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Int. J. Mol. Sci. 2013, 14(6), 10683-10693; doi:10.3390/ijms140610683

RANK/RANK-L/OPG in Patients with Bone Metastases Treated with Anticancer Agents and Zoledronic Acid: A Prospective Study

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Received: 15 April 2013 / Revised: 9 May 2013 / Accepted: 13 May 2013 / Published: 23 May 2013
(This article belongs to the Special Issue Molecular Bases of Cancer Research)
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Patients with solid cancer frequently develop bone metastases (BM). Zoledronic acid (Zometa®, ZA), routinely used to treat patients with BM, acts on osteoclasts and also has antitumor properties. We aimed to assess the effect of ZA over time in novel bone turnover markers (RANK/receptor activator of nuclear factor-k B ligand (RANK-L)/ Osteoprotegerin (OPG)) and to correlate these with serum N-terminal telopeptide (NTX). The study prospectively evaluated levels of RANK, RANK-L and OPG transcripts by real-time PCR and NTX expression by ELISA in the peripheral blood of 49 consecutive patients with advanced breast, lung or prostate cancer. All patients received the standard ZA schedule and were monitored for 12 months. Median baseline values of RANK, RANK-L and OPG were 78.28 (range 7.34–620.64), 319.06 (21.42–1884.41) and 1.52 (0.10–58.02), respectively. At 12 months, the median RANK-L value had decreased by 22% with respect to the baseline, whereas median OPG levels had increased by about 96%. Consequently, the RANK-L/OPG ratio decreased by 56% from the baseline. Median serum NTX levels decreased over the 12-month period, reaching statistical significance (p < 0.0001). Our results would seem to indicate that ZA modulates RANK, RANK-L and OPG expression, thus decreasing osteoclast activity.
Keywords: RANK; RANK-L; OPG; NTX; bone metastases RANK; RANK-L; OPG; NTX; bone metastases
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Mercatali, L.; Ricci, M.; Scarpi, E.; Serra, P.; Fabbri, F.; Ricci, R.; Liverani, C.; Zanoni, M.; Zoli, W.; Maltoni, R.; Gunelli, E.; Amadori, D.; Ibrahim, T. RANK/RANK-L/OPG in Patients with Bone Metastases Treated with Anticancer Agents and Zoledronic Acid: A Prospective Study. Int. J. Mol. Sci. 2013, 14, 10683-10693.

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