Effects of new bisphosphonic acids on tumor-induced bone destruction in the rat.

This report is concerned with therapeutic studies utilizing new bisphosphonic acids on tumor-induced osteolytic metastases. The bone metastases on SD rats were induced by intraarterial and intraosseous transplantation of Walker carcinosarcoma 256 B ascites cells. The treatment was carried out using disodium-3-amino-1-hydroxypropylidene-1,1-bisphosphonate (ADP), diglycidyl-[3-(3, 3-bisphosphono-3-hydroxy-propylamino)-2-hydroxypropyl-]urazol++ +-Na2 (DDU) and 1,2,4-triglycidylurazol (TGU). The extent of bone metastases was determined by X-ray on the 5th and 10th days following tumor inoculation, as well as both microradiographically and histologically upon termination of the experiment. High dose DDU produced a clear reduction of the tumor osteolysis, but these positive results were surpassed using APD. The best results were achieved by pretreatment with APD 24 h prior to tumor inoculation.