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Original Investigation
April 28, 2003

Central Nervous System Active Medications and Risk for Fractures in Older Women

Author Affiliations

From the Department of Medicine and Center for Chronic Disease Outcomes Research, VA Medical Center (Dr Ensrud), and Division of Epidemiology, School of Public Health (Dr Ensrud and Ms Bowman), and College of Pharmacy (Dr Hanlon), University of Minnesota, Minneapolis; and Department of Epidemiology and Biostatistics, University of California, San Francisco (Ms Blackwell and Drs Bauer, Schwartz, Nevitt, and Whooley); Department of Medicine, University of California, Los Angeles (Dr Mangione); and Department of Medicine, VA Medical Center, San Francisco (Dr Whooley). No proprietary interest had a role in the collection, analysis, or interpretation of the data or in the decision to submit the paper for publication.

Arch Intern Med. 2003;163(8):949-957. doi:10.1001/archinte.163.8.949

Background  Use of central nervous system (CNS) active medications may increase the risk for fractures. Prior studies are limited by incomplete control of confounders.

Methods  To determine whether use of CNS active medications, including benzodiazepines, antidepressants, anticonvulsants, and narcotics, increases fracture risk in elderly, community-dwelling women, we examined use of these 4 categories of medications in a cohort of 8127 older women and followed the participants prospectively for incident nonspine fractures, including hip fractures. Current use of CNS active medications was assessed by interview with verification of use from containers between 1992 and 1994 and between 1995 and 1996. Use was coded as a time-dependent variable. Incident nonspine fractures occurring after the initial medication assessment until May 31, 1999, were confirmed by radiographic reports.

Results  During an average follow-up of 4.8 years, 1256 women (15%) experienced at least one nonspine fracture, including 288 (4%) with first hip fractures. Compared with nonusers, women taking narcotics (multivariate hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.06-1.83) and those taking antidepressants (multivariate HR, 1.25; 95% CI, 0.99-1.58) had increases in the risks for any nonspine fractures. Women taking tricyclic antidepressants and those using selective serotonin reuptake inhibitors (SSRIs) had similar fracture rates. There were no independent associations between benzodiazepine use or anticonvulsant use and risk for nonspine fracture. Women taking antidepressants compared with nonusers had a 1.7-fold increase in the risk for hip fracture (multivariate HR, 1.65; 95% CI, 1.05-2.57). We did not observe independent associations between use of any of the other 3 classes of CNS active medications and risk of hip fracture.

Conclusions  Community-dwelling older women taking narcotics have an increased risk for any nonspine fracture, and those taking antidepressants have a greater risk for nonspine fractures, including hip fracture. Rates of fracture were similar in women taking tricyclic antidepressants and those using SSRIs. Benzodiazepine use and anticonvulsant use were not independently associated with an increased risk of nonspine fractures, including hip fracture.