The role of income and educational level as risk factors for atypical femur fractures: A Nationwide Danish Case-Cohort Study with Blinded Radiographic Review

Socioeconomic factors and atypical femur fracture (AFF) risk during bisphosphonate treatment are poorly understood. Among Danish bisphosphonate users, medium, and long educational levels were associated with lower AFF rates, with medium education remaining associated with lower AFF risk after adjustment, even within a universal healthcare system. Purpose Atypical femur fracture (AFF) is a rare but serious fracture type associated with bisphosphonate (BP) treatment. While clinical risk factors are well studied, socioeconomic factors among BP users remain unexplored. We therefore examined whether income and educational level were associated with AFF risk in Denmark. Methods We included all radiologically confirmed AFF cases from 2010 to 2014, identified through blinded reviews of potential AFFs among individuals aged >= 50 years, and register-data for a random sample of the general population >= 50 (n = 100,253). Health, income, and education data were obtained from Danish national registers. We estimated incidence rates (IR), incidence rate ratios (IRR), and hazard ratios (HR) using Cox regression. Results Among 164 AFF cases, 116 had BP exposure, and exposure was higher among AFF cases than in the background population (70.7% vs. 7.9%, p < 0.05). The AFF IR among BP users was 32.5 per 10,000 person-years (CI 27.1-39.0). Crude AFF rates differed by income and education, but income was not associated with AFF risk in adjusted Cox regression. BP users with medium or long education had a lower IRR than those with low/missing education (medium: IRR (CI): 0.56 (0.36-0.86); long: IRR (CI): 0.53 (0.28-0.95)). In age- and sex-adjusted Cox analyses, medium education remained associated with a lower AFF risk 0.63 (0.41-0.96). Conclusion Socioeconomic differences in AFF rates were observed among BP users, but adjusted analyses did not support an independent association between income and AFF risk. Medium education was associated with lower AFF risk after adjustments.