A Placebo-Controlled, Single-Blind Study to Determine the Appropriate Alendronate Dosage in Postmenopausal Japanese Patients with Osteoporosis.

Abstract

Abstract. Alendronate (4-amino-1-hydroxybutylidene-1,1-bisphosphonate) is a potent inhibitor of bone resorption.The efficacy and safety of 36 weeks of treatment with alendronate were evaluated in Japanese women with osteoporosis, osteoporotic osteopenia or artificial menopause. The bone mineral density (BMD) of the lumbar vertebrae, markers of bone and calcium metabolism and clinical symptoms were monitored.A total of 113 randomly selected patients with osteoporosis or osteopenia were enrolled in the study, of whom 12 were excluded from the analyses because of lack of data. As a result, 101 patients were evaluated for the safety of the drug. Since eight patients were excluded from the efficacy analysis, 93 were evaluated. The incidence of adverse effects in the placebo (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 gastrointestinal 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 and P groups, respectively (P<0.001, L vs. P and H vs. P). Serum alkaline phosphatase activity, serum osteocalcin and urinary deoxypyridinoline excretion were significantly decreased in a dose-related manner. Serum calcium and phosphorus were also significantly decreased after alendronate administration.Serum intact PTH was transiently increased. The present results indicate that alendronate effectively decreases bone turnover in a dose-related manner and increases lumbar BMD at a dosage of 2.5 mg/day, the lowest dose used in this study, in Japanese patients with osteoporosis.

Low Serum Levels of Undercarboxylated Osteocalcin in Postmenopausal Osteoporotic Women Receiving an Inhibitor of Bone Resorption

“…Third, we only measured serum ucOC levels and did not consider serum total OC levels. Shiraki et al (1998) showed that ALN decreased serum total OC levels accompanied by suppression of bone turnover. As both ucOC and carboxylated OC are released from osteoblasts into circulation, bone turnover may convert a proportion of ucOC.…”

“…The bone formation marker osteocalcin (OC) is a bone-specific protein synthesized by osteoblasts. Serum total OC levels have been shown to decrease alongside suppression of bone turnover by ALN (Shiraki et al 1998).…”

Skeletal Benefits of Two Years of Alendronate Treatment Are Similar for Early Postmenopausal Asian and Caucasian Women

“…A single-masked study [8] reported the effects of alendronate treatment at doses of 2.5 and 10 mg daily; lumbar spine BMD increases of approximately 3% were observed among postmenopausal women without osteoporosis at 36 weeks, relative to baseline. However, the number of women in each treatment group (5-8 per group) was too small to make meaningful comparisons with the present study.…”

Clinical trial: comparison of alendronate and alfacalcidol in glucocorticoid‐associated osteoporosis in patients with ulcerative colitis

“…The 5 mg ⁄ day of alendronate is the maximum dose approved in Japan, which was effective as 10 mg ⁄ day in increasing BMD for the Japanese patients with osteoporosis in the 3-year study. 23 The effectiveness of 5 mg ⁄ day alendronate was also shown in Japanese patients with primary osteoporosis 24 and in postmenopausal Japanese women 25 where it increased lumber BMD by 4-6% of the baseline value after 12-month treatment. In addition, weekly therapy of alendronate was not available in Japan, when we started conducting the study.…”