Zoledronic acid to prevent and treat cancer metastasis: new prospects for an old drug.

Zoledronic acid (zoledronate, Zometa™; Novartis Pharmaceuticals, Basel, Switzerland) is a nitrogen-containing bisphosphonate. Zoledronate rapidly binds to bone mineral where it is then ingested by osteoclasts. Once internalized, zoledronate inhibits the mevalonate pathway, which stops osteoclast function, and thus slows bone resorption. Zoledronate is approved for the prevention of skeletal morbidity in metastatic bone disease from solid tumors and multiple myeloma. Zoledronate is also recommended as an option for the treatment of cancer therapy-induced bone loss. In recent large Phase III studies in early breast cancer, zoledronate reduced both local and distant recurrences in women with induced or established natural menopause. Postulated mechanisms underlying the anticancer properties of zoledronate include antiangiogenic and immunomodulatory effects. A clearer understanding of these mechanisms will enable the full potential of zoledronate to be realized.