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 mu g/ dED-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 mu g ED- 71, respectively). Total hip BMD also increased with 0.75 and 1.0 mu g 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 mu g ED- 71 groups, respectively). Bone formation and resorption markers were suppressed by approximately 20% after 12 months of 0.75 and 1.0 mu g 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 mu g ED- 71 groups, respectively, but none of them developed sustained hypercalcemia. Conclusions: These results demonstrate that ED- 71 treatment at around 0.75 mu g/ d can effectively and safely increase lumbar and hip BMD in osteoporotic patients with vitamin D supplementation.