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

International Journal of Molecular Sciences

Laura Mercatali⁴  Marianna Ricci⁴  Emanuela Scarpi³  Patrizia Serra³  Francesca Fabbri³  Rossana Ricci⁴  Chiara Liverani⁴  Michele Zanoni²  Wainer Zoli²  Roberta Maltoni¹  Erica Gunelli⁴  Dino Amadori⁴ 

[1] Department of Medical Oncology, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), via P. Maroncelli 40, 47014 Meldola (FC), Italy; E-Mail:;Biosciences Laboratory, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), via P. Maroncelli 40, 47014 Meldola (FC), Italy; E-Mails:;Unit of Biostatistics and Clinical Trials, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), via P. Maroncelli 40, 47014 Meldola (FC), Italy; E-Mail:;Osteoncology and Rare Tumors Center, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), via P. Maroncelli 40, 47014 Meldola (FC), Italy; E-Mails:

关键词: RANK;    RANK-L;    OPG;    NTX;    bone metastases;   

DOI  :  10.3390/ijms140610683

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland