Atypical Femoral Fracture in Rheumatoid Arthritis Patients Treated with Bisphosphonates: A Nested Case-Control Study

Objective To examine the clinical characteristics of atypical femoral fracture (AFF) and to determine the risk factors for and clinical outcomes of AFFs in rheumatoid arthritis (RA) patients treated with bisphosphonates (BPs). Methods A nested case-control study was conducted using data derived from the medical records of all RA patients treated with BPs at Seoul St. Mary's Hospital, a tertiary rheumatology center, from January 1, 2008 to December 31, 2014. All of the patients with RA and had been treated with BPs for at least 1 year. Ten RA patients with AFF were identified, and each of these patients (cases) was age- and sex-matched with 4 RA patients without AFF (controls). Results Five hundred fifty-two RA patients had BP exposure. Of the 10 with AFF, all were female (mean ± SD age 66.3 ± 8.7 years), and 90% of cases involved fracture of the proximal femur. The mean ± SD length of BP exposure in patients with AFF was 7.4 ± 3.2 years. Compared with controls, patients with AFF had a longer exposure to BPs and more often had a femorotibial angle of <175 degrees (both P < 0.001). There were no differences in RA duration, medications taken during the previous 6 months, and bone mineral density in the femur and lumbar spine between patients with and those without AFF. Multivariate logistic analyses identified longer BP exposure (odds ratio 2.386 [95% confidence interval 1.066-5.343]) as being associated with an increased risk of AFF. Conclusion RA patients who have a valgus deformity and are receiving long-term BP treatment are at higher risk of AFF compared with matched control patients with RA. These patients should be carefully followed up with hip radiography or dual x-ray absorptiometry.