INHIBITION BY DIPHOSPHONATES OF BONE-RESORPTION INDUCED BY THE WALKER TUMOR OF THE RAT

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  • 1 January 1984
    • journal article
    • research article
    • Vol. 44  (7) , 3007-3011
Abstract
An animal model is described to test the effect of diphosphonates, which are powerful antiosteolytic agenst, aginst bone tumors. This model consists of injecting Walker tumor cells into 1 iliac artery of a series of rats while the contralateral artery is clamped during the injection, and waiting 7 days to obtain a significant destruction of the femur and tibia of the rats. The parenteral administration of 3 diphosphonates, dichloromethylene diphosphonate, ethanehydroxydiphosphonate, and aminopropanediphosphonate, at 16 and 160 .mu.mol/kg per day, protects the bones by decreasing the extent of osteolysis. This protective effect is seen both in the tumor-injected leg and in the contralateral leg and is significant when compared to nontreated animals. The most active of the drugs was dichloromethylene-diphosphonate: ethanehydroxydiphosphonate and aminopropanediphosphonate were less active, especially at the higher dosage. All diphosphonates produce a marked decrease of the number of osteoclasts; ethanehydroxydiphosphonate at the higher dosage, induced a large increase of nonmineralized bone. These results are discussed in light of recent clinical work, showing that this animal model is a useful tool to test the effect of new drugs against osteolysis of cancer.