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骨转换标志物
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本文 最后修改 时间 2018/01/16.
检测的是什么物质?

   骨转换标志物是一些骨骼重建过程中,存在于血液或尿液中的产物,可用于评价骨吸收和骨形成率是否正常,提示潜在的骨骼疾病。骨转换标志物还可预测骨折风险,监测骨骼疾病患者的疗效,如骨质疏松症。

        骨骼是一种活跃的,处于不断更新的结缔组织,每年的更新率约为10%。骨骼主要由I型胶原构成,组成了骨骼坚韧的框架结构。钙也是骨骼的重要成分,使骨骼系统尤为坚固。胶原和钙的结合,赋予了骨骼坚固的同时也能承受压力。机体超过90%的钙是沉积于骨骼和牙齿中,其余约1%的钙存在于血液中。

        在人的一生中,陈旧的骨骼在不断被吸收,取而代之的是不断生成的新骨,以维持骨骼系统的健康。在骨吸收过程中,破骨细胞能溶解少量骨骼,同时经过酶的作用可降解蛋白质结构。骨形成是始于成骨细胞的活化,形成新的骨骼蛋白质结构,继而被钙和磷矿化形成新骨骼。这样一种微观的重建过程维持了骨骼系统的强韧。

        在儿童时代的早期和青少年时期,新骨的形成速度大于旧骨的吸收速度,因此骨骼系统得以生长和不断强韧,直到达到骨峰值(骨骼密度和强度的最大值),通常为25至30岁。在这个时期后,骨吸收的速度开始大于骨形成,使骨质开始不断流失。在女性绝经后的几年里,骨质的流失速度最快。男性则通常在70岁后才会发生明显的骨质流失。

如何使用骨转换标志物?
        可选择一个或几个标志物来判断骨吸收和骨形成的速度。当医生评价骨质流失或骨骼疾病时,骨转换标志物可作为骨密度的附加信息,帮助临床判断。这些标志物被广泛应用于评价抗骨吸收的治疗疗效,帮助医生了解药物用量是否合适。与X线检测(一至两年)相比,通过骨转换标志物可使临床很快(三至六个月)对疗效做出评价。如果治疗效果不理想时,能及时更换治疗方式。

        由于乳腺癌和前列腺癌患者发生骨转移的概率较高,有些研究也表明骨转换标志物可辅助临床预测骨转移的并发症,或选用抗骨吸收药物,如二膦酸盐。骨转换标志物还可用于评价抗骨质流失的疗效。

骨转换标志物检测

        如下是一些血液或尿液中检测的骨吸收或骨形成标志物。研究者们还在不断寻找能预测不同疾病骨质流失的新检测标志物。在进行一些标志物的检测结果解释时,需考虑饮食状况、是否经常运动,以及标本采集的时间。

        尿液或血液中的一些骨吸收标志物:

  • C-端肽(I型胶原羧基端端肽CTx):为蛋白基质中羧基末端的肽链;可辅助监测绝经后女性和低骨质人群(骨量减少)的抗骨吸收治疗,如二膦酸盐、激素替代治疗法。
  • N-端肽(I型胶原氨基端端肽NTx):为蛋白基质中氨基末端的肽链;专家建议应于骨质疏松症治疗之前检测,了解基础水平,并在治疗后3至6个月再进行检测。
  • 脱氧吡啶(DPD):环状结构的胶原降解产物。
  • 吡啶交联:为一组胶原降解产物,包含DPD;用于疗效检测;不如端肽对骨骼胶原具有特异性。
  • 抗酒石酸的酸性磷酸酶(TRAP)5b:5b是在骨吸收过程中破骨细胞产生的TRAP异构体。

        血液中的一些骨形成标志物:

  • 骨源性的碱性磷酸酶:为碱性磷酸酶(ALP)的一种同工酶;与成骨细胞功能相关,对于骨骼的矿化具有重要作用;推荐在进行骨质疏松症治疗前进行检测,了解基础水平。并于治疗后3至6个月再进行检测;检测结果可能受肝源性ALP干扰。
  • 骨钙素:一种由成骨细胞形成的蛋白质;构成新骨的非胶原结构;部分骨钙素进入血液循环;骨钙素能辅助预测绝经后女性的骨质流失率,也可作为反映骨重建的标志物;可用于帮助选择有效的治疗骨质疏松症的药物,但治疗后的变化不如端肽敏感;同样推荐在进行治疗前进行检测,3至6个月后再次检测。此标志物受到华法林药物的影响。
  • P1NP(I型前胶原氨基端端肽):由成骨细胞合成;可反映胶原和骨骼的形成速度;能与骨吸收标志物C-或N-端肽共同检测;是最为敏感的骨形成标志物,尤其对骨形成或抗骨吸收治疗监测有效;推荐在进行治疗前进行检测,3至6个月后再次检测。

        血液或尿液中骨转换标志物水平增高,提示骨吸收或骨形成速度升高,但无法提示原因。当标志物用于进行疗效监测时,骨吸收标志物水平下降提示治疗有效。

        若同时检测几项标志物,需空腹进行采血。并且需留意标本采集的时间,如第二次晨尿。

        很多骨转换标志物在临床应用上还存在较多限制,但研究者们在不断开拓新的临床应用价值。目前这些标志物主要用于评价代谢性骨病的疗效检测,以准确调整药物的剂量。

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