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European Biological Variation Study (EuBIVAS): within and between-subject biological variation estimates of β-isomerized C-terminal telopeptide of type I collagen (β-CTX), N-terminal propeptide of type I collagen (PINP), osteocalcin, intact fibroblast growth factor 23 and uncarboxylated-unphosphorylated matrix-Gla protein—a cooperation between the EFLM Working Group on Biological Variation and the International Osteoporosis Foundation-International Federation of Clinical Chemistry Committee on Bone Metabolism

European Biological Variation Study (EuBIVAS): within and between-subject biological variation estimates of β-isomerized C-terminal telopeptide of type I collagen (β-CTX), N-terminal propeptide of type I collagen (PINP), osteocalcin, intact fibroblast growth factor 23 and uncarboxylated-unphosphorylated matrix-Gla protein—a cooperation between the EFLM Working Group on Biological Variation and the International Osteoporosis Foundation-International Federation of Clinical Chemistry Committee on Bone Metabolism
European Biological Variation Study (EuBIVAS): within and between-subject biological variation estimates of β-isomerized C-terminal telopeptide of type I collagen (β-CTX), N-terminal propeptide of type I collagen (PINP), osteocalcin, intact fibroblast growth factor 23 and uncarboxylated-unphosphorylated matrix-Gla protein—a cooperation between the EFLM Working Group on Biological Variation and the International Osteoporosis Foundation-International Federation of Clinical Chemistry Committee on Bone Metabolism
We have calculated the biological variation (BV) of different bone metabolism biomarkers on a large, well-described cohort of subjects. BV is important to calculate reference change value (or least significant change) which allows evaluating if the difference observed between two consecutive measurements in a patient is biologically significant or not.

Introduction: Within-subject (CVI) and between-subject (CVG) biological variation (BV) estimates are essential in determining both analytical performance specifications (APS) and reference change values (RCV). Previously published estimates of BV for bone metabolism biomarkers are generally not compliant with the most up-to-date quality criteria for BV studies. We calculated the BV and RCV for different bone metabolism markers, namely β-isomerized C-terminal telopeptide of type I collagen (β-CTX), N-terminal propeptide of type I collagen (PINP), osteocalcin (OC), intact fibroblast growth factor 23 (iFGF-23), and uncarboxylated-unphosphorylated Matrix-Gla Protein (uCuP-MGP) using samples from the European Biological Variation Study (EuBIVAS).

Methods: In the EuBIVAS, 91 subjects were recruited from six European laboratories. Fasting blood samples were obtained weekly for ten consecutive weeks. The samples were run in duplicate on IDS iSYS or DiaSorin Liaison instruments. The results were subjected to outlier and variance homogeneity analysis before CV-ANOVA was used to obtain the BV estimates.

Results: We found no effect of gender upon the CVI estimates. The following CVI estimates with 95% confidence intervals (95% CI) were obtained: β-CTX 15.1% (14.4-16.0%), PINP 8.8% (8.4-9.3%), OC 8.9% (8.5-9.4%), iFGF23 13.9% (13.2-14.7%), and uCuP-MGP 6.9% (6.1-7.3%).

Conclusions: The EuBIVAS has provided updated BV estimates for bone markers, including iFGF23, which have not been previously published, facilitating the improved follow-up of patients being treated for metabolic bone disease.
Biological variation, Bone markers, CTX, FGF23, MGP, Osteocalcin, PINP, Reference change value
0937-941X
1461-1470
Cavalier, Etienne
bc312308-1b70-4434-ab15-28860479d2e9
Lukas, P.
b3d1aac2-ef31-44eb-b01f-78ae61e38ae7
Bottani, M.
03a97f46-6417-4515-b53d-3ac2ae791846
Aarsand, A.K.
cdd19cbd-b6ba-451b-8cee-640dcbf89beb
Cooper, Cyrus
e05f5612-b493-4273-9b71-9e0ce32bdad6
Ceriotti, F.
1c87eabf-8675-4c0f-bb09-f6b0cc077a2d
Cavalier, Etienne
bc312308-1b70-4434-ab15-28860479d2e9
Lukas, P.
b3d1aac2-ef31-44eb-b01f-78ae61e38ae7
Bottani, M.
03a97f46-6417-4515-b53d-3ac2ae791846
Aarsand, A.K.
cdd19cbd-b6ba-451b-8cee-640dcbf89beb
Cooper, Cyrus
e05f5612-b493-4273-9b71-9e0ce32bdad6
Ceriotti, F.
1c87eabf-8675-4c0f-bb09-f6b0cc077a2d

Cavalier, Etienne, Lukas, P., Bottani, M., Aarsand, A.K., Cooper, Cyrus and Ceriotti, F. (2020) European Biological Variation Study (EuBIVAS): within and between-subject biological variation estimates of β-isomerized C-terminal telopeptide of type I collagen (β-CTX), N-terminal propeptide of type I collagen (PINP), osteocalcin, intact fibroblast growth factor 23 and uncarboxylated-unphosphorylated matrix-Gla protein—a cooperation between the EFLM Working Group on Biological Variation and the International Osteoporosis Foundation-International Federation of Clinical Chemistry Committee on Bone Metabolism. Osteoporosis International, 31 (8), 1461-1470. (doi:10.1007/s00198-020-05362-8).

Record type: Article

Abstract

We have calculated the biological variation (BV) of different bone metabolism biomarkers on a large, well-described cohort of subjects. BV is important to calculate reference change value (or least significant change) which allows evaluating if the difference observed between two consecutive measurements in a patient is biologically significant or not.

Introduction: Within-subject (CVI) and between-subject (CVG) biological variation (BV) estimates are essential in determining both analytical performance specifications (APS) and reference change values (RCV). Previously published estimates of BV for bone metabolism biomarkers are generally not compliant with the most up-to-date quality criteria for BV studies. We calculated the BV and RCV for different bone metabolism markers, namely β-isomerized C-terminal telopeptide of type I collagen (β-CTX), N-terminal propeptide of type I collagen (PINP), osteocalcin (OC), intact fibroblast growth factor 23 (iFGF-23), and uncarboxylated-unphosphorylated Matrix-Gla Protein (uCuP-MGP) using samples from the European Biological Variation Study (EuBIVAS).

Methods: In the EuBIVAS, 91 subjects were recruited from six European laboratories. Fasting blood samples were obtained weekly for ten consecutive weeks. The samples were run in duplicate on IDS iSYS or DiaSorin Liaison instruments. The results were subjected to outlier and variance homogeneity analysis before CV-ANOVA was used to obtain the BV estimates.

Results: We found no effect of gender upon the CVI estimates. The following CVI estimates with 95% confidence intervals (95% CI) were obtained: β-CTX 15.1% (14.4-16.0%), PINP 8.8% (8.4-9.3%), OC 8.9% (8.5-9.4%), iFGF23 13.9% (13.2-14.7%), and uCuP-MGP 6.9% (6.1-7.3%).

Conclusions: The EuBIVAS has provided updated BV estimates for bone markers, including iFGF23, which have not been previously published, facilitating the improved follow-up of patients being treated for metabolic bone disease.

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More information

Accepted/In Press date: 19 February 2020
e-pub ahead of print date: 8 April 2020
Keywords: Biological variation, Bone markers, CTX, FGF23, MGP, Osteocalcin, PINP, Reference change value

Identifiers

Local EPrints ID: 441710
URI: http://eprints.soton.ac.uk/id/eprint/441710
ISSN: 0937-941X
PURE UUID: 3abc997c-4dea-4c9c-868e-44dc0c42aefa
ORCID for Cyrus Cooper: ORCID iD orcid.org/0000-0003-3510-0709

Catalogue record

Date deposited: 24 Jun 2020 16:30
Last modified: 15 Sep 2021 01:41

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Contributors

Author: Etienne Cavalier
Author: P. Lukas
Author: M. Bottani
Author: A.K. Aarsand
Author: Cyrus Cooper ORCID iD
Author: F. Ceriotti

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