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Objectives Evidence suggests vitamin D deficiency is associated with developing frailty. However, cardiometabolic factors are related to both conditions and may confound and/or mediate the vitamin D–frailty association. We aimed to determine the association of vitamin D concentration with incidence of frailty, and the role of cardiometabolic diseases (cardiovascular disease, diabetes, hyperlipidemia, hypertension) in this relationship. Design Prospective longitudinal cohort study (7 visits from 1994–2008). Setting Baltimore, Maryland. Participants Three hundred sixty-nine women from the Women's Health and Aging Study II aged 70–79 years, free of frailty at baseline. Measurements Serum circulating 25-hydroxyvitamin D (25[OH]D) concentration was assessed at baseline and categorized as

mately three-times greater risk of incident frailty and three to five times greater risk of lower extremity mobility limitations (all P < .05). In fully adjusted models, HbA1c of 8.0% or greater (vs < 5.5%) was associated with incident frailty (hazard ratio (HR) = 3.33, 95% confidence interval (CI) = 1.24–8.93), walking difficulty (HR = 3.47, 95% CI = 1.26–9.55), low walking speed (HR = 2.82, 95% CI = 1.19–6.71), and low physical performance (HR = 3.60, 95% CI = 1.52–8.53). CONCLUSION: Hyperglycemia is associated with the development of frailty and lower extremity mobility limitations in older women. Future studies should identify mediators of these relationships. J Am Geriatr Soc 60:1701– 1707, 2012.

To systematically review and quantitatively synthesize the effect of vitamin D therapy on fall prevention in older adults.Systematic review and meta-analysis.MEDLINE, CINAHL, Web of Science, EMBASE, Cochrane Library, LILACS, bibliographies of selected articles, and previous systematic reviews through February 2009 were searched for eligible studies.Older adults (agedor = 60) who participated in randomized controlled trials that both investigated the effectiveness of vitamin D therapy in the prevention of falls and used an explicit fall definition.Two authors independently extracted data, including study characteristics, quality assessment, and outcomes. The I(2) statistic was used to assess heterogeneity in a random-effects model.Of 1,679 potentially relevant articles, 10 met inclusion criteria. In pooled analysis, vitamin D therapy (200-1,000 IU) resulted in 14% (relative risk (RR)=0.86, 95% confidence interval (CI)=0.79-0.93; I(2)=7%) fewer falls than calcium or placebo (number needed to treat =15). The following subgroups had significantly fewer falls: community-dwelling (aged80), adjunctive calcium supplementation, no history of fractures or falls, duration longer than 6 months, cholecalciferol, and dose of 800 IU or greater. Meta-regression demonstrated no linear association between vitamin D dose or duration and treatment effect. Post hoc analysis including seven additional studies (17 total) without explicit fall definitions yielded smaller benefit (RR=0.92, 95% CI=0.87-0.98) and more heterogeneity (I(2)=36%) but found significant intergroup differences favoring adjunctive calcium over none (P=.001).Vitamin D treatment effectively reduces the risk of falls in older adults. Future studies should investigate whether particular populations or treatment regimens may have greater benefit.