Inhaled corticosteroids and the risk of fracture in chronic obstructive pulmonary disease

Background: Inhaled corticosteroids are used increasingly to treat people with COPD, but the extent to which these drugs increase the risk of fracture is unclear. Aim: To quantify the dose-response relationship between fracture risk and inhaled corticosteroids in people with COPD, independent of the effects of percent predicted FEV1 and oral corticosteroids. Design: Nested case-control study. Methods: Cases and controls were COPD patients aged ≥40 years or more at diagnosis, with a FEV₁ measurement recorded in The Health Improvement Network database, up to 5 July 2005. Cases (people with a fracture event after 1 January 1998, n=1235) were assigned up to four controls (n=4598), matched by gender and general practice. Results: Mean FEV₁ was 57.5% in cases, and 58.5% in controls. Inhaled corticosteroids had been prescribed in 69% of cases (median dose 269 mcg/day) and 66% (226 mcg/day) of controls. Oral corticosteroids had been prescribed in 60% of cases (median annual prescription rate 0.6) and 56% of controls (also 0.6 per year). Risk of fracture increased with increasing mean daily doses of inhaled corticosteroid (p for trend 0.007), and was most marked in those whose daily dose was 51600 mcg (OR 1.80, 95% CI 1.04-3.11). This effect was virtually unchanged by adjustment for mean percent predicted FEV1 and annual prescription rate for oral corticosteroids (OR for highest dose exposure 1.74, 95% CI 1.00-3.01). Discussion: Our findings add to the evidence that the use of inhaled corticosteroids is associated with a small increase in fracture risk, particularly at higher doses.