Anxiolytics, sedatives, antidepressants, neuroleptics and the risk of fracture

Osteoporos Int. 2006;17(6):807-16. doi: 10.1007/s00198-005-0065-y. Epub 2006 Mar 7.

Abstract

Introduction: Our objective was to study the association between fracture risk and the use of anxiolytics and sedatives (benzodiazepines, etc.), neuroleptics and antidepressants.

Subjects and methods: This was a case control study. All cases consisted of subjects who had sustained a fracture during the year 2000 (n=124,655). For each case, three controls (n=373,962) matched for age and gender were randomly drawn from the background population. Exposure was defined as the use of neuroleptics, antidepressants and anxiolytics/sedatives, psychiatric disease (manic depressive states, schizophrenia, other psychoses), and other confounders. The effect of dose was examined as a defined daily dose per day (DDD/day). The values referred to are confounder-adjusted.

Results: For anxiolytics and sedatives, there was a small increase in overall fracture risk (OR: around 1.1) even with limited doses (<0.1 DDD/day). No dose-response relationship was observed for anxiolytics and sedatives. For neuroleptics, a limited increase in overall fracture risk was observed (OR: around 1.2 from <0.05 DDD/day with no dose-response relationship). For antidepressants, a dose-response relationship was observed for fracture risk (OR: increasing from 1.15, 95% CI: 1.11-1.19 at <0.15 DDD/day to 1.40, 95% CI: 1.35-1.46 for >or=0.75 DDD/day). The risk of fracture was higher with selective serotonin re-uptake inhibitors than with tricyclic antidepressants.

Conclusions: Small increases in fracture risk were seen with the use of anxiolytics and sedatives and neuroleptics without a dose-response relationship. The increase may be linked to an increased risk of falls. For antidepressants, a dose-response relationship was found, with a higher fracture risk for selective serotonin re-uptake inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Anxiety Agents / adverse effects*
  • Antidepressive Agents / adverse effects*
  • Antipsychotic Agents / adverse effects*
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Denmark / epidemiology
  • Dose-Response Relationship, Drug
  • Female
  • Fractures, Bone / chemically induced*
  • Fractures, Bone / epidemiology
  • Hospital Records
  • Humans
  • Hypnotics and Sedatives / adverse effects*
  • Infant
  • Male
  • Middle Aged
  • Odds Ratio
  • Risk Factors

Substances

  • Anti-Anxiety Agents
  • Antidepressive Agents
  • Antipsychotic Agents
  • Hypnotics and Sedatives