背景:为了评估与24个月以上膝骨关节炎(OA)MRI上骨髓病变(BMLs)相关的生化标志物短期变化的预后价值,此外,在MRI上评估与组织更新和炎症相关的生化标志物与BMLs之间的关系。
方法:分析了骨关节炎倡议(n=600)中来自美国国立卫生研究院OA生物标志物联盟的数据。根据MRI骨关节炎膝关节评分(MOAKS)系统(0-3)测量BML,在15个膝盖区域。血清和尿生化指标评估如下:血清C端交联端肽I型胶原(CTX-I),血清交联的I型胶原N端肽(NTX-I),尿CTX-Iα和CTX-Iβ,尿NTX-I,尿C末端交联的II型胶原端肽(CTX-II),血清基质金属蛋白酶(MMP)降解的I型,II,和III胶原蛋白(C1M,C2M,C3M),血清高敏IIb型胶原前肽(hsPRO-C2),和基质金属蛋白酶产生的C反应蛋白(CRPM)的新表位。使用对协变量进行调整的回归模型检查了12个月的生化标志物变化与24个月的BML之间的关联。C1M,C2M,C3M,在基线和超过24个月时检查hsPRO-C2、CRPM和BMLs。
结果:在24个月时,血清CTX-I和尿CTX-Iβ的增加与受任何BML影响的亚区数量变化的几率增加有关。hsPRO-C2的增加与24个月内受任何BML影响的亚区域数量恶化的几率降低相关。C1M和C3M与基线时受影响的BML相关。
结论:血清CTX-I的短期变化,hsPRO-C2和尿CTX-Iβ在MRI上具有预测BML进展的潜力。MRI上C1M和C3M与基线BML的关联值得进一步研究。
To assess the prognostic value of short-term change in biochemical markers as it relates to bone marrow lesions (BMLs) on MRI in knee osteoarthritis (OA) over 24 months and, furthermore, to assess the relationship between biochemical markers involved with tissue turnover and inflammation and BMLs on MRI.
Data from the Foundation for the National Institutes of Health OA Biomarkers Consortium within the Osteoarthritis Initiative (n = 600) was analyzed. BMLs were measured according to the MRI Osteoarthritis Knee Score (MOAKS) system (0-3), in 15 knee subregions. Serum and urinary biochemical markers assessed were as follows: serum C-terminal crosslinked telopeptide of type I collagen (CTX-I), serum crosslinked N-telopeptide of type I collagen (NTX-I), urinary CTX-Iα and CTX-Iβ, urinary NTX-I, urinary C-terminal cross-linked telopeptide of type II collagen (CTX-II), serum matrix metalloproteinase (MMP)-degraded type I, II, and III collagen (C1M, C2M, C3M), serum high sensitivity propeptide of type IIb collagen (hsPRO-C2), and matrix metalloproteinase-generated neoepitope of C-reactive protein (CRPM). The association between change in biochemical markers over 12 months and BMLs over 24 months was examined using regression models adjusted for covariates. The relationship between C1M, C2M, C3M, hsPRO-C2, and CRPM and BMLs at baseline and over 24 months was examined.
Increases in serum CTX-I and urinary CTX-Iβ over 12 months were associated with increased odds of changes in the number of subregions affected by any BML at 24 months. Increase in hsPRO-C2 was associated with decreased odds of worsening in the number of subregions affected by any BML over 24 months. C1M and C3M were associated with BMLs affected at baseline.
Short-term changes in serum CTX-I, hsPRO-C2, and urinary CTX-Iβ hold the potential to be prognostic of BML progression on MRI. The association of C1M and C3M with baseline BMLs on MRI warrants further investigation.