{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T05:13:28Z","timestamp":1767849208538,"version":"3.49.0"},"reference-count":28,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2013,5,23]],"date-time":"2013-05-23T00:00:00Z","timestamp":1369267200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Patients with solid cancer frequently develop bone metastases (BM). Zoledronic acid (Zometa\u00ae, 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\u2013620.64), 319.06 (21.42\u20131884.41) and 1.52 (0.10\u201358.02), 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 &lt; 0.0001). Our results would seem to indicate that ZA modulates RANK, RANK-L and OPG expression, thus decreasing osteoclast activity.<\/jats:p>","DOI":"10.3390\/ijms140610683","type":"journal-article","created":{"date-parts":[[2013,5,23]],"date-time":"2013-05-23T12:56:11Z","timestamp":1369313771000},"page":"10683-10693","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["RANK\/RANK-L\/OPG in Patients with Bone Metastases  Treated with Anticancer Agents and Zoledronic Acid:  A Prospective Study"],"prefix":"10.3390","volume":"14","author":[{"given":"Laura","family":"Mercatali","sequence":"first","affiliation":[{"name":"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"},{"name":"Biosciences Laboratory, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), via P. Maroncelli 40, 47014 Meldola (FC), Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marianna","family":"Ricci","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emanuela","family":"Scarpi","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrizia","family":"Serra","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Fabbri","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rossana","family":"Ricci","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Liverani","sequence":"additional","affiliation":[{"name":"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"},{"name":"Biosciences Laboratory, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), via P. Maroncelli 40, 47014 Meldola (FC), Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele","family":"Zanoni","sequence":"additional","affiliation":[{"name":"Biosciences Laboratory, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), via P. Maroncelli 40, 47014 Meldola (FC), Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wainer","family":"Zoli","sequence":"additional","affiliation":[{"name":"Biosciences Laboratory, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), via P. Maroncelli 40, 47014 Meldola (FC), Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta","family":"Maltoni","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erica","family":"Gunelli","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dino","family":"Amadori","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toni","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2013,5,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1038\/nrc867","article-title":"Metastasis to bone: Causes, consequences and therapeutic opportunities","volume":"2","author":"Mundy","year":"2002","journal-title":"Nat. Rev. Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1634\/theoncologist.2007-0159","article-title":"Osteonecrosis of the jaw in patients with bone metastases treated with bisphosphonates: A retrospective study","volume":"3","author":"Ibrahim","year":"2008","journal-title":"Oncologist"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"43","DOI":"10.3322\/canjclin.57.1.43","article-title":"Cancer statistics 2007","volume":"57","author":"Jemal","year":"2007","journal-title":"CA Cancer J. 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Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.1016\/j.urology.2009.11.049","article-title":"Implications of serum bone turnover markers in prostate cancer patients with bone metastasis","volume":"75","author":"Kamiya","year":"2010","journal-title":"Urology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1002\/cncr.23775","article-title":"Zoledronic acid and skeletal complications in patients with solid tumors and bone metastases: Analysis of a national medical claims database","volume":"113","author":"Hatoum","year":"2008","journal-title":"Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1002\/1097-0142(20010801)92:3<460::AID-CNCR1344>3.0.CO;2-D","article-title":"Receptor activator of nuclear factor-kappaB ligand and osteoprotegerin: Potential implications for the pathogenesis and treatment of malignant bone diseases","volume":"92","author":"Hofbauer","year":"2001","journal-title":"Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/ncponc0381","article-title":"Mechanisms of disease: Roles of OPG, RANK-L and RANK in the pathophysiology of skeletal metastasis","volume":"3","author":"Blair","year":"2006","journal-title":"Nat. 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Breast Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1159\/000327585","article-title":"The role of CXCR4 in the prediction of bone metastases from breast cancer: A pilot study","volume":"80","author":"Sacanna","year":"2011","journal-title":"Oncology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1182\/blood-2003-02-0380","article-title":"Soluble receptor activator of nuclear factor kappaB ligand-osteoprotegerin ratio predicts survival in multiple myeloma: Proposal for a novel prognostic index","volume":"102","author":"Terpos","year":"2003","journal-title":"Blood"},{"key":"ref_28","first-page":"255","article-title":"Bone metastases detection by circulating biomarkers: OPG and RANK-L","volume":"39","author":"Mercatali","year":"2011","journal-title":"Int. J. Oncol"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/14\/6\/10683\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:46:55Z","timestamp":1760219215000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/14\/6\/10683"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,5,23]]},"references-count":28,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2013,6]]}},"alternative-id":["ijms140610683"],"URL":"https:\/\/doi.org\/10.3390\/ijms140610683","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,5,23]]}}}