Journal
JOURNAL OF CELLULAR BIOCHEMISTRY
Volume 88, Issue 2, Pages 286-289Publisher
WILEY-LISS
DOI: 10.1002/jcb.10346
Keywords
1 alpha('')25-dihydroxy-2 beta-(3-hydroxypropoxy)vitamin D3; ED-71; 1 alpha-hydroxyvitamin D3; 1 alpha(')25-dihydroxyvitamin D3; osteoporosis; alfacalcidol
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As a candidate for active vitamin D analogs that have selective effects on bone, 1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)vitamin D3 (ED-71) has been synthesized and is currently under clinical trials. In ovariectomized rat model for osteoporosis, ED-71 caused an increase bone mass at the lumbar vertebra to a greater extent than 1alpha-hydroxyvitamin D3 (alfacalcidol), while enhancing calcium absorption and decreasing serum parathyroid hormone levels to the same degree as alfacalcidol. ED-71 lowered the biochemical and histological parameters of bone resorption more potently than alfacalcidol, while maintaining bone formation markers. An early phase It clinical trial was conducted with 109 primary osteoporotic patients. The results indicate that oral daily administration of ED-71 (0.25, 0.5, 0.75, and 1.0 mug) for 6 months increased lumbar bone mineral density in a dose-dependent manner without causing hypercalcemia and hypercalciuria. ED-71 also exhibited a dose-dependent suppression of urinary deoxypyridinoline with no significant reduction in serum osteocalcin. These results demonstrate that ED-71 has preferential effects on bone with diminished effects on intestinal calcium absorption. ED-71 offers potentially a new modality of therapy for osteoporosis with selective effects on bone. (C) 2002 Wiley-Liss, Inc.
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