A New Active Vitamin D, ED-71, Increases Bone Mass in Osteoporotic Patients under Vitamin D Supplementation: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

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 microg/d ED-71 for 12 months. All the subjects received 200 or 400 IU/d vitamin D(3). 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 microg ED-71, respectively). Total hip BMD also increased with 0.75 and 1.0 microg 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 microg ED-71 groups, respectively). Bone formation and resorption markers were suppressed by approximately 20% after 12 months of 0.75 and 1.0 microg 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 microg ED-71 groups, respectively, but none of them developed sustained hypercalcemia. CONCLUSIONS: These results demonstrate that ED-71 treatment at around 0.75 microg/d can effectively and safely increase lumbar and hip BMD in osteoporotic patients with vitamin D supplementation.