Effect of Annual Intramuscular Vitamin D on Fracture Risk in Elderly Men and Women--a Population-based, Randomized, Double-blind, Placebo-controlled Trial

Objectives: Low trauma fractures in older people incur enormous physical, social and economic costs. Previous research indicates that an annual intramuscular injection of vitamin D may reduce fracture rates in this group. This strategy requires validation in a population setting.

Methods: Randomized, double-blind, placebo-controlled trial of 300,000 IU intramuscular (i.m.) vitamin D2 (ergocalciferol) injection or matching placebo every autumn over 3 years. 9440 people (4354 men and 5086 women) aged 75 yrs and over were recruited from general practice registers in Wessex, England. Primary outcome measure was all non-vertebral fracture. Secondary outcomes were hip and wrist fractures, and all falls.

Results: 585 subjects had incident non-spine fractures (hip 110, wrist 116, ankle 37). Hazard ratios (HRs) for fracture in the vitamin D group were: 1.09 [95% confidence interval (CI) 0.93-1.28, P = 0.29] for any first fracture, 1.49 (95% CI 1.02-2.18, P = 0.04) for hip and 1.22 (95% CI 0.85-1.76, P = 0.28) for wrist. There was no effect on falls: HR 0.98 (0.93-1.04). No protective effect was observed in any subgroup when the cohort was stratified by sex, age, previous fracture or mobility.

Conclusions: An annual i.m. injection of 300,000 IU vitamin D2 is not effective in preventing non-vertebral fractures among elderly men and women resident in the general population.