Cavalier E1,2, Lukas P3, Bottani M4, Aarsand AK5,6,7, Ceriotti F8, Coşkun A7,9, Díaz-Garzón J7,10, Fernàndez-Calle P7,10, Guerra E11, Locatelli M11, Sandberg S5,6,7,12, Carobene A7,11; European Federation of Clinical Chemistry and Laboratory Medicine Working Group on Biological Variation and IOF-IFCC Committee on Bone Metabolism
Osteoporos Int. 2020 Apr 8. doi: 10.1007/s00198-020-05362-8. [Epub ahead of print]
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.
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).
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.
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%).
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.