Biochemical markers for prediction of 4-year response in bone mass during bisphosphonate treatment for prevention of postmenopausal osteoporosis

Short-term changes in biochemical markers of bone turnover (bone markers) have been suggested as predictors of long-term response in bone mass during antiresorptive treatment. In the Danish cohort (n = 306) of the Early Postmenopausal Intervention Cohort (EPIC) Study (n = 1609) of oral alendronate (ALN) for prevention of postmenopausal osteoporosis, bone markers (urine C-telopeptides of type I collagen (uCTX), urine N-telopeptide cross-links of type I collagen (uNTX), serum total osteocalcin measured by ELISA [total OC (ELISA)], and serum total osteocalcin measured by RIA [total OC (RIA)]) were measured at 6-month intervals. The correlation between 6-month change in uCTX and 4-year change in spine and hip bone mineral density (BMD) was r = -0.41 and r = -0.42, respectively (P < 0.001). The corresponding values for the other bone markers were r = -0.53 and r = -0.42 (uNTX), r = -0.46 and r = -0.47 [total OC (ELISA)], and r = -0.43 and r = -0.41 [total OC (RIA)], all P < 0.001. ROC curves were used to analyse the ability of the bone markers to predict a change in spine BMD greater than 0%. The best performance [defined as the maximum value of (sensitivity plus specificity)] was found at the cut-off values of a -29% change from baseline in uCTX, a -45% change from baseline in uNTX, a -13% change from baseline in total OC (ELISA), and a -15% change from baseline in total OC (RIA). At these values the corresponding sensitivity was 66% (uCTX), 76% (uNTX), 70% [total OC (ELISA)], and 83% [total OC (RIA)]. The specificity was 80% (uCTX), 75% (uNTX), 71% [total OC (ELISA)], and 55% [total OC (RIA)]. The positive predictive value (PPV) was 82% (uCTX), 80% (uNTX), 77% [total OC (ELISA)], and 71% [total OC (RIA)]. The negative predictive value (NPV) was 64% (uCTX), 70% (uNTX), 64% [total OC (ELISA)], and 71% [total OC (RIA)]. In conclusion, the bone markers predicted a change in spine BMD greater than 0% with a high PPV and specificity. There was a trend toward better performance in this respect for the bone resorption markers.