title: Propoxyphene use and risk for hip fractures in older adults.
abstract: BACKGROUND
  Published guidelines have identified propoxyphene as an inappropriate medication for use in aged patients. It is no more effective than acetaminophen, yet has been associated with the same adverse effects (AEs) associated with other opioid drugs. In particular, its central nervous system-related AEs, dizziness and sedation, may increase the risk for fracture resulting from falls in older adults. Nonetheless, US studies have reported widespread use of propoxyphene in the elderly US population.
  
  
  OBJECTIVE
  The aim of this study was to examine the risk for fracture associated with propoxyphene use in older adults.
  
  
  METHODS
  This prospective cohort study used a large administrative claims data set from adults aged > or =65 years. A time-varying (lagged) covariate defined each person as a propoxyphene user or nonuser based on propoxyphene exposure in the 14 days before each fracture event in the cohort. Another time-varying measure stratified propoxyphene users based on their mean daily dose of propoxyphene (high dose = >260 mg; low dose = < or =260 mg of propoxyphene hydrochloride or equivalent napsylate salt). Time-dependent Cox regression models were used to estimate the association between propoxyphene exposure and occurrence of hip fracture (using International Classification of Diseases, Ninth Revision, Clinical Modification code 820.xx).
  
  
  RESULTS
  A total of 362,503 patients were included in the analysis. During a mean follow-up of 464 days, approximately 10% (37,569) of the sample had > or =1 propoxyphene prescription filled and approximately l% (5065) sustained a hip fracture. Propoxyphene users had a 2-fold higher risk for hip fracture (hazard ratio [HR] [95% CI], 2.05 [1.87-2.25]) compared with nonusers of analgesics. Multivariate analysis found a dose-response relationship between propoxyphene and hip fracture risk (low dose, HR [95% CI], 1.45 [1.26-1.67]; high dose, HR [95% CI], 2.05 [1.85-2.29]). Other opioid analgesics were associated with an increased risk for hip fractures.
  
  
  CONCLUSIONS
  The results of this cohort database study suggest that propoxyphene use among adults aged > or =65 years is associated with increased risk for hip fracture and suggest a need for interventions to reduce propoxyphene use in older adults. Clinicians should be aware of the risk for hip fracture with other opioids as well and weigh them against potential benefits when prescribing for older adults.
authors.affiliation: Department of Pharmaceutical Health Services Research, University of Maryland, Baltimore, Maryland, USA. sachin_kamal_bahl@merck.com
authors.forename: Sachin J
authors.initials: SJ
authors.lastname: Kamal-Bahl
authors.forename: Bruce C
authors.initials: BC
authors.lastname: Stuart
authors.forename: Mark H
authors.initials: MH
authors.lastname: Beers
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects*; D011431:Dextropropoxyphene / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004363:Drug Utilization; D005260:Female; D006620:Hip Fractures / Q000209:etiology*; D006801:Humans; D007345:Insurance Claim Review; D008297:Male; D006278:Medicare; D011446:Prospective Studies; D012306:Risk
chemical_list: D000701:Analgesics, Opioid; D011431:Dextropropoxyphene