Biological variability in assessing the clinical value of biochemical markers of bone turnover

Analytical and biological variability of three bone markers, deoxypyridinol ine (DPD), Cross-Laps (CTx) and galactosylhydroxylysine (GHYL) were compare d. From 14 healthy subjects (six women, eight men; age 29-44 years) recruit ed from our laboratory staff, two sets of samples of early morning urine we re obtained - four samples taken weekly for 4 weeks (all subjects) and thre e samples taken monthly for 3 months from five subjects. Data were expresse d as the ratio to creatinine concentration. All the methods met the analyti cal goals (CVA less than or equal to 1/2CV(1within-subject)) DPD 0.06, CTx 0.05 and GHYL 0.07 with CV1within-subject being 0.22, 0.29 and 0.38, respec tively. The reference values were of limited usefulness particularly for CT x and GHYL, the index of individuality (II) being 0.50 and 0.48 respectivel y. As the index of heterogeneity (IH) was not significant, being 0.23 for C Tx, 0.28 for DPD and 0.46 for GHYL, which are all <1.71 (1 + 2S.D.), within -subject variances can be used to calculate the reference change value (RCV ): 0.58 for DPD, 0.54 for CTx and 1.08 for GHYL. Moreover, we found constan t variations in DPD and CTx, week to week and month to month. Our findings suggest that DPD and CTx provide more reliable results than GHYL, showing a lower within-subject variation, a lower and rime-constant RCV allowing rel iable monitoring without regard for timing. (C) 2000 Elsevier Science B.V. All rights reserved.