A new active vitamin D analog, ED-71, causes increase in bone mass with preferential effects on bone in osteoporotic patients.
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 II 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 microgram) 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.
Kubodera
N
N
Chugai Pharmaceutical Co., Ltd., 2-1-9, Kyobashi, Chuo-ku, Tokyo 104-8301, Japan. kuboderanbr@chugai-pharm.co.jp
Tsuji
N
N
Uchiyama
Y
Y
Endo
K
K
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D001862:Bone Resorption / Q000188:drug therapy; D001842:Bone and Bones / Q000187:drug effects*; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006887:Hydroxycholecalciferols / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000188:drug therapy*; D010052:Ovariectomy; D051381:Rats; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood
D000276:Adjuvants, Immunologic; D006887:Hydroxycholecalciferols; D014807:Vitamin D; C097949:1,25-dihydroxyvitamin D; D002117:Calcitriol; C547512:eldecalcitol; C008088:alfacalcidol