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The Vitamin D Analogue EB 1089 Prevents Skeletal Metastasis and Prolongs Survival Time in Nude Mice Transplanted with Human Breast Cancer Cells¹

Calcium Research Laboratory, Department of Medicine, McGill University and Royal Victoria Hospital, Montreal, Quebec H3A 1A1, Canada [K. E. A., V. P., D. G., R. K.]; Centre Hospitalier de L’Université de Montreal Research Center, Hôpital Saint-Luc, Montreal, Quebec H2X 1P1, Canada [N. D., P-E. C., L-G. S-M.]; and Leo Pharmaceuticals Ltd., Ballerup, Denmark [L. B.]

1,25-Dihydroxyvitamin D has potent antiproliferative and anti-invasive properties in vitro in cancer cells. However, its calcemic effect in vivo limits its therapeutic applications. Here, 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 line MDA-MB-231 in nude mice. Animals injected with tumor cells were implanted simultaneously with osmotic minipumps containing either EB 1089 or vehicle. Both groups remained normocalcemic for the duration of the experiment. The total number of bone metastases, the mean surface area of osteolytic lesions, and tumor burden within bone per animal were markedly decreased in EB1089-treated mice. Furthermore, longitudinal analysis revealed that mice treated with EB1089 displayed a marked increase in survival and developed fewer bone lesions and less hind limb paralysis over time as compared with untreated animals. These results suggest that EB1089 may be beneficial in the prevention of metastatic bone lesions associated with human breast cancer.

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