Interlaboratory Variation of Biochemical Markers of Bone Turnover

Abstract

Biochemical markers of bone metabolism are used to assess skeletal turnover, but the variability of marker assays is still an issue of practical concern. We describe the results of an international proficiency testing program for biochemical bone markers among clinical laboratories. Two serum and two urine pools (normal and increased marker concentrations) were sent on dry ice to 79 laboratories for analysis within 2 weeks of receipt. Data were submitted by 73 laboratories. The within-method interlaboratory CVs (CV(IL)s) were as follows: serum bone-specific alkaline phosphatase (n = 47 laboratories), 16-48%; serum osteocalcin (n = 31), 16-42%; urinary free deoxypyridinoline (n = 30), 6.4-12%; urinary total deoxypyridinoline and pyridinoline (n = 29), 27-28%; urinary N-terminal cross-linked telopeptide of type I collagen (n = 10), 39%; serum C-terminal cross-linked telopeptide of type I collagen (ICTP; n = 8), 22-27%; urinary hydroxyproline (n = 13), 12%. Analytical results showed both systematic and nonsystematic deviations. In identical samples, results obtained for the same marker by the same method differed up to 7.3-fold. In urine-based assays, correction for urinary creatinine slightly increased CVs. Even with identical assays and methods, results for most biochemical markers of bone turnover differ markedly among laboratories.