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®, 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.
authors.affiliation: 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. t.ibrahim@irst.emr.it.
authors.forename: Laura
authors.initials: L
authors.lastname: Mercatali
authors.forename: Marianna
authors.initials: M
authors.lastname: Ricci
authors.forename: Emanuela
authors.initials: E
authors.lastname: Scarpi
authors.forename: Patrizia
authors.initials: P
authors.lastname: Serra
authors.forename: Francesca
authors.initials: F
authors.lastname: Fabbri
authors.forename: Rossana
authors.initials: R
authors.lastname: Ricci
authors.forename: Chiara
authors.initials: C
authors.lastname: Liverani
authors.forename: Michele
authors.initials: M
authors.lastname: Zanoni
authors.forename: Wainer
authors.initials: W
authors.lastname: Zoli
authors.forename: Roberta
authors.initials: R
authors.lastname: Maltoni
authors.forename: Erica
authors.initials: E
authors.lastname: Gunelli
authors.forename: Dino
authors.initials: D
authors.lastname: Amadori
authors.forename: Toni
authors.initials: T
authors.lastname: Ibrahim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001859:Bone Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary*; D001943:Breast Neoplasms / Q000473:pathology; D024042:Collagen Type I / Q000097:blood; D004164:Diphosphonates / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D053244:Osteoprotegerin / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000097:blood; D011446:Prospective Studies; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D000077211:Zoledronic Acid
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D024042:Collagen Type I; D004164:Diphosphonates; D007093:Imidazoles; D053244:Osteoprotegerin; D010455:Peptides; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C052929:collagen type I trimeric cross-linked peptide; D000077211:Zoledronic Acid