β-CTX、BAP、uNTx联合检测对于诊断肺癌骨转移的价值

目的探讨血清β-Ⅰ型胶原羧基端肽(β-CTX)、骨碱性磷酸酶(BAP)、尿Ⅰ型胶原交联氨基末端肽(uNTx)诊断肺癌骨转移的价值。方法选取64例肺癌骨转移患者(转移组)、60例肺癌未发生骨转移的患者(对照组);检测2组的血清β-CTX、BAP、uNTx水平;分析三项指标单独及联合应用时诊断肺癌骨转移的临床价值。结果转移组患者的β-CTX、BAP、uNTx水平均高于对照组,差异具有统计学意义(P<0.05);≥2个转移部位患者的β-CTX、BAP、uNTx水平均高于1个转移部位的患者,差异具有统计学意义(P<0.05)。β-CTX诊断肺癌骨转移的灵敏度为49.21%、特异度为76.42%、AUC值为0.675;BAP诊断肺癌骨转移的灵敏度为57.88%、特异度为79.85%、AUC值为0.738;uNTx诊断肺癌骨转移的灵敏度为68.33%、特异度为81.30%、AUC值为0.758;β-CTX、BAP、uNTx联合应用诊断肺癌骨转移的灵敏度为91.27%、特异度为80.55%、AUC值为0.889。结论β-CTX、BAP、uNTx联合应用诊断肺癌骨转移能显著提高诊断的灵敏度。     

血清碱性磷酸酶、Ⅰ型前胶原氨基端前肽与Ⅰ型胶原羧基端肽β特殊序列在恶性肿瘤骨转移诊断中的应用价值

目的探讨血清碱性磷酸酶(ALP)、Ⅰ型前胶原氨基端前肽(PINP)与Ⅰ型胶原羧基端肽β特殊序列(β-CTX)在恶性肿瘤骨转移诊断中的临床价值。方法选取2019年1月至2020年5月河南科技大学第二附属医院收治的76例晚期恶性肿瘤骨转移患者(骨转移组)和72例无骨转移的晚期恶性肿瘤患者(无骨转移组),比较2组患者血清ALP、PINP和β-CTX水平,以及三者单独及联合检测对恶性肿瘤骨转移的诊断效能。结果骨转移组患者血清ALP、PINP和β-CTX水平分别为(284.19±70.40)u/L、(120.86±24.29)ng/mL、(0.89±0.62)ng/mL,均明显高于无骨转移组的(253.25±67.34)u/L、(84.63±30.98)ng/mL、(0.44±0.27)ng/mL,差异均有统计学意义(t=2.730,P=0.007;t=7.892,P<0.001;t=5.831,P<0.001)。ALP诊断恶性肿瘤骨转移的敏感性为083、特异性为0.64、曲线下面积为0.67,PINP分别为0.90、0.74、0.81,β-CTX分别为0.76、0.78、0.78,三者联合检测分别为0.84、0.96、0.89。结论血清ALP、PINP和β-CTX对恶性肿瘤骨转移具有较高的诊断价值,对临床有重要应用价值,联合检测的诊断价值优于单项检测,为恶性肿瘤骨转移的早期诊断提供一种简单有效的诊断方法。     

血清碱性磷酸酶、Ⅰ型前胶原氨基端前肽与I型胶原羧基端肽β特殊序列在恶性肿瘤骨转移诊断中的应用价值

目的 探讨血清碱性磷酸酶(ALP)、Ⅰ型前胶原氨基端前肽(PINP)与Ⅰ型胶原羧基端肽β特殊序列(β-CTX)在恶性肿瘤骨转移诊断中的临床价值.方法 选取2019年1月至2020年5月河南科技大学第二附属医院收治的76例晚期恶性肿瘤骨转移患者(骨转移组)和72例无骨转移的晚期恶性肿瘤患者(无骨转移组),比较2组患者血清...     

乳腺癌骨转移患者骨代谢指标PICP、β-CTx与治疗效果的关系

目的 探讨骨代谢指标Ⅰ型胶原羧基端前肽(carboxyl-terminal propeptide of type 1 procollagen,PICP)、β胶原降解产物(beta collagen degradation products,β-CTx)与乳腺癌骨转移患者治疗反应的关系.方法 测定56例乳腺癌骨转移患者治疗前后骨代谢指标PICP和β-CTx,比较治疗前后骨代谢指标与治疗效果的关系,并进行随访.结果 56例乳腺癌骨转移患者中,临床获益组36例,治疗3月后PICP和β-CTx明显下降(P=0.016,P=0.001);病情进展组20例,治疗3月后PICP和β-CTx有所升高(P=0.008,P=0.042).临床获益组中20例患者骨代谢指标先于影像学检查提示临床治疗有效.结论 PICP和β-CTx可作为乳腺癌骨转移患者评价疗效的辅助指标.     

联合检测血清NTx和BSP对乳腺癌和肺癌骨转移的意义

摘 要 目的: 探讨骨代谢生化指标血清Ⅰ型胶原交联氨基末端肽（Ntelopeptide of type Ⅰ collagen，NTx）和骨涎酸蛋白(bone sialoprotein, BSP)的检测对肺癌和乳腺癌骨转移的临床意义。方法：选择2006年1月至2006年7月长海医院肿瘤科经病理确诊的肺癌或乳腺癌患者105例，分为两组，其中骨转移组50例，无骨转移组55例。应用ELISA法检测患者血清NTx和BSP浓度。结果：骨转移组患者血清NTx和BSP水平均明显高于无骨转移组（P<0.01）。NTx诊断骨转移的灵敏度和特异度分别为90.0％和67.3％，BSP诊断骨转移的灵敏度和特异度分别为84.0％和70.9％。临床发生骨相关事件（skeletal related event，SRE）的骨转移患者，血清NTx水平明显高于未发生SRE的骨转移患者（P<0.05）。在6~13个月随访期内，21例患者确诊了新发骨转移；采用Cox比例风险回归模型分析，血清NTx浓度升高提示骨转移发生的相对危险度为1.127；乳腺癌患者血清BSP增高是唯一预测骨转移的危险因素（P<0.05），其相对危险度为1.058。随访期共有33例患者死亡；无论肺癌还是乳腺癌，血清BSP增高患者的累积生存率均明显低于血清BSP正常组（P<0.05）。结论：血清NTx和BSP是诊断肺癌和乳腺癌骨转移的重要参考指标，其水平的增高是预测骨转移发生的高危因素；BSP可能是肺癌和乳腺癌患者独立预后指标。     

uNTX、sICTP及sBALP表达在恶性肿瘤骨转移中的临床意义

目的探讨尿Ⅰ型胶原交联氨基末端肽（uNTX）、血清Ⅰ型胶原羧基末端肽（sICTP）及骨碱性磷酸酶（sBALP）表达在恶性肿瘤骨转移患者中的临床意义。方法对32例恶性肿瘤骨转移患者,在治疗前后分别采用酶联免疫吸附法（ELISA）、小麦菌凝集素沉淀法,测定uNTX、sICTP及sBALP水平。随访骨相关事件（SREs）及生存状况。结果患者基线uNTX/Cr、sICTP及sBALP水平明显高于正常,其浓度与骨转移负荷呈正相关性,与疼痛强度无显著相关性。治疗3个月时uNTX/Cr、sICTP及sBALP水平明显降低,而放射性核素全身骨显像（ECT）尚无明显改变;32例患者中24例基线uNTX/Cr水平高于正常水平,治疗后降至正常水平的15例患者骨相关事件发生率为53%,而治疗后仍维持在较高水平的9例患者为89%（P=0.039）;32例患者中27例基线sICTP水平高于正常,治疗后16例降至正常,11例仍维持在较高水平,两者骨相关事件发生率为50%和91%（P=0.032）;26例基线sBALP水平高于正常值,治疗后16例降至正常水平,10例仍维持在较高水平,两者骨相关事件发生率为50%和90%（P=0.038）。uNTX/Cr、sICTP及sBALP水平与肿瘤患者生存率无明显相关性。结论骨代谢标记物uNTX、sICTP及sBALP对恶性肿瘤骨转移的诊断、疗效的监测及骨相关事件的预测具有一定的价值。     

骨转移瘤患者骨密度和血清骨代谢指标变化的临床研究

目的 :研究骨转移瘤患者骨密度和骨代谢状态的变化。方法 :采用双能 X线骨密度仪(DEXA)测量 2 0例骨转移瘤患者骨密度 (BMD) ,同时采用放射免疫法测定血清骨钙素 (BGP) , 型胶原羧基末端肽 (ICTP)水平 ,并与 2 0例正常人作对照。结果 :骨转移瘤组 L2 、L3、L4,右股骨颈 ,右Ward区和右大转子 BMD显著下降 (P<0 .0 5～ P<0 .0 0 1)。骨转移瘤组血清 BGP、ICTP显著升高 (P<0 .0 5～ P<0 .0 0 1)。结论 :骨转移瘤患者腰椎、髋部 BMD下降 ,血清 BGP、ICTP升高 ,骨转换增快。     

肺癌患者血清ＮＴｘ、ＩＣＴＰ和ＢＡＰ水平与骨转移的相关性研究

目的　探讨联合检测骨代谢生化指标血清Ⅰ型胶原氨基末端肽（ＮＴｘ）、Ⅰ型胶原羧基端肽（ＩＣＴＰ）及骨特异性碱性磷酸酶（ＢＡＰ）对诊断肺癌骨转移的临床意义。方法　选择经细胞学和病理学确诊的肺癌患者１０６例,分为两组,其中骨转移组６１例,无骨转移组４５例。用ＥＬＩＳＡ法检测两组患者血清ＮＴｘ、ＩＣＴＰ及ＢＡＰ浓度。结果　骨转移组患者血清ＮＴｘ、ＩＣＴＰ及ＢＡＰ水平分别为（２５.３６±１１.０７）ｎｍｏｌ／Ｌ、（２９.１８±１０.７４）μｇ／Ｌ和（７８.３１±１６.５３）μｇ／Ｌ,明显高于无骨转移组的（１２.１６±７.６２）ｎｍｏｌ／Ｌ、（１１.０２±５.３２）μｇ／Ｌ和（２４.０１±７.９８）μｇ／Ｌ,差异具有统计学意义（Ｐ＜０.０１）;ＮＴｘ、ＢＡＰ、ＩＣＴＰ诊断骨转移的灵敏度和特异度分别为９０.１６％和８４.４４％、８０.３２％和７７.７８％、７０.４９％和９１.１１％;多发骨转移组患者血清ＮＴｘ、ＩＣＴＰ及ＢＡＰ水平明显高于单发骨转移组（Ｐ＜０.０５）;骨转移组患者血清ＮＴｘ、ＩＣＴＰ及ＢＡＰ水平与疼痛程度呈正相关;不同性别、病理类型、转移部位患者的血清ＮＴｘ、ＩＣＴＰ及ＢＡＰ水平差异无显著性（Ｐ＞０.０５）。结论　血清ＮＴｘ、ＩＣＴＰ及ＢＡＰ水平对肺癌骨转移诊断的灵敏度和特异度较高,与骨转移数目和疼痛程度相关,是诊断肺癌骨转移的重要参考指标。     

乳腺癌骨转移患者溶骨性骨代谢指标与治疗效果的关系

目的 探讨特异性的溶骨性骨代谢指标血I型胶原吡啶交联羧基末端肽(sICTP)、尿I型胶原吡啶交联氨基末端肽(uNTx)和尿吡啶酚(uPyd)与乳腺癌骨转移患者治疗反应的关系.方法 应用酶联免疫吸附试验(ELISA),测定120例乳腺癌患者的sICTP、uNTx和uPyd,比较其在骨转移和无骨转移患者中浓度的差别,并对乳腺癌骨转移患者进行随访,比较患者治疗前后sICTP、uNTx和aPyd指标与治疗效果的关系.结果 骨转移组患者的sICTP、uNTx和uPyd水平均明显高于无骨转移组(P<0.01),56例乳腺癌骨转移患者的sICTP、uNTx和uPyd指标间两两相关(均r>0.5,P<0.01).获得随访的45例乳腺癌骨转移患者中,临床受益组25例,sICTP、uNTx和uPyd治疗3个月后明显下降(P=0.025,P<0.001,P<0.001).病情进展组20例,治疗3个月后,sICTP、uNTx和uPyd无明显变化(P>0.05);而病情进展后,sICTP、uNTx和uPyd明显升高(P=0.011,P=0.002,P=0.002).Logistic回归分析结果显示,uPyd和uNTx治疗后降低的患者治疗收益的概率增加(OR=17.0,P=0.019;OR=16.7,P=0.015),而治疗后sICTP指标下降与治疗受益无关(P=0.841).结论 sICTP、uNTx和uPyd可作为乳腺癌骨转移患者评价疗效和转归监测的辅助指标.     

骨代谢生化指标在恶性肿瘤骨转移诊断中的价值

目的：探讨溶骨性骨代谢生化指标尿Ⅰ型胶原交联氨基末端肽（NTx）、血Ⅰ型胶原交联羧基末端肽（ICTP）定量检测诊断恶性肿瘤骨转移的价值。方法：用ELISA方法测定77例恶性肿瘤患者尿NTx和血ICTP水平。结果：骨转移组患者尿NTx和血ICTP均明显高于无骨转移组以及正常值范围（P〈0．01）。骨转移患者尿NTx与血ICTP成正相关（r=0．880，P〈0．01）。尿NTx诊断恶性肿瘤骨转移的灵敏度、特异度和准确度分别为82．5％、83．8％和83．2％（P〈0．05）。血ICTP的灵敏度、特异度和准确度分别为87．5％、73．0％和80．6％（P〈0．05）。骨转移患者尿NTx与血ICTP水平与骨转移范围成正相关（r=0．453、0．475，P〈0．01），与骨痛程度无显著相关（r=0．010、0．083，P〉0．05）。结论：NTx和血ICTP对恶性肿瘤患者骨转移的诊断有重要的参考意义，可协助及时诊断恶性肿瘤骨转移。     

骨转换标志物在非小细胞肺癌骨转移临床应用中价值的研究

背景与目的:骨转移导致骨质破坏,可引起骨转换标志物(bone turnover markers)水平的改变;因此,本研究旨在探讨骨转换标志物在非小细胞肺癌(non-small cell lung cancer,NSCLC)骨转移诊断及病情评价方面的应用价值.方法:定量检测76例NSCLC骨转移患者血清中碱性磷酸酶(alkaline phosphatase,AKP)、β-Ⅰ型胶原羧基端肽(β-C-terminal telopeptide of type Ⅰ collagen,β-CTx)、骨钙素(osteocalcin,OST)和骨特异性碱性磷酸酶(bone-specific alkaline phosphatase,BALP)水平,并与44例健康人群进行对照.结果:骨转移组患者血清中AKP、β-CTx和BALP水平均明显高于正常对照组.各骨转换标志物之间有很好的相关性,BALP和OST的表达水平与骨转移程度呈正相关性.β-CTx表达水平较高和BALP表达水平较低的患者发生病理性骨折可能性增加.结论:骨代谢标志物在NSCLC骨转移患者诊断及病情判断方面有重要的参考价值,在临床上有广泛的应用前景.     

血清骨特异性碱性磷酸酶及Ⅰ型胶原吡啶交联终肽与乳腺癌骨转移的相关性分析

 目的　分析血清骨特异性碱性磷酸酶（BAP）和Ⅰ型胶原吡啶交联终肽（ICTP）水平在乳腺癌骨转移与非骨转移患者中的分布及其与临床特征的相关性。方法　收集乳腺癌患者血清217例，通过影像学将患者分为骨转移组（109例）和非骨转移组（108例）。应用酶联免疫吸附法测定两组血清中的BAP及ICTP水平。结果　乳腺癌骨转移组血清BAP及ICTP水平中位数分别为24.8 μg／L（7.6~213.7 μg／L）和7.0 μg／L（1.4~32.4 μg／L），高于非骨转移组的21.2 μg／L（7.3～68.8 μg／L）和4.1 μg／L（0.0～15.8 μg／L）（P＝0.003和P＝0.000），多发骨转移组的BAP及ICTP水平中位数分别为32.3 μg／L（9.4~213.7 μg／L）和7.6 μg／L（1.4～32.4 μg／L），高于单发骨转移组的18.1 μg／L（7.6～60.0 μg／L）和4.9 μg／L（1.8～10.5 μg／L）（P＝0.001和P＝0.010）。血清BAP检测诊断乳腺癌骨转移的灵敏度为45.0 %（49／109），特异度为83.3 %（90／108）；血清ICTP的灵敏度为46.8 %（51／109），特异度为84.3 %（91／108）；两者联合检测的灵敏度为61.5 %（67／109），特异度为71.3 %（77／108）。结论　检测血清BAP及ICTP诊断乳腺癌骨转移的灵敏度较低，不适合作为诊断指标。两者联合检测可以提高灵敏度，对辅助诊断有一定价值。     

Bone metabolic markers in bone metastasis of breast cancer

Background. The efficacy and cost-performance benefit of radionuclide bone scintigraphy in monitoring metastatic bone activity remain controversial. Bone metabolic markers are now expected to play a role in the diagnosis and follow-up of bone metastasis. Methods. We investigated several bone metabolic markers in patients with breast cancer. We measured three metabolic markers of bone resorption: pyridinoline cross-linked carboxy terminal telopeptide (ICTP), C-telopeptides of type I collagen (CTx), and the free form of deoxypyridinoline (fDPD), and four metabolic markers of bone formation: procollagen I carboxy terminal peptide (PICP), total alkaline phosphatase (Al-p), bone-specific alkaline phosphatase (BAl-p), and osteocalcin (BGP) in 210 patients without and 268 patients with bone metastasis. Patients without bone metastasis were analyzed in terms of menstruation status. Patients with bone metastasis were analyzed in terms of bone metastatic burden and tumor lesion "condition" (ie, determination by X-ray and/or computed tomography and bone scan findings of new lesion, progression of disease, no change, improvement, and complete remission, according to the criteria of the International Unite Against Cancer). Results. In patients without bone metastasis, ICTP did not change with menopause. All markers other than ICTP were significantly elevated with menopause. In patients with bone metastasis, all markers, except for BGP, were significantly elevated according to metastatic bone tumor burden. Among the seven markers, ICTP showed the best receiver operating characteristic curves. ICTP also showed the best correlation to bone metastatic burden among the markers by Spearman's rank correlation coefficient. In patients stratified by "condition", ICTP, CTx, fDPD, Al-p, and BAl-p showed significant elevation in patients with progression, new lesion, and no change, while PICP and BGP showed only minimal elevation in those patients. Conclusion. Bone metabolic markers, particularly ICTP, appear to be valuable for the diagnosis of bone metastasis from breast cancer. Received: April 22, 1999 / Accepted: July 15, 1999     

Risk Factors,Patterns, and Distribution of Bone Metastases and Skeletal-Related Events in High-Risk Breast Cancer Patients

Background: More than a quarter of breast cancer patients are at risk to develop recurrent metastases to the bone. Objective: This study was designed to identify risk factors and predilections of bone metastasis and skeletal-related events (SRE) in a population of breast cancer survivors initially diagnosed in advanced stages and with high-risks of relapse. Methods: Associated risk factors, distribution, and attainable treatment of bone metastasis and SRE were analyzed in a cohort of 1,329 breast cancer patients. The association with dependent variables was subsequently analyzed using multivariable logistic regression. Sociodemographic and adverse clinical characteristics were included as covariates of progression into bone metastasis and SREs. Results: Of 1329 breast cancer patients, 246 patients (18.5%) were diagnosed as metastatic breast cancer in which 232 of them (94.3%) had bone metastases. Spines were the most common sites of bone metastases (25.6%). In multivariable analysis, advanced stage at diagnosis (OR=1.840, 95%CI:1.198-2.826, P=0.005), luminal subtype (OR=1.788, 95%CI:1.206-2.652, P=0.045), lobular histology (OR=1.795, 95%CI:1.012-3/184, P=0.046), positive axillary lymph node (OR=1.771, 95%CI:1.087-2.886, P=0.022), multiple metabolic comorbidities (OR=2.193, 95%CI:1.371-3.508, P=0.001), early menopause (OR=2.136, 95%CI:1.116-4.464, P=0.046) were significantly associated with risk of recurrent bone metastases. SREs occurred in 89 (68.5%) patients. Several risk factors for SREs were early menopausal age (OR=2.342, P=0.024), advanced stages (OR=1.404, P=0.039), lobular histology (OR=2.279, P=0.007), and having multiple metabolic comorbidities (OR=1.728, P=0.039). Conclusion: Bone metastases and SREs are relatively high in breast cancer patients diagnosed in advanced stages. Luminal subtypes, having multiple metabolic comorbidities, and lobular histology are associated with higher risks of recurrent bone metastases. Living in rural areas and advanced stage at diagnosis as a risk factors for bone metastases might represent a social gradient of care delivery.     

Markers of bone turnover for the management of patients with bone metastases from prostate cancer

Although increased bone formation is a prominent feature of patients with osteosclerotic metastases from prostate cancer, there is also some evidence for increased bone resorption. The aim of this study was to compare the clinical utility of new bone resorption markers to that of bone formation in patients with bone metastases from prostate cancer before and after bisphosphonate treatment. Thirty-nine patients with prostate cancer and bone metastasis, nine patients with prostate cancer without bone metastases, nine patients with benign prostatic hyperplasia and 355 healthy age-matched men were included. Urinary non-isomerized (alpha CTX) and beta isomerized (beta CTX) type I collagen C-telopeptides (CTX) and a new assay for serum CTX were used to assess bone resorption. Bone formation was determined by serum osteocalcin, serum total (T-ALP) and bone (BAP) alkaline phosphatase and serum type I collagen C-terminal propeptide (PICP). Fourteen patients with bone metastases were also evaluated 15 days after a single injection of the bisphosphonate pamidronate (120 mg). Levels of all bone formation and bone resorption markers were significantly (P < 0.006-0.0001) higher in patients with prostate cancer and bone metastasis than in patients with benign prostatic hyperplasia, patients with prostate cancer without bone metastases and healthy controls. In patients with bone metastases the median was increased by 67% for serum osteocalcin, 128% for T-ALP, 138% for BAP, 79% for PICP, 220% for urinary alpha CTX, 149% for urinary beta CTX and 214% for serum CTX. After bisphosphonate treatment all three resorption markers significantly decreased by an average of 65% (P = 0.001), 71% (P = 0.0010) and 61% (P = 0.0015) for urinary alpha CTX, urinary beta CTX and serum CTX, respectively, whereas no significant change was observed for any bone formation markers. Patients with prostate cancer and bone metastases exhibit a marked increase in bone resorption, which decreases within a few days of treatment with pamidronate. These findings suggest that these new resorption markers may be useful for the management of these patients.     

Tartrate-resistant acid phosphatase 5b activity is a useful bone marker for monitoring bone metastases in breast cancer patients after treatment.

Metabolic markers of bone metabolism may be useful for the diagnosis and monitoring of bone metastasis in breast cancer patients. Serum tartrate-resistant acid phosphatase 5b (TRACP5b) activity is a novel bone resorption marker. The treatment response of serum TRACP5b activity, bone alkaline phosphatase (BAP) activity, and concentrations of NH(2)-terminal telopeptide of type 1 collagen (NTX) in 68 breast cancer patients with bone metastasis were determined. These patients were treated and followed up as clinically indicated. Fifty-four healthy women were recruited as control. Serum TRACP5b activity, BAP activity, and NTX level of breast cancer patients with bone metastasis were significantly higher than those of normal controls. In normal subjects, serum TRACP5b activity and NTX level are significantly correlated (P < 0.0001). Neither was correlated with BAP activity. In breast cancer patients with bone metastasis, all marker pairs correlated to each other significantly (P < 0.0001). Biomarkers were examined repeatedly in 38 patients who were evaluable for treatment response. Based on clinical criteria, 20 patients were responders and 18 were nonresponders. In the 20 responders, serum TRACP5b activity and NTX level decreased significantly (P < 0.0001 and 0.0107, respectively) after treatment. In the 18 nonresponders, only NTX level showed significant increase (P = 0.0342) after treatment; TRACP5b and BAP were unchanged. By means of multiple logistic regression with stepwise selection, we determined that TRACP5b activity has a higher probability than NTX level to indicate treatment response as a function of percent change after treatment (18 times versus 12 times). Our data support the use of either TRACP5b activity or NTX level to follow up breast cancer patients with bone metastasis after treatment instead of the prevailing BAP activity.     

双膦酸盐治疗乳腺癌骨转移患者的临床病理特征及预后分析*

目的:探讨乳腺癌骨转移患者的临床、病理、治疗及预后因素。方法:收集2005年1 月至2013年4 月天津医科大学肿瘤医院收治的183 例至少接受6 个月双膦酸盐治疗的乳腺癌骨转移患者的临床资料,根据双膦酸盐类型分为帕米膦酸二钠组、唑来膦酸组及帕米膦酸二钠序贯唑来膦酸组,探讨骨转移的特点、骨相关事件（skeletal-related events,SREs）、治疗及预后特征。结果:胸椎和肋骨为骨转移的常见转移部位,骨转移至发生首次SREs的中位时间为4.2 个月,51.9%（95/ 183）患者发生SREs,累计SREs事件数达167 次,其中110 次（65.9%）发生在骨转移后1 年内,SREs类型以骨放疗为主。患者在不同双膦酸盐药物组的SREs发生率差异无统计学意义（P > 0.05）。 183 例患者骨转移后的中位生存期为43.1 个月,激素受体状态、无病生存期、是否合并内脏转移及脊柱转移与否是乳腺癌骨转移患者的独立预后因素（P < 0.05）。 结论:胸椎和肋骨是乳腺癌骨转移的常见转移部位,SREs主要发生在骨转移后1 年内并以骨放疗为主。激素受体阴性、无病生存期短、合并内脏及脊柱转移是影响乳腺癌患者骨转移不良预后的独立因素。      

Normalization of bone markers is associated with improved survival in patients with bone metastases from solid tumors and elevated bone resorption receiving zoledronic acid

BACKGROUND: For patients with bone metastases, high N-telopeptide of type I collagen (NTX) levels correlate with increased risks of skeletal-related events and death. However, the relation between NTX decreases and clinical benefits is unclear. METHODS: Correlations between NTX normalization during treatment and clinical outcome were retrospectively analyzed in 3 large, phase 3 trials. Urinary NTX levels were measured at baseline and at Month 3 in patients with bone metastases from breast cancer (BC; n = 578), hormone-refractory prostate cancer (HRPC; n = 472), or nonsmall-cell lung cancer and other solid tumors (NSCLC/OST; n = 291) who received zoledronic acid or control (pamidronate for BC; placebo for HRPC and NSCLC/OST) for up to 24 months. NTX levels were characterized as normal (N; <64 nmol/mmol creatinine) or elevated (E; > or =64 nmol/mmol creatinine). RESULTS: After 3 months of zoledronic acid, most N-group patients maintained normal levels; however, most E-group patients normalized their NTX levels (BC, 81%; HRPC, 70%; NSCLC/OST, 81%). In contrast, NTX levels normalized with pamidronate in 65% of BC, with placebo in 8% of HRPC, and in 17% of NSCLC/OST E-group patients. Normalized NTX correlated with improved overall survival versus persistently elevated NTX (significant for zoledronic acid-treated patients; trend for placebo-treated patients). Moreover, percentage reductions from baseline NTX levels correlated with benefits regardless of whether patients transitioned from E to N. CONCLUSIONS: Zoledronic acid normalizes or maintains normal NTX levels in most patients with bone metastases. Normalized NTX within 3 months of treatment, versus persistently elevated NTX, was associated with reduced risks of skeletal complications and death.     

Value of urinary hydroxyproline and bone isoenzyme of alkaline phosphatase in the early detection and follow-up of bone metastasis in breast cancer patients

A multiparametric biological study of 178 evaluable breast cancer patients was performed to evaluate the usefulness of individual parameters for the prediction, diagnosis and follow-up of bone metastasis (BM) as compared to physical tests. Serum and urinary calcium and phosphorus were of little discriminative value. The sensitivity and specificity for the urinary hydroxyproline/creatinine ratio (UHP/creat.) were respectively 75% and 81.4% versus 43.2% and 91.4% for the bone isoenzyme of alkaline phosphatase in serum (BIE). During an average follow-up of 14.3 months for 51 patients with bone metastasis, variations in UHP-creat. and BIE correlated with clinical and physical findings; the best correlation was given by UHP/creat. Twenty patients who were initially free of bone metastasis were followed-up for a mean metastasis-free interval of 14 months; UHP/creat. predicted the appearance of bone metastasis in 50% of cases with a lead time of 5.5 months versus 40% and 8.5 months for BIE. Combined use of UHP/creat. and BIE gave a prediction rate of 70% and a mean lead time of 7 months, and this combination of markers thus merits consideration in the management of breast cancer patients.