Hunter David J, Li Jiang, LaValley Michael, Bauer Doug C, Nevitt Michael, DeGroot Jeroen, Poole Robin, Eyre David, Guermazi Ali, Gale Dan, Felson David T
Clinical Epidemiology Research and Training Unit, Boston University School of Medicine, Boston, MA, USA.
Arthritis Res Ther. 2007;9(5):R108. doi: 10.1186/ar2314.
We used data from a longitudinal observation study to determine whether markers of cartilage turnover could serve as predictors of cartilage loss on magnetic resonance imaging (MRI). We conducted a study of data from the Boston Osteoarthritis of the Knee Study (BOKS), a completed natural history study of knee osteoarthritis (OA). All subjects in the study met American College of Rheumatology criteria for knee OA. Baseline and follow-up knee magnetic resonance images were scored for cartilage loss by means of the WORMS (Whole Organ Magnetic Resonance Imaging Score) semiquantitative grading scheme. Within the BOKS population, 80 subjects who experienced cartilage loss and 80 subjects who did not were selected for the purposes of this nested case control study. We assessed the baseline levels of cartilage degradation and synthesis products by means of assays for type I and II cleavage by collagenases (Col2:3/4C(short) or C1,2C), type II cleavage only with Col2:3/4C(longmono) (C2C), type II synthesis (C-propeptide), the C-telopeptide of type II (Col2CTx), aggrecan 846 epitope, and cartilage oligomeric matrix protein (COMP). We performed a logistic regression to examine the relation of levels of each biomarker to the risk of cartilage loss in any knee. All analyses were adjusted for gender, age, and body mass index (BMI); results stratified by gender gave similar results. One hundred thirty-seven patients with symptomatic knee OA were assessed. At baseline, the mean (standard deviation) age was 67 (9) years and 54% were male. Seventy-six percent of the subjects had radiographic tibiofemoral OA (Kellgren & Lawrence grade of greater than or equal to 2) and the remainder had patellofemoral OA. With the exception of COMP, none of the other biomarkers was a statistically significant predictor of cartilage loss. For a 1-unit increase in COMP, the odds of cartilage loss increased 6.09 times (95% confidence interval [CI] 1.34 to 27.67). After the analysis of COMP was adjusted for age, gender, and BMI, the risk for cartilage loss was 6.35 (95% CI 1.36 to 29.65). Among subjects with symptomatic knee OA, a single measurement of increased COMP predicted subsequent cartilage loss on MRI. The other biochemical markers of cartilage synthesis and degradation do not facilitate prediction of cartilage loss. With the exception of COMP, if changes in cartilage turnover in patients with symptomatic knee OA are associated with cartilage loss, they do not appear to affect systemic biomarker levels.
我们使用了一项纵向观察研究的数据,以确定软骨转换标志物是否可作为磁共振成像(MRI)上软骨损失的预测指标。我们对波士顿膝关节骨关节炎研究(BOKS)的数据进行了研究,这是一项已完成的膝关节骨关节炎(OA)自然史研究。该研究中的所有受试者均符合美国风湿病学会的膝关节OA标准。通过WORMS(全器官磁共振成像评分)半定量分级方案对基线和随访时的膝关节磁共振图像进行软骨损失评分。在BOKS人群中,为了这项巢式病例对照研究,选择了80名发生软骨损失的受试者和80名未发生软骨损失的受试者。我们通过检测胶原酶对I型和II型的裂解产物(Col2:3/4C(short)或C1,2C)、仅用Col2:3/4C(longmono)(C2C)裂解的II型产物、II型合成产物(C-前肽)、II型C-末端肽(Col2CTx)、聚集蛋白聚糖846表位以及软骨寡聚基质蛋白(COMP)来评估软骨降解和合成产物的基线水平。我们进行了逻辑回归分析,以检验每个生物标志物水平与任何膝关节软骨损失风险之间的关系。所有分析均对性别、年龄和体重指数(BMI)进行了校正;按性别分层的结果相似。对137例有症状的膝关节OA患者进行了评估。基线时,平均(标准差)年龄为67(9)岁,54%为男性。76%的受试者有放射学上的胫股关节OA(Kellgren&Lawrence分级大于或等于2级),其余为髌股关节OA。除COMP外,其他生物标志物均不是软骨损失的统计学显著预测指标。COMP每增加1个单位,软骨损失的几率增加6.09倍(95%置信区间[CI]1.34至27.67)。在对COMP的分析校正了年龄、性别和BMI后,软骨损失的风险为6.35(95%CI 1.36至29.65)。在有症状的膝关节OA受试者中,单次测量COMP升高可预测MRI上随后的软骨损失。软骨合成和降解的其他生化标志物无助于预测软骨损失。除COMP外,如果有症状的膝关节OA患者软骨转换的变化与软骨损失相关,它们似乎不会影响全身生物标志物水平。