Evaluation of a fully automated serum assay for C-terminal cross-linking telopeptide of type I collagen in osteoporosis

Background: Biochemical markers of bone turnover can provide prognostic inf ormation about the risk of osteoporotic fracture and are useful tools for m onitoring efficacy-of antiresorptive therapy. A serum-based automated assay may be of better clinical value than urinary markers because of lower impr ecision and day-to-day within-person variability. Our aim was to evaluate t he technical and clinical performances of a new, fully automated:assay for serum C-terminal cross-linking telopeptide of type I collagen (CTX), a mark er of bone resorption. Methods: Serum CTX was measured on the Elecsys 2010 automated analyzer (Roc he). Results were compared with those of the manual ELISA. We measured seru m CTX concentrations in 728 healthy women, ages 31-89 years. We investigate d the ability of this assay to predict the rate of postmenopausal forearm b one loss evaluated by four repeated bone mineral density measurements using dual-x-ray absorptiometry in 305 women followed prospectively for 4 years. Finally, in a cohort of healthy, untreated, postmenopausal women, we compa red baseline serum TX in 55 women who subsequently had a fracture (20 verte bral and 35 peripheral fractures) with values in the 380 women who did not fracture during a mean 5 years of follow-up. Results: The within- (n = 21) and between-run (n = 21) CVs:were <4.1% and 5 .7%, respectively. In 728 healthy women, serum CTX concentrations (automate d) correlated with-those of the manual ELISA (I = 0.82; P <0.0001). The med ian long-term within-person variability assessed by four repeated measureme nts over 3 months in 18 postmenopausal women was 9.4%. Compared with 254 pr emenopausal women, serum CTX was 39% (P <0.0001) higher in 45 perimenopausa l women and 86% (P <0.0001) higher in 429 postmenopausal women (mean age, 6 4 years). Baseline serum CTX correlated negatively with changes of bone mas s measured at the mid (r = -0.23; P <0.0001) and distal (r = -0.27; P <0001 ) radius. Postmenopausal women with serum CTX greater than the mean + 2 SD values in premenopausal women accounted for 42% of the population, lost bon e at the mid radius on average eightfold more rapidly than the other women (-0.27% +/- 2.92% vs -2.25% +/- 3.95%; P <0.0001), and had increased risk o f fracture with a relative risk (95% confidence interval) of 1.8 (1.01-3.1) after adjustment for physical activity. Conclusions: The automated assay for serum CTX is precise and predicts rate of bone loss and fracture risk in postmenopausal women. Because it is conv enient to use and has high throughput, this serum bone resorption marker ma y be useful for the investigation of patients with osteoporosis. <(c)> 2001 American Association for Clinical Chemistry.