Mercatali Laura, Ricci Marianna, Scarpi Emanuela, Serra Patrizia, Fabbri Francesca, Ricci Rossana, Liverani Chiara, Zanoni Michele, Zoli Wainer, Maltoni Roberta, Gunelli Erica, Amadori Dino, Ibrahim Toni
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.
Int J Mol Sci. 2013 May 23;14(6):10683-93. doi: 10.3390/ijms140610683.
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.
实体癌患者常发生骨转移（BM）。唑来膦酸（择泰®，ZA）常用于治疗BM患者，它作用于破骨细胞，还具有抗肿瘤特性。我们旨在评估ZA在新型骨转换标志物（核因子κB受体活化因子/核因子κB受体活化因子配体（RANK-L）/骨保护素（OPG））方面随时间的影响，并将这些与血清N端肽（NTX）相关联。该研究前瞻性地通过实时PCR评估了49例连续的晚期乳腺癌、肺癌或前列腺癌患者外周血中RANK、RANK-L和OPG转录本的水平，并通过ELISA评估了NTX的表达。所有患者均接受标准的ZA治疗方案，并监测12个月。RANK、RANK-L和OPG的基线中位数分别为78.28（范围7.34 - 620.64）、319.06（21.42 - 1884.41）和1.52（0.10 - 58.02）。在12个月时，RANK-L的中位数相对于基线下降了22%，而OPG水平的中位数增加了约96%。因此，RANK-L/OPG比值从基线下降了56%。血清NTX水平在12个月期间中位数下降，达到统计学意义（p < 0.0001）。我们的结果似乎表明ZA调节RANK、RANK-L和OPG的表达，从而降低破骨细胞活性。
