Impact of drug interactions, dosage, and duration of therapy on the risk of hip fracture associated with benzodiazepine use in older adults

Pharmacoepidemiol Drug Saf. 2010 Dec;19(12):1248-55. doi: 10.1002/pds.2031. Epub 2010 Oct 7.

Abstract

Purpose: To determine how concomitant use of potentially interacting drugs, drug dosage, and duration of therapy modify the risk of hip fracture associated with use of benzodiazepines and benzodiazepine-related drugs (BDZ) in older adults.

Methods: A nested case-control study was conducted in Medicare patients 65 years or older, enrolled in the Pennsylvania drug assistance program (PACE) between 1994 and 2005. We included 17,198 patients with a hip fracture leading to hospitalization and 85,990 controls matched on hospitalization (index date). BDZ and interacting drug use within 2 weeks preceding the index date was determined using information on date of drug dispensing, days supplied, quantity dispensed, and strength. Date of the first BDZ prescription within the year preceding the index date was used as surrogate for duration of therapy.

Results: While the adjusted relative risk (RR) for overall BDZ use and hip fracture was 1.2 (95% confidence interval 1.1, 1.2), the RRs for concomitant use of alprazolam, lorazepam, and zolpidem and their interacting drugs were 1.5 (1.3, 1.7), 1.9 (1.7, 2.2), and 1.7 (1.4, 2.0), and 2.1 (1.5, 2.8) for BDZ use initiated within 14 days preceding the index date. RR increased with increasing BDZ dose and was highest for defined daily BDZ doses >1 [RR: 1.3 (1.2, 1.5)].

Conclusions: BDZ associated hip fracture risk increases with concomitant use of interacting drugs, higher doses, and is highest at initiation. Clinicians should avoid concomitant use of BDZ and interacting drugs, because their impact on hip fracture risk is at least additive.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Benzodiazepines / administration & dosage
  • Benzodiazepines / adverse effects*
  • Case-Control Studies
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Female
  • Hip Fractures / epidemiology
  • Hip Fractures / etiology*
  • Hospitalization
  • Humans
  • Male
  • Medicare
  • Pennsylvania
  • Risk
  • Time Factors
  • United States

Substances

  • Benzodiazepines