Increased Sclerostin Serum Levels Associated with Bone Formation and Resorption Markers in Patients with Immobilization-Induced Bone Loss
Abstract
Context: Sclerostin, a Wnt signaling antagonist on the osteoblasts produced by osteocytes, is regulated by mechanical strain and is implicated in the pathogenesis of disuse bone loss. There are no data on sclerostin in humans. Objective: The aim of the study was to evaluate sclerostin in patients immobilized after stroke, compared with control subjects, and to analyze its relationship with markers of bone formation and resorption. Design: This was a cross-sectional study. Setting and patients: We studied 40 postmenopausal women immobilized after a single episode of stroke 6 months or longer after onset, and 40 postmenopausal women from the general community. Bone status was assessed by quantitative ultrasound measurements at the calcaneus. Bone alkaline phosphatase (b-AP), carboxy-terminal telopeptide of type I collagen (CrossLaps), and sclerostin were evaluated by ELISA. We also used ELISA to measure serum levels of Dickkopf-1, another soluble inhibitor of Wnt/β-catenin signaling, highly expressed by osteocytes. Results: Immobilized patients had higher sclerostin serum levels (median 0.975 ng/ml; 25th to 75th percentiles 0.662–1.490) than controls (median 0.300 ng/ml; 25th to 75th percentiles 0.165–0.400: P < 0.0001) and an increased bone turnover with a more significant rise in bone resorption (CrossLaps) than formation (b-AP) markers. Sclerostin correlated negatively with b-AP (r = −0.911; P < 0.0001) and positively with CrossLaps (r = 0.391; P = 0.012). Dickkopf-1 did not significantly differ between the groups. Patients also had quantitative ultrasound measurements index lower than controls (P < 0.001). Conclusions: This study shows for the first time that long-term immobilized patients present hypersclerostinemia associated with reduced bone formation, and suggests that sclerostin could be a link between mechanical unloading and disuse osteoporosis in humans.
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Mechanical unloading downregulates anabolic factors and stimulates osteocytes to produce sclerostin and DKK-1 (inhibitors of osteoblast activity) and factors that stimulate local osteoclastogenesis.
“On the other hand, mechanical unloading downregulates anabolic factors and stimulates osteocytes to produce sclerostin and DKK-1, which are inhibitors of osteoblast activity [185–188], as well as specific factors that stimulate local osteoclastogenesis [189].”
From Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells (2015) · cites this paper as [187]
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- Authors
- Gaudio, A., Pennisi, P., Bratengeier, C., Torrisi, V., Lindner, B., Mangiafico, R. A., Pulvirenti, I., Hawa, G., Tringali, G., & Fiore, C. E.
- Affiliations
- University of Catania (IT)
- Biomarker Design Forschungs GmbH (C.B., B.L., G.H.), A-1210 Wien, Austria
- Istituto Ricerca Medica Ambientale (V.T., G.T.), 95024 Acireale, Italy
- Corresponding author
- Fiore, Carmelo E.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2010-05-01
- Volume
- 95
- Issue
- 5
- Pages
- 2248-2253
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2080784991
- Cited by
- 315
- References
- 38
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 6 · 2023: 15 · 2022: 22 · 2021: 19 · 2020: 18 · 2019: 15 · 2018: 10 · 2017: 16 · 2016: 12 · 2015: 23 · 2014: 29 · 2013: 39 · 2012: 31
- FWCI
- 36.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Physiology › Spaceflight effects on biology
- Keywords
- sclerostin, disuse osteoporosis, stroke, bone formation markers, bone resorption markers, DKK1, Wnt/β-catenin signaling, osteocytes, mechanical unloading, postmenopausal women, quantitative ultrasound, bone turnover
- MeSH terms
- Aged, Aged, 80 and over, Bone Development, Bone Resorption, Coronary Disease, Cross-Sectional Studies, Depression, Diabetes Mellitus, Female, Genetic Markers, Humans, Immobilization, Osteoblasts, Osteocytes, Paresis, Reference Values, Body Mass Index, Postmenopause, Bone Morphogenetic Proteins, Stroke, Adaptor Proteins, Signal Transducing
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