Zoledronic acid reduces osteosarcoma lung metastases in mice

Treatment with zoledronic acid can reduce lung metastases and improve survival in mice inoculated with an osteosarcoma cell line, according to a report in the December 22nd issue of Cancer.

Bisphosphonate like zoledronic acid have proven useful in treating bone metastases, but their effect on visceral metastases has not been well studied, Dr. Dominique Heymann, from the Universite de Nantes in France, and colleagues note. To investigate, the researchers created a murine model of lung metastasis using animals intravenously inoculated with a spontaneous osteosarcoma cell line. They performed autopsies at death or several weeks later to assess the presence of metastases in mice treated with zoledronic acid and in control animals.Treatment with zoledronic acid, either two or five times a week, was associated with a significant improvement in actuarial survival relative to non-treatment (p = 0.036). Moreover, no lung metastases were seen in any of the zoledronic acid-treated mice that survived more than 21 days postinjection.In vitro analysis showed that incubation with zoledronic acid for 48 hours inhibited proliferation of the cancerous cells, apparently related to an arrest in the S-phase of the cell cycle. Treatment with the drug appeared to increase the activity of caspase-3, but not caspase-1.The findings suggest that zoledronic acid “could benefit patients with nonskeletal metastases, including osteosarcoma patients who remain at high risk of eventual relapse, with overt metastatic disease, with tumors that recur after treatment, or that show a low degree of necrosis after administration of chemotherapy and continue to have an unsatisfactory outcome,” the authors conclude. (Source: Cancer 2005;104:2522-2529: Reuters Health: Oncolink: January 2006.)