Muscle weakness and bone fragility likely are responsible for the age-related increase in falls and fractures in elderly persons. Even slightly decreased vitamin D levels may have a negative effect on bone metabolism and muscle strength. Elderly persons have reduced exposure to sunlight and dietary vitamin D intake, and even persons with normal serum vitamin D levels (more than 12 mcg per L [30.3 nmol per L]) may have 1,25-dihydroxyvitamin D3 deficiency because of a variety of metabolic factors. Previous studies have shown the value of vitamin D supplementation in institutionalized or osteopenic elderly women. Dukas and colleagues performed a community-based, randomized, double-blind, placebo-controlled trial to investigate whether supplementation with alfacalcidol, a prodrug of calcitriol, reduces falls in community-dwelling elderly men and women.
A total of 191 women and 187 men were included in the intention-to-treat analysis, with 192 participants randomized to alfa-calcidol and 186 to placebo. The number of fallers rather than the number of falls was compared as a primary outcome, although results for number of falls also were presented. Muscle strength, balance, blood pressure, and bone quality were measured as secondary outcomes. Participants kept a diary of falls and were told to inform the study center of their falls within 48 hours. A detailed medical history that included comorbidities and dietary calcium intake was obtained from all participants. Blood samples were drawn at each visit. 1,25-dihydroxyvitamin D3 and intact parathormone (iPTH) serum concentrations were measured at baseline and at weeks 12 and 24.
Groups were similar at baseline. Of the 378 participants, 321 completed the study (158 women [82.7 percent] and 163 men [87.2 percent]). In the multivariate-adjusted logistic regression analysis, treatment with alfacalcidol over 36 weeks was associated with fewer fallers than placebo, but the difference was not significant. In subgroup analysis, however, calcium intake affected the alfacalcidol group. Participants who consumed more than 512 mg of calcium daily and took alfacalcidol had significantly fewer falls than control patients with the same calcium intake (odds ratio, 0.45). The impact was the same in both men and women.
Levels of iPTH decreased significantly in all alfacalcidol-treated patients, regardless of calcium intake. Alfacalcidol treatment also was associated significantly with increased serum calcium levels compared with placebo.
Supplementation with alfacalcidol for 36 weeks reduces the number of fallers and falls in an elderly community-based population when the minimum daily calcium intake is 512 mg or more. It also increases serum calcium levels and decreases parathyroid hormone secretion. The study suggests that there is a synergistic effect of calcitriol and calcium, which is likely to mediate the effect of vitamin D on muscle. Findings from other studies suggest that iPTH is an independent risk factor for decreased muscle strength and falls, but this study indicates that a benefit from decreased iPTH requires a specified minimal calcium intake.