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.
BACKGROUND
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.


METHODS
We conducted a randomized, double-blind, placebo-controlled clinical trial of 219 osteoporotic patients (49-87 yr of age).


METHODS
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).


METHODS
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.
Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Health Biosciences, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan. toshimat@clin.med.tokushima-u.ac.jp
Toshio
T
Matsumoto
Takami
T
Miki
Hiroshi
H
Hagino
Toshitsugu
T
Sugimoto
Sumiaki
S
Okamoto
Takako
T
Hirota
Yusuke
Y
Tanigawara
Yasufumi
Y
Hayashi
Masao
M
Fukunaga
Masataka
M
Shiraki
Toshitaka
T
Nakamura
D015502:Absorptiometry, Photon; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood / Q000652:urine; D015519:Bone Density / Q000187:drug effects*; D016723:Bone Remodeling; D002117:Calcitriol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006621:Hip Joint / Q000000981:diagnostic imaging / Q000378:metabolism; D006728:Hormones / Q000097:blood; D006801:Humans; D006934:Hypercalcemia / Q000139:chemically induced; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000000981:diagnostic imaging / Q000188:drug therapy*; D010349:Patient Compliance; D014807:Vitamin D / Q000627:therapeutic use* / Q000031:analogs & derivatives
D015415:Biomarkers; D006728:Hormones; D014807:Vitamin D; D002117:Calcitriol; C547512:eldecalcitol; D002118:Calcium