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 - University Of Zurich; ARMBRECHT, GABRIELE - Humboldt University; GANGLER, STEPHANIE - University Of Zurich; THEILER, ROBERT - University Of Zurich; RIZZOLI, RENE - Geneva University Hospital; DAWSON-HUGHES, BESS - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; KANIS, JOHN - University Of Sheffield Medical School; HOFBAUER, LORENZ - Technical University Dresden; SCHIMMER, RALPH - University Of Zurich; VELLAS, BRUNO - University Of Toulouse; DA SILVA, JOSE - University Of Coimbra; ORAV, JOHN - Harvard University; KRESSIG, R - University Hospital For Geriatric Medicine And Rehabilitation Felix Platter; EGLI, ANDREAS - University Of Zurich; LANG, WEI - University Of Zurich; WANNER, GUIDO - Privatklinik Bethanien; BISCHOFF-FERRARI, HEIKE - University Of Zurich

Submitted to: Journal of Bone and Mineral Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/23/2024
Publication Date: 4/13/2024
Citation: Kistler-Fischbacher, M., Armbrecht, G., Gangler, S., Theiler, R., Rizzoli, R., Dawson-Hughes, B., Kanis, J.A., Hofbauer, L.C., Schimmer, R.C., Vellas, B., Da Silva, J.A., Orav, J.E., Kressig, R.W., Egli, A., Lang, W., Wanner, G.A., Bischoff-Ferrari, H. 2024. Effects of vitamin D3, omega-3s and a simple strength training exercise program on bone health: the Do-Health randomized controlled trial. Journal of Bone and Mineral Research. https://doi.org/10.1093/jbmr/zjae054.
DOI: https://doi.org/10.1093/jbmr/zjae054

Interpretive Summary: Evidence that vitamin D, omega-3 fatty acids, and exercise affect bone density in healthy older adults is limited. We examined whether treatment with vitamin D, omega-3 fatty acids, or a simple home-based exercise program for 3 years, alone or in combination, improved lumbar spine or hip bone density in 1,493 generally healthy adults age 70 years and older. The study interventions were vitamin D3 (2000 IU per day), omega-3 fatty acids (1g/d), and simple exercises (30 minutes 3 times per week), alone or in combination. We found that omega-3 fatty acids and the simple home-based exercise program had no benefit to bone density in these generally healthy and active older adults. In contrast, supplementation with vitamin D modestly increased bone density of the total hip overall and of the lumbar spine among the men. We conclude that vitamin D supplementation provides some benefit to bone mineral density in healthy older adults.

Technical Abstract: Introduction: Evidence on the effects of Vitamin D, omega-3s and exercise on 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 three years, improve lumbar spine (LS), femoral neck (FN) or total hip (TH) aBMD assessed by DXA. Methods: aBMD was a secondary outcome in DO-HEALTH, a 3-year, multicenter, double-blind, randomized 2x2x2 factorial design trial in generally healthy older adults age =70 years. The study interventions were vitamin D3 (2000 IU/d), omega-3s (1g/d), and SHEP (3x30 min/wk), applied alone or in combination in 8 treatment arms. Mixed effect 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 sex, physical activity level, dietary calcium intake, serum 25(OH)D levels, and fracture history were conducted. Results: DXA scans were available for 1493 participants (mean age 75 years; 80.4% were physically active, 44% had 25(OH)D levels <20 ng/ml). At the LS and FN sites, none of the treatments showed a benefit. At the TH, vitamin D vs. 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/cm2). Furthermore, there was a benefit for vitamin D vs. no vitamin D treatment on LS aBMD in the subgroup of men (interaction P = 0.003; change in AM: 0.0070 [95% CI 0.0007, 0.0132] g/cm2). Conclusions: Omega-3 and SHEP had no benefit on aBMD in generally healthy, active and largely vitamin D replete adults age 70 and older. However, our study supports a small benefit of 2000 IU vitamin D daily on total hip aBMD overall and on lumbar spine aBMD among men