RANK/RANK-L/OPG in patients with bone metastases treated with anticancer agents and zoledronic acid: A prospective study

Laura Mercatali, Marianna Ricci, Emanuela Scarpi, Patrizia Serra, Francesca Fabbri, Rossana Ricci, Chiara Liverani, Michele Zanoni, Wainer Zoli, Roberta Maltoni, Erica Gunelli, Dino Amadori, Toni Ibrahim

Research output: Contribution to journalArticlepeer-review


Patients with solid cancer frequently develop bone metastases (BM). Zoledronic acid (Zometa® Meldola, 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.

Original languageEnglish
Pages (from-to)10683-10693
Number of pages11
JournalInternational Journal of Molecular Sciences
Issue number6
Publication statusPublished - 2013


  • Bone metastases
  • NTX
  • OPG
  • RANK
  • RANK-L

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Spectroscopy
  • Inorganic Chemistry
  • Catalysis
  • Molecular Biology
  • Computer Science Applications
  • Medicine(all)

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