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 journalArticle

10 Citations (Scopus)

Abstract

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
Volume14
Issue number6
DOIs
Publication statusPublished - 2013

Fingerprint

zoledronic acid
RANK Ligand
metastasis
Cytoplasmic and Nuclear Receptors
Antineoplastic Agents
bones
Bone
Ligands
Prospective Studies
Neoplasm Metastasis
Bone and Bones
ligands
acids
Acids
Osteoclasts
serums
Osteoprotegerin
cancer
Bone Remodeling
schedules

Keywords

  • 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)

Cite this

@article{dc316d125e7f4daa8d60fb20ec6aa95d,
title = "RANK/RANK-L/OPG in patients with bone metastases treated with anticancer agents and zoledronic acid: A prospective study",
abstract = "Patients with solid cancer frequently develop bone metastases (BM). Zoledronic acid (Zometa{\circledR} 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.",
keywords = "Bone metastases, NTX, OPG, RANK, RANK-L",
author = "Laura Mercatali and Marianna Ricci and Emanuela Scarpi and Patrizia Serra and Francesca Fabbri and Rossana Ricci and Chiara Liverani and Michele Zanoni and Wainer Zoli and Roberta Maltoni and Erica Gunelli and Dino Amadori and Toni Ibrahim",
year = "2013",
doi = "10.3390/ijms140610683",
language = "English",
volume = "14",
pages = "10683--10693",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
publisher = "MDPI AG",
number = "6",

}

TY - JOUR

T1 - RANK/RANK-L/OPG in patients with bone metastases treated with anticancer agents and zoledronic acid

T2 - A prospective study

AU - Mercatali, Laura

AU - Ricci, Marianna

AU - Scarpi, Emanuela

AU - Serra, Patrizia

AU - Fabbri, Francesca

AU - Ricci, Rossana

AU - Liverani, Chiara

AU - Zanoni, Michele

AU - Zoli, Wainer

AU - Maltoni, Roberta

AU - Gunelli, Erica

AU - Amadori, Dino

AU - Ibrahim, Toni

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

KW - Bone metastases

KW - NTX

KW - OPG

KW - RANK

KW - RANK-L

UR - http://www.scopus.com/inward/record.url?scp=84878169309&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84878169309&partnerID=8YFLogxK

U2 - 10.3390/ijms140610683

DO - 10.3390/ijms140610683

M3 - Article

C2 - 23702841

AN - SCOPUS:84878169309

VL - 14

SP - 10683

EP - 10693

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 6

ER -