Effects of two new vitamin D3 derivatives, 22-oxa-1 alpha-25-dihydroxyvitamin D3 (OCT) and 2 beta-(3-hydroxypropoxy)-1 alpha, 25-dihydroxyvitamin D3 (ED-71), on bone metabolism in organ culture.
We have tested two new vitamin D3 derivatives, 22-oxa-1 alpha, 25-dihydroxyvitamin D3 (OCT) and 2 beta-(3-hydroxypropoxy)-1 alpha, 25-dihydroxyvitamin D3 (ED-71), for their effects on bone metabolism compared with 1 alpha, 25-dihydroxyvitamin D3 (1,25(OH)2D3) in two organ-culture systems. In a previous study (Abe et al. 1987), it was reported that OCT had weak activity in stimulating bone resorption in vitro. In the present study, however, OCT stimulated bone resorption in cultured fetal rat long bones and inhibited collagen synthesis in cultured neonatal mouse calvariae in a dose-dependent manner with significant effects at 10(-10) M and maximal responses at 10(-8) M. Its potency and effectiveness were identical to 1,25(OH)2D3. On the other hand, ED-71, which has been found to prevent bone loss in vivo (Okano et al. 1989b), was less active in vitro. The activity of ED-71 at 10(-8) M on bone resorption was similar to 1,25(OH)2D3, but it did not stimulate resorption at 10(-10) M. Its inhibitory effect on collagen synthesis was weaker than for OCT of 1,25(OH)2D3. The activity of all three compounds on bone resorption was not inhibited by indomethacin or cortisol. 1,25(OH)2D3 and OCT significantly inhibited [3H]-thymidine incorporation into mouse calvariae at 10(-9) M, while ED-71 inhibited [3H]-thymidine incorporation only at 10(-8) M. These results indicate that OCT and 1,25(OH)2D3 have similar effects on bone in organ culture. Pharmacokinetic differences may explain the marked difference in response to those two agents in vivo. ED-71 is less potent, particularly in inhibiting bone formation. Such differences may have importance in the development of vitamin D analogs for clinical use.
Sato
K
K
Bone & Calcified Tissue Res. Lab. of Chugai Pharmaceutical Co. Tokyo, Japan.
Nishii
Y
Y
Woodiel
F N
FN
Raisz
L G
LG
D000818:Animals; D016723:Bone Remodeling / Q000187:drug effects; D001862:Bone Resorption / Q000139:chemically induced; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology; D003094:Collagen / Q000096:biosynthesis; D004247:DNA / Q000096:biosynthesis; D051379:Mice; D009924:Organ Culture Techniques; D010012:Osteogenesis / Q000187:drug effects; D051381:Rats; D014807:Vitamin D / Q000031:analogs & derivatives
D014807:Vitamin D; D003094:Collagen; D004247:DNA; D002117:Calcitriol; C547512:eldecalcitol; C051883:maxacalcitol