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This article is part of the supplement: Basic science, rationale, background and future of denosumab: a RANK ligand inhibitor

Highly Accessed Review

Tumor metastasis to bone

Mandeep S Virk and Jay R Lieberman*

Author Affiliations

The New England Musculoskeletal Institute and Department of Orthopaedic Surgery, University of Connecticut Health Center, Farmington Avenue, Farmington, Connecticut 06030, USA

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Arthritis Research & Therapy 2007, 9(Suppl 1):S5  doi:10.1186/ar2169

Published: 29 June 2007

Abstract

Establishment of skeletal metastasis involves bidirectional interactions between the tumor cell and the cellular elements in the bone microenvironment. A better understanding of the pathophysiology of bone metastasis will be critical in developing the means to prevent bone metastasis or inhibit its progression. The receptor activator of nuclear factor-κB (RANK)/RANK ligand pathway has emerged as the key pathway regulating osteolysis in skeletal metastasis. A number of candidate factors, including the Wnt (wingless int) proteins, endothelin-1, and bone morphogenetic proteins, have been implicated in the establishment of osteoblastic metastasis. The complex nature of tumor-bone microenvironment interactions and the presence of multiple pathways that lead to bone metastasis suggests that simultaneous targeting of these pathways in the metastatic cascade are required for effective treatment. This review discusses current understanding of the pathophysiologic mechanisms that underlie the establishment of bone metastasis and potential molecular therapeutic strategies for prevention and treatment of bone metastasis.