Effect of daily oral minodronate on vertebral fractures in Japanese postmenopausal women with established osteoporosis: a randomized placebo-controlled double-blind study

Abstract

SUMMARY; A randomized placebo-controlled trial was conducted to examine the effect of daily oral 1 mg minodronate on vertebral fractures in 704 postmenopausal women with established osteoporosis for 24 months. Minodronate treatment reduced vertebral fractures by 59% without serious adverse events. Minodronate is a safe and effective bisphosphonate for osteoporosis treatment.

Introduction: Minodronate increases bone mineral density (BMD) in postmenopausal osteoporotic patients. However, its efficacy in reducing osteoporotic fractures has not been tested.

Methods: To examine anti-fracture efficacy and safety of daily oral minodronate in postmenopausal women with established osteoporosis, a randomized, double-blind, placebo-controlled trial was conducted in 704 postmenopausal women (55 to 80 years) with one to five vertebral fractures and low BMD. Subjects were randomly assigned to receive daily oral 1 mg minodronate (n = 359) or placebo (n = 345) for 24 months, with daily supplements of 600 mg calcium and 200 IU vitamin D(3).

Results: Daily 1 mg minodronate for 24 months reduced the risk of vertebral fractures by 59% (95% CI, 36.6-73.3%). Furthermore, when fractures during the first 6 months were eliminated, the risk of vertebral fractures from 6 to 24 months was reduced by 74% in minodronate-treated group. Minodronate treatment also reduced height loss. Bone turnover markers were suppressed by about 50% after 6 months of minodronate treatment and remained suppressed thereafter. The overall safety profile including gastrointestinal safety was similar between the two groups.

Conclusions: Daily oral minodronate is safe, well-tolerated, and is effective in reducing vertebral fracture risk in postmenopausal women with established osteoporosis.

Trial registration: ClinicalTrials.gov NCT00212667.

Fig. 1

Enrollment and outcomes. A total of 1,083 subjects were screened, and 704 subjects were randomized to take either minodronate (359 subjects) or placebo (345 subjects)

Fig. 2

Kaplan–Meier estimates of the effect of daily oral 1 mg minodronate for 24 months on the risk of vertebral fractures in osteoporotic subjects. Cumulative incidence of vertebral fractures from the start of the study. Minodronate treatment reduced relative risk of vertebral fractures by 59%

Fig. 3

Effect of daily oral 1 mg minodronate for 24 months on height changes of osteoporotic patients. a Minodronate treatment significantly reduced height reduction at both 12 months (*p < 0.05) and 24 months (**p < 0.01). b Height changes in minodronate-treated patients with (closed triangle, n = 27) or without (closed diamond, n = 242) vertebral fracture, and placebo-treated patients with (open triangle, n = 61) or without vertebral fracture (open diamond, n = 200) are shown. Data are means ± SE

Fig. 4

Effect of daily oral 1 mg minodronate for 24 months on the changes in bone turnover markers in osteoporotic patients. Data are means ± SE