We have established an animal model of bone
metastasis using the PC-3 human prostate tumor cell line. In order to assess whether inhibition of
bone resorption would prevent the development of bone
metastasis, the diphosphonate
etidronate (
EHDP) was administered to 20 mice at a dose of 30 mg/kg subcutaneously daily starting 2 days prior to injection of
tumor cells. Control mice received daily
injections of the saline vehicle. In the
EHDP-treated mice, there was no significant reduction in the incidence of bone
metastasis, the size of the lesions, or the number of bone lesions per mouse. Approximately 50% of the mice developed bone
metastasis, which was similar to the control group and similar to what was observed in earlier studies with this animal model. Histomorphometric analysis of bones showed marked inhibition of mineralization in
EHDP-treated mice, thus indicating
biological effect on the bone. Therefore, the use of
EHDP in biologically effective doses failed to reduce the incidence, size, or number of bone
metastases in this animal model.