Effect of Vitamin D3, Omega-3 Fatty Acids, and Exercise on Serum Sclerostin Levels and Bone Turnover Markers

Abstract

Context Sclerostin inhibits canonical Wnt signaling, a pathway promoting bone formation. The effects of vitamin D3, omega-3 fatty acids (omega-3s), and exercise on serum sclerostin levels and bone metabolism are unclear. Objective To investigate the effects of 2000 IU/day vitamin D3, 1 g/day omega-3s, and a simple home-based strength exercise program (SHEP), alone or in combination, on serum sclerostin and bone turnover marker levels. Methods Sclerostin, procollagen type 1 N propeptide (P1NP) and C-terminal telopeptide (β-CTx) levels were predefined secondary outcomes of DO-HEALTH, a double blind, randomized controlled trial in healthy physically active older adults in 5 European countries. Outcome measures were changes in yearly serum sclerostin, P1NP, and β-CTx levels over 3 years, adjusted for age, sex, prior falls, study site, baseline body mass index, and baseline level of the respective outcome. Results A total of 1848 participants were included (mean age 74.8 ± 4.4 years, 58.9% women, 41.4% 25(OH)D < 20 ng/mL, 83.9% at least moderately physically active at baseline). Vitamin D3 and omega-3s supplementation alone 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 =. 002). Omega-3s plus SHEP led to a greater decrease in sclerostin levels than no omega-3s/control exercise (-1.93 pmol/L [-3.31, -0.54], P =. 007). For P1NP and β-CTx there were no significant effects for any of the individual treatments and treatment combinations. Conclusion In this 3-year prevention trial among largely vitamin D replete adults age 70 and older, SHEP alone or in combination with omega-3s reduced serum sclerostin levels, while vitamin D3 and omega-3s alone did not affect serum sclerostin levels.