Context: ED-71 has been shown to increase lumbar bone mineral density (BMD) in osteoporotic subjects. However, vitamin D insufficiency might have influenced the effect of ED-71 on BMD.

Objective: Our objective was to examine whether ED-71 can increase BMD in osteoporotic patients under vitamin D supplementation.

Design, Setting, and Patients: We conducted a randomized, double-blind, placebo-controlled clinical trial of 219 osteoporotic patients (49–87 yr of age).

Interventions: Subjects were randomly assigned to receive placebo or 0.5, 0.75, or 1.0 μg/d ED-71 for 12 months. All the subjects received 200 or 400 IU/d vitamin D₃.

Main outcome measures: We assessed changes in lumbar and hip BMD and bone turnover markers from baseline.

Results: Lumbar BMD increased with ED-71 treatment for 12 months (2.2, 2.6, and 3.1% from baseline and 2.9, 3.4, and 3.8% vs. placebo group in subjects receiving 0.5, 0.75, and 1.0 μg ED-71, respectively). Total hip BMD also increased with 0.75 and 1.0 μg ED-71 (−0.8, 0.6, and 0.9% from baseline and 0.1, 1.5, and 1.8% vs. placebo group in the 0.5, 0.75, and 1.0 μg ED-71 groups, respectively). Bone formation and resorption markers were suppressed by approximately 20% after 12 months of 0.75 and 1.0 μg ED-71 treatment. Transient hypercalcemia over 2.6 mmol/liter occurred in 7, 5, and 23% of subjects in the 0.5, 0.75, and 1.0 μg ED-71 groups, respectively, but none of them developed sustained hypercalcemia.

Conclusions: These results demonstrate that ED-71 treatment at around 0.75 μg/d can effectively and safely increase lumbar and hip BMD in osteoporotic patients with vitamin D supplementation.