Rechallenge of patients who had discontinued alendronate therapy because of upper gastrointestinal symptoms

Background: There have been reports from physicians in clinical practice th at up to 30% of patients taking bisphosphonate therapy develop upper gastro intestinal (UGI) symptoms, many or most of which they assume to be related to the drug. However, in several large placebo-controlled clinical trials o f bisphosphonates, the incidence of UGI symptoms has been greater than or e qual to 30%, even among patients receiving placebo, perhaps reflecting a hi gh background incidence of UGI events in osteoporotic patients. Objective: To assess the relationship between alendronate treatment and UGI complaints in patients who had discontinued treatment with alendronate in clinical practice because of UGI symptoms, we compared the incidence of suc h events on rechallenge with alendronate or placebo. Methods: This was a multicenter, double-blind trial in which postmenopausal women with osteoporosis who had previously discontinued alendronate therap y because of a UGI adverse experience were randomized to daily treatment wi th either alendronate 10 mg or matching placebo (1:1 ratio) for 8 weeks. Th e primary end point was the cumulative incidence of discontinuations due to any UGI adverse experience. Secondary end points were the incidence of any clinical adverse experiences and the percentage change from baseline in ur inary N-telopeptide adjusted for urinary creatinine at week 8. Results: A total of 172 women were included in the study. They were a mean of 20.9 years past menopause, ranging in age from 41 to 90 years (mean, 67. 0 years); 90.7% were white. On rechallenge, 14.8% (13/88) of patients in th e alendronate group and 16.7% (14/84) in the placebo group discontinued tre atment because of UGI adverse experiences. Conclusion: The results of this study suggest that many UGI adverse experiences reported during therapy wit h alendronate may reflect a high background incidence of UGI complaints and an increased sensitivity to detection of such complaints, rather than a ca usal relationship to therapy.