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Bone. 1995 Oct;17(4):391-5.

Studies on two new vitamin D analogs, EB 1089 and KH 1060: effects on bone resorption and osteoclast recruitment in vitro.

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Department of Internal Medicine, University Hospital, Uppsala, Sweden.


We have investigated the effects on bone resorption of two new potent antiproliferative vitamin D3 analogs, EB 1089 and KH 1060, by studying recruitment of osteoclasts in murine bone marrow cultures and 45Ca release from prelabeled neonatal mouse calvarial bones. Binding studies to vitamin D receptor protein, from human osteosarcoma MG-63 cells, demonstrated kd values of 8.5 x 10(-11) for 1 alpha,25(OH)2D3, 6.5 x 10(-11) for KH 1060, and 2.7 x 10(-10) for EB 1089. 1 alpha,25(OH)2D3 and EB 1089 were equipotent stimulators of osteoclast recruitment in murine bone marrow cultures, with EC50 at 10(-10) mol/L, whereas KH 1060 was about tenfold more potent with an EC50 at 10(-11) mol/L. In serum-free media, 1 alpha,25(OH)2D3 enhanced 45Ca release from neonatal mouse calvarial bones with EC50 at 10(-11) mol/L, but in the presence of 10% fetal calf serum (FCS) the stimulatory effect was significantly diminished, with a threshold value at 10(-10) mol/L. EB 1089 stimulated bone resorption with an estimated EC50 at 3 x 10(-11) mol/L, whereas KH 1060 was about tenfold more potent than 1 alpha,25(OH)2D3, and stimulated bone resorption with an EC50 at 10(-12) mol/L. The effects of EB 1089 and KH 1060 on 45Ca release were not significantly affected by the addition of 10% FCS. Addition of vitamin D binding protein to serum-free incubations of neonatal mouse calvarial bones, significantly inhibited the bone resorbing effect of 1 alpha,25(OH)2D3, but did not affect EB 1089 and KH 1060 induced 45Ca release.(ABSTRACT TRUNCATED AT 250 WORDS).

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