Discriminative value of biochemical markers of bone turnover in assessing the activity of Paget's disease

Abstract

Clinical biochemical markers of bone turnover are usually increased in Paget's disease. However, the analysis of “new” markers, such as serum bone alkaline phosphatase (BAP), carboxy‐terminal propeptide of type I procollagen (PICP), tartrate‐resistant acid phosphatase (TRAP), telopeptide carboxy‐terminal propeptide of type I collagen (ICTP), and urinary pyridinoline (PYR) and deoxipyridinoline (D‐PYR), may improve the diagnostic efficacy and the evaluation of Paget's disease compared with conventional markers, such as serum total alkaline phosphatase (TAP) and urinary hydroxyproline (HYP). To evaluate the diagnostic accuracy and the changes of biochemical markers of bone turnover according to Paget's disease activity, we measured the levels of all these markers in three groups of pagetic patients classified according to their serum TAP activity: G‐I, patients with serum TAP lower than 250 U/l (upper limit) (n = 15); G‐II, patients with serum TAP between 251 and 500 U/l (n = 18); and G‐HI, patients with serum TAP greater than 501 U/l (n = 26). Serum TAP and BAP showed the highest diagnostic accuracy among the markers of bone formation with a sensitivity of 78% and 84%, respectively, when the specificity was 100%. Urinary PYR was the most sensitive marker of bone resorption. Also, urinary PYR showed the highest proportion of increased values in pagetic patients (73%) compared with urinary HYP (64%), urinary D‐PYR (60%), serum ICTP (41%), or serum TRAP (39%). In pagetic patients with normal serum TAP activity (G‐I), serum BAP concentration was increased in 60% of patients, and urinary PYR was increased in 40% of patients. However, when serum TAP was greater than 500 U/l (G‐III), almost all markers of bone formation and resorption were increased. These results suggest that when Paget's disease activity is high, most biochemical markers of bone turnover are increased. However, when the disease activity is low, serum BAP and urinary PYR improve the detection of such disease. Moreover, the determination of serum TAP activity and, to a similar extent, serum BAP concentration associated with the measurement of urinary PYR excretion provides the best biochemical approach for assessing Paget's disease activity.