Comparison of Bone Turnover Biomarkers in Serum and Urine Measured on an Automated Analytical Platform

Abstract

Background: Matched serum and urine samples from patients who had total hip replacement were used to assess serum-validated immunoassay reagents for use in urine.

Methods: Samples were evaluated by an automated electrochemiluminescent immunoassay (cobas e411; Roche Diagnostics) for C-terminal telopeptide of type I collagen isoform β (β-Crosslaps), osteocalcin N-terminal midfragment (N-MID OC), N-terminal propeptide of type I collagen (PINP), and interleukin 6 (IL-6). Spike and recovery experiments were utilized to assess urinary matrix effects. Correlations between serum and both raw and creatinine-corrected urinary measures were assessed. Short-term precision was assessed.

Results: Spike and recovery experiments indicated minimal matrix effects of urine for the β-Crosslaps assay. Potential matrix effects were observed for the other analytes because N-MID OC and IL-6 tended to be slightly overrecovered, whereas PINP was underrecovered. There were strong correlations between serum β-Crosslaps and raw (Spearman ρ [rs] = 0.725, P < 0.0001) and creatinine-corrected (rs = 0.793, P < 0.0001) urinary measures and moderate correlations between serum N-MID OC and raw (rs = 0.582, P < 0.0001) and creatinine-corrected (rs = 0.482, P < 0.0001) urinary measures. PINP was not detected in urine, and no significant serum-urine correlations were found for IL-6. Short-term precision for urinary levels of β-Crosslaps, N-MID OC, and IL-6 were 1.6%, 6.3% and 14.4%, respectively.

Conclusions: Urinary measurements of β-Crosslaps and N-MID OC assays were correlated with serum measurements and had good short-term precision. Urinary PINP was not detectable. IL-6 can be measured in urine using this technology, but the levels did not correlate with serum levels, and the short-term precision was variable.

Keywords: Crosslaps; IL-6; PINP; automation; biomarkers; osteocalcin; osteolysis; urine.