Inhibition by a new bisphosphonate (AHBuBP) of bone resorption induced by the MBT-2 tumor of mice

Abstract

A new bisphosphonate, 4-amino-1-hydroxybuthylidene-1,1-bisphosphonate (AHBuBP), was compared with 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (AHPrBP) and 1-hydroxyethylidene-1,1-bisphosphonate (HEBP) in terms of its effect on tumor-induced osteolysis using a bladder tumor in mice (MBT-2). Tumor cells were inoculated subcutaneously (SC) over the calvaria in mice, resulting in a local tumor causing fragmentation of the bone. The tumor-induced osteolysis associated with osteoclasts proliferation was accompanied with reactive new bone formation. This osteolysis was evaluated by measuring the increased area of bone resorption in reduced opacity to radiograph and histologic study. The results showed the following sequence of potency: AHBuBP greater than AHPrBP = HEBP. This inhibition was obtained with no apparent effect on the growth of the MBT-2 tumor. The authors conclude that AHBuBP appears to be an interesting new bisphosphonate with possible clinical application.