BACKGROUND: Although both vitamin D (25-hydroxyvitamin D [25(OH)D]) insufficiency and the frailty syndrome are more prevalent in women than men, sex-specific associations have not been explored. We estimated sex-specific associations of low 25(OH)D with frailty. Vitamin D insufficiency can result in hyperparathyroidism, and thus, parathyroid hormone (PTH) was explored as a potential mediator in the relationship between 25(OH)D levels and frailty.

METHODS: The sample included 444 male and 561 female participants aged 65 years and older from the InCHIANTI study for whom 25(OH)D levels and frailty information were available. Frailty was defined as the presence of at least three of the five following criteria: slowness, weakness, low energy expenditure, exhaustion, and weight loss. Logistic regression models estimated the association between serum levels of 25(OH)D and PTH with frailty, controlling for potential confounders.

RESULTS: Independent of covariates, men with 25(OH)D <50 nmol/L had greater odds of frailty than those with 25(OH)D > or =50 nmol/L (odds ratio [OR] = 4.94, 95% confidence interval [CI] = 1.80-13.61). In women, the adjusted OR for frailty (95% CI) was 1.43 (0.58-3.56). The 25(OH)D ORs differed between men and women (p = .041). ORs changed little after controlling for PTH. However, when low energy expenditure was excluded from the frailty definition, adjusted OR for frailty in men (95% CI) was 2.18 (0.59-8.04); controlling for PTH attenuated this OR by 32%. In women, the OR (95% CI) for frailty (low energy expenditure excluded) was 1.54 (0.31-7.58) and was attenuated by 6% after controlling for PTH.

CONCLUSIONS: Vitamin D insufficiency was associated with frailty in men, but not in women. Results suggest that PTH mediates the relationship between 25(OH)D and nonenergy expenditure aspects of frailty.