Effects of vitamin D3, omega-3s, and a simple strength training exercise program on bone health: the DO-HEALTH randomized controlled trial
Authors: Kistler-Fischbacher Melanie , Armbrecht Gabriele , Gängler Stephanie , Theiler Robert , Rizzoli René , Dawson-Hughes Bess , Kanis John A , Hofbauer Lorenz C , Schimmer Ralph C , Vellas Bruno , Da Silva José A P , John Orav E , Kressig Reto W , Andreas Egli , Lang Wei , Wanner Guido A , Bischoff-Ferrari Heike A ,   DO-HEALTH Research Group, Bischoff-Ferrari Heike A , Egli Andreas , Rival Sandrine , Wanner Guido A , Vellas Bruno , Guyonnet Sophie , Rizzoli René , Biver Emmanuel , Merminod Fanny , Kressig Reto W , Bridenbaugh Stephanie , Suhm Norbert , Da Silva José A P , Duarte Cátia C M , Pinto Filipa Ana , Felsenberg Dieter , Börst Hendrikje , G A  , Blauth Michael , Spicher Anna , Felson David T , Eugene V Mccloskey , Johansson Elena , Watzl Bernhard , Gomez Rodriguez Manuel , Hofbauer Lorenz , Tsourdi Elena , Rauner Martina , Siebert Uwe , Kanis John A , Halbout Philippe , M Ferrari Stephen , Gut Benno , Ba Marième , Wittwer Schegg Jonas , Etheve Stéphane , Eggersdorfer Manfred , Delannoy Carla Sofa , Reuschling Monika , Orav Endel J , Willett Walter C , JoAnn E Manson , Dawson-Hughes Bess , Staehelin Hannes B , Walter Paul W , Dick Walter , Fried Michael , lvon Eckardstein Arnold , Theiler Robert , Simmen Hans-Peter , Langhans Wolfgang , Zinkernagel Annelies , Mueller Nicolas , Distler Oliver , Graetz Klaus , Nitschke Ina , Dietrich Thomas , Baer Walter , Landau Klara , Ruschitzka Frank , Manz Markus , Burckhardt Peter 
Published: April 2024

Abstract
Evidence on the effects of Vitamin D, omega-3s, and exercise on areal bone mineral density (aBMD) in healthy older adults is limited. We examined whether vitamin D3, omega-3s, or a simple home-based exercise program (SHEP), alone or in combination, over 3 years, improve lumbar spine (LS), femoral neck (FN), or total hip (TH) aBMD assessed by DXA. Areal BMD was a secondary outcome in DO-HEALTH, a 3-year, multicenter, double-blind, randomized 2 × 2 × 2 factorial design trial in generally healthy older adults age ≥ 70 years. The study interventions were vitamin D3 (2000IU/d), omega-3s (1 g/d), and SHEP (3 × 30 min/wk), applied alone or in combination in eight treatment arms. Mixed effects models were used, adjusting for age, sex, BMI, prior fall, study site, and baseline level of the outcome. Main effects were assessed in the absence of an interaction between the interventions. Subgroup analyses by age, sex, physical activity level, dietary calcium intake, serum 25(OH)D levels, and fracture history were conducted. DXA scans were available for 1493 participants (mean age 75 years; 80.4% were physically active, 44% had 25(OH)D levels &lt;20 ng/mL). At the LS and FN sites, none of the treatments showed a benefit. At the TH, vitamin D versus no vitamin D treatment showed a significant benefit across 3 years (difference in adjusted means [AM]: 0.0035 [95% CI, 0.0011, 0.0059] g/cm). Furthermore, there was a benefit for vitamin D versus no vitamin D treatment on LS aBMD in the male subgroup (interaction P = .003; ∆AM: 0.0070 [95% CI, 0.0007, 0.0132] g/cm). Omega-3s and SHEP had no benefit on aBMD in healthy, active, and largely vitamin D replete older adults. Our study suggests a small benefit of 2000 IU vitamin D daily on TH aBMD overall and LS aBMD among men; however, effect sizes were very modest and the clinical impact of these findings is unclear.