Components of biological variation of biochemical markers of bone turnover in Paget's bone disease.

The aims of this study were to evaluate the components of biological variation of the new markers of bone turnover in patients with Paget's bone disease and to compare the results with data obtained in healthy subjects. Fifteen patients with Paget's disease in a stable period of the disease and 12 healthy premenopausal women were included for a 1 year follow-up study. Within- and between-subject biological variation, indices of individuality, and critical differences were evaluated for the following biochemical markers: in serum, total (tAP), and bone (bAP) alkaline phosphatases, procollagen type I N-terminal propeptide (PINP) and beta-carboxyterminal telopeptide of type I collagen (sCTx); in urine, hydroxyproline (Hyp), and amino (NTx) and beta-carboxyterminal (CTx) telopeptides of collagen type I. Serum markers of bone turnover showed lower biological variability than urinary markers. Within-subject biological variation was higher in pagetic patients than in healthy subjects for all serum markers. In both groups, bAP presented the lowest within-subject biological variation. In pagetic patients, all markers presented indices of individuality of <0.6, indicating their usefulness for patient monitoring. Critical differences were lower for serum markers than for urinary markers. Among pagetic patients, serum bAP and PINP showed the lowest critical differences with values close to 30%, whereas urinary CTx presented the highest critical differences (near 70%). Conversely, in healthy subjects, tAP was the marker with the lowest critical differences, being two-fold higher in pagetic patients. This study confirms the lower sensitivity of urinary markers to detect significant changes and indicates that data obtained on biological variations from healthy populations cannot always be extrapolated to pathological conditions. In addition, serum bAP and PINP seem to be the markers that best reflect a significant change in activity of Paget's disease.