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Nature 445, E19 (22 February 2007) | doi:10.1038/nature05657; Published online 21 February 2007

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Bone Metastasis: Can osteoclasts be excluded?

T. John Martin1 & Gregory R. Mundy2

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Arising from: D. H. Jones et al. Nature 440, 692–696 (2006); Jones et al. reply

The RANK/RANKL signalling mechanism is the final common pathway of osteoclast formation and activity1. Inhibitors of RANK ligand (RANKL) that bind to RANK (for 'receptor activator of NF-kappaB'), such as osteoprotegerin (OPG), neutralizing antibodies against RANKL and soluble RANK antagonists, are well described inhibitors of bone metastasis in preclinical and clinical models, presumably because of their effects on osteoclasts2. Jones et al.3 show that OPG inhibits bone metastasis after intracardiac injection of B16F10 murine melanoma cells, but claim that bone metastases are entirely independent of osteoclast formation and bone resorption: rather, they are caused by an effect on cell migration through RANK. However, we question whether these surprising conclusions are rigorously supported by their data3.

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