The bisphosphonate zoledronic acid inhibits the development of plasmacytoma induced in BALB/c mice by intraperitoneal injection of pristane

Objectives: Bisphosphonates (BPs) are mostly used in the palliative care of myeloma-associated osteolytic lesions. Recent studies have suggested that BPs may also exert direct antitumor effects on myeloma cells. We have investigated the effect of the potent bisphosphonate, zoledronic acid (ZOL), on the development of pristane (2,6,10,14-tetramethylpentadecane)-induced plasmacytoma (PCT) in six-week-old BALB/c mice. Methods: Different groups of pristane-treated mice also received ZOL (100 mu g/kg) commencing after the development of PCT or ZOL (20 mu g/kg) from the first day. Control groups received pristane alone, ZOL alone (20 mu g/kg), or phosphate-buffered saline. The study was terminated on day 300, and the remaining mice were autopsied and abdominal tissues were examined histologically for PCT. Results and conclusions: Statistical analysis revealed a significant delay in PCT development in the group receiving pristane plus ZOL (20 mu g/kg) from the first day compared to the groups receiving pristane alone and pristane combined with ZOL (100 mu g/kg) after the appearance of PCT (Log-rank, P = 0.0001 and 0.0001; respectively). Kaplan-Meier analysis revealed a significant difference in survival between the group treated with pristane alone and the groups receiving pristane plus ZOL (20 mu g/kg) from the first day or ZOL (100 mu g/kg) after the appearance of PCT (Log-rank, P = 0.016 and 0.023; respectively). These results indicate a direct anti-tumor effect of ZOL in pristane-induced PCT development BALB/c mice, which may contribute to their significantly increased survival. This hypothesis should now be further investigated in clinical trials.