Validation of a novel, rapid, high precision sclerostin assay not confounded by sclerostin fragments

Matthew M Drake, Jennifer S. Fenske, Frank A. Blocki, Claudia Zierold, Natasha Appelman-Dijkstra, Socrates Papapoulos, Sundeep Khosla

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Sclerostin is a 190 amino acid protein secreted primarily by osteocytes. It was initially identified due to mutations in the SOST gene associated with high bone mass phenotypes. Much recent work has sought to determine the importance of sclerostin across an array of conditions which affect the human skeleton. However, accurate measurement of sclerostin from serum and plasma sources remains a significant impediment, with currently available commercial assays showing marked differences in measured sclerostin values. Accordingly, sclerostin assay standardization remains an important but unmet need before sclerostin measurements can be used for the clinical management of bone disease. Here we characterize a novel automated chemiluminescent sclerostin assay (LIAISON® DiaSorin) which overcomes many of these limitations. Important assay characteristics include: a wide dynamic range (50–6500 pg/mL); high intra- (<2.5%) and inter- (<5%) assay precision; matched serum and plasma equivalence (<10% difference); specificity for the intact sclerostin molecule; and rapid assay results. Serum sclerostin levels measured with the LIAISON® assay in a population-based sample of adult men (n = 278) and women (n = 348) demonstrated that sclerostin levels were significantly higher in men as compared to women and were positively associated with age in both sexes, consistent with previously published work. In postmenopausal women, serum sclerostin levels measured with the LIAISON® assay were reduced in response to treatment with either estrogen or teriparatide, again consistent with previous findings. Collectively, the above data demonstrate that the LIAISON® sclerostin assay provides a reliable tool for more confident assessment of emergent mechanisms wherein sclerostin may impact a number of bone related pathologies.

Original languageEnglish (US)
Pages (from-to)36-43
Number of pages8
JournalBone
Volume111
DOIs
StatePublished - Jun 1 2018

Fingerprint

Serum
Teriparatide
Luminescent Measurements
Bone and Bones
Osteocytes
Bone Diseases
Skeleton
Estrogens
Pathology
Amino Acids
Mutation
Population
Genes
Proteins
Therapeutics
MASS syndrome

Keywords

  • Bone
  • Estrogen
  • Intact
  • Parathyroid hormone
  • Sclerostin
  • SOST
  • Standardization

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

Cite this

Validation of a novel, rapid, high precision sclerostin assay not confounded by sclerostin fragments. / Drake, Matthew M; Fenske, Jennifer S.; Blocki, Frank A.; Zierold, Claudia; Appelman-Dijkstra, Natasha; Papapoulos, Socrates; Khosla, Sundeep.

In: Bone, Vol. 111, 01.06.2018, p. 36-43.

Research output: Contribution to journalArticle

Drake, Matthew M ; Fenske, Jennifer S. ; Blocki, Frank A. ; Zierold, Claudia ; Appelman-Dijkstra, Natasha ; Papapoulos, Socrates ; Khosla, Sundeep. / Validation of a novel, rapid, high precision sclerostin assay not confounded by sclerostin fragments. In: Bone. 2018 ; Vol. 111. pp. 36-43.
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abstract = "Sclerostin is a 190 amino acid protein secreted primarily by osteocytes. It was initially identified due to mutations in the SOST gene associated with high bone mass phenotypes. Much recent work has sought to determine the importance of sclerostin across an array of conditions which affect the human skeleton. However, accurate measurement of sclerostin from serum and plasma sources remains a significant impediment, with currently available commercial assays showing marked differences in measured sclerostin values. Accordingly, sclerostin assay standardization remains an important but unmet need before sclerostin measurements can be used for the clinical management of bone disease. Here we characterize a novel automated chemiluminescent sclerostin assay (LIAISON{\circledR} DiaSorin) which overcomes many of these limitations. Important assay characteristics include: a wide dynamic range (50–6500 pg/mL); high intra- (<2.5{\%}) and inter- (<5{\%}) assay precision; matched serum and plasma equivalence (<10{\%} difference); specificity for the intact sclerostin molecule; and rapid assay results. Serum sclerostin levels measured with the LIAISON{\circledR} assay in a population-based sample of adult men (n = 278) and women (n = 348) demonstrated that sclerostin levels were significantly higher in men as compared to women and were positively associated with age in both sexes, consistent with previously published work. In postmenopausal women, serum sclerostin levels measured with the LIAISON{\circledR} assay were reduced in response to treatment with either estrogen or teriparatide, again consistent with previous findings. Collectively, the above data demonstrate that the LIAISON{\circledR} sclerostin assay provides a reliable tool for more confident assessment of emergent mechanisms wherein sclerostin may impact a number of bone related pathologies.",
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AU - Appelman-Dijkstra, Natasha

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AB - Sclerostin is a 190 amino acid protein secreted primarily by osteocytes. It was initially identified due to mutations in the SOST gene associated with high bone mass phenotypes. Much recent work has sought to determine the importance of sclerostin across an array of conditions which affect the human skeleton. However, accurate measurement of sclerostin from serum and plasma sources remains a significant impediment, with currently available commercial assays showing marked differences in measured sclerostin values. Accordingly, sclerostin assay standardization remains an important but unmet need before sclerostin measurements can be used for the clinical management of bone disease. Here we characterize a novel automated chemiluminescent sclerostin assay (LIAISON® DiaSorin) which overcomes many of these limitations. Important assay characteristics include: a wide dynamic range (50–6500 pg/mL); high intra- (<2.5%) and inter- (<5%) assay precision; matched serum and plasma equivalence (<10% difference); specificity for the intact sclerostin molecule; and rapid assay results. Serum sclerostin levels measured with the LIAISON® assay in a population-based sample of adult men (n = 278) and women (n = 348) demonstrated that sclerostin levels were significantly higher in men as compared to women and were positively associated with age in both sexes, consistent with previously published work. In postmenopausal women, serum sclerostin levels measured with the LIAISON® assay were reduced in response to treatment with either estrogen or teriparatide, again consistent with previous findings. Collectively, the above data demonstrate that the LIAISON® sclerostin assay provides a reliable tool for more confident assessment of emergent mechanisms wherein sclerostin may impact a number of bone related pathologies.

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