A Scoping Review to Assess Risk of Fracture Associated with Anxiolytic Medications

Abstract

Introduction. Recent research has focused on evaluating the impact of pharmalogical sources on fracture risk. The purpose of this study was to review the literature on anxiolytic medications that may be associated with an increased risk of fracture.

Methods. A search was conducted in MEDLINE and Embase databases to identify primary clinical studies of patients who sustained a fracture while prescribed anxiolytic medications and were published prior to July 2021. Anxiolytics defined by ATC Class N05B, beta blockers, and zolpidem were included. The search terms consisted of variations of the following: (“Psychotropic Drugs” or MeSH terms) AND (“Fracture” or MeSH terms). 

Results. Of 3,213 studies, 13 (0.4%) met inclusion criteria and were evaluated. Fractures associated with benzodiazepine were reported in 12 of 13 studies; the highest risk occurred in patients aged 60 years and older, RR=2.29, 95% CI (1.48-4.40). The ATC Class N05B showed an increased fracture risk for those < 55 years of age that differed by sex: for men RR=5.42, 95% CI(4.86-6.05) and for women it was RR=3.33, 95% CI (3.03-3.66). Zolpidem also showed an increase fracture risk, RR=2.29, 95% CI(1.48-3.56), but only during the first 4 weeks of treatment. A relative risk of 0.77, 95% CI(.72-.83) was observed for beta blockers.

Conclusions.  Fractures are a mainstay of traumatic injuries and are accompanied by economical, physiological, and psychological hardship. Fortunately, with proper assessment and prophylactic measures, fracture risk can be reduced dramatically. Anxiolytic medications have been described widely to increase fracture risk, such as benzodiazepines  in 60+ year old patients, and ATC Class N05B Anxiolytics increased fracture risk of RR=5.42, 95% CI (4.86-6.05) in 55+ year old men and  in 55+ year old women. Yet, some studies showed that at low doses, nitrazepam lowered fracture risk. Other anxiolytic medications, such as zolpidem and beta blockers, also showed a decrease in fracture risk; however, only one study has been published on each of these medications. Ultimately, this scoping review helped to illuminate the inconsistency of anxiolytic fracture risk assessment while simultaneously illustrating the necessary steps to guide future research.