La eficacia de altas dosis de vitamina D3 administrada por vía oral una vez al año: Un ensayo aleatorizado, doble ciego, controlado con placebo (estudio fundamental D) de caídas y fracturas en mujeres mayores

OBJECTIVE: To determine whether a single annual dose of 500,000IU cholecalciferol administered orally to older women in fall or winter would reduce the risk of falls and fracture. METHODS: This single centre double-blind, placebo-controlled trial randomly assigned 2,256 community-dwelling women (median age 76 years, IQR 73, 80.0 years) to receive a single oral dose of cholecalciferol 500,000IU or placebo each autumn/winter for 3 to 5 years. Falls and fractures were ascertained for 4 to 6 years using monthly calendars and details confirmed by telephone interview. Fractures were radiologically confirmed. Biochemistry was done on a sub-study of 137 randomly-selected participants at baseline as well as 12-months post-dose (coinciding with immediate pre-dose for the current year). In 2006 and 2007 blood sampling was also done at oneand three-month post-dose. Serum 25-hydroxyvitamin D (25D) levels were measured in batches using DiaSorin immunoassay. RESULTS: The vitamin D group had more falls and fractures than the placebo group. The fall rate was 83.4 vs 72.7 per 100 person-years, vitamin D vs placebo groups, respectively and an Incidence Rate Ratio (IRR): 1.15; 95%CI 1.02, 1.30; p=0.025. The rate of fracture was 4.9 vs 3.9 per 100 p-y and the IRR: 1.26; 1.00, 1.59; p=0.047. The increased rate of falling in the vitamin D group was higher in the first three months following dosing (p=0.017). This temporal pattern was also apparent in fracture rates although not significance (interaction p=0.36). The cumulative incidence of first fall and first fracture were both increased in the vitamin D group (hazard ratios; 95% CI: Falls 1.16; 1.05, 1.28 p=0.003; Fractures 1.26; 0.99, 1.59 p=0.057). In the sub-study, the median baseline serum 25D was 49nmol/L. Less than 3% of the sub-study participants had baseline levels ,25nmol/L. In the vitamin D group, one-, three- and 12-month median post dose levels were approximately 120nmol/L, 90 nmol/L and 70nmol/L, respectively. CONCLUSIONS: The results indicate that high-dose vitamin D administered orally once yearly to older community-dwelling women increased the risk of falls and fractures.