骨转移瘤

发生在全身各部位的恶性肿瘤,都可能发生癌细胞在血液中播散、转移,继而种植到骨,导致骨转移瘤.骨转移是恶性肿瘤血行转移造成的后果. 虽然骨和软组织本身会发生恶性肿瘤,但实际上骨转移瘤更为常见,骨转移瘤是骨原发肿瘤的35～40倍.     

骨代谢标记物在实体瘤骨转移诊治中的临床意义

目的探讨血清骨源性碱性磷酸酶(BALP)及尿Ⅰ型胶原交联氨基末端肽(uNTx)的表达在实体瘤骨转移诊治中的临床意义。方法对500例恶性肿瘤骨转移患者在治疗前采用酶联免疫吸附法(ELISA)测定uNTx、BALP水平。定期复查(2月1次),行近期疗效评价。结果伴骨转移的患者基线uNTx、BALP水平明显升高(P<0.05),其浓度与骨转移负荷呈正相关(P<0.05),但与骨癌痛无明显相关性。血清BALP、uNTx水平与对骨转移后生存率的影响无统计学意义(P>0.05)。结论骨代谢标记物对于骨转移的诊断有一定的价值,对治疗的反应敏感性优于影像学检查。     

CT联合全身骨显像在骨转移瘤中的诊断价值

目的：评价CT联合全身骨显像在骨转移瘤中的诊断价值。方法：连续性回顾分析2013年1月至2015年12月期间全身骨显像阳性并同期行同部位CT检查且有原发肿瘤病史的患者资料,根据全身显像核素增浓灶的数目分为单发及多发（具有2个及其以上的病灶）,以病理诊断或临床随访诊断为标准,分别对CT、全身骨显像及两者联合这三种不同检查方式在骨转移瘤中的诊断价值进行研究,利用配对χ2（或校正χ2）检验比较CT、全身骨显像与两者联合在单发及多发骨转移瘤诊断中的正确诊断率是否存在统计学差异,利用统计学软件绘制CT、全身骨显像及两者联合在诊断单发及多发骨转移瘤中的ROC曲线。结果：经病理或随访临床证实的212例患者纳入此研究,其中单发核素增浓灶患者91例,多发核素增浓灶患者121例。CT、全身骨显像与两者联合相比在诊断单发及多发骨转移瘤中存在统计学差异（P＜0．05）,两者联合诊断单发及多发核素增浓灶的ROC曲线下面积高于单独全身骨显像或CT,并且可以提供更多的诊断及鉴别诊断信息。结论：CT联合全身骨显像可以为骨转移瘤的诊断及鉴别诊断提供更多有价值的信息,能有效提高骨转移瘤、尤其是单发骨转移瘤的诊断准确性。     

前列腺癌骨转移机制研究进展

骨转移是前列腺癌晚期的主要特征,临床表现为病理性骨折、脊神经压迫症状和剧烈的疼痛.现综述前列腺癌骨转移的解剖学特点、动物模型的建立、器官特异性、癌细胞与骨的相互作用及其标记物的最新研究进展,以增进对前列腺癌骨转移机制的了解.     

核素骨显像联合肿瘤标记物检测对乳腺癌骨转移的诊断价值

目的：观察核素骨显像联合肿瘤标记物对乳腺癌骨转移的诊断价值。方法选择乳腺癌患者82例,按照核素骨显像结果分为转移组43例及未转移组39例,另选取40例健康体检女性作为对照组。观察核素骨显像以及肿瘤标记物检测结果,并对其诊断价值进行考察。结果转移组血清CA125、CA15-3及CEA表达水平及阳性率显著高于未转移组及对照组,骨转移灶数目≤2患者血清CA125、CA15-3以及CEA表达水平及阳性率均显著低于骨转移灶数目＞2的患者,差异均具有统计学意义（P＜0．05）。且随着骨转移分级程度的升高,患者乳腺癌相关肿瘤标记物CA125、CA15-3及CEA表达水平及阳性率均呈升高趋势,各分级间差异有统计学意义（ P＜0．05）。结论核素骨显像联合肿瘤标记物检测可提高诊断敏感性,对于乳腺癌骨转移的诊断具有重要的参考价值。     

蛋白酶体抑制剂用于肺癌骨转移治疗的研究

转移是癌症致死的主要原因,骨转移是排第三的好发部位.肺癌是排第四的嗜骨转移肿瘤.目前对于肺癌骨转移的治疗仪限于抑制骨破坏,不能促进新骨形成.在应用万珂治疗多发骨髓瘤的过程中,发现其可以治疗骨髓瘤骨病,既能抑制骨破坏,又能促进新骨的形成.能否将其用于肺癌乃至实体瘤骨转移的预防或治疗呢?本文就肿瘤骨转移现状及蛋白酶体抑制剂在多发性骨髓瘤骨病中作用做一综述,为将来蛋白酶体抑制剂用于实体瘤骨转移预防和治疗提供参考.     

骨转移生化代谢指标研究进展

骨代谢生化指标是骨吸收或骨生成过程中释放到血液中一些终末产物,通过酶联免疫吸附试验法(ELISA)检测,对骨转移的诊断和疗效评估具有较高的特异性和敏感性,相对于影像学检查更适合骨转移癌的早期诊断和疗效监测,在评估预后方面也具有一定的优越性.应用骨代谢生化指标联合影像学检查,对骨转移的早期诊断、监测疗效及评估预后在临床中的价值更大.     

核素骨显像在肺癌骨转移的临床应用价值

目的探讨肺癌骨转移的核素骨显像临床特点。方法收集我院从1998年1月~2003年12月之间确诊为肺癌的骨转移患者166例,并对其核素骨显像及骨X线片的临床资料回顾分析。结果腺癌和小细胞癌并骨转移发生率较高,鳞癌次之。骨转移顺序为胸部(65.1%)、脊柱(52.4%)、骨盆(25.9%)、肢体(12.7%)、颅骨(6.0%);骨X线片发生骨转移的阳性率23.2%而骨显像阳性率为96.4%。结论提示核素骨显像对骨转移瘤的早期诊断有较高临床价值,X线及骨显像在骨转移瘤不同阶段可表现出不一致情况。     

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。     

血清骨性标记物NTx和BALP与前列腺癌骨转移的关系及临床意义

目的 探讨前列腺癌患者血清骨性标记物Ⅰ型胶原交联氨基末端肽（NTx）和骨源性碱性磷酸酶（BALP）表达与前列腺癌骨转移程度的关系及临床意义。方法 收集2014年1月至2015年12月79例前列腺癌患者的临床资料,根据全身核素骨扫描结果,按照Soloway法将骨转移程度分为0～3级,分析血清骨性标记物NTx和BALP表达在不同程度前列腺癌骨转移中的差异。结果 79例前列腺癌患者中,骨转移0级32例、1级16例、2级20例、3级11例。79例患者NTx、BALP的表达量分别为（130.9±16.4）nmoL／mmoL Cr和（234.2±31.6）U／L。NTx 和BALP水平与TNM分期、Gleason评分、PSA水平有关,与年龄无关。骨转移阳性组NTx 和BALP水平明显高于阴性组。NTx、BALP诊断前列腺癌骨转移的灵敏度分别为87.2％、86.7％,特异度分别为72.1％、79.9％。结论血清骨性标记物NTx和BALP对前列腺癌骨转移的进展程度有一定的诊断价值,其可作为评价骨转移病变范围的指标。     

Early identification and intervention matters: A comprehensive review of current evidence and recommendations for the monitoring of bone health in patients with cancer

Bone metastases are common in patients with advanced solid tumors, and many individuals experience debilitating skeletal-related events (SREs; e.g. pathologic fracture, hypercalcemia, radiotherapy or surgery to bone, and spinal cord compression). These events substantially affect disease outcomes, including survival and quality of life, and healthcare systems. Plain radiography is the most widely used imaging modality for the detection of bone metastases; skeletal scintigraphy, computed tomography, positron emission tomography and magnetic resonance imaging offer greater sensitivity but their use in routine practice is restricted by high costs and limited availability. Biomarkers of bone turnover may also have a role in the early detection of bone metastases and can provide valuable prognostic information on disease progression. SREs can be delayed or prevented using agents such as the receptor activator of nuclear factor kappa B ligand (RANKL) inhibitor, denosumab, and bisphosphonates. Painful bone metastases can be treated with radiofrequency ablation, radiotherapy, or radionuclides such as radium-223 dichloride, which has been shown to delay the onset of SREs in men with castration-resistant prostate cancer. Close monitoring of bone health in patients with advanced cancer may lead to early identification of individuals with bone metastases who could benefit from early intervention to prevent SREs. This review examines current guideline recommendations for assessing and monitoring bone health in patients with advanced cancer, use of biomarkers and treatment of patients with bone metastases. The emerging evidence for the potential survival benefit conferred by early intervention with denosumab and bisphosphonates is also discussed, together with best practice recommendations.     

The relative use of eight collagenous and noncollagenous markers for diagnosis of skeletal metastases in breast, prostate, or lung cancer patients.

The present study was sought to assess the relative use of eight biomarkers for the detection of bone metastases in cancer forms frequently spreading to the skeleton. Participants were 161 patients with either breast, prostate, or lung cancer. The presence and extent of bone metastases was assessed by imaging techniques (computer tomography and/or magnetic resonance imaging) and Technetium-99m scintigraphy. Serum or urinary level of the bone resorption markers (alphaalphaCTX, betabetaCTX, NTX, and ICTP), formation marker (BSAP), and osteoclastogenesis markers (osteoprotegerin, RANKL, and TRAP5b) was measured by commercially available immunoassays. When assessed on a group basis, all biomarkers, except for osteoprotegerin and RANKL, were significantly elevated in patients compared with those without bone metastases (P<0.05). Biomarkers had greater diagnostic value in breast and prostate cancer patients, yet alphaalphaCTX, NTx, and ICTP were able to discriminate lung cancer patients with or without bone metastases (P<0.05). Strong linear associations were seen between the extent of skeletal infiltration and levels of the different biomarkers, except for osteoprotegerin and RANKL. Furthermore, all biomarkers (except for osteoprotegerin and RANKL) were indicative at the early stage of skeletal involvement (one to five metastases). When expressing sensitivity as the percentage increase in biomarker level relative to patients without bone metastases, alphaalphaCTX showed the largest relative increases at each stage of the metastatic disease. These results suggest that closer monitoring of cancer patients with serial measures of biomarkers might facilitate the timely diagnosis of skeletal metastases.     

骨代谢标志物ICTP、BAP对肺癌骨转移的诊断意义

背景与目的骨代谢标志物是一类源于骨基质或骨细胞的代谢指标,可反映骨代谢情况。本研究旨在探讨血清骨代谢生化指标I型胶原交联羧基端肽(cross-linked telopeptide of type I collage,ICTP)和骨特异性碱性磷酸酶(bone-specific alkaline phosphatase,BAP)在肺癌骨转移诊断中的意义及其临床应用价值。方法采用前瞻性对照方法,共入组110例,分为3组。初治肺癌患者共90例,临床分期为IV期,分为骨转移组50例和非骨转移组40例,健康对照组20例,采用酶联免疫法和电化学发光免疫测定法检测所有入组者治疗前的血清骨代谢生化指标ICTP和BAP水平,对骨转移的各因素与血清ICTP和BAP的相关性进行统计学分析。结果骨转移组的血清ICTP和BAP水平显著高于非骨转移组和健康对照组(P<0.05)。多发性骨转移组(骨转移数≥3)的血清BAP水平显著高于少发性骨转移组(骨转移数<3)(P<0.05)。混合性骨转移组的血清BAP水平显著高于溶骨性骨转移组(P<0.05)。ICTP和BAP在肺癌骨转移诊断中的敏感性分别为18%和40%,特异性分别为98.3%和95...     

Bone metastases: When and how lung cancer interacts with bone

Bone metastasis is a common and debilitating consequence of lung cancer: 30%-40% of patients with non-small cell lung cancer develop bone metastases during the course of their disease. Lung cancer cells find a favorable soil in the bone microenvironment due to factors released by the bone matrix, the immune system cells, and the same cancer cells. Many aspects of the cross-talk among lung tumor cells, the immune system, and bone cells are not clear, but this review aims to summarize the recent findings in this field, with particular attention to studies conducted to identify biomarkers for early detection of lung cancer bone metastases.     

Markers of bone turnover in prostate cancer.

Prostate cancer is the most common malignancy in elderly men and is often associated with bone metastases. Although bone metastases are osteosclerotic, histological and biochemical studies clearly indicate an increase of both bone formation and bone resorption, providing the rational for using bisphosphonate as a palliative treatment in these patients. The recent development of specific and sensitive biochemical markers, reflecting the overall rate of bone formation and bone resorption, has improved the non-invasive assessment of bone turnover abnormalities in patients with prostate cancer. The immunoassays for bone-specific alkaline phosphatase and type I collagen propeptides are currently the most sensitive markers to assess bone, formation. The best indices of bone resorption are the immunoassay for the pyridinoline cross-links and the related peptides that can be measured in urine and more recently in serum. A better knowledge of the biochemistry, especially of the age-related post-translational modifications of type I collagen in the abnormal bone matrix, associated with bone metastases from prostate cancer may lead to markers of increased sensitivity. A recent example is the demonstration that the isomerization and racemization of the aspartic acid residue in C-telopeptides of type I collagen is impaired in patients with prostate cancer and bone metastases, a pattern than can be detected with specific conformational antibodies.The most sensitive markers of bone formation and bone resorption are markedly increased in patients with bone metastases compared with patients with cancer but without metastases, the levels correlating with the extent of the bone involvement. However, their sensitivity remains limited, suggesting that the currently available biochemical markers cannot be used as a surrogate for bone scintigraphy in the diagnosis of bone involvement. A few studies have suggested that the measurement of bone markers may be useful in the assessment of response to anti-endocrine therapy, although available data indicate a lower sensitivity than with prostates specific antigen. Additional longitudinal studies are required to assess the potential use of bone markers, especially to identify patients who relapse during the course of the treatment and, more specifically 3 those that result from the progression in bone metastases.Clearly, the established use of bone markers is for monitoring effects of bisphosphonate treatment. Several studies have shown a rapid decrease of bone resorption markers in patients with prostate cancer and bone metastases, the magnitude of the decrease correlating with the efficacy of the treatment in reducing bone pain. Thus, bone markers are likely to become a useful and objective tool to monitor bisphosphonate treatment and individual the therapy scheme.     

骨转移生化指标研究进展

肿瘤骨转移发生时,破骨细胞和成骨细胞释放至血和尿中的骨生化指标明显升高,有望用于骨转移的早期诊断,但其准确性和有效性尚待大样本的前瞻性研究评价.大多数骨生化指标高水平与骨转移患者不良预后显著相关,对疾病进展和疗效监测则具有重要临床意义.     

Markers of bone metabolism in prostate cancer

Although bone metastases from prostate cancer are described as osteoblastic, markers of both osteoblastic and osteoclastic activity are strikingly elevated in men with metastatic prostate cancer. Elevated markers of osteoblastic and osteoclastic activity are associated with adverse clinical outcomes in men with prostate cancer--outcomes including shorter time to skeletal complications, disease progression, and death. Bone marker measurement appears to be a promising method for monitoring the efficacy of bone-targeted therapy. Additional studies are needed to assess the potential role of bone markers in identifying men at highest risk for development of bone metastases.     

Diagnostic value of bone-turnover metabolites in the diagnosis of bone metastases in patients with lung carcinoma

BACKGROUND: Several biochemical markers of bone formation and bone resorption have been developed recently. The authors evaluated the usefulness of new biomarkers, such as urinary deoxypyridinoline (D-PYD), serum pyridinoline cross-linked C-telopeptides of Type I collagen (1CTP), and urinary pyridinoline cross-linked N-telopeptides of Type I collagen (NTx), in the assessment of bone metastases in patients with lung carcinoma. METHODS: The serum concentrations of 1CTP and the urinary concentrations of D-PYD and NTx were measured in 100 lung carcinoma patients, of whom 20 patients had bone metastases and 80 patients did not. Receiver operating characteristic (ROC) curves were drawn for these markers to compare their usefulness in detecting bone metastases originating in lung carcinoma. RESULTS: Urinary concentrations of NTx in patients with bone metastases were significantly greater than in patients without bone metastases (147.1 +/- 129.3 pmol bone collagen equivalents [BCE]/micromol Cr vs. 47.2 +/- 29.9 pmol BCE/micromol Cr; P < 0.0001). Urinary concentrations of D-PYD in patients with bone metastases also were significantly greater than in patients without bone metastases (10.0 +/- 3.6 BCE/micromol Cr vs. 6.6 +/- 2.2 pmol BCE/micromol Cr; P = 0.0001). No significant difference was observed in serum concentrations of 1CTP between patients with and without bone metastases. A moderate but significant correlation was seen between NTx and D-PYD (correlation coefficient [R] = 0.435; P < 0.0001) and between D-PYD and 1CTP (R = 0.525; P < 0.0001). NTx had a better ROC curve than D-PYD and 1CTP (the areas under the ROC curve were 0.84, 0.79, and 0.62, respectively). Using the threshold of 62.5 pmol BCE/micromol Cr for NTx, sensitivity, specificity, and accuracy were 0.800, 0.737, and 0.750, respectively. CONCLUSIONS: In the current study, the measurement of NTx appeared to be most useful as a marker of bone metastases in patients with lung carcinoma.     

Dual focal adhesion kinase/Pyk2 inhibitor has positive effects on bone tumors: implications for bone metastases

BACKGROUND: Lytic bone metastases occur frequently in cancer patients and present major clinical issues including lack of effective therapies. The mechanism of lytic bone metastases involves interactions between tumor cells, bone matrix, and bone cells. Both focal adhesion kinase (FAK) and Pyk2 are implicated in the biology and physiology of bone and cancer. METHODS: The efficacy of PF-562,271 was evaluated using MDA-MB-231 cells implanted in the tibia of nude rats. The drug was administered orally at a dose of 5 mg/kg, 7 days per week for 28 days. Serum and urine biomarkers, imaging, and histologic techniques were deployed to monitor tumor take rate, disease progression, and response to therapy. RESULTS: The compound was well tolerated. Both compound-treated groups demonstrated significant and similar increases in osteocalcin and cancellous bone parameters. Radiographic evaluation of tumor-bearing tibiae revealed tumor expansion in nontreated rats compared with a decrease in tumor growth and signs of bone healing in rats treated with PF-562,271. Tartrate-resistant acid phosphatase and fluorescent in situ hybridization analysis revealed that the majority of bone resorption at the tumor site was performed by osteoclasts of rat origin. CONCLUSIONS: The oral administration of PF-562,271 at a dose of 5 mg/kg suppressed the growth and local spread of intratibial tumors and restored tumor-induced bone loss. The unique ability of PF-562,271 to both curb tumor growth and safely increase bone formation may be an effective therapy for many cancer patients with bone metastases and cancer-associated osteoporosis.     

ICTP在诊断乳腺癌骨转移中的临床价值

目的：探讨ICTP在诊断乳腺癌骨转移中的临床价值。方法：用EIA法测定60例乳腺癌患者和23例健康体检者的ICTP血清水平。结果：乳腺癌骨转移患者ICTP血清水平较非骨转移和正常对照组显著升高,其诊断敏感性为77.8%,特异性为91.3%。多处骨转移患者血清ICTP阳性率和血清水平较单处骨转移患者显著升高且随着乳腺癌分期的升高,血清ICTP阳性率和血清水平也升高。结论：ICTP对乳腺癌骨转移患者的早期诊断,病情监测和临床分期判断具有重要意义。