CN1454263A - 骨质疏松症的诊断和/或骨质疏松症骨折危险的预测方法 - Google Patents
骨质疏松症的诊断和/或骨质疏松症骨折危险的预测方法 Download PDFInfo
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Abstract
以提供新型的骨吸收标记为基础,从而提供一种能够迅速、简便并且正确地对骨质疏松症进行诊断和/或对骨质疏松症骨折危险进行预测的方法,其特征在于,测定尿中的γ-GTP。
Description
技术领域
本发明涉及一种能够迅速、简便并且正确地对骨质疏松症进行诊断和/或对骨质疏松症骨折危险进行预测的方法。
背景技术
骨组成在正常状态下其骨密度减少为特征的骨质疏松症,在性别中是尤其多发于女性的疾病。尤其在40岁以后的女性中伴随绝经的绝经后骨质疏松症较为多见。另外,在70岁以后,无论男女都会出现老年性骨质疏松症。
在骨密度减少较轻度时,并不立刻出现临床症状,但随着减少程度的变大,也就变得越容易引起骨折或骨变形。脊椎容易引起骨折或骨变形,而出现由于锥体的压迫骨折或脊椎变形引起的腰痛等症状。
另外,大腿骨颈部或骨盆的骨折,有时会使患者失去运动功能,从而对以后的生活带来很大影响。
现在,骨质疏松症的诊断,是通过X线照相等物理学方法进行,但是该方法须要大规模的诊断装置,并且不仅具有由于使用X线产生的安全性问题,还存在只有在骨密度明显减少的发病后期才能有效诊断的缺点。
所以,通过对以绝经后骨质疏松症或老年性骨质疏松症为代表的各种骨质疏松症进行早期发现并且诊断、从而对骨折危险进行预测,有望确立可以有效治疗的迅速、简便并且准确的方法。
近年,通过从血液或尿中检测与骨代谢有关的因子,并且以此为骨代谢标记进行测定,从而使诊断骨质疏松症的方法获得了急速的进步。骨代谢标记与骨吸收标记和骨形成标记有很大区别,但是,其中已知骨基质主要成分的I型胶原交联成分的分解产物Pyridinoline(Pyr)、去氧Pyridinoline(D-Pyr)、I型胶原C末端端肽片断(CTx)、I型胶原C末端端肽片断(ICTP)、I型胶原N端端肽片断(NTx)、破骨细胞产生的酒石酸抵抗性酸性磷酸酯酶(TRAP)作为骨吸收标记有效。但是,人们正在探索在特异性和灵敏度方面更优良的骨吸收标记。
发明内容
所以,本发明目的在于提供一种以新型骨吸收标记的提供为基础的能够迅速、简便并且正确地对骨质疏松症进行诊断和/或对骨质疏松症骨折危险进行预测的方法。
本发明发明人等鉴于上述问题,进行了种种探讨,结果发现,尿中的γ-谷氨酰转肽酶(以下简称为γ-GTP)可以用作骨吸收标记,γ-GTP越多,骨密度就越低,骨质疏松症处于发病期,或者通过给予骨质疏松症的治疗药发现使γ-GTP减少和骨密度的恢复(增加),通过利用这种相关性,发现了能够迅速、简便并且正确地对骨质疏松症进行诊断和/或对骨质疏松症骨折危险进行预测的方法。
γ-GTP已知为作为特异性的反映肝胆道类疾病的标记的转移酶。在特开平10-87507号公报中公开了γ-GTP具有促进破骨细胞分化的活性,但是,本次发现尿中的γ-GTP作为特异骨吸收标记发挥作用是不能根据所述公报公开的内容而完全预知的以外发现。
本发明是根据所述见解而完成的,本发明的骨质疏松症的诊断和/或骨质疏松症骨折危险的预测方法,如权利要求1所述,其特征在于,测定尿中的γ-GTP。
另外,权利要求2所述的方法是在权利要求1所述的方法中,其特征在于,在尿中添加γ-GTP活性测定用基质,通过由显色程度测定γ-GTP的活性,从而测定γ-GTP。
另外,本发明的骨密度的监控方法,如权利要求3所述,其特征在于,测定尿中的γ-GTP。
另外,本发明,如权利要求4所述,其特征在于,将尿中的γ-GTP作为骨吸收标记使用。
另外,本发明的试剂,如权利要求5所述,其特征在于,至少含有γ-GTP活性测定用基质的、用于对骨质疏松症进行诊断和/或对骨质疏松症骨折危险进行预测的试剂。
附图说明
图1是表示治疗开始前的尿中γ-GTP和尿中NTx的相关图。
图2是表示治疗3个月后两者的相关图。
图3是表示治疗6个月后两者的相关图。
图4是表示治疗12个月后两者的相关图。
图5是表示治疗中的尿中γ-GTP和尿中NTx的推移图。
具体实施方式
以下对本发明的实施方式进行说明。
本发明的骨质疏松症的诊断和/或骨质疏松症骨折危险的预测方法,其特征在于,测定尿中的γ-GTP。
对于尿中的γ-GTP的测定方法无特殊的限制,可以根据利用对γ-GTP的特异抗体的酶免疫定量法(EIA)、放射性免疫定量法(RIA)、利用高效液相色谱法(HPLC)的定量方法等,其中优选通过在尿中添加γ-GTP活性测定用基质,由显色程度来测定γ-GTP活性的方法(酶法)。根据酶法,由于无须对检体进行前处理等,在短时间内可以确定结果,所以具有能够简便、快速测定的优点。另外,用于该方法的测定试剂作为肝胆道类疾病等的诊断试剂有各种市售品,在本发明中,利用该市售的测定试剂,可以以与肝胆道类疾病等的诊断中的操作方法(用法、用量)相同的方法测定。γ-GTP的测定值如果须要可以根据尿中的肌酸酐值进行修正。
作为γ-GTP活性测定用基质,可以使用所述市售诊断试剂中的各种合成基质,例如,L-γ-谷酰基对硝基酰基苯胺、L-γ-谷酰基-3-羧基-4-硝基酰基苯胺、L-γ-谷酰基-3-羧基-4-羟基酰基苯胺、L-γ-谷酰基-对-N-乙基-N-羟基乙基氨基酰基苯胺、L-γ-谷酰基-3,5-二溴-4-羟基酰基苯胺、L-γ-谷酰基-α-萘胺、L-γ-谷酰基-3-羧基-1,4-亚苯基二胺等。另外,作为L-谷酰基的受体物质通常添加甘氨酰甘氨酸。
由γ-GTP活性的显色程度的测定,根据由γ-GTP活性测定用基质游离产生的显色物质、由基质游离产生的物质产生的显色物质的显色程度进行测定,为能够进一步高精度地测定,优选根据比色法测定。比色测定可以以与肝胆道类疾病等的诊断中的比色测定相同的方法进行测定。如果使用各种自动分析装置,可以在短时间内对大量的检体进行处理。
为使测定简便,也可以视觉测定。此时,由于尿为检体,显色优选黄色以外的颜色。作为能够制作黄色以外显色的基质,可以举出L-γ-谷酰基-3,5-二溴-4-羟基酰基苯胺(3,5-二溴-4-羟基酰基苯胺(DBHA)游离,通过单酚单氧酶的作用,而DBHA与N-甲基-N-(3-甲基苯基)-N’-琥珀酰基二胺氧化缩和生成绿色色素)。
在以上方法中,若测定尿中的γ-GTP,由于γ-GTP具有骨吸收标记的作用,所以γ-GTP越多,说明骨密度越低,骨质疏松症正处于发病期。另一方面,由于γ-GTP的减少意味着骨密度的恢复(增加),所以症状正处于改善期。所以,利用该相关性,可以迅速、简便并且正确地对骨质疏松症进行诊断和/或对骨质疏松症骨折危险进行预测。另外,对于各个患者通过多次测定尿中的γ-GTP来对骨密度进行监测,从而可以容易地对骨质疏松症治疗药的选择或者其效果进行判定。以下在实施例中对本发明进行详细说明,但本发明不受以下限制。
(方法)
以无肝胆道类疾病的未对骨质疏松症进行治疗的绝经女性35人为对象,在征求同意的前提下测定血清和尿中的γ-GTP(各个测定根据将关东化学社制的Merck Liquid γ-GT J用作测定试剂的酶法,根据操作程序利用日立制作所社制7170型自动分析装置进行测定)。
另外,作为对照的骨吸收标记,将尿中的I型胶原N末端端肽片断(NTx)用作对照的骨形成标记并测定血清中的碱性磷酸酯酶(ALP)(前者的测定根据将持田制药社制Osteomark用作测定试剂的ELISA法,后者的测定根据将和光纯药工业社制L型EWaKoATP·J用作测定试剂的酶法进行测定)。
另外,用Lunar社制DPX对腰椎和大腿骨颈部的密度进行测定。从所述测定的时间点,对每个人在12个月期间作为激素补充疗法的治疗,每日单独服用结合型***0.625mg或每日服用它和甲羟孕酮2.5mg,在治疗开始后3个月、6个月、12个月测定血清中和尿中的γ-GTP、尿中的NTx、血清中的ALP。另外,在治疗开始后6个月和12个月测定骨密度。
(结果)
发现根据激素补充疗法的治疗中,尿中γ-GTP和尿中NTx之间有显著的正相关(参照图1~图4)。两者显示相同的推移,在治疗12个月后尿中的γ-GTP平均减少21.4%,尿中的NTx平均减少37.7%。
骨密度在治疗12个月后,腰椎骨密度(L2-L4 BMD)平均增加6.0%,大腿骨颈部骨密度(Femoral neck BMD)平均增加1.7%(参照图5)。另外,血清ALP在治疗12个月后平均减少18.5%。血清中γ-GTP在治疗中无显著变化。
由以上结果可知,尿中的γ-GTP越多,骨密度就越低;在激素补充疗法中测定的γ-GTP的减少和骨密度的恢复(增加)一致;另外,尿中的γ-GTP与可以有效地作为骨吸收标记的尿中的NTx显示相同的推移;所以尿中的γ-GTP可以有效地作为骨吸收标记。
如前述,γ-GTP由于具有促进破骨细胞的分化作用,所以尿中的γ-GTP可以有效地用作具有现存骨吸收标记中不具有的性质的标记。
根据本发明,提供了尿中作为新型的骨吸收标记的γ-GTP,通过测定尿中的γ-GTP可以迅速、简便并且准确地对骨质疏松症进行诊断和/或对骨质疏松症骨折危险进行预测。
Claims (5)
1.一种骨质疏松症的诊断和/或骨质疏松症骨折危险的预测方法,通过测定尿中的γ-谷氨酰转肽酶(γ-GTP)进行诊断和预测。
2.根据权利要求1所述的方法,通过在尿中添加γ-GTP活性测定基质,由显色程度测定γ-GTP的活性,从而测定γ-GTP。
3.一种骨密度的监测方法,通过测定尿中的γ-GTP进行监测。
4.尿中的γ-GTP作为骨吸收标记的使用。
5.一种试剂,至少含有γ-GTP活性测定用基质,并且用于对骨质疏松症进行诊断和/或对骨质疏松症骨折危险进行预测。
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JP2000279261 | 2000-09-14 | ||
JP2000279261A JP3709332B2 (ja) | 2000-09-14 | 2000-09-14 | 骨粗鬆症の診断および/または骨粗鬆症骨折リスクの予測の方法 |
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US (1) | US20030166038A1 (zh) |
EP (1) | EP1318202A4 (zh) |
JP (1) | JP3709332B2 (zh) |
KR (1) | KR20030040453A (zh) |
CN (1) | CN1454263A (zh) |
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CN103598875A (zh) * | 2013-11-16 | 2014-02-26 | 沈阳医学院 | 一种用于预测骨质疏松发生风险的人体骨密度预测装置 |
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JP2005124402A (ja) * | 2003-10-21 | 2005-05-19 | Pharmaceuticals & Medical Devices Agency | 骨疾患のモデル動物 |
KR102227938B1 (ko) * | 2018-06-20 | 2021-03-16 | 한국생산기술연구원 | 골다공증 예측 방법 |
KR102323516B1 (ko) * | 2019-10-31 | 2021-11-09 | 한국생산기술연구원 | 비균질 인공뼈 시편 제조방법 및 비균질성을 갖는 뼈의 골다공증 예측 방법 |
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US3769173A (en) * | 1972-08-21 | 1973-10-30 | Warner Lambert Co | Determination of gamma-glutamyl transpeptidase in biological fluids |
JPH09299337A (ja) * | 1996-05-10 | 1997-11-25 | Masataka Shiraki | 骨疾患罹患リスクの予測方法 |
GB9610281D0 (en) * | 1996-05-16 | 1996-07-24 | Ralston Stuart H | Diagnostic method and apparatus |
JP4034381B2 (ja) * | 1996-06-28 | 2008-01-16 | 株式会社エーシーバイオテクノロジーズ | γ−グルタミルトランスペプチターゼの新規な用途 |
CN1183159C (zh) * | 1997-09-24 | 2005-01-05 | 三共株式会社 | 破骨细胞形成抑制因子单克隆抗体、其用途和试剂盒 |
JP2000041679A (ja) * | 1998-07-31 | 2000-02-15 | Nissho Corp | 骨密度の予測方法 |
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- 2001-09-12 WO PCT/JP2001/007897 patent/WO2002022863A1/ja not_active Application Discontinuation
- 2001-09-12 US US10/257,325 patent/US20030166038A1/en not_active Abandoned
- 2001-09-12 CN CN01815376A patent/CN1454263A/zh active Pending
- 2001-09-12 CA CA002422235A patent/CA2422235A1/en not_active Abandoned
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103598875A (zh) * | 2013-11-16 | 2014-02-26 | 沈阳医学院 | 一种用于预测骨质疏松发生风险的人体骨密度预测装置 |
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EP1318202A1 (en) | 2003-06-11 |
JP2002085091A (ja) | 2002-03-26 |
KR20030040453A (ko) | 2003-05-22 |
JP3709332B2 (ja) | 2005-10-26 |
WO2002022863A1 (fr) | 2002-03-21 |
CA2422235A1 (en) | 2003-03-13 |
RU2003110428A (ru) | 2004-08-27 |
US20030166038A1 (en) | 2003-09-04 |
EP1318202A4 (en) | 2007-03-14 |
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