Effects of a new bisphosphonate (AHBuBP) on osteolysis induced by human prostate cancer cells in nude mice.

A new bisphosphonate, 4-amino-1-hydroxybutylidene-1, 1-bisphosphonate (AHBuBP), was compared with 3-amino-1-hydroxypropylidene-1, 1-bisphosphonate (AHPrBP) and 1-hydroxyethylidene-1, 1-bisphosphonate (HEBP) assessing their effects on tumor induced osteolysis using human prostate adenocarcinoma cells in nude mice. The method consisted of inoculating transplantable human prostate cancer cells subcutaneously over the calvaria in nude mice resulting in a local tumor causing fragmentation of the bone. The parameters included assessing the extent of decreased osteolysis in bone as judged by X-ray and histological examination. The results showed the following sequence of potency: AHBuBP greater than AHPrBP greater than HEBP. The compounds were active not only when administered preventively before establishment of bone resorption, but also in an inhibitory fashion once the variables were already under the influence of the tumor. This inhibition was obtained with no apparent effect on the growth of the tumor. AHBuBP appears to be an interesting new bisphosphonate for future clinical use.