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)