Combined Therapies of Bone Disease with Bisphosphonates

S.      P. Syddall; P.      D. Ottewell; I.      Holen

Abstract

Bisphosphonates are standard treatment for cancer-induced bone disease, a common feature of many advanced malignancies. Traditionally used to inhibit bone turnover and reduce the risk of skeletal-related events, there is now increasing pre-clinical evidence that these agents may also affect tumour burden and disease progression. In particular, combining bisphosphonates with chemotherapeutic agents has been demonstrated to cause substantially increased anti-tumour effects compared to giving the single agents. Clinical studies are in progress to determine whether adding bisphosphonates to standard anti-cancer therapy results in improved outcome for patients. Here we give an overview of the key pre-clinical studies of anti-tumour effects of bisphosphonates, alone and in combination with other agents, and introduce some of the ongoing clinical trials that aim to determine the clinical relevance of bisphosphonates in combination therapy.

Keywords: Zoledronic acid, metastatic bone disease, synergy, bone, Combined Therapies, Bone Disease, Bisphosphonates, advanced malignancies, chemotherapeutic agents, synergy, bone, kidney, prostate, lytic and sclerotic elements, anti-scaling agents, Paget's disease, cholesterol, post-translational modification, osteoclast activity, anti-cancer agents, umour cell apoptosis, MB-231, MCF-7, Hs 578T, alendronate, ibandronate, pamidronate, risedronate, bovine cortical bone slices, cervical intraepithelial neoplasia, lung cancer cells, tumour vascularisation, anti-tumourigenic, osteolytic lesions, non-bone metastases, prostate cancer, zole-dronic acid, T-cell leukemia, regulating tumour growth, COMBINATION THERAPY, invasive cancer, doxorubicin, chemotherapeutic agent, prostate cancer cell lines, mouse breast cancer, intra-cardiac injection, osteolytic bone disease, anatomical, invasive breast cancer, angiogenesis, neo-adjuvant anthracycline, antitumour effects