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United States Department of Agriculture

Agricultural Research Service

Research Project: MUSCULOSKELETAL HEALTH IN THE ELDERLY

Location: Jean Mayer Human Nutrition Research Center On Aging

Title: A pooled analysis to define vitamin D dose requirements for fracture prevention in seniors)

Author
item Bischoff-ferrari, Heike
item Willett, Walter
item Orav, E
item Lips, Paul
item Lyons, Ronan
item Flicker, Leon
item Wark, John
item Jackson, Rebecca
item Cauley, Jane
item Meyer, Haakon
item Pfeifer, Michael
item Sanders, Kerrie
item Staehelin, Hannes
item Theiler, Robert
item Meunier, Pierre
item Dawson-hughes, Bess

Submitted to: New England Journal of Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/29/2011
Publication Date: 7/5/2012
Citation: Bischoff-Ferrari, H., Willett, W., Orav, E.J., Lips, P., Lyons, R., Flicker, L., Wark, J., Jackson, R., Cauley, J., Meyer, H., Pfeifer, M., Sanders, K., Staehelin, H., Theiler, R., Meunier, P., Dawson-Hughes, B. 2012. A pooled analysis to define vitamin D dose requirements for fracture prevention in seniors. New England Journal of Medicine. 367(1):40-49.

Interpretive Summary: One strategy to prevent fractures in the elderly may be broad vitamin D supplementation. However, data from several study-level meta-analyses are conflicting. The discordant findings may in part be explained by different inclusion criteria of trials or different adjustments made for adherence. We have conducted an individual-patient-level meta-analysis of 11 available double-blind vitamin D intervention trials, taking into account the impact of vitamin D dose, use of additional vitamin D supplements, and adherence. The objective was to assess the effect of vitamin D on fracture risk. The analysis included data in 31,022 participants of whom 91% were women and mean age was 76 years. There were 1,111 incident hip and 3,770 non-vertebral fractures. Comparing all participants randomized to vitamin D versus control, there was a 10% non-significant reduction of hip (HR = 0.90; 95% CI: 0.80-1.01) and a 7% reduction of non-vertebral fractures (HR = 0.93; 0.87-0.99). When considering actual dose of vitamin D taken, fracture reduction was demonstrated only at the highest quartile (range 792-2000 IU; median 800 IU/day) compared to control, with a 30% reduction at the hip and a 14% reduction at any non-vertebral site. We conclude that vitamin D lowered fracture risk at the hip and any non-vertebral site; however, this was significant only at the highest actual dose level (median 800 IU /day).

Technical Abstract: Meta-analyses reached conflicting results regarding vitamin D and fracture reduction. We pooled individual participant-level data from 11 double-blind RCTs of oral vitamin D supplementation (daily, weekly, 4-monthly) with or without calcium compared with placebo or calcium in seniors age 65 and older. Primary endpoints were incidence of hip and any non-vertebral fractures using Cox regression analyses; adjusting for age, gender, type of dwelling, and study. Beyond the intent-to-treat analyses, our primary aim was to refine this comparison by including quartiles of actual dose of vitamin D by incorporating adherence and supplement use outside the study protocol at the participant level. 31,022 seniors (mean age 76 years, 91% women) with 1111 incident hip and 3770 nonvertebral fractures. Comparing participants randomized to vitamin D versus control, there was a 10% non-significant reduction of hip (HR = 0.90; 95% CI: 0.80-1.01) and a 7% reduction of non-vertebral fractures (HR = 0.93; 0.87-0.99). By quartiles of actual dose, fracture reduction was demonstrated only at the highest actual intake level (median 800 IU; range 792-2000 IU/day) compared to control, with a 30% reduction at the hip (HR=0.70; 0.58-0.86) and a 14% reduction at any non-vertebral site (HR = 0.86; 0.76-0.96). The highest actual dose reduced hip fractures in community-dwelling (HR = 0.68; 0.48-0.96) and institutionalized (HR = 0.70; 0.55-0.89) seniors. Vitamin D lowered fracture risk at the hip and any non-vertebral site; however, this was only at the highest actual dose level (median 800 IU; range 792-2000 IU/day).

Last Modified: 8/24/2016
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