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
- Affiliations
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- 1Division of Geriatrics, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
- 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Inha University Hospital, Inha University College of Medicine, Incheon, Korea
- 3Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
- 4Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, Korea
- 5Division of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
- 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.
