Randomized controlled trial of vitamin D supplementation in older people to optimize bone health

Randomized controlled, single-center trial in community-dwelling adults aged 70 years and older from northeast England. A total of 379 participants were randomized in a 1:1:1 allocation to the three vitamin D3 dose groups, and 343 completed 12 months.

Oral vitamin D3 once monthly for 12 months at one of three doses: 12,000 IU/mo, 24,000 IU/mo, or 48,000 IU/mo. The doses corresponded approximately to 400 IU/d, 20 μg/d, and 40 μg/d, respectively, and were compared as a dose-ranging regimen.

Vitamin D3 supplementation increased circulating 25(OH)D and lowered parathyroid hormone, but it did not improve hip bone mineral density over 12 months and there was no clear dose-related skeletal benefit. Hip BMD change did not differ between 24,000 IU and 12,000 IU (P = 0.39) or 48,000 IU and 12,000 IU (P = 0.08), and femoral neck BMD also showed no significant between-dose differences (P = 0.43 and P = 0.62). Twelve-month 25(OH)D concentrations were 55.9, 64.6, and 79.0 nmol/L in the 12,000, 24,000, and 48,000 IU groups, respectively, with P < 0.01 for the lower dose versus the two higher doses. There were no dose-related differences in adverse events or falls; 3 cases of hypercalcemia occurred and no nephrolithiasis was reported.

The trial was relatively short for a bone-health outcome and was conducted in a single regional sample of older adults, limiting generalizability. Although 379 were randomized, only 343 completed 12 months, and the available data do not address longer-term fracture outcomes. Participants were allowed limited background calcium or vitamin D supplementation, which may reduce isolation of the intervention effect.