Endocrinol Metab.  2025 Feb;40(1):73-81. 10.3803/EnM.2024.2100.

Elevated Circulating Sclerostin Levels in Frail Older Adults: Implications beyond Bone Health

• Baek JY
• Ahn SH
• Jang IY
• Jung HW
• Ji E
• Park SJ
• Jo Y
• Lee E
• Ryu D
• Hong S
• Kim BJ

• KMID: 2565255
• DOI: http://doi.org/10.3803/EnM.2024.2100

Abstract

Background
Sclerostin, initially recognized for its pivotal role in bone metabolism, has gained attention for its multifaceted impact on overall human health. However, its influence on frailty—a condition that best reflects biological age—has not been thoroughly investigated.
Methods
We collected blood samples from 244 older adults who underwent comprehensive geriatric assessments. Sclerostin levels were quantified using an enzyme-linked immunosorbent assay. Frailty was assessed using two validated approaches: the phenotypic model by Fried and the deficit accumulation frailty index (FI) by Rockwood.
Results
After controlling for sex, age, and body mass index, we found that serum sclerostin levels were significantly elevated in frail individuals compared to their robust counterparts (P<0.001). There was a positive correlation between serum sclerostin concentrations and the FI (P<0.001). Each standard deviation increase in serum sclerostin was associated with an odds ratio of 1.87 for frailty (P=0.003). Moreover, participants in the highest quartile of sclerostin levels had a significantly higher FI and a 9.91-fold increased odds of frailty compared to those in the lowest quartile (P=0.003 and P=0.039, respectively).
Conclusion
These findings, which for the first time explore the association between circulating sclerostin levels and frailty, have significant clinical implications, positioning sclerostin as one of potential blood-based biomarkers for frailty that captures the comprehensive physical, mental, and social aspects of the elderly, extending beyond its traditional role in bone metabolism.

Keyword

Sclerostin; Frailty; Aging; Biomarkers

Figure

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  Fig. 1. Differences in serum sclerostin levels according to phenotypic frailty status (A) before and (B) after adjusting for sex, age, and body mass index (BMI). The estimated means with 95% confidence intervals were generated and compared using an analysis of covariance. Post hoc analysis was performed with Bonferroni correction. Delta (Δ) indicates a change in the value of a variable between groups. Phenotypic frailty is defined based on Fried’s criteria.

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  Fig. 2. Differences in the frailty index according to serum sclerostin quartiles (A) before and (B) after adjusting for sex, age, and body mass index (BMI). The estimated means with 95% confidence intervals were generated and compared using an analysis of covariance. Post hoc analysis was performed using Tukey’s method. Serum sclerostin quartiles: Q1=13.6 to 29.4 pmol/L; Q2=29.5 to 37.9 pmol/L; Q3=38.0 to 49.8 pmol/L; Q4=49.9 to 138.8 pmol/L. The frailty index is calculated based on Rockwood’s proposal. aStatistically significant difference from the lowest quartile (Q1).

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  Fig. 3. Odds ratios (ORs) for phenotypic frailty according to serum sclerostin quartiles (A) before and (B) after adjusting for sex, age, and body mass index (BMI). P values were analyzed by logistic regression analysis before and after adjusting for sex, age, and BMI. Phenotypic frailty is defined based on Fried’s criteria. CI, confidence interval. aStatistically significant difference from the lowest quartile (Q1).

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