Osteoporotic fractures are major public health problems that have been associated with low vitamin D levels. Previous data strongly suggest that doses of vitamin D = 700 IU/day reduce fractures and possibly falls. Basic and small clinical trials suggest that omega-3 fatty acids may also have beneficial skeletal effects, but effects on fractures are not known. Large primary prevention trials with high daily doses of vitamin D and/or omega-3 fatty acids in general populations (i.e., unselected for disease risk) are lacking. We propose an ancillary study to the VITAL study, a large, randomized, double-blind, placebo-controlled trial of vitamin D (in the form of vitamin D3 [cholecalciferol]) and/or marine omega-3 fatty acid (eicosapentaenoic acid [EPA] + docosahexaenoic acid [DHA]) supplements, to advance knowledge and test the effects of vitamin D3 (2000 IU/d) and/or fish oil (EPA+DHA, 1g/d) for primary prevention of fractures, bone loss, falls, and frailty. Growing enthusiasm for supplemental vitamin D to support bone health, and use of fish oil, which may also have skeletal effects, underscores the urgent need for a timely initiation of this ancillary study in conjunction with the newly funded VITAL parent study (U01CA 138962). The proposed ancillary study will include 20,000 women and men (>age 65 and 60, respectively) from the 5-year, NIH-sponsored, parent VITAL trial and a sub-cohort from that trial of 700 participants from Clinical and Translational Science Centers (CTSCs) in Boston, Chicago, Houston, and San Francisco to critically test these hypotheses: Primary Aims: In the VITAL cohort, will vitamin D3 and/or EPA+DHA reduce incident a) total fractures and b) hip or non-vertebral fractures? Secondary Aims: In the CTSC sub-cohort, will vitamin D3 and/or EPA+DHA reduce bone loss of the spine, hip, and total body, as assessed by Dual X-ray Absorptiometry at baseline and year 2 and do effects vary with (a) baseline and follow up blood levels of these nutrients, (b) gender, (c) race/skin pigmentation, and (d) body mass index? Tertiary Aims: In the VITAL cohort, will Vitamin D3 and/or EPA+DHA supplementation a) reduce the risk of falls as assessed by annual questionnaires and b) reduce frailty as determined by the questionnaire- based frailty index? Baseline and follow-up blood collections will be matched for season by month to prevent seasonal bias for vitamin D levels. In order to complete pre-randomization measurements among participants in the CTSC sites, it is essential that this ancillary study be undertaken in parallel to the parent VITAL trial placebo "run-in" to get baseline and follow-up measurements, which is scheduled to begin in mid-2010. This time-sensitive ancillary study will rigorously test the role of these nutritional supplements in improving skeletal health and will provide positive or informative null results on the effects of vitamin D and omega-3 fatty acids on fractures, bone density, falls, and frailty. We expect that findings from this ancillary study will inform clinical practice on whether high daily dose vitamin D and/or fish oil reduces the burden of age-related increases in fractures, which would result in widespread public health benefits.

Public Health Relevance

Osteoporotic fractures and low vitamin D levels are major public health concerns. Several lines of evidence suggest that supplemental vitamin D may reduce the risk of fractures, bone loss, and falls, but the effects of high-dose vitamin D on these endpoints are lacking. We propose to conduct a time-sensitive, ancillary study to the large, randomized, controlled clinical trial - the VITamin D and OmegA-3 TriaL (VITAL) - to evaluate the role of high dose vitamin D and/or omega-3 fatty acids in the primary prevention of fractures, bone loss, falls, and also frailty;findings from this proposed ancillary study will advance science and inform clinical practice on the role(s) of vitamin D and/or omega-3 fatty acid supplements in bone health and fracture prevention.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR060574-03
Application #
8318916
Study Section
Special Emphasis Panel (ZAR1-CHW (M1))
Program Officer
Chen, Faye H
Project Start
2010-09-17
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
3
Fiscal Year
2012
Total Cost
$195,072
Indirect Cost
$41,472
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115