Bisphosphonate Therapy in the Treatment of Multiple Myeloma

M.      A. Lawson; J.      Ashcroft; P.      I. Croucher

Abstract

Multiple myeloma is an incurable B cell neoplasm caused by the monoclonal expansion of malignant plasma cells in the bone marrow, often resulting in devastating bone disease. For over 2 decades bisphosphonates have been successfully used to treat the tumourinduced bone disease associated with multiple myeloma. This review will focus on preclinical studies and investigations in patients with multiple myeloma that have led to our current understanding of the mechanisms of action of bisphosphonates in myeloma bone disease. Major advances in the use of bisphosphonates, including findings that they may have additional benefits such as anti-tumour effects and promoting patient survival will be discussed.

Keywords: Bisphosphonates, myeloma, anti-resorptive, anti-tumour, bone, osteoclasts, osteolytic lesions, Multiple Myeloma, M-spike, M-protein, Bence-Jones Protein, lymphatohaemopoietic cancer, Osteoclast-derived molecules, dickkopf-1 (DKK1), frizzled-related protein (sFRP)-2, myeloma-derived DKK1, MM-derived osteoclasts, anti-DKK1, OSTEOCLAST INHIBITION, clodronate (CLOD), etidronate (ETID), protein prenylation, bone mineral density (BMD), Anti-Tumour Effects, anti-resorptive potency, SCID-hu model, Angiogenesis, Bisphosphoante-Associated Osteonecrosis of the Jaw (BONJ), vascular insufficiency, B-cell activating factor, Hepatocyte growth factor, Interleukin 1 alpha