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

E. Cavalier, P. Lukas, M. Bottani, A.K. Aarsand, F. Ceriotti, A. Coşkun, J. Díaz-Garzón, P. Fernàndez-Calle, E. Guerra, M. Locatelli, S. Sandberg, A. Carobene, K. Åkesson, H.P. Bhattoa, O. Bruyère, C. Cooper, R. Eastell, P. Garnero, A. Heijboer, N.R. JorgensenJ. Kanis, K. Makris, C.Z. Ulmer, S. Vasikaran, on behalf of the European Federation of Clinical Chemistry and Laboratory Medicine Working Group on Biological Variation and IOF-IFCC Committee on Bone Metabolism

Research output: Contribution to journalArticlepeer-review

Abstract

Summary: 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. © 2020, International Osteoporosis Foundation and National Osteoporosis Foundation.
Original languageEnglish
Pages (from-to)1461-1470
Number of pages10
JournalOsteoporosis Int.
Volume31
Issue number8
DOIs
Publication statusPublished - 2020

Keywords

  • Biological variation
  • Bone markers
  • CTX
  • FGF23
  • MGP
  • Osteocalcin
  • PINP
  • Reference change value
  • beta isomerized C terminal telopeptide of type I collagen
  • collagen
  • fibroblast growth factor 23
  • N terminal propeptide of type I collagen
  • osteocalcin
  • unclassified drug
  • adult
  • aged
  • Article
  • biological variation
  • body mass
  • bone metabolism
  • cohort analysis
  • controlled study
  • female
  • human
  • human experiment
  • male
  • normal human
  • predictive value
  • priority journal
  • protein blood level
  • protein function
  • reference value
  • sex difference

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