The effect of prostaglandin synthesis inhibitors and diphosphonates on tumour-mediated osteolysis

Abstract

Previous studies have shown that the prostaglandin synthesis inhibitor indomethacin reduced osteolysis produced by the experimental VX2 carcinoma, probably by inhibiting the stimulation of osteoclasts by prostaglandin E2. This study was carried out to determine whether prostaglandin inhibitors affect the tumour osteolysis produced by human mammary carcinoma as well as the VX2 carcinoma. The effect of diphosphonates on reducing tumour osteolysis was also investigated, since diphosphonates directly affect bone resorption. The results indicated that various non-steroidal, anti-inflammatory agents which inhibit prostaglandin synthesis reduced the osteolysis produced by human mammary or rabbit VX2 carcinomas. The diphosphonate compounds also produced a significant inhibition of tumour osteolysis. The results confirm the findings of Powles and his colleagues (1) that aspirin (also a prostaglandin synthesis inhibitor) reduced the osteolysis induced by human mammary carcinoma. It is suggested that these agents be evaluated as adjuvant therapy in patients with apparently 'early' mammary cancer in a controlled clinical trial.