Although numerous studies have shown potent antiproliferative and differentiation-inducing effects of
1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) and its analogs on cells not directly related to bone metabolism, only few reports focussed on the effects of these analogs on bone. We compared the action of several recently developed analogs with that of 1,25-(OH)2D3 on human (MG-63) and rat (ROS 17/2.8) osteoblast-like cells and on in vitro
bone resorption. In MG-63 cells the analogs
EB1089 and
KH1060 were about 166,000 and 14,000 times more potent than 1,25-(OH)2D3 in stimulating
type I procollagen and 100 and 6,000 times more potent in stimulating
osteocalcin production, respectively. Also in ROS 17/2.8 cells
EB1089 and
KH1060 were most potent in inducing
osteocalcin synthesis. In vitro
bone resorption was 2.3 and 17.5 times more potently stimulated by
EB1089 and
KH1060, respectively. In MG-63 cells, 1,25-(OH)2D3 and the analogs inhibited cell proliferation, whereas both 1,25-(OH)2D3 and the analogs stimulated the growth of ROS 17/2.8 cells. Differences in potency could neither be explained by affinity for the
vitamin D receptor nor by a differential involvement of
protein kinase C in the action of the analogs. Together, these data show that also in bone the analogs
EB1089 and
KH1060 are more potent than 1,25-(OH)2D3 but that the potency of the analogs compared to 1,25-(OH)2D3 is dependent on the
biological response. On the basis of these observations it can be concluded that the reported reduced calcemic effect in vivo is not the result of a decreased responsiveness of bone to these analogs. Lastly, in view of eventual clinical application of 1,25-(OH)2D3-analogs, the observed stimulation of in vitro
bone resorption and growth of an
osteosarcoma cell line warrant in vivo studies to further examine these effects.