Oxidative and nonoxidative benzodiazepines and the risk of femur fracture

Benzodiazepine use is a well-identified risk factor for falls and the resul ting femur fractures in elderly adults. Benzodiazepines not requiring hepat ic biotransformation may be safer than agents undergoing oxidation because oxidative activity has been shown to decline with age. The association betw een the use of either oxidative or nonoxidative benzodiazepines and the ris k of femur fracture among elderly adults Living in nursing homes was studie d. A nested case-control study was conducted using the Systematic Assessmen t of Geriatric drug use via Epidemiology (SAGE) database; the records of 9, 752 patients hospitalized for incident femur fracture during the period 199 2 to 1996 mere extracted, matching by age, gender, state, and index date to the records of 38,564 control patients. Conditional logistic regression mo dels were conducted to estimate the odds ratios (ORs) for femur fracture wi th adjustment for potential confounders. The adjusted OR for the overall us e of benzodiazepines mas 1.10 (95% confidence interval [CI], 0.98-1.20); th e risk seemed of only slightly greater magnitude for exposure to nonoxidati ve agents (1.18; 95% CI, 1.03-1.36) than to oxidative benzodiazepines (1.08 ; 95%, CI, 0.95-1.23). Among the latter, the effect nas mainly accounted fo r by the use of agents with a long elimination half-life. A dose relationsh ip was observed exclusively among users of long half-life oxidative benzodi azepines. The risk associated with the use of nonoxidative benzodiazepines showed no relationship to the age of the patients. In contrast, patients ag ed 85 years or older receiving oxidative benzodiazepines at high dosages or as needed had a two- to three-fold increased risk of femur fracture than d id patients in the younger age group, Among older individuals, the use of b enzodiazepines slightly increased the risk of femur fracture, mainly irresp ective of the metabolic fate of the drug. Our results suggest that the use of nonoxidative benzodiazepines does not carry a lower risk for femur fract ure than does the use of oxidative benzodiazepines. However, the latter age nts may be associated with a somewhat higher risk of side effects among the oldest old, especially at higher dosages.