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: To examine whether ED-71 can increase BMD in osteoporotic patients under vitamin D supplementation.

Design, Setting, and Patients: Randomized, double-blind, placebo-controlled clinical trial of 219 osteoporotic patients (49 to 87 yr).

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

Main outcome measures: Changes in lumbar, hip BMD and bone turover 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 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 0.5, 0.75 and 1.0 µg ED-71, 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/L occurred in 7, 5 and 23% of subjects in 0.5, 0.75 and 1.0 µg ED-71, respectively, but none of them developed sustained hypercalcemia.

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