11年间骨关节炎相关血清生化标志物与基于膝关节MRI的成像生物标志物在中年成年人中的关联。
Association between osteoarthritis-related serum biochemical markers over 11 years and knee MRI-based imaging biomarkers in middle-aged adults.
作者信息
Singh A, Venn A, Blizzard L, Jones G, Burgess J, Parameswaran V, Cicuttini F, March L, Eckstein F, Wirth W, Ding C, Antony B
机构信息
Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.
Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia; Department of Endocrinology, Royal Hobart Hospital, Hobart, Australia.
出版信息
Osteoarthritis Cartilage. 2022 May;30(5):756-764. doi: 10.1016/j.joca.2022.02.616. Epub 2022 Feb 28.
OBJECTIVE
To describe the associations between osteoarthritis (OA)-related biochemical markers (COMP, MMP-3, HA) and MRI-based imaging biomarkers in middle-aged adults over 10-13 years.
METHODS
Blood serum samples collected during the Childhood Determinants of Adult Health (CDAH)-1 study (year:2004-06; n = 156) and 10-13 year follow-up at CDAH-3 (n = 167) were analysed for COMP, MMP-3, and HA using non-isotopic ELISA. Knee MRI scans obtained during the CDAH-knee study (year:2008-10; n = 313) were assessed for cartilage volume and thickness, subchondral bone area, cartilage defects, and BML.
RESULTS
In a multivariable linear regression model describing the association of baseline biochemical markers with MRI-markers (assessed after 4-years), we found a significant negative association of standardised COMP with medial femorotibial compartment cartilage thickness (β:-0.070; 95%CI:-0.138,-0.001), and standardised MMP-3 with patellar cartilage volume (β:-141.548; 95%CI:-254.917,-28.179) and total bone area (β:-0.729; 95%CI:-1.340,-0.118). In multivariable Tobit regression model, there was a significant association of MRI-markers with biochemical markers (assessed after 6-9 years); a significant negative association of patellar cartilage volume (β:-0.001; 95%CI:-0.002,-0.00004), and total bone area (β:-0.158; 95%CI-0.307,-0.010) with MMP-3, and total cartilage volume (β:-0.001; 95%CI:-0.001,-0.0001) and total bone area (β:-0.373; 95%CI:-0.636,-0.111) with COMP. No significant associations were observed between MRI-based imaging biomarkers and HA.
CONCLUSION
COMP and MMP-3 levels were negatively associated with knee cartilage thickness and volume assessed 4-years later, respectively. Knee cartilage volume and bone area were negatively associated with COMP and MMP-3 levels assessed 6-9 years later. These results suggest that OA-related biochemical markers and MRI-markers are interrelated in early OA.
目的
描述骨关节炎（OA）相关生化标志物（软骨寡聚基质蛋白（COMP）、基质金属蛋白酶-3（MMP-3）、透明质酸（HA））与基于磁共振成像（MRI）的影像学标志物在10至13年期间中年成年人中的关联。
方法
采用非同位素酶联免疫吸附测定法（ELISA）对在成人健康儿童决定因素（CDAH）-1研究（年份：2004 - 2006；n = 156）期间采集的血清样本以及在CDAH-3研究中10至13年随访时（n = 167）的样本进行COMP、MMP-3和HA分析。对在CDAH膝关节研究（年份：2008 - 2010；n = 313）期间获得的膝关节MRI扫描进行评估，以测量软骨体积和厚度、软骨下骨面积、软骨缺损和骨髓病变（BML）。
结果
在描述基线生化标志物与MRI标志物（4年后评估）关联的多变量线性回归模型中，我们发现标准化COMP与股骨内侧髁间室软骨厚度呈显著负相关（β：-0.070；95%置信区间：-0.138，-0.001），标准化MMP-3与髌软骨体积（β：-141.548；95%置信区间：-254.917，-28.179）和总骨面积（β：-0.729；95%置信区间：-1.340，-0.118）呈显著负相关。在多变量托比特回归模型中，MRI标志物与生化标志物（6至9年后评估）存在显著关联；髌软骨体积（β：-0.001；95%置信区间：-0.002，-0.00004）和总骨面积（β：-0.158；95%置信区间：-0.307，-0.010）与MMP-3呈显著负相关，总软骨体积（β：-0.001；95%置信区间：-0.001，-0.0001）和总骨面积（β：-0.373；95%置信区间：-0.636，-0.111）与COMP呈显著负相关。未观察到基于MRI的影像学标志物与HA之间存在显著关联。
结论
COMP和MMP-3水平分别与4年后评估的膝关节软骨厚度和体积呈负相关。膝关节软骨体积和骨面积与6至9年后评估的COMP和MMP-3水平呈负相关。这些结果表明，OA相关生化标志物和MRI标志物在早期OA中相互关联。
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