INHIBITION BY A NEW BISPHOSPHONATE (YM175) OF BONE-RESORPTION INDUCEDBY THE MBT-2 TUMOR OF MICE

A new bisphosphonate, disodium dihydrogen (cycloheptylamino) methylene bisphosphonate monohydrate (YM175), was compared with 3-amino-1-hydro xypropylidene-1, 1-bisphosphonate (AHPrBP) and 1-hydroxyethylidene-1,1 -bisphosphonate (HEBP) in terms of its effect on tumour induced osteol ysis using a bladder tumour in mice (MBT-2). The method consisted of i noculating tumour cells subcutaneously (SC) over the calvaria in mice, resulting in a local tumour causing fragmentation of the bone. The co mpounds were active not only when administered preventively before est ablishment of bone resorption, but also in an inhibitory fashion once the variables were already under the influence of the tumour. This ost eolysis was evaluated by measuring the increased area of bone resorpti on in reduced opacity to radiograph and histology. The results showed the following sequence of potency: YM175 > AHPrBP = HEBP. This inhibit ion was obtained with no apparent effect on the growth of the MBT-2 tu mour. YM175 appears to be an interesting new bisphosphonate with possi ble clinical application.