Therapeutic use of bisphosphonates in breast cancer: Studies with zoledronic acid

Bisphosphonates are synthetic derivatives of phosphonate, a normal constituent of bone. These agents are potent inhibitors of osteoclastic resorption, and as such are being explored for the management of various pathological conditions including osteoporosis, hypercalcemia, bone metastases and certain aspects of cancer. Among the first agents to be developed in the class, clodronic acid has shown conflicting results with respect to its ability to reduce osseous metastases, while pamidronic acid reduced hypercalcemia effectively compared with placebo in patients with breast cancer and multiple myeloma. Recent exploratory studies have shown that the novel bisphosphonate zoledronic acid reduces hypercalcemia more effectively than pamidronic acid in patients with various malignancies, In a recent phase III trial designed to show equivalence, zoledronic acid was as effective as pamidronic acid in the number of skeletal-related events arising over a predefined period of time. Furthermore, a trend in radiation therapy delay was observed in the zoledronic acid group. Zoledronic acid appears to be an effective agent in reducing the complications from bone involvement in cancer patients and it has shown efficacy in the prevention of osteoporosis in healthy postmenopausal women. For these reasons, it is being investigated as an adjunct to adjuvant therapy for postmenopausal patients with early breast cancer treated with nonsteroidal aromatase inhibitors, because efficient and prolonged estrogen deprivation with the latter agents may result in an increased risk of bone degradation in some patients.