Academic Unit of Bone Metabolism, University of Sheffield, Sheffield, UK.
Bone. 2012 May;50(5):1141-7. doi: 10.1016/j.bone.2012.02.003. Epub 2012 Feb 12.
Robust validated reference intervals for bone turnover markers (BTMs) are required to assess fracture risk and effectiveness of therapy. However, there are currently limited reference intervals for BTMs in premenopausal women, especially comparing manual and automated assays. This study determined the BTM reference intervals using automated and manual assays, compared the results obtained from two different assays, and evaluated the factors that may affect BTM levels. This was a cross-sectional registry study in 194 healthy, premenopausal, European Caucasian women aged 35 to 39years from France (n=98) and Denmark (n=96). Two independent specialized laboratories, one in France (Synarc) and the other in Denmark (Nordic Bioscience), analyzed blood and urine samples from each woman for BTM levels. The type of assay used in this study significantly affected the reference intervals obtained for serum cross-linked C-terminal telopeptide of type I collagen (sCTX) and urinary cross-linked N-terminal telopeptides of type I collagen (uNTX/Cr; both P<0.001), but not for serum procollagen type I amino-terminal propeptide (PINP; P=0.28). The Serum Crosslaps® ELISA; Microtitre-plate based ELISA; Metra BAP EIA; and UniQ® PINP RIA assays yielded higher BTM reference values. The reference intervals for the BTMs, as measured with Serum β-Crosslaps, Elecsys® 2010 Systems; VITROS® ECI System; Ostase®, Access® Immunoassay System; and Total PINP, Elecsys® 2010 Systems assays, were 0.111-0.791ng/mL for sCTX, 12.3-59.7nmol BCE/mmol creatinine for uNTX/Cr, 5.8-17.5ng/mL for bone alkaline phosphatase (ALP), and 17.3-83.4ng/mL for PINP, respectively. When measured with Serum Crosslaps® ELISA, Microtitre-plate based ELISA, Metra BAP EIA, and UniQ® PINP RIA, the reference intervals were 0.177-0.862ng/mL for sCTX, 22.6-95.7nmol BCE/mmol creatinine for uNTX/Cr, 14.8-38.8U/L for bone ALP, and 19.5-75.2ng/mL for PINP, respectively. The clinical interpretation of the BTMs of a subject should be based on comparison with a BTM reference interval, measured with the same assay method.
评估骨折风险和治疗效果需要有可靠的经验证的骨转换标志物（BTM）参考区间。然而，目前围绝经期女性的 BTM 参考区间有限，特别是手动和自动检测方法之间的比较。本研究使用自动和手动检测方法确定了 BTM 参考区间，比较了两种不同检测方法的结果，并评估了可能影响 BTM 水平的因素。这是一项在法国（n=98）和丹麦（n=96）的 194 名健康的、处于围绝经期的、欧洲白种人女性中进行的横断面登记研究，年龄 35-39 岁。两个独立的专业实验室，一个在法国（Synarc），另一个在丹麦（Nordic Bioscience），分别分析了每个女性的血液和尿液样本中的 BTM 水平。用于本研究的检测方法显著影响了血清交联型 I 胶原 C 端肽（sCTX）和尿交联型 I 胶原 N 端肽（uNTX/Cr；均 P<0.001）的参考区间，但对血清 I 型前胶原氨基端前肽（PINP；P=0.28）没有影响。血清 Crosslaps®ELISA；微孔板基于 ELISA；Metra BAP EIA；和 UniQ®PINP RIA 检测方法得出了更高的 BTM 参考值。使用血清 β-Crosslaps、Elecsys®2010 系统；VITROS®ECI 系统；Ostase®、Access®免疫测定系统；和总 PINP、Elecsys®2010 系统检测的 BTM 参考区间分别为 sCTX 0.111-0.791ng/mL，uNTX/Cr 12.3-59.7nmol BCE/mmol 肌酐，骨碱性磷酸酶（ALP）5.8-17.5ng/mL，PINP 17.3-83.4ng/mL。当使用血清 Crosslaps®ELISA、微孔板基于 ELISA、Metra BAP EIA 和 UniQ®PINP RIA 进行检测时，sCTX 的参考区间分别为 0.177-0.862ng/mL，uNTX/Cr 22.6-95.7nmol BCE/mmol 肌酐，骨 ALP 14.8-38.8U/L，PINP 19.5-75.2ng/mL。应基于与同一检测方法测量的 BTM 参考区间进行比较，对个体的 BTM 进行临床解读。
