Early response in biochemical markers predicts long-term response in bone mass during hormone replacement therapy in early postmenopausal women

Based on data from 153 early postmenopausal women who completed a double-bl ind, randomized 3 year study of graded hormone replacement therapy (HRT) do ses or placebo, we investigated the value of hone markers to predict preven tion of bone loss. Absolute values of serum and urinary Cross-Laps (S-CTX a nd U-CTX) after 2 weeks of treatment were significantly correlated to 3 yea r bone mass response (r = -0.28/-0.35; p < 0.001). These associations were fully expressed at 6 months (r = -0.61/-0.64; p < 0.001), Receiver operatin g characteristic analyses revealed that the predictive capacity of one meas urement of a resorption marker after 6 months' treatment performed similarl y as assessment of hip bone mass over 3 years in predicting preservation of spinal bone mass over 3 years. Comparable results were obtained using perc ent change from baseline in resorption markers at both 5 and 12 months, whe reas for formation markers percent change was superior to absolute value at 6 months but not at 12 months. Values of accuracy for S-CTX for a cutoff o f 1881 pmol/L at 6 months were 85.2% (sensitivity), 74.3% (specificity), 90 .5% (positive predictive value), and 63.4% (negative predictive value); U-C TX performed similarly, whereas the values For the formation markers were s lightly lower. A cutoff for S-CTX of 1245 pmol/L eliminated false-positive individuals (those who had a decrease below the cutoff but lost bone). In t he false-negative group, which was composed of individuals whose S-CTX did not decrease below the cutoff but had preserved bone mass, S-CTX,vas signif icantly associated with spinal bone mass response (r -0.41; p < 0.01), indi cating these women had been treated with a dose that was not at its optimum for their individual bone turnover. For this cutoff, the values were 49.5% (sensitivity), 97.1% (specificity), 98% (positive predictive value), and 4 0% (negative predictive value). In conclusion, early hone marker measuremen ts predict long-term preservation of bone mass during HRT. Resorption marke rs seem superior to formation markers, which reflects that the primary effe ct of HRT is on bone resorption, A strategy with two cutoff levels may opti mize the use of bone markers to predict bone mass response, Whether resorpt ion markers can be used to guide individualized treatment remains to be inv estigated. (Bone 26:561-569; 2000) (C) 2000 by Elsevier Science Inc. All ri ghts reserved.