Effects of anticholinergic and sedative medication use on fractures: A self-controlled design study

J Am Geriatr Soc. 2021 Nov;69(11):3212-3224. doi: 10.1111/jgs.17377. Epub 2021 Jul 22.

Abstract

Background/objectives: Unintentional falls are a leading cause of injury for older adults, and evidence is needed to understand modifiable risk factors. We evaluated 1-year fall-related fracture risk and whether dispensing of medications with anticholinergic/sedating properties is temporally associated with an increased odds of these fractures.

Design: A retrospective cohort study with nested self-controlled analyses conducted between January 1, 2014, and December 31, 2016.

Setting: Twenty percent nationwide, random sample of US Medicare beneficiaries.

Participants: New users of medications with anticholinergic/sedating properties who were 66+ years old and had Medicare Parts A, B, and D coverage but no claims for medications with anticholinergic/sedating properties in the year before initiation were eligible.

Measurements: We followed new users of medications with anticholinergic/sedating properties until first non-vertebral, fall-related fracture (primary outcome), Medicare disenrollment, death, or end of study data. We estimated the 1-year risk with corresponding 95% confidence intervals (CIs) of first fracture after new use. We applied the self-controlled case-crossover and case-time-control designs to estimate odds ratios (ORs) and 95% CIs by comparing anticholinergic and/or sedating medication exposure (any vs. none) during a 14-day hazard period preceding the fracture to exposure to these medications during an earlier 14-day control period.

Results: A total of 1,097,989 Medicare beneficiaries initiated medications with anticholinergic/sedating properties in the study period. The 1-year cumulative incidence of fall-related fracture, accounting for death as a competing risk, was 5.0% (95% CI: 5.0%-5.0%). Using the case-crossover design (n = 41,889), the adjusted OR for the association between anticholinergic/sedating medications and fractures was 1.03 (95% CI: 0.99, 1.08). Accounting for the noted temporal trend using the case-time-control design (n = 209,395), the adjusted OR was 1.60 (95% CI: 1.52, 1.69).

Conclusion: Use of anticholinergic/sedating medication was temporally associated with an increased odds of fall-related fractures. Patients and their healthcare providers should consider pharmacologic and non-pharmacologic treatments for the target condition that are safer.

Keywords: aging; bone fracture; cholinergic antagonists; hypnotics and sedatives; inappropriate prescribing.

Publication types

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

MeSH terms

  • Accidental Falls / statistics & numerical data*
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Cholinergic Antagonists / adverse effects*
  • Female
  • Fractures, Bone / epidemiology*
  • Humans
  • Hypnotics and Sedatives / adverse effects*
  • Incidence
  • Male
  • Medicare / statistics & numerical data
  • Retrospective Studies
  • Risk Factors
  • United States / epidemiology

Substances

  • Cholinergic Antagonists
  • Hypnotics and Sedatives