Claudon Aurélie, Vergnaud Philippe, Valverde Cécile, Mayr Anita, Klause Ursula, Garnero Patrick
CCBR-SYNARC, Biochemical Markers, Lyon, France.
Clin Chem. 2008 Sep;54(9):1554-63. doi: 10.1373/clinchem.2008.105866. Epub 2008 Aug 1.
Serum C-terminal cross-linked telopeptide of type I collagen (CTX-I), N-terminal propeptide of type I collagen (PINP), and osteocalcin (OC) are among the most sensitive bone turnover markers for evaluating osteoporosis. Each marker is currently measured individually by manual or automated immunoassays that are time consuming and require substantial sample volume. We evaluated the performance characteristics of a novel, fully automated, protein-array chip system that allows the simultaneous measurement of CTX-I, PINP, OC, and intact parathyroid hormone (PTH) in 20 microL of serum.
We measured CTX-I, PINP, OC, and PTH using multiplex and corresponding automated single assays in 157 healthy premenopausal women, 74 healthy men, and 56 postmenopausal osteoporotic women before and 6 months after treatment with oral ibandronate (150 mg/month).
Within- and between-run CVs of the multiplex assay were similar to those of single measurement assays (<10% for all markers), whereas the limit of quantification was lower, except for OC. Multiplex values highly correlated (r > 0.93, P < 0.0001 for all markers) with the corresponding single assays, and measured concentrations were comparable. After 6 months of ibandronate, CTX-I, PINP, and OC decreased by a median of 48%, 63%, and 52%, respectively (P < 0.0001 for all 3 markers), magnitudes similar to those of the corresponding single assays.
The automated protein-array chip demonstrated similar analytical precision, improved analytical sensitivity, and comparable measured concentrations to those of single assays. The multiplex assay should be useful for assessing bone metabolism in large clinical studies, particularly when sample volume is limited.
血清I型胶原C端交联末肽（CTX-I）、I型胶原N端前肽（PINP）和骨钙素（OC）是评估骨质疏松症最敏感的骨转换标志物。目前，每种标志物都是通过手动或自动化免疫测定法单独测量的，这些方法耗时且需要大量样本。我们评估了一种新型的全自动蛋白质阵列芯片系统的性能特征，该系统能够在20微升血清中同时测量CTX-I、PINP、OC和完整甲状旁腺激素（PTH）。
我们在157名健康绝经前女性、74名健康男性和56名绝经后骨质疏松症女性口服伊班膦酸钠（150毫克/月）治疗前及治疗6个月后，使用多重检测和相应的自动化单检测法测量CTX-I、PINP、OC和PTH。
多重检测的批内和批间变异系数与单检测法相似（所有标志物均<10%），而除OC外，定量限更低。多重检测值与相应的单检测法高度相关（所有标志物r>0.93，P<0.0001），且测量浓度具有可比性。伊班膦酸钠治疗6个月后，CTX-I、PINP和OC分别下降了中位数48%、63%和52%（所有3种标志物P<0.0001），下降幅度与相应的单检测法相似。
自动化蛋白质阵列芯片显示出与单检测法相似的分析精密度、更高的分析灵敏度和可比的测量浓度。多重检测在大型临床研究中评估骨代谢时应会很有用，尤其是在样本量有限时。
