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

• Published in: The journal of clinical endocrinology and metabolism 2005-09, Vol.90 (9), p.5031-5036
• Main Authors: Matsumoto, Toshio, Miki, Takami, Hagino, Hiroshi, Sugimoto, Toshitsugu, Okamoto, Sumiaki, Hirota, Takako, Tanigawara, Yusuke, Hayashi, Yasufumi, Fukunaga, Masao, Shiraki, Masataka, Nakamura, Toshitaka
• Format: Article
• Language: English
• Subjects: Absorptiometry, Photon; Aged; Aged, 80 and over; Biological and medical sciences; Biomarkers - blood; Biomarkers - urine; Bone Density - drug effects; Bone Remodeling; Calcitriol - administration & dosage; Calcitriol - adverse effects; Calcitriol - analogs & derivatives; Calcitriol - blood; Calcitriol - therapeutic use; Calcium - metabolism; Dose-Response Relationship, Drug; Double-Blind Method; Endocrinopathies; Female; Fundamental and applied biological sciences. Psychology; Hip Joint - diagnostic imaging; Hip Joint - metabolism; Hormones - blood; Humans; Hypercalcemia - chemically induced; Lumbar Vertebrae - diagnostic imaging; Lumbar Vertebrae - metabolism; Male; Medical sciences; Middle Aged; Osteoporosis - diagnostic imaging; Osteoporosis - drug therapy; Patient Compliance; Vertebrates: endocrinology; Vitamin D - therapeutic use
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2004-2552

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.