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唑来膦酸治疗骨转移患者血清和龈沟液中核因子-κB 配体和骨保护素水平。

Nuclear factor-kappa B ligand and osteoprotegerin levels in serum and gingival crevicular fluid in patients with bone metastases treated with zoledronic acid.

机构信息

Medical Oncology Department, Kayseri Training and Research Hospital, Kayseri, 38039, Turkey,

出版信息

Med Oncol. 2014 Mar;31(3):837. doi: 10.1007/s12032-013-0837-8. Epub 2014 Jan 22.

DOI:10.1007/s12032-013-0837-8
PMID:24448976
Abstract

Bone metastases are frequently observed in patients with certain types of cancer and are significant cause of morbidity. Zoledronic acid (ZA) is routinely prescribed for patients with bone metastases by affecting osteoclast function. We aimed to assess the effect of ZA over time in patients with bone metastases by analyzing novel bone turnover marker levels including receptor activator of nuclear factor-k B ligand (RANKL) and osteoprotegerin (OPG) in serum and gingival crevicular fluid (GCF). Also, associations between these bone turnover markers with hematological and biochemistry dysregulation were studied. The study enrolled patients with bone metastases including 32 patients diagnosed with solid tumors and 15 patients with multiple myeloma. In these patients, GCF and serum RANKL and OPG levels were measured and compared with measures of hematological and biochemical parameters before and after 3 months of ZA therapy. Mean subject age was 54 years old with a range of 28-80 years. Skeletal-related events were observed in 8.5% of all patients. After the 3-month treatment of ZA therapy, no significant differences were found in serum and GCF levels of RANKL and OPG when compared with before treatment levels. GCF RANKL levels at baseline and following 3 months of ZA therapy were significantly higher in patients with solid tumors when compared patients diagnosed with multiple myeloma (p=0.001; p<0.001, respectively). GCF OPG levels after the entire course of ZA therapy were greater in patients with 5 or more bone metastases (p=0.04). For patients with multiple myeloma, control GCF OPG was negatively correlated with control platelet and WBC counts (p=0.018 and p=0.027, respectively). A negative correlation was observed between control serum RANKL and control serum OPG levels in myeloma patients (p=0.001). After 3 months of ZA therapy, no significant differences were observed in GCF and serum RANKL and OPG levels when compared with baseline. A negative correlation was observed between serum control RANKL and OPG levels in myeloma patients. OPG levels were greater in patients with 5 or more bone metastases. In patients diagnosed with multiple myeloma, GCF OPG levels were negatively associated with WBC and platelet counts.

摘要

骨转移在某些类型的癌症患者中经常发生,是发病率的重要原因。唑来膦酸(ZA)通过影响破骨细胞功能,常规用于治疗骨转移患者。我们旨在通过分析包括核因子κ B 受体激活剂配体(RANKL)和骨保护素(OPG)在内的新型骨转换标志物在血清和龈沟液(GCF)中的水平,来评估 ZA 随时间推移对骨转移患者的影响。还研究了这些骨转换标志物与血液学和生物化学失调之间的关系。该研究纳入了骨转移患者,包括 32 名实体瘤患者和 15 名多发性骨髓瘤患者。在这些患者中,测量了 GCF 和血清 RANKL 和 OPG 水平,并与 ZA 治疗前 3 个月和治疗后 3 个月的血液学和生化参数进行了比较。平均受试者年龄为 54 岁,范围为 28-80 岁。所有患者中有 8.5%发生了骨骼相关事件。在接受 ZA 治疗 3 个月后,与治疗前相比,血清和 GCF 中 RANKL 和 OPG 水平无显著差异。与多发性骨髓瘤患者相比,实体瘤患者的 GCF RANKL 水平在基线和接受 ZA 治疗 3 个月后均显著升高(p=0.001;p<0.001)。在接受整个 ZA 治疗后,多发性骨髓瘤患者的 GCF OPG 水平更高(p=0.04)。对于多发性骨髓瘤患者,对照 GCF OPG 与对照血小板和白细胞计数呈负相关(p=0.018 和 p=0.027)。骨髓瘤患者对照血清 RANKL 与对照血清 OPG 水平之间存在负相关(p=0.001)。在接受 ZA 治疗 3 个月后,与基线相比,GCF 和血清 RANKL 和 OPG 水平无显著差异。骨髓瘤患者血清对照 RANKL 和 OPG 水平之间存在负相关。多发性骨髓瘤患者的 OPG 水平在 5 个或更多骨转移的患者中更高。在多发性骨髓瘤患者中,GCF OPG 水平与白细胞和血小板计数呈负相关。

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