The effects of marine fatty acid omega-3 supplements on incident fractures and bone mineral density in generally healthy adults

Although preclinical studies suggest that omega-3 fatty acids may benefit skeletal health, there are few randomized controlled trials investigating effects of supplemental omega-3 on bone outcomes. This VITamin D and OmegA-3 TriaL (VITAL) ancillary study investigated effects of marine omega-3 (1 g/d; EPA + DHA in a 1.2:1 ratio) vs. placebo supplements on fracture risk and bone density/structure. VITAL is a 2x2 factorial randomized placebo-controlled trial that studied effects of supplemental marine omega-3 fatty acids and/or vitamin D3 vs. placebo on cancer and cardiovascular events. The intervention took place from November 2011 through December 2017; median follow-up was 5.3 yr. The study included 25 871 U.S. men (aged ≥50) and women (aged ≥55) without baseline cancer or cardiovascular disease, not selected for low bone density or fracture history. Primary outcomes were adjudicated incident total, nonvertebral, and hip fractures in the overall cohort. In a subcohort of 771 individuals, we measured 2-yr changes in areal bone mineral density (aBMD) by dual X-ray absorptiometry, and volumetric bone mineral density (vBMD), cortical thickness, and bone strength indices at the radius and tibia by peripheral quantitative computed tomography. Supplemental omega-3 vs. placebo had no effect on total (HR, 1.02; 95% CI, 0.92-1.13; p = .73), nonvertebral (HR, 1.01; 95% CI, 0.91-1.12; p = .80), or hip fractures (HR, 0.89; 95% CI, 0.61-1.30; p = .55). In the subcohort, omega-3 supplementation resulted in a small increase in whole body aBMD (+0.03% vs. -0.41%, p = .006) and no effect on aBMD at the spine or hip, or vBMD or bone strength indices at the radius or tibia. No serious adverse effects were observed. Supplementation with marine omega-3 fatty acids did not reduce incident fracture risk. It led to a small increase in whole body aBMD but had no other effects on BMD or bone strength measures compared to placebo in generally healthy midlife and older adults.