A range of biomarkers of bone metabolism are thought to mediate adipose tissue-bone crosstalk and fulfil a homeostatic role. While considered clinically relevant, their utility and application appears limited by lack of data characterising biological variability and reference intervals rather than by analytical issues. We have therefore studied the biological variation (BV) of these biomarkers. Concentrations of Dikkopf-related protein 1, leptin, osteoprotegerin, sclerostin, lipocalin2 (Lcn2) and resistin were measured by Luminex assays in serum samples from the EuBIVAS study. Samples were taken once per week, over 10 consecutive weeks, from 91 subjects in cohorts from 5 European countries. Estimates of analytical variation (CVA), within-subject (CVI) and between-subject (CVG) BV were calculated and analytical imprecision (CVAPS) and analytical bias (BAPS) specifications, index of individuality (II), reference change values (RCV) for increase and decrease and the number of samples required to estimate the homeostatic set points (NHSPs) were derived. Mean concentrations differed between males and females for leptin, osteoprotegerin, and sclerostin, and for osteoprotegerin and sclerostin between females in fertile and menopausal ages. No male-to-female differences were observed in CVI estimates. Index of individuality was below 0.6, for all measurands. Determination of reference intervals (RI) limits indicated that all, with the exception Lcn2, described data which were non-gaussian distributed and that only leptin differed between sexes. Availability of high-quality biological variation enables objective assessment of the bone metabolism biomarker results which may enhance their clinical utility. The data indicates that they exhibit significant individuality.
Novel biomarkers in bone pathophysiology: Establishing reference intervals and biological variations estimates for serum leptin, sclerostin, lipocalin-2, osteoprotegerin, resistin and Dickkopf-related protein-1 from the European biological variation study (EuBIVAS) populations / Sansoni, V.; Lombardi, G.; Diaz-Garzon, J.; Calle, P. F.; Bartlett, W. A.; Coskun, A.; Itkonen, O.; Jonker, N.; Sandberg, S.; Aarsand, A. K.; Banfi, G.; Carobene, A.. - In: CLINICA CHIMICA ACTA. - ISSN 0009-8981. - 570:(2025). [10.1016/j.cca.2025.120213]
Novel biomarkers in bone pathophysiology: Establishing reference intervals and biological variations estimates for serum leptin, sclerostin, lipocalin-2, osteoprotegerin, resistin and Dickkopf-related protein-1 from the European biological variation study (EuBIVAS) populations
Banfi G.;
2025-01-01
Abstract
A range of biomarkers of bone metabolism are thought to mediate adipose tissue-bone crosstalk and fulfil a homeostatic role. While considered clinically relevant, their utility and application appears limited by lack of data characterising biological variability and reference intervals rather than by analytical issues. We have therefore studied the biological variation (BV) of these biomarkers. Concentrations of Dikkopf-related protein 1, leptin, osteoprotegerin, sclerostin, lipocalin2 (Lcn2) and resistin were measured by Luminex assays in serum samples from the EuBIVAS study. Samples were taken once per week, over 10 consecutive weeks, from 91 subjects in cohorts from 5 European countries. Estimates of analytical variation (CVA), within-subject (CVI) and between-subject (CVG) BV were calculated and analytical imprecision (CVAPS) and analytical bias (BAPS) specifications, index of individuality (II), reference change values (RCV) for increase and decrease and the number of samples required to estimate the homeostatic set points (NHSPs) were derived. Mean concentrations differed between males and females for leptin, osteoprotegerin, and sclerostin, and for osteoprotegerin and sclerostin between females in fertile and menopausal ages. No male-to-female differences were observed in CVI estimates. Index of individuality was below 0.6, for all measurands. Determination of reference intervals (RI) limits indicated that all, with the exception Lcn2, described data which were non-gaussian distributed and that only leptin differed between sexes. Availability of high-quality biological variation enables objective assessment of the bone metabolism biomarker results which may enhance their clinical utility. The data indicates that they exhibit significant individuality.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
