Abstract
Sclerostin, bone formation antagonist is in the spotlight as a potential biomarker for diseases presenting with associated bone disorders such as chronic kidney disease (CDK-MBD). Accurate measurement of sclerostin is therefore important. Several immunoassays are available to measure sclerostin in serum and plasma. We compared the performance of three commercial ELISA kits. We measured sclerostin concentrations in serum and EDTA plasma obtained from healthy young (18–26 years) human subjects using kits from Biomedica, TECOmedical and from R&D Systems. The circulating sclerostin concentrations were systematically higher when measured with the Biomedica assay (serum: 35.5 ± 1.1 pmol/L; EDTA: 39.4 ± 2.0 pmol/L; mean ± SD) as compared with TECOmedical (serum: 21.8 ± 0.7 pmol/L; EDTA: 27.2 ± 1.3 pmol/L) and R&D Systems (serum: 7.6 ± 0.3 pmol/L; EDTA: 30.9 ± 1.5 pmol/L). We found a good correlation between the assay for EDTA plasma (r > 0.6; p < 0.001) while in serum, only measurements obtained using TECOmedical and R&D Systems assays correlated significantly (r = 0.78; p < 0.001). There was no correlation between matrices results when using the Biomedica kit (r = 0.20). The variability in values generated from Biomedica, R&D Systems and TECOmedical assays raises questions regarding the accuracy and specificity of the assays. Direct comparison of studies using different kits is not possible and great care should be given to measurement of sclerostin, with traceability of reagents. Standardization with appropriate material is required before different sclerostin assays can be introduced in clinical practice.
Highlights
Sclerostin is a 190-residue secreted protein member of the DAN/Cerberus protein family
Sclerostin, bone formation antagonist is in the spotlight as a potential biomarker for diseases presenting with associated bone disorders such as chronic kidney disease (CDK-MBD)
Sclerostin concentrations are increased in disorders such as hypoparathyroidism [13], type II diabetes [14, 15] cancer induced bone disease [16] and Paget’s disease [17] and decreased in primary hyperparathyroidism [18,19,20] and ankylosing spondylitis [21], recently increased disease activity in ankylosing spondylitis has been associated with higher sclerostin concentrations [22]
Summary
Sclerostin is a 190-residue secreted protein member of the DAN/Cerberus protein family. Sclerostin is secreted by osteocytes [7] and articular chondrocytes [8] and its absence favours bone formation by lack of inhibition of the canonical Wnt/bcatenin signalling [9,10,11], leading to osteoblast differentiation, proliferation and activity [5, 12]. Circulating sclerostin concentrations are altered in metabolic bone diseases. Sclerostin may play a role of importance in patients with chronic kidney disease associated with mineral and bone disorder (for review see [23]). High concentrations of circulating sclerostin are suggested to be associated with arterial stiffness, cardiovascular calcification and inflammation, leading to higher morbidity and mortality. Measurement of circulating sclerostin may be helpful in the diagnosis of bone remodelling disorders and assessment of therapeutic effectiveness but concordant results between various assays are necessary for clinical trial comparison. We tested and compared three platebased enzyme-linked immunosorbent assays (ELISA) in serum and ethylene diamine tetra acetic acid (EDTA) plasma samples from healthy young individuals
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