Is Zolpidem Associated with Increased Risk of Fractures in the Elderly with Sleep Disorders? A Nationwide Case Cross-Over Study in Taiwan

PLoS One. 2015 Dec 30;10(12):e0146030. doi: 10.1371/journal.pone.0146030. eCollection 2015.

Abstract

Background: We conducted a study using a case-crossover design to clarify the risk of acute effects of zolpidem and benzodiazepine on all-sites of fractures in the elderly.

Design of study: Case-crossover design.

Methods and materials: Elderly enrollees (n = 6010) in Taiwan's National Health Insurance Research Database with zolpidem or benzodiazepine use were analyzed for the risk of developing fractures.

Results: After adjusting for medications such as antipsychotics, antidepressants, and diuretics, or comorbidities such as hypertension, osteoarthritis, osteoporosis, rheumatoid arthritis and depression, neither zolpidem nor benzodiazepine was found to be associated with increased risk in all-sites fractures. Subjects without depression were found to have an increased risk of fractures. Diazepam is the only benzodiazepine with increased risk of fractures after adjusting for medications and comorbidities. Hip and spine were particular sites for increased fracture risk, but following adjustment for comorbidities, the associations were found to be insignificant.

Conclusion: Neither zolpidem nor benzodiazepine was associated with increased risk of all-site fractures in this case cross-over study after adjusting for medications or comorbidities in elderly individuals with insomnia. Clinicians should balance the benefits and risks for prescribing zolpidem or benzodiazepine in the elderly accordingly.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Benzodiazepines / adverse effects
  • Benzodiazepines / therapeutic use
  • Case-Control Studies
  • Cross-Over Studies
  • Female
  • Fractures, Bone / chemically induced*
  • Humans
  • Hypnotics and Sedatives / adverse effects*
  • Hypnotics and Sedatives / therapeutic use
  • Male
  • Pyridines / adverse effects*
  • Pyridines / therapeutic use
  • Risk Factors
  • Sleep Wake Disorders / drug therapy*
  • Taiwan
  • Zolpidem

Substances

  • Hypnotics and Sedatives
  • Pyridines
  • Benzodiazepines
  • Zolpidem

Grants and funding

This work was supported by grant number Tri-Service-General-Hospital (TSGH)-C103-019. This work was also funded by Ministry of Science and Technology of Taiwan under the contract number MOST-103-2221-E-009-117- and MOST -103-2221-E-009-141-, and "Center for Bioinformatics Research of Aiming for the Top University Program" of the National Chiao Tung University and Ministry of Education, Taiwan, R.O.C. for the project 103W962. This work was also supported in part by the UST-UCSD International Center of Excellence in Advanced Bioengineering sponsored by the Taiwan Ministry of Science and Technology I-RiCE Program under Grant Number: MOST-103-2911-I-009-101-. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.