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

Analytical and biological variability of three bone markers, deoxypyridinoline (DPD), CrossLaps (CTx) and galactosylhydroxylysine (GHYL) were compared. From 14 healthy subjects (six women, eight men; age 29-44 years) recruited from our laboratory staff, two sets of samples of early morning urine were obtained - four samples taken weekly for 4 weeks (all subjects) and three samples taken monthly for 3 months from five subjects. Data were expressed as the ratio to creatinine concentration. All the methods met the analytical goals (CV(A)< or =1/2CV(I(within-subject))) DPD 0.06, CTx 0.05 and GHYL 0.07 with CV(I(within-subject)) being 0.22, 0.19 and 0.38, respectively. The reference values were of limited usefulness particularly for CTx and GHYL, the index of individuality (II) being 0.50 and 0.48 respectively. As the index of heterogeneity (IH) was not significant, being 0.23 for CTx, 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 constant 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 time-constant RCV allowing reliable monitoring without regard for timing.