Central nervous system-active medications and risk for falls in older women

University of California, San Francisco, San Francisco, California, United States
Archives of Internal Medicine (Impact Factor: 17.33). 05/2003; 163(8):949-57. DOI: 10.1001/archinte.163.8.949
Source: PubMed


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 tri-cyclic 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.

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    • "Opioids cause increased somnolence, agitation, constipation, dizziness and cognitive impairment which can reduce mobility. Community-dwelling older women taking opioids have an increased risk for any nonspine fracture including hip fracture,23 the ability to participate in physical rehabilitation is decreased, resulting in loss of bone and/or muscle mass, which further results in delayed bone healing.23 King, et al.24 reported the inhibitory effect of opioids for bone union in an animal cancer model; morphine did not alter tumor growth or tumor burden but accelerated sarcoma-induced bone destruction and doubled the incidence of spontaneous fractures in a dose-dependent manner. Furthermore, morphine increased osteoclast activity, suggesting enhancement of sarcoma-induced osteolysis.24 "
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    ABSTRACT: Purpose Pain from vertebral or femoral neck fractures is a particularly important problem in clinical orthopaedics. Transient receptor potential vanilloid 1 (TRPV1) is a ligand-gated nonselective cation channel, and there are recent reports on an association between bone pain and TRPV1. However, an increase in TRPV1 activity has not been reported following femoral fracture. Materials and Methods We applied a neurotracer [Fluoro-gold (FG)] onto femur to detect dorsal root ganglia (DRGs) innervating the cortex of the femur in 30 Sprague Dawley rats. Seven days after application, a closed mid-diaphyseal fracture of the femur was performed. FG labeled TRPV1-immunoreactive (ir) DRGs innervating the femur were examined in nonfractured controls, and 3 days, 1 week, 2 weeks, and 4 weeks after fracture. We evaluated bone healing of the femur and compared the ratio of TRPV1-ir DRG neurons innervating the femur at the time points. Results Four weeks after fracture, complete bone union was observed. There was no significant difference in the ratio of FG labeled DRG neurons to total DRG neurons at each time point. The percentages of TRPV1-ir neurons in DRGs innervating the femur at 3 days and 1 week after fracture were significantly higher than those in control, 2 weeks, and 4 weeks after fracture (p<0.05). Conclusion Fracture induced an increase of TRPV1-ir neurons in DRGs innervating the fractured femur within 3 days, and decreased during bone healing over 4 weeks. These findings show that TRPV1 may play a role in sensory sensation of bone fracture pain.
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    • "There is also evidence for antidepressants increasing hippocampal neurogenesis with similar potential benefits (Malberg, 2004). Conversely, antipsychotic medication use has been associated with increased mortality (Schneider et al., 2005; Wang et al., 2005; Simoni- Wastila et al., 2009) and poorer cognition (CATIE-AD paper), antidepressant use with increased risk of hip fracture (Ensrud et al., 2003), and use of all major classes of psychotropic medications with increased risk of falls (Woolcott et al., 2009). Given this mixture of possible beneficial and harmful effects of psychotropic medication use in AD, and in the absence of long-term randomized controlled trials for efficacy and safety, it is important to examine whether use of these medications is associated with differential outcomes in population studies. "
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    • "Use of antidepressants, antipsychotics, and anxiolytics was indicated if the participant reported using one or more medication in these drug classes at least once during the baseline year. We chose to examine psychotropic medications over other classes of medications because they are among the strongest predictors of new onset functional impairment identified in the research literature and yet little is known about their association with recovery from incident functional limitations since (Berry & Miller, 2008; Ensrud et al., 2003; Lawlor, Patel, & Ebrahim, 2003). These were handled as three individual dichotomous variables. "
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