膝关节影像学骨关节炎患者血清和尿液生物标志物的昼夜变化

Diurnal variation of serum and urine biomarkers in patients with radiographic knee osteoarthritis.

作者信息

Kong S Y, Stabler T V, Criscione L G, Elliott A L, Jordan J M, Kraus V B

机构信息

Duke University Medical Center, Durham, North Carolina 27710, USA.

出版信息

Arthritis Rheum. 2006 Aug;54(8):2496-504. doi: 10.1002/art.21977.

DOI:10.1002/art.21977

PMID:16868970

Abstract

OBJECTIVE

To evaluate diurnal variation of biomarkers in subjects with osteoarthritis (OA) of the knee.

METHODS

Twenty subjects with radiographic knee OA were admitted to the General Clinical Research Center of Duke University for an overnight stay to undergo serial blood and urine sampling. Biomarkers measured included serum hyaluronan (HA), cartilage oligomeric matrix protein (COMP), keratan sulfate (KS-5D4), aggrecan neoepitope (CS846), high-sensitivity C-reactive protein (hsCRP), osteocalcin, transforming growth factor beta1 (TGFbeta1), and type II collagen (CII)-related epitopes (neoepitope from cleavage of CII [C2C], carboxy-terminus of three-quarter peptide from cleavage of CI and CII [C1,2C], and type II procollagen carboxy-propeptide [CPII] in serum, and C-terminal telopeptides of CII [CTX-II] and C2C in urine).

RESULTS

Levels of serum HA, COMP, KS-5D4, and TGFbeta1 increased significantly from T0 (before arising from bed) to T1 (1 hour after arising). More diurnal variation in HA was observed in patients with higher daily mean HA concentrations. CPII increased significantly from T0 to T2 (4 hours after arising). Urinary concentrations of CTX-II were also found to vary with morning activity, decreasing significantly from T0 to T2. Urinary C2C concentrations increased significantly from T0 until T3 (early evening). No diurnal variations in CS846, hsCRP, osteocalcin, serum C2C, or C1,2C were observed. Six biomarkers (serum C2C, C1,2C, COMP, KS-5D4, TGFbeta1, and urinary CTX-II) were associated with radiographic knee OA (expressed as the sum of Kellgren/Lawrence radiographic severity grades), with the strongest correlations observed with measurements obtained at later time points (either T2 or T3).

CONCLUSION

Our study results suggest that serum and urine sampling for HA, COMP, KS-5D4, TGFbeta1, CPII, urinary CTX-II, and urinary C2C should be standardized in future OA clinical trials. Serum and urine sampling at late midday time points may be the optimal approach for OA studies, although this result should be validated in a larger cohort.

摘要

目的

评估膝骨关节炎（OA）患者生物标志物的昼夜变化。

方法

20例膝关节X线片显示为OA的患者入住杜克大学综合临床研究中心过夜，接受系列血液和尿液样本采集。检测的生物标志物包括血清透明质酸（HA）、软骨寡聚基质蛋白（COMP）、硫酸角质素（KS-5D4）、聚集蛋白聚糖新表位（CS846）、高敏C反应蛋白（hsCRP）、骨钙素、转化生长因子β1（TGFβ1）以及血清中II型胶原（CII）相关表位（CII裂解产生的新表位[C2C]、CII和CI裂解产生的四分之三肽的羧基末端[C1,2C]以及II型前胶原羧基端前肽[CPII]），尿液中CII的C末端端肽（CTX-II）和C2C。

结果

血清HA、COMP、KS-5D4和TGFβ1水平从T0（起床前）到T1（起床后1小时）显著升高。每日平均HA浓度较高的患者HA的昼夜变化更大。CPII从T0到T2（起床后4小时）显著升高。还发现尿CTX-II浓度随早晨活动而变化，从T0到T2显著降低。尿C2C浓度从T0到T3（傍晚）显著升高。未观察到CS846、hsCRP、骨钙素、血清C2C或C1,2C的昼夜变化。六种生物标志物（血清C2C、C1,2C、COMP、KS-5D4、TGFβ1和尿CTX-II）与膝关节X线片OA相关（表示为Kellgren/Lawrence X线严重程度分级之和），在较晚时间点（T2或T3）获得的测量值之间观察到最强的相关性。