Anticholinergic Medication Use and Risk of Fracture in Elderly Adults with Depression

Limited research exists regarding the effect of anticholinergics on falls and fractures in elderly nursing home residents in the United States. This study examined the risk of fractures associated with anticholinergic medication use in elderly nursing home residents with depression. A nested case-control design involving a cohort of elderly adults with depression from the 2007 to 2010 Minimum Data Set (MDS)-linked Medicare data was used to evaluate the risk of fractures. The study sample included Medicare beneficiaries aged 65 and older diagnosed with depression having at least one nursing home stay during 2007 to 2010 and no history of falls or fractures in 2007 (base period). Cases were individuals with incident fractures after the baseline period. For each case, four age- and sex-matched controls were selected using incidence density sampling. Anticholinergic exposure was defined using the Anticholinergic Drug Scale (ADS). Prescription of Level 2 or 3 anticholinergic medications within 30 days before the event date was the primary exposure. The primary outcome was an inpatient or outpatient claim for a fracture between January 1, 2008, and December 31, 2010. A conditional logistic regression model stratified on matched case-control sets was used to evaluate association between anticholinergic use and fractures, controlling for other risk factors of the outcome. The study sample consisted of 40,452 individuals with fractures and 161,808 matched controls. After adjusting for other risk factors, high-level anticholinergic use was associated with 14% greater fracture risk than nonuse (odds ratio (OR) = 1.14, 95% confidence interval (CI) = 1.11-1.17). The high risk of fractures remained consistent across levels of anticholinergic potency (Level 2, OR = 1.15, 95% CI = 1.11-1.19; Level 3, OR = 1.10, 95% CI = 1.07-1.15). The study findings remained consistent in multiple sensitivity analyses. Overall, use of high-level anticholinergic medications was associated with greater risk of fracture than no use in elderly adults with depression. Given safety concerns, there is a need to optimize anticholinergic use in elderly adults.