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1 Center for Chronic Disease Outcomes Research, Veterans Affairs Medical Center, Minneapolis, Minnesota.
2 Department of Medicine and Division of Epidemiology and Community Health, University of Minnesota, Minneapolis.
3 Department of Epidemiology and Biostatistics, University of California, San Francisco.
4 Research Institute, California Pacific Medical Center, San Francisco.
5 Department of Epidemiology, University of Pittsburgh, Pennsylvania.
Departments of 6 Epidemiology and 7 Medicine, University of Maryland, Baltimore.
8 University Outpatient Clinic and Institute of Social and Preventive Medicine, Department of Community Medicine and Public Health, University of Lausanne, Switzerland.
Address correspondence to Kristine E. Ensrud, MD, MPH, One Veterans Drive, Minneapolis, MN 55417. E-mail: ensru001{at}umn.edu
Background. A standard phenotype of frailty was associated with an increased risk of adverse outcomes including mortality in a recent study of older adults. However, the predictive validity of this phenotype for fracture outcomes and across risk subgroups is uncertain.
Methods. To determine whether a standard frailty phenotype was independently associated with risk of adverse health outcomes in older women and to evaluate the consistency of associations across risk subgroups defined by age and body mass index (BMI), we ascertained frailty status in a cohort of 6724 women 
69 years and followed them prospectively for incident falls, fractures, and mortality. Frailty was defined by the presence of three or more of the following criteria: unintentional weight loss, weakness, self-reported poor energy, slow walking speed, and low physical activity. Incident recurrent falls were defined as at least two falls during the subsequent year. Incident fractures (confirmed with x-ray reports), including hip fractures, and deaths were ascertained during an average of 9 years of follow-up.
Results. After controlling for multiple confounders such as age, health status, medical conditions, functional status, depressive symptoms, cognitive function, and bone mineral density, frail women were subsequently at increased risk of recurrent falls (multivariate odds ratio = 1.38, 95% confidence interval [CI], 1.02–1.88), hip fracture (multivariate hazards ratio [MHR] = 1.40, 95% CI, 1.03–1.90), any nonspine fracture (MHR = 1.25, 95% CI, 1.05–1.49), and death (MHR = 1.82, 95% CI, 1.56–2.13). The associations between frailty and these outcomes persisted among women 80 years. In addition, associations between frailty and an increased risk of falls, fracture, and mortality were consistently observed across categories of BMI, including BMI 30 kg/m2.
Conclusion. Frailty is an independent predictor of adverse health outcomes in older women, including very elderly women and older obese women.
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