Martinetti A, Bajetta E, Ferrari L, Zilembo N, Seregni E, Del Vecchio M, Longarini R, La Torre I, Toffolatti L, Paleari D, Bombardieri E
Nuclear Medicine Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
Endocr Relat Cancer. 2004 Dec;11(4):771-9. doi: 10.1677/erc.1.00775.
Osteoprotegerin (OPG) is a potent antiresorptive molecule that binds NF-kappaB ligand, the final effector for osteoclastogenesis. OPG production is regulated by a number of cytokines and hormones. Osteopontin (OPN) is a secreted adhesive glycoprotein involved in tumour angiogenesis, and also a non-collagenous protein involved in bone turnover. OPN serum value is associated with tumour burden and survival in advanced breast cancer patients. The short-term effects of anastrozole on OPG and OPN serum values, and the usefulness of these analytes during follow-up were studied in 34 consecutive advanced breast cancer patients receiving anastrozole 1 mg/day. Blood samples were taken before treatment and at 2, 4, 8 and 12 weeks. OPG and OPN values were measured by ELISA. The results were analysed for all patients, and also separately for patients with (group A, 22 patients) and without (group B, 12 patients) bone metastasis. Whether the survival of all patients was related to their OPN serum values was also tested by placing patients into three groups (terciles) according to their baseline OPN values. No significant changes in OPG and OPN values were observed in the complete patient group. There was no difference in baseline OPG and OPN serum values between patients in groups A and B. In group A, a significant percentage increase in both OPG and OPN values from baseline was detected during treatment. No significant changes were reported for group B patients. Furthermore, in group A, a significant increase in both analytes was evident only for patients with progressive disease (PD). The Kaplan-Meier adjusted survival estimates for patients grouped according to tercile OPN values differed significantly (P = 0.001, log rank test). In conclusion, in the short term, anastrozole does not seem to affect OPG and OPN serum values in patients without bone disease. OPG and OPN appear to be useful predictors of the outcome of skeletal disease and elevated OPN values may be associated with short survival in advanced breast cancer patients.
骨保护素（OPG）是一种强效抗吸收分子，可结合核因子-κB配体，后者是破骨细胞生成的最终效应因子。OPG的产生受多种细胞因子和激素调控。骨桥蛋白（OPN）是一种分泌性黏附糖蛋白，参与肿瘤血管生成，也是一种参与骨转换的非胶原蛋白。OPN血清值与晚期乳腺癌患者的肿瘤负荷和生存期相关。本研究对34例连续接受1mg/天阿那曲唑治疗的晚期乳腺癌患者，观察了阿那曲唑对OPG和OPN血清值的短期影响，以及这些分析物在随访期间的效用。在治疗前及治疗后2、4、8和12周采集血样。采用酶联免疫吸附测定法（ELISA）检测OPG和OPN值。对所有患者的结果进行分析，并分别对有骨转移（A组，22例患者）和无骨转移（B组，12例患者）的患者进行分析。还根据患者基线OPN值将其分为三组（三分位数），以检验所有患者的生存期是否与其OPN血清值相关。在整个患者组中，未观察到OPG和OPN值有显著变化。A组和B组患者的基线OPG和OPN血清值无差异。在A组中，治疗期间检测到OPG和OPN值较基线均有显著百分比升高。B组患者未报告有显著变化。此外，在A组中，仅疾病进展（PD）患者的两种分析物均有显著升高。根据三分位数OPN值分组的患者，其经Kaplan-Meier调整的生存估计值有显著差异（P = 0.001，对数秩检验）。总之，短期内，阿那曲唑似乎不影响无骨病患者的OPG和OPN血清值。OPG和OPN似乎是骨骼疾病预后的有用预测指标，OPN值升高可能与晚期乳腺癌患者生存期短有关。
