A randomized, placebo-controlled, 6-month study of once-weekly alendronate oral solution for postmenopausal osteoporosis.
OBJECTIVE
This study evaluated the overall safety and tolerability of once-weekly (OW) alendronate 70 mg oral solution (OS) versus OW placebo OS.


METHODS
Postmenopausal, osteoporotic women were enrolled at 51 centers in the United States in a 6-month double-blind, randomized trial. Patients were randomized (1:1) to OW alendronate 70 mg OS or placebo OS. The primary end point was the proportion of patients reporting any upper gastrointestinal (UGI) adverse event (AE) at 6 months. Secondary end points included mean percentage change in urinary N-telopeptide of type I human collagen (NTx) and serum bone-specific alkaline phosphatase (BSAP) at 6 months.


RESULTS
Initially, 454 women were enrolled; 392 (86.3%) completed the study. The mean (SD) age was 65.2 (10) years, and the mean (SD) time since menopause was 19.1 (12) years. The proportion of patients experiencing any UGI AE was significantly higher with alendronate OS (23.7%) compared with placebo solution (15.3%), with a treatment difference of 8.3% (95% CI, 0.8%-15.8%; P = 0.024). The proportion of patients experiencing any esophageal AE was 4.0% with alendronate and 3.0% with placebo (treatment difference, 1.0% [95% CI, -2.7% to 4.8%]). In addition, 4.5% of alendronate and 8.7% of placebo patients discontinued the study due to any clinical AE, and 3.3% of alendronate and 1.8% of placebo patients discontinued due to a UGI AE (difference, 1.5% [95% CI, -1.5% to 4.4%]). Alendronate OS produced significantly greater reductions in both NTx and BSAP than placebo (differences, -47.5% and -38.7%, respectively [both, P < 0.001]).


CONCLUSIONS
In this 6-month study, patients receiving OW alendronate 70 mg OS had a higher rate of UGI AEs than placebo patients. However, rates of serious UGI AEs, discontinuations due to UGI AEs, and esophageal AEs were similar between groups. UGI AEs in the study were generally mild to moderate in severity and did not result in treatment discontinuation. In addition, OW alendronate 70 mg OS significantly reduced biochemical markers of bone turnover.
Cryer
Byron
B
Division of Digestive Diseases, Dallas Veterans Affairs Medical Center, Dallas, Texas 75216, USA. Byron.Cryer@utsouthwestern.edu
Binkley
Neil
N
Simonelli
Christine
C
Lewiecki
E Michael
EM
Lanza
Frank
F
Chen
Erluo
E
Petruschke
Richard A
RA
Mullen
Christine
C
de Papp
Anne E
AE
D000284:Administration, Oral; D000368:Aged; D019386:Alendronate / Q000008:administration & dosage* / Q000009:adverse effects*; D000469:Alkaline Phosphatase / Q000097:blood; D015415:Biomarkers / Q000652:urine; D001842:Bone and Bones / Q000187:drug effects*; D003094:Collagen / Q000187:drug effects / Q000652:urine; D024042:Collagen Type I; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004935:Esophageal Diseases / Q000139:chemically induced / Q000453:epidemiology; D005260:Female; D006801:Humans; D009325:Nausea / Q000139:chemically induced / Q000453:epidemiology; D015663:Osteoporosis, Postmenopausal / Q000175:diagnosis / Q000188:drug therapy*; D010455:Peptides / Q000187:drug effects / Q000652:urine; D019999:Pharmaceutical Solutions / Q000008:administration & dosage / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D041742:Upper Gastrointestinal Tract / Q000187:drug effects*
D015415:Biomarkers; D024042:Collagen Type I; D010455:Peptides; D019999:Pharmaceutical Solutions; C052929:collagen type I trimeric cross-linked peptide; D003094:Collagen; D000469:Alkaline Phosphatase; D019386:Alendronate