VITamin D and OmegA-3 TriaL: Effects on Bone Structure and Architecture
Phase: NA
Conditions: Bone Density, Body Composition, Bone Health
Sponsor: Brigham and Women's Hospital

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
VITamin D and OmegA-3 TriaL: Effects on Bone Structure and Architecture (VITAL) 
NCT01747447 
December 28th, 2020 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Study Protocol 
 
VITamin D and OmegA-3 TriaL (VITAL) is a randomized, placebo-controlled study 
examining whether vitamin D3 (cholecalciferol) and omega-3 fatty acids prevent cancer and 
cardiovascular disease. VITAL participants (n = 25,871) were randomized to receive either both 
200 IU/day vitamin D3 and 1 g/day omega-3 fatty acids, vitamin D3 and placebo, omega-3 fatty 
acids and placebo, or both placebo pills. Males ≥ 50 years of age and females ≥ 55 years of age 
were included if they had no history of cardiovascular disease or cancer, other than 
nonmelanoma skin cancer, at the time of enrollment. Participants with serious medical conditions 
such as renal failure or cirrhosis, were excluded. Throughout the duration of the trial, individuals 
could not exceed more than 800 IU/d of vitamin D, which is the US Recommended Dietary 
Allowance for older adults [1, 2].  
From the VITAL Cohort, 1,054 participants were enrolled in the Harvard Clinical and 
Translational Science Center (CTSC) sub-cohort. These individuals lived within driving distance 
of the CTSC. Participants in the bone density sub-cohort were recruited from the CTSC sub-
cohort and had not been on bisphosphonates in the past two years. Additionally, these 
participants were not taking denosumab, calcitonin, tamoxifen, raloxifene, or other bone active 
medications. These participants had bone density and body composition measurements, as well 
as physical performance tests at baseline (n = 771) and 2-year follow-up (n = 687) [3, 4]. 
Participants underwent Dual-energy X-ray absorptiometry (DXA; Discovery W, APEX 
Software Version 4.2, Hologic, Bedford, MA, USA) to measure areal bone mineral density at the 
lumbar spine, total hip, femoral neck, and whole body as well as adipose tissue measurements 
and lean tissue measurements [3]. In addition, participants received peripheral quantitative 
computed tomography (pQCT; XCT 3000; Stratec Medizintechnik GmbH, Birkenfeld, 

Germany) scans at baseline (n  = 677) and 2-year follow-up (n = 600) to measure changes in 
volumetric bone mineral density (vBMD), cortical thickness, and measures of bone strength at 
both the radius and tibia [4]. At two-year follow-up, a subset of participants had high-resolution 
peripheral quantitative computed tomography (HR-pQCT) scans [3].  
 
Statistical Analysis Plan 
 
 
This study utilized the intention-to-treat principle. In its design, the study had power to 
detect differences in aBMD of 1.03% at the spine, 1.22% at the femoral neck, and 0.42% in the 
whole body. These differences were based on a projected sample size of 600 and 10% loss to 
follow-up. The actual differences came to 0.91% at the spine, 1.08% at the femoral neck, and 
0.37% in the whole body with 771 participants enrolled [4].  
To compare continuous variables across the different subgroups, we used t tests and 
analysis of variance (Wilcoxon rank sum and Kruskal-Wallis tests). To compare proportions, we 
used chi-square tests. Analyses were conducted using SAS (SAS Institute, Cary, NC, USA). A p 
value greater than 0.5 was considered significant in the analyses. Results were reported as mean 
(standard deviation) or median (25th, 75th percentiles). The primary analysis looked at the effects 
of vitamin D versus placebo on measures of bone health [4].  
 
 
 
 
 
 
 
 
 
 
 

 
 
References 
 
1   Manson JE, Cook NR, Lee IM, et al. Vitamin D supplements and prevention of cancer and 
cardiovascular disease. N Engl J Med. 2019; 380(1): 33– 44. 
 
2   Institute of Medicine Committee to Review Dietary Reference Intakes for Vitamin D, 
Calcium. The National Academies Collection: Reports funded by National Institutes of Health. 
In AC Ross, CL Taylor, AL Yaktine, HB Valle, eds. Dietary reference intakes for calcium and 
vitamin D. Washington, DC: National Academies Press (US) National Academy of Sciences; 
2011. 
 
3   Donlon CM, LeBoff MS, Chou SH, et al. Baseline characteristics of participants in the 
VITamin D and OmegA‐3 TriaL (VITAL): effects on bone structure and architecture. Contemp 
Clin Trials. 2018; 67: 56– 67. 
 
4    LeBoff MS, Chou SH, Murata EM, Donlon CM, Cook NR, Mora S,  Lee IM, Kotler G, 
Bubes V, Buring JE, Manson JE. Effects of Supplemental Vitamin D on Bone Health Outcomes 
in Women and Men in the VITamin D and OmegA-3 TriaL (VITAL). J Bone Miner Res. 2020; 
35(5): 883-893.