VITAL-Bone Health: rationale and design of two ancillary studies evaluating the effects of vitamin D and/or omega-3 fatty acid supplements on incident fractures and bone health outcomes in the VITamin D and OmegA-3 TriaL (VITAL).

Rationale: Although vitamin D is widely used to promote skeletal health, definitive data on benefits and risks of supplemental vitamin D alone on bone are lacking. Results from large, randomized controlled trials in the general population are sparse. Data on the effects of supplemental omega-3 fatty acids (FAs) on bone are also limited.

Design: The VITamin D and OmegA-3 TriaL (VITAL) is a double-blind, placebo-controlled trial assessing the role of vitamin D3 (2000 IU/d) and omega-3 FA (1g/d) supplements in reducing risks of cancer and cardiovascular disease among U.S. men aged ≥50 and women aged ≥55. To comprehensively test effects of supplemental vitamin D and/or omega-3 FAs on skeletal health, the VITAL: Effects on Fractures ancillary study is determining the effects of these supplements on incident fractures among 25,875 participants enrolled in the parent trial. Study investigators adjudicate fractures through a detailed review of medical records and radiological images (hip and femur). In a complementary ancillary, VITAL: Effects on Structure and Architecture is determining the effects of supplemental vitamin D and/or omega-3 FAs on bone with detailed phenotyping during in-person visits. Comprehensive assessments of bone density, turnover, structure/architecture, body composition, and physical performance are being performed at baseline and 2 years post-randomization.

Conclusion: Results from these studies will clarify the relationship between supplemental vitamin D and/or omega-3 FAs on bone health outcomes, and inform clinical care and public health guidelines on the use of supplemental vitamin D for the primary prevention of fractures in women and men.