The vitamin D analogue EB 1089 prevents skeletal metastasis and prolongs survival time in nude mice transplanted with human breast cancer cells

1,25-Dihydroxyvitamin D has potent antiproliferative and anti-invasive prop erties ill vitro in cancer cells. However, its calcemic effect in vivo limi ts its therapeutic applications, Acre, we report the efficacy of EB 1089, a low calcemic analogue of vitamin D, on the development of osteolytic bone metastases after intracardiac injection of the human breast cancer cell Lin e MDA-MB-231 in nude mice. Animals injected with tumor cells were implanted simultaneously with osmotic minipumps containing either EB1089 or vehicle. Both groups remained normocalcemic for the duration of the experiment. The total number of bone metastases, the mean surface area of osteolytic lesio ns, and tumor burden within bone per animal were markedly decreased in EB10 89-treated mice. Furthermore, Longitudinal analysis revealed that mice trea ted with EB1089 displayed a marked increase in survival and developed fewer bone lesions and less hind limb paralysis over time as compared with untre ated animals. These results suggest that EB1089 may be beneficial in the pr evention of metastatic bone lesions associated with human breast cancer.