measured in radiographs of cases and controls. Ninety-six of 906 patients (10.6%) had a ST/FS fracture. Of these, 63 with low-energy fractures were individually matched with 126 controls with hip fracture. BPs were used by 9.5% of cases and by 8.7% of controls (OR, 1.10; 95% CI, 0.39-3.06) with comparable duration of therapy between groups (54 ± 35 vs. 54 ± 52 months, P=0.53). CT was comparable between cases and controls, BP users and non-users, and was not related to treatment duration. Atypical fractures were observed in 10/63 ST/FS cases (15.9%). Compared to patients with ordinary ST/FS fractures, those with atypical fractures were using more frequently BPs (OR, 17.0; 95% CI, 2.6-113.3) and glucocorticoids (OR, 5.3; 95% CI, 0.9-28.6). Among patients with atypical fractures, CT was comparable between BP users and non-users. In conclusion, atypical femoral fractures have a low prevalence (1.1% of all femoral fractures), compared to ordinary ST/FS fractures are more frequent in bisphosphonate users, but equally occur in patients never treated with bisphosphonates.