Clinical value of bisphosphonates in cancer therapy.

The therapeutic opportunities for an improved management of malignant bone disease are currently extensively studied. The conventional management of symptomatic bone lesions in patients with advanced cancer involves various combinations of local and systemic standard anticancer therapies and the symptomatic treatment of skeletal complications. In recent years, bisphosphonates have demonstrated high efficacy to avoid skeletal complications from metastatic bone lesions and to prevent cancer treatment-induced bone loss. Especially in the treatment of patients with bone metastases, secondary to breast cancer, a widespread use of bisphosphonates has been established. With the development of highly potent new-generation bisphosphonates, such as zoledronate, the therapeutic opportunities for bisphosphonates are going to expand. Several current studies have investigated the benefit of zoledronate therapy for bone metastases from a variety of tumor types, including prostate cancer, lung and renal cell cancer and multiple myeloma. Furthermore, bisphosphonates have been shown to significantly reduce antineoplastic therapy-induced bone loss. According to recently published data, it is suggested that bisphosphonates not only play a role in the inhibition of osteoclast-mediated bone resorption, but also have antitumor effects inhibiting tumor cell proliferation, adhesion and invasion, as well as angiogenesis and induction of apoptosis. Further preclinical and clinical investigations are necessary to elucidate the role of bisphosphonates, and large randomized clinical trials should be conducted to confirm the clinical value of bisphosphonates for the prevention of relapse, as well as for the maintainance of net bone density, e.g. during aromatase inhibitor therapy.