Effect of vitamin D3, omega-3 fatty acids and exercise on serum sclerostin: A 3-year report of the DO-HEALTH trial

Authors: TSOURDI, ELENA - Technical University Dresden; GANGLER, STEPHANIE - University Of Zurich; RAUNER, MARTINA - Technical University Dresden; DAWSON-HUGHES, BESS - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; ORAV, E - Harvard School Of Public Health; TSAI, MICHAEL - University Of Minnesota; LANG, WEI - University Of Zurich; KANIS, JOHN - University Of Sheffield Medical School; THEILER, ROBERT - University Of Zurich; EGLI, ANDREAS - University Of Zurich; BISCHOFF-FERRARI, HEIKE - University Of Zurich; HOFBAUER, LORENZ - Technical University Dresden

Submitted to: Journal of Clinical Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/6/2024
Publication Date: 12/30/2024
Citation: Tsourdi, E., Gangler, S., Rauner, M., Dawson-Hughes, B., Orav, E.J., Tsai, M., Lang, W., Kanis, J.A., Theiler, R., Egli, A., Bischoff-Ferrari, H.A., Hofbauer, L.C. 2024. Effect of vitamin D3, omega-3 fatty acids and exercise on serum sclerostin: A 3-year report of the DO-HEALTH trial . Journal of Clinical Endocrinology and Metabolism. 110(9). https://doi.org/10.1210/clinem/dgae859.
DOI: https://doi.org/10.1210/clinem/dgae859

Interpretive Summary: Sclerostin is a natural inhibitor of bone formation. This analysis was done to determine the effects of 2000 IU/d vitamin D3, 1g/d omega-3 fatty acids, and a simple home-based strength exercise program on serum sclerostin levels. This study was done in the 3-year randomized, placebo-controlled DO-HEALTH trial in 1,963 healthy adults aged 70 years and older. The exercise intervention significantly lowered the serum sclerostin concentration, whereas vitamin D and omega-3 fatty acids had no significant effect. Decreasing natural sclerostin levels in the blood may be one means by which exercise is favorable to bone health.

Technical Abstract: Context: Sclerostin inhibits canonical Wnt signalling, a pathway promoting bone formation. The effects of vitamin D3, omega-3 fatty acids (omega-3s), and exercise on sclerostin serum levels are unclear. Objective: To investigate the effects of 2000 IU/d vitamin D3, 1g/d omega-3s, and a simple home-based strength exercise program (SHEP), alone or in combination, on serum levels of sclerostin. Design, setting and participants: Sclerostin levels were a pre-defined secondary outcome of DO-HEALTH, a double blind, randomized controlled trial in generally healthy and physically active older adults in five European countries. Outcome Measures: Changes in yearly serum sclerostin levels over 3 years, adjusted for age, sex, prior falls, study site, baseline BMI, and baseline sclerostin level. Results: 1,963 of 2,157 participants were included (mean age 74.9 +/- 4.5 years, 61.5 % women, 40.4 % 25(OH)D < 20 ng/mL, 83.1 % at least moderately physically active at baseline). Regarding individual treatments, vitamin D3 (p= 0.056) and omega-3s supplementation (p=0.462) did not change sclerostin levels significantly, while SHEP compared with control exercise (joint mobility) led to greater decrease in sclerostin levels [-1.56 pmol/L (-2.54, -0.58), p=0.002]. For the combination of treatments, only omega-3s and SHEP led to a greater decrease in sclerostin levels compared to no omega-3s/ control exercise [-1.93pmol/L (-3.31, -0.54), p=0.007]. Conclusions: In this 3-year prevention trial among generally healthy, active and largely vitamin D replete adults age 70 and older, vitamin D3 and omega-3s alone did not influence sclerostin concentrations, while a simple home-based strength training alone or in combination with omega-3s lowered sclerostin serum levels.