To examine the risk of non-vertebral fracture in relation to inhaled corticosteroid (ICS) exposure among adults with respiratory disease.
Nested case-control study within a cohort of 89,877 UnitedHealthcare members 40 years or older with physician insurance claims for chronic obstructive pulmonary disease (COPD) or asthma, enrolled for at least 1 year from 1/1/1997-6/30/2001. Cases (n=1,722) experienced treatment for a non-vertebral fracture, with the index date the first fracture claim. Controls (n=17,220) were randomly selected and assigned a random index date. ICS, the primary exposure, was estimated from pharmacy claims for dispensings 1, 3, 6, and 12 months before the index date, with estimated cumulative dose through 0-6, 7-12 and 0-12 months. Covariates included demographics, oral corticosteroid and other medication exposure, comorbidities, health care utilization, disease severity indicators, and health care utilization and costs. Odds ratios (OR) adjusted for all covariates were estimated by logistic regression.
Fracture risk increased with age, female gender, respiratory disease severity, non-respiratory care costs, depression, stroke, anticonvulsant use, and bone disorders. There was little evidence for increased fracture risk with ICS exposure. The ORs for exposure in the preceding 30 days were 1.05 (95% CI: 0.89-1.24), 1.13 (0.90-1.40), and 0.97 (0.78-1.21) for all ICS, fluticasone propionate, and other ICS, respectively, and were close to one in more distant exposure periods. No dose-response effect was present. In analyses limited to 6,932 COPD patients, there was no increased fracture risk for recent ICS (OR=0.86, 95% CI: 0.59-1.25), fluticasone (OR=1.07, 95% CI: 0.66-1.74), or other ICS (OR=0.69, 95% CI: 0.40-1.18) exposure.CONCLUSIONS: In data that could readily reproduce the major epidemiologic features of non-vertebral fracture, there was no demonstrable risk with the use of ICS as a class, or with preparations containing fluticasone at any cumulative dose or duration among patients with COPD or asthma.
In contemporary managed care settings in the US, concern about non-vertebral fracture should not enter into the decision as to whether to use ICS.
C.B. Johannes, GlaxoSmithKline. This research study was funded by GlaxoSmithKline through a contract with Ingenix Epidemiology.