Use of inhaled corticosteroids and the risk of fracture

Background: Previous studies have found an association between the use of inhaled corticosteroids and fracture, but the extent to which this association is due to inhaled corticosteroids or to related factors, such as the severity of airflow obstruction, is disputed. We report a new approach in which we combine data on people with airflow obstruction from a large Medical Research Council study of the assessment and management of older people in the community with longitudinal data from their computerized general practice records. Methods: Our cohort includes 1,671 study participants with a diagnosis of asthma or COPD (mean age, 80.6 years). We determined the dose-response relationship between inhaled corticosteroid exposure and time to first fracture using Cox regression, allowing for a wide range of potential confounding factors. Results: During a mean follow-up period of 9.4 years, 982 patients (59%) received a prescription for an inhaled corticosteroid and 187 patients had a fracture. After adjusting for the effects of age and gender, we found a dose-related increase in fracture risk with exposure to inhaled corticosteroids (rate ratio for mean daily dose > 601 μg, 2.53; 95% confidence interval [CI], 1.65 to 3.89; overall trend p < 0.0001). The results were similar after adjusting for oral corticosteroid exposure, airflow obstruction diagnosis, historical fracture, and bronchodilator use (rate ratio, 4.21; 95% CI, 2.19 to 8.13), and also in the subset of people with no exposure to oral corticosteroids (rate ratio, 4.54; 95% CI, 1.23 to 16.74). Conclusions: Our findings provide further evidence that inhaled corticosteroid use is an independent risk factor for fracture.