Fontana A, Delmas P D
Hôpital Edouard Herriot, Inserm Research Unit, Lyon, France.
Cancer. 2000 Jun 15;88(12 Suppl):2952-60. doi: 10.1002/1097-0142(20000615)88:12+<2952::aid-cncr11>3.0.co;2-m.
Bone metastases are a frequent complication of cancer disease. The evaluation of metastatic bone disease is crucial for the primary cancer staging because it will influence the therapeutic decision. The diagnosis of bone metastases usually relies on skeletal X-ray and bone scintigraphy. This latter technique is a sensitive diagnostic tool but lacks specificity. Moreover, the assessment of efficacy in the treatment of bone metastasis is difficult because the increased radionucleotide uptake does not always reflect an active metastatic area but may correspond to a bone reconstruction in patients responding to treatment. Markers of bone remodeling could help the clinician in the diagnosis and follow-up of bone metastases.
A common feature of both types of bone metastases (lytic or sclerotic) is an alteration of bone remodeling activity. The rate of formation or degradation of the bone matrix can be assessed either by measuring a prominent enzymatic activity of the bone forming or resorbing cells or by measuring bone matrix components released into the circulation during formation or resorption. They have been separated into markers of formation and resorption, but when both events are coupled and in balance, either of these markers will reflect the overall rate of bone turnover. These markers are of unequal specificity and sensitivity, and some of them have not been fully investigated yet in bone metastases. None of these markers is disease specific.
Several studies of breast carcinoma showed increased levels of pyridinium cross-links in patients with bone metastases. However, in most studies, breast carcinoma patients without evidence of metastatic bone disease excreted pyridinium cross-links at a much higher rate than healthy controls. Similar findings have been observed with other types of primary cancer including lung, prostate, kidney, throat, and digestive carcinoma. Markers of bone formation had a low sensitivity in the diagnosis of bone metastasis, but they could be useful for prostate carcinoma, in which studies have shown that all patients without bone metastasis had normal value of bone alkaline phosphatase. Bone markers can be used for the follow-up of treatment, especially bisphosphonates therapy. Bisphosphonate infusion induces a large decrease of pyridinium cross-link level. Some studies suggest that a high level of resorption markers after treatment could reflect a resistance to the treatment. Moreover, some studies have shown that level of pyridinium cross-links before treatment could be a predictive factor of the response in multiple myeloma and prostate carcinoma.
Bone markers have improved greatly in terms of sensitivity and specificity and could be useful for an early diagnosis of bone metastases. However, the clinical value of the use of bone markers in the diagnosis of bone metastasis has not been clearly shown yet with the possible exception of BPAL in prostate carcinoma. When bone is the only site of metastases, bone markers may be useful for monitoring patients with bone metastases. Markers of bone resorption are sensitive to changes in bone turnover induced by treatment. Bone resorption markers may be particularly useful for the follow-up of bisphosphonate treatment, which is increasingly used in the management of bone metastases.
骨转移是癌症疾病常见的并发症。转移性骨病的评估对于原发癌分期至关重要，因为它会影响治疗决策。骨转移的诊断通常依赖于骨骼X线检查和骨闪烁显像。后一种技术是一种敏感的诊断工具，但缺乏特异性。此外，评估骨转移治疗的疗效很困难，因为放射性核素摄取增加并不总是反映活跃的转移区域，而可能对应于对治疗有反应的患者的骨重建。骨重塑标志物有助于临床医生对骨转移进行诊断和随访。
两种类型的骨转移（溶骨性或成骨性）的一个共同特征是骨重塑活动的改变。骨基质的形成或降解速率可以通过测量成骨细胞或破骨细胞的显著酶活性，或通过测量在形成或吸收过程中释放到循环中的骨基质成分来评估。它们已被分为形成标志物和吸收标志物，但当这两个过程相互关联且平衡时，这些标志物中的任何一个都将反映骨转换的总体速率。这些标志物的特异性和敏感性各不相同，其中一些在骨转移中尚未得到充分研究。这些标志物都不是疾病特异性的。
多项乳腺癌研究表明，骨转移患者的吡啶交联水平升高。然而，在大多数研究中，没有骨转移证据的乳腺癌患者排泄吡啶交联的速率比健康对照高得多。在包括肺癌、前列腺癌肾衰竭、喉癌和消化道癌在内的其他类型的原发性癌症中也观察到了类似的结果。骨形成标志物在骨转移诊断中的敏感性较低，但它们可能对前列腺癌有用，在前列腺癌的研究中表明，所有无骨转移的患者骨碱性磷酸酶值均正常。骨标志物可用于治疗随访，尤其是双膦酸盐治疗。输注双膦酸盐会导致吡啶交联水平大幅下降。一些研究表明，治疗后高水平的吸收标志物可能反映对治疗的耐药性。此外，一些研究表明，治疗前吡啶交联水平可能是多发性骨髓瘤和前列腺癌反应的预测因素。
骨标志物在敏感性和特异性方面有了很大提高，可能有助于骨转移的早期诊断。然而，除了前列腺癌中的骨碱性磷酸酶外，骨标志物在骨转移诊断中的临床价值尚未明确显示。当骨是唯一的转移部位时，骨标志物可能有助于监测骨转移患者。骨吸收标志物对治疗引起的骨转换变化敏感。骨吸收标志物可能对双膦酸盐治疗的随访特别有用，双膦酸盐治疗在骨转移管理中越来越常用。
