A PLACEBO-CONTROLLED, SINGLE-BLIND STUDY TO DETERMINE THE APPROPRIATEALENDRONATE DOSAGE IN POSTMENOPAUSAL JAPANESE PATIENTS WITH OSTEOPOROSIS

Alendronate (4-amino-1-hydroxybutylidene-1,1-bisphosphonate) is a pote nt inhibitor of bone resorption. The efficacy and safety of 36 weeks o f treatment with alendronate were evaluated in Japanese women with ost eoporosis, osteoporotic osteopenia or artificial menopause. The bone m ineral density (BMD) of the lumbar vertebrae, markers of bone and calc ium metabolism and clinical symptoms were monitored. A total of 113 ra ndomly selected patients with osteoporosis or osteopenia were enrolled in the study, of whom 12 were excluded from the analyses because of l ack of data. As a result, 101 patients were evaluated for the safety o f the drug. Since eight patients were excluded from the efficacy analy sis, 93 were evaluated. The incidence of adverse effects in the placeb o (P), alendronate 2.5 mg/day (L) and alendronate 10 mg/day (H) groups increased with increasing dose of alendronate, being 6.1, 14.3 and 18 .2%, respectively. The most common adverse effects were gastrointestin al symptoms, none of which was serious. Lumbar BMD increased after 36 weeks of drug administration to 5.21%, 5.64% and -0.90% in the L, H an d P groups, respectively (P<0.001, L vs. P and H vs. P). Serum alkalin e phosphatase activity, serum osteocalcin and urinary deoxypyridinolin e excretion were significantly decreased in a dose-related manner. Ser um calcium and phosphorus were also significantly decreased after alen dronate administration. Serum intact PTH was transiently increased. Th e present results indicate that alendronate effectively decreases bone turnover in a dose-related manner and increases lumbar BMD at a dosag e of 2.5 mg/day, the lowest dose used in this study, in Japanese patie nts with osteoporosis.