In Vitro and In Vivo Antiresorptive Effects of Bisphosphonates in Metastatic Bone Disease

Abstract

Bone metastases commonly occur in the course of malignant tumor disease. For many years, attempts have been made to identify factors for the management of cancer-induced skeletal complications. Nowadays, synthetic antiresorptive agents are considered to be indispensable for the treatment of cancer-related skeletal events, such as bone metastasis. The most common of these drugs are the bisphosphonates, which represent one of the most significant advances over the last 10 years in the field of supportive care and cancer. They are used for the treatment of cancer-induced hypercalcemia, for the prevention and treatment of postmenopausal osteoporosis, for patients with bone metastases secondary to breast cancer and multiple myeloma. A third-generation bisphosphonate, zolendronate, has been shown to minimize the destructive consequences of bone metastases and to exert a profound effect on tumor-induced osteolysis and tumor growth in bone. Zoledronate is already used for the treatment of hypercalcemia of malignancy, multiple myeloma-related osteolytic events and for patients with documented bone metastases from solid tumors in conjunction with standard antineoplastic therapy. The structure-function activity of the three generations of bisphosphonates developed to date, the in vitro models used for studying their effects on osteoclasts and osteoblasts, as well as the results of clinical trials obtained by the third generation bisphosphonate, zoledronic acid, are presented.