Comparison of results from commercial assays for plasma CTX: The need for harmonization.

INTRODUCTION: Plasma C-terminal telopeptide of type I collagen (CTX) is the nominated reference bone resorption marker. We set out to test the agreement of patients' results between the available plasma CTX assays. METHODS: Samples were collected from patients attending tertiary hospitals and clinics for investigation and management of metabolic bone disease. Plasma (EDTA) samples were collected from fasted patients between 7.00 am and 11.00 am, divided into three portions and stored at -20°C until analysis. Plasma CTX was measured by enzyme-linked immunosorbent assay (ELISA) (Immunodiagnostic Systems plc), E170 (Roche Diagnostics) and IDS-iSYS (Immunodiagnostic Systems plc) methods. Agreement of patient sample results was assessed by Passing and Bablok regression. Commutability of the calibrators in each kit was assessed by assaying each calibrator in the alternate methods and comparing the observed results with those expected based on the relevant patients' samples method comparison; ±8.1% was set as the criterion for commutablity. RESULTS: 161 specimens were analysed. Regression parameters (slope, intercept) were 0.788, 0.2 ng/L for Roche vs ELISA, 1.266 and -109 ng/L for iSYS vs ELISA and 1.605 and -109 ng/L for iSYS vs Roche. Only the ELISA calibrator assayed in the Roche assay gave a result within 8.1% of the expected value. CONCLUSIONS: There is significant disagreement between the results generated for patient samples by the 3 CTX assays and limited commutability of the currently supplied calibrator materials between assays. Harmonization of the results from the different assays would greatly enhance the value of CTX as the reference bone resorption marker.