Reduced Serum Sclerostin Linked to Higher Arterial Stiffness Risk in JPOS Women
Overview
In a longitudinal study of 556 Japanese community-dwelling women aged ≥50 years, lower baseline serum sclerostin levels were significantly associated with increased risk of arterial stiffness over 4 years. Women in the lowest sclerostin tertile had a 2.5-fold higher adjusted odds of developing increased arterial stiffness compared to those in the highest tertile.
Background
Sclerostin, an inhibitor of the Wnt/β-catenin pathway, regulates bone formation and is secreted by osteocytes. This pathway also influences vascular endothelium and arterial stiffness development. While anti-sclerostin antibodies like romosozumab are used to treat osteoporosis, concerns exist regarding their cardiovascular safety. Prior studies on serum sclerostin and atherosclerosis have been mostly cross-sectional and inconsistent, with limited data from general populations.
Data Highlights
Sclerostin Tertile
Increased Arterial Stiffness Rate (%)
Adjusted OR (Age, Baseline baPWV)
Adjusted OR (Multivariate)
High (Reference)
12.4
1.00
1.00
Medium
16.1
1.58 (P=0.205)
1.65 (P=0.181)
Low
22.2
2.16 (P=0.027)
2.50 (P=0.014)
Key Findings
Lower serum sclerostin levels at baseline were associated with higher incidence of increased arterial stiffness over 4 years.
Women in the lowest sclerostin tertile had a 2.5-fold increased odds of arterial stiffness after adjusting for multiple confounders.
The trend of increasing arterial stiffness risk with decreasing sclerostin levels was statistically significant (P=0.013).
Adjustments included age, baseline baPWV, BMI, hypertension, hyperlipidemia, diabetes, renal function, and bone mineral content.
The study used brachial-ankle pulse wave velocity (baPWV) with a cutoff of 1800 cm/s to define increased arterial stiffness.
Clinical Implications
Serum sclerostin may serve as a biomarker for predicting arterial stiffness risk in postmenopausal women. Monitoring sclerostin levels could help identify individuals at higher cardiovascular risk. Caution is warranted when using anti-sclerostin therapies, considering potential vascular effects.
Conclusion
This longitudinal analysis demonstrates that reduced serum sclerostin concentrations are independently associated with increased arterial stiffness risk in Japanese community-dwelling women, highlighting a potential link between bone metabolism regulators and vascular health.
References
JPOS Cohort Study (2024) -- Link Between Reduced Serum Sclerostin Concentrations and Higher Arterial Stiffness Risk
