Effect of vitamin D3, omega-3 fatty acids, and exercise on serum sclerostin levels and bone turnover markers

J Clin Endocrinol Metab. 2024 Dec 9:dgae859. doi: 10.1210/clinem/dgae859. Online ahead of print.

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/d vitamin D3, 1g/d omega-3s, and a simple home-based strength exercise program (SHEP), alone or in combination, on serum sclerostin and bone turnover marker levels.

Design, setting and participants: Sclerostin, procollagen type 1 N propeptide (P1NP) and C-terminal telopeptide (β-CTx) levels were pre-defined secondary outcomes of DO-HEALTH, a double blind, randomized controlled trial in healthy physically active older adults in five European countries.

Outcome measures: Changes in yearly serum sclerostin, P1NP and β-CTx levels over 3 years, adjusted for age, sex, prior falls, study site, baseline BMI, and baseline level of the respective outcome.

Results: 1,848 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=0.002]. Omega-3s plus 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]. For P1NP and β-CTx there were no significant effects for any of the individual treatments and treatment combinations.

Conclusions: 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.