Rechallenge of patients who had discontinued alendronate therapy because of upper gastrointestinal symptoms.
BACKGROUND
There have been reports from physicians in clinical practice that up to 30% of patients taking bisphosphonate therapy develop upper gastrointestinal (UGI) symptoms, many or most of which they assume to be related to the drug. However, in several large placebo-controlled clinical trials of bisphosphonates, the incidence of UGI symptoms has been > or =30%, even among patients receiving placebo, perhaps reflecting a high 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 such 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 therapy because of a UGI adverse experience were randomized to daily treatment with either alendronate 10 mg or matching placebo (1:1 ratio) for 8 weeks. The 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 urinary 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 the alendronate group and 16.7% (14/84) in the placebo group discontinued treatment because of UGI adverse experiences.


CONCLUSIONS
The results of this study suggest that many UGI adverse experiences reported during therapy with alendronate may reflect a high background incidence of UGI complaints and an increased sensitivity to detection of such complaints, rather than a causal relationship to therapy.
Miller
P D
PD
Colorado Center for Bone Research, Lakewood, USA.
Woodson
G
G
Licata
A A
AA
Ettinger
M P
MP
Mako
B
B
Smith
M E
ME
Wang
L
L
Yates
S J
SJ
Melton
M E
ME
Palmisano
J J
JJ
D019386:Alendronate / Q000009:adverse effects* / Q000627:therapeutic use; D003094:Collagen / Q000652:urine; D024042:Collagen Type I; D004064:Digestive System / Q000187:drug effects*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D010024:Osteoporosis / Q000188:drug therapy; D010349:Patient Compliance; D010455:Peptides / Q000652:urine; D010919:Placebos; D017698:Postmenopause
D024042:Collagen Type I; D010455:Peptides; D010919:Placebos; C052929:collagen type I trimeric cross-linked peptide; D003094:Collagen; D019386:Alendronate