The risk of nonvertebral fracture related to inhaled corticosteroid exposure among adults with chronic respiratory disease

Chest. 2005 Jan;127(1):89-97. doi: 10.1378/chest.127.1.89.


Objective: To examine nonvertebral fracture risk in relation to inhaled corticosteroid (ICS) exposure among adults with respiratory disease.

Design and patients: Nested case-control study within a cohort of 89,877 UnitedHealthcare members aged > or = 40 years with physician insurance claims for COPD or asthma, enrolled for > or = 1 year from January 1, 1997 to June 30, 2001.

Methods: Cases (n = 1,722) represented patients with a first treated nonvertebral fracture (the index date is the first fracture claim). Control subjects (n = 17,220) were randomly selected from the person-time and assigned a random index date. ICS exposure was ascertained 1 month, 3 months, 6 months, and 12 months before the index date, with estimated cumulative dose through 0 to 6 months, 7 to 12 months, and 0 to 12 months. Covariates included demographics, oral corticosteroid and other medication exposure, comorbidities, and indicators of respiratory disease severity. Odds ratios (ORs) adjusted for all covariates were estimated by logistic regression.

Results: No increased fracture risk with ICS exposure as a class or with fluticasone propionate alone was detected. ORs for exposure in the preceding 30 days were 1.05 (95% confidence interval [CI], 0.89 to 1.24), 1.13 (95% CI, 0.90 to 1.40), and 0.97 (95% CI, 0.78 to 1.21) for all ICS, fluticasone propionate, and other ICS, respectively. No dose-response effect was present. Among patients with COPD only (n = 6,932), no increased risk was found for recent ICS exposure (OR, 0.86; 95% CI, 0.59 to 1.25).

Conclusions: Concern about nonvertebral fracture risk should not strongly influence the decision to use recommended doses of ICS for adult patients with asthma or COPD in managed-care settings in the United States. This study could not evaluate very-high ICS dose, long-term ICS exposure, or vertebral fracture risk.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Asthma / drug therapy*
  • Comorbidity
  • Fractures, Bone / chemically induced
  • Fractures, Bone / epidemiology*
  • Glucocorticoids / adverse effects*
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Odds Ratio
  • Pulmonary Disease, Chronic Obstructive / drug therapy*


  • Glucocorticoids