A model to monitor the efficacy of alendronate treatment in women with osteoporosis using a biochemical marker of bone turnover

Markers of bone turnover have been suggested to be useful in monitoring the long-term efficacy of antiresorptive therapy on hone mineral density (BMD) . In this study, we developed a new model based on the combination of a mar ker level and its percent change at 6 months of therapy to predict longterm response in BMD, Serum bone alkaline phosphatase (BAP) was measured in 307 late postmenopausal women (mean age 64 years) with osteoporosis enrolled i n a 2 year placebo-controlled trial of the bisphosphonate alendronate (10 m g/day), Under treatment, the maximal decrease was observed at 6 months (-44 %) with no further change during the 2 year period. Both BAP levels at 6 mo nths and percent BAP change at 6 months correlated with the percent change of spine BMD at 2 years (r = -0.51 and -0.53, respectively, p < 0.001 for b oth). Logistic regression analysis showed that BAP levels and percent BAP c hange at 6 months are independent predictors of long-term positive BMD resp onse, defined as greater than or equal to 3% increase in spine BMD at 2 yea rs. The most relevant clinical option that could lead to therapeutic adjust ment is likely to be an accurate identification of nonresponders, and thus predictive models need to be highly specific. For a 90% specificity, the co mbination of both the percent change and BAP levels at 6 months resulted in a significantly (p < 0.05) higher sensitivity (72%) than using percent BAP change (61%) or BAP level at 6 months (59%) alone. This combination model was also more effective than using the least-significant change (a decrease of BAP at 6 months of >44%) based on the within-patient variability in the placebo group. In the combination model, positive BMD responders vs. nonre sponders could easily be distinguished by a line on a two-scale graph (BAP level at 6 month vs. percent BAP change at 6 months). In conclusion, the co mbination of BAP level and of its percent change after 6 months of treatmen t in a logistic model improved the prediction of the long-term BMD response to alendronate treatment compared with percent BAP change alone, This new model may be useful for quick and accurate identification of noncompliant p atients (i.e., nonresponders) vs. responders to alendronate treatment, alth ough prospective studies are required to determine accurately the rate of f alse positives and false negatives. Because this model is independent of th e study design, it should be broadly applicable. (Bone 24:603-609; 1999) (C ) 1999 by Elsevier Science Inc. All rights reserved.