title: Long-term use of fluticasone propionate/salmeterol fixed-dose combination and incidence of nonvertebral fractures among patients with COPD in the UK General Practice Research Database.
abstract: BACKGROUND
  There has been inconsistent evidence on the association between use of inhaled corticosteroids (ICS) and increased risk of nonvertebral fractures in patients with asthma or chronic obstructive pulmonary disease (COPD). In a large population-based study in the United Kingdom, we estimated the association between fluticasone propionate/salmeterol fixed-dose combination (FSC) and other ICS use and nonvertebral fracture incidence among patients with COPD.
  
  
  METHODS
  We identified a cohort of patients aged ≥ 45 years with COPD in the General Practice Research Database (GPRD) between 2003 and 2006. We used a nested case-control design to estimate the odds of incident nonvertebral fractures associated with prior prescriptions of FSC and other ICS, applying conditional logistic regression and controlling for potential confounders. Exposure to FSC and other ICS was assessed by recency, duration, and number of prescriptions. Average daily dose was defined as low, medium, high, or very high using fluticasone propionate equivalents.
  
  
  RESULTS
  We identified 1523 nonvertebral fracture cases among 53 191 patients with COPD at risk in the cohort. Use of FSC in the year prior to the index date was associated with a statistically significant increase in the odds of nonvertebral fractures (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.07-1.47); however, there was no increase in the odds of nonvertebral fractures for other ICS use (OR, 1.12; 95% CI, 0.97-1.30). When examining results by the recent use of prescriptions, an exposure that occurred farther from the index date was associated with a significant increase in nonvertebral fracture (26-52 days prior OR, 1.36; 95% CI, 1.04-1.77; 53-365 days prior OR, 1.39; 95% CI, 1.07-1.78), whereas categories of more recent use (0-12 days prior or 13-25 days prior) were not associated with nonvertebral fractures relative to no FSC use. No pattern of association between increasing levels of FSC or other ICS average daily dose and increased odds of nonvertebral fracture was observed.
  
  
  CONCLUSIONS
  We did not observe a consistent association between prescriptions of FSC or other ICS in terms of recent use or average daily dose in the prior year and increases in the odds of nonvertebral fractures in patients with COPD, although ever use of FSC was associated with a slight elevation in the odds.
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC, USA.
authors.forename: David P
authors.initials: DP
authors.lastname: Miller
authors.forename: Stephanie E
authors.initials: SE
authors.lastname: Watkins
authors.forename: Tim
authors.initials: T
authors.lastname: Sampson
authors.forename: Kourtney J
authors.initials: KJ
authors.lastname: Davis
mesh_terms: D000280:Administration, Inhalation; D000368:Aged; D000369:Aged, 80 and over; D000420:Albuterol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000730:Androstadienes / Q000008:administration & dosage / Q000009:adverse effects*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects*; D016022:Case-Control Studies; D015897:Comorbidity; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D000068298:Fluticasone; D050723:Fractures, Bone / Q000139:chemically induced / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D012307:Risk Factors; D000068299:Salmeterol Xinafoate; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D001993:Bronchodilator Agents; D004338:Drug Combinations; D000068299:Salmeterol Xinafoate; D000068298:Fluticasone; D000420:Albuterol