A novel synthetic vitamin D analogue, 2 beta-(3-hydroxypropoxy)1 alpha, 25-dihydroxyvitamin D3 (ED-71), increases bone mass by stimulating the bone formation in normal and ovariectomized rats.
We performed dosing experiments to evaluate the bone mass increasing action of a novel, synthetic vitamin D derivative, 2 beta-(3-hydroxypropoxy)-1 alpha,25(OH)2D3 (ED-71), in normal and estrogen-deficient rats. The first experiment consisted of 31 Sprague-Dawley rats, 28 weeks of age. The second experiment consisted of 44 animals who were ovariectomized (OVX) or sham operated at the age of 12 weeks. ED-71 was given twice a week for the duration of 12 weeks. At the end of the experiments, serum chemistries were examined and lumbar vertebrae were assessed histomorphometrically. Serum alkaline-phosphatase levels tended to decrease by ED-71 administration in the first experiment and their elevated values after ovariectomy were also depressed by ED-71 in the second experiment. Serum osteocalcin levels, however, increased by the agent. In the first experiment, cancellous bone volume (BV/TV) increased dose dependently. Bone formation rates (BFR/BS) also increased. In the second experiment, BV/TV significantly decreased by ovariectomy and it increased in ED-71-treated groups, but not in 1 alpha-(OH)D3-treated group. BFR/BS increased by ED-71. Activation frequency did not decrease by ED-71 in either experiment. These data clearly demonstrated that ED-71 administration was capable of increasing the bone mass by stimulating bone formation in normal and estrogen-deficient rats.
Tsurukami
H
H
Department of Orthopaedic Surgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
Nakamura
T
T
Suzuki
K
K
Sato
K
K
Higuchi
Y
Y
Nishii
Y
Y
D000469:Alkaline Phosphatase / Q000032:analysis / Q000097:blood; D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D001846:Bone Development; D016723:Bone Remodeling / Q000187:drug effects; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology; D002118:Calcium / Q000032:analysis / Q000097:blood; D003404:Creatinine / Q000097:blood; D004967:Estrogens / Q000172:deficiency / Q000502:physiology; D005260:Female; D008159:Lumbar Vertebrae / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D009924:Organ Culture Techniques; D015675:Osteocalcin / Q000097:blood; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014807:Vitamin D / Q000031:analogs & derivatives
D004967:Estrogens; D015675:Osteocalcin; D014807:Vitamin D; D003404:Creatinine; D000469:Alkaline Phosphatase; D002117:Calcitriol; C547512:eldecalcitol; D002118:Calcium