Identification of progressors in osteoarthritis by combining biochemical and MRI-based markers.
Identification of progressors in osteoarthritis by combining biochemical and MRI-based markers.
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DOI：
10.1186/ar2774
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发表时间：
2009
影响因子：
4.9
通讯作者：
Karsdal MA
中科院分区：
文献类型：
--
作者：
Dam EB;Loog M;Christiansen C;Byrjalsen I;Folkesson J;Nielsen M;Qazi AA;Pettersen PC;Garnero P;Karsdal MA
目前，没有治疗骨关节炎的药物(DMOADS)获得FDA(美国食品和药物管理局)的批准；部分原因可能是试验设计不充分，因为在安慰剂组中，疗效演示需要疾病进展。我们调查了基于生化和磁共振成像(MRI)的标记物的组合是否为识别具有高进展风险的受试者提供了有效的诊断和预后工具。具体地说，我们研究了结合分解、数量和质量的标记的聚合软骨寿命标记。这项研究包括健康人和患有放射学骨关节炎的受试者。共159名受试者(女性占48%，年龄56.0±15.9岁，体重指数26.1±4.2 kg/m2)。在基线和21个月后，对生化指标(尿胶原II型C-端肽片段，CTX-II)和基于MRI的标记物进行定量。MRI标记物包括软骨体积、厚度、面积、粗糙度、均匀度和胫股内侧间隙的曲率。从X线片和21个月时测量关节间隙宽度，以评估关节损伤的进展。软骨粗糙度的诊断准确率最高，以受试者-操作者特征曲线下面积(AUC)为0.80(95%可信区间：0.69~0.91)，在区分放射学骨关节炎和健康对照的个体标志物中(高于其他所有标志物，P<；0.05)。诊断方面，软骨寿命评分为0.84(0.77~0.92，高于粗糙度：P=0.03)。对于基于基线标记值的纵向放射学进展的预测，AUC最高的个体预后标记物的均质性为0.71(0.56至0.81)。在预后方面，软骨寿命评分为0.77(0.62~0.90，略高于均质性：P=0.12)。当比较长寿得分最高四分位数和最低四分位数的患者时，进展的优势比为20.0(95%可信区间：6.4至62.1)。生化和MRI生物标记物的结合改善了膝骨性关节炎的诊断和预后，并可能有助于选择纳入DMOAD临床试验的高危患者。
At present, no disease-modifying osteoarthritis drugs (DMOADS) are approved by the FDA (US Food and Drug Administration); possibly partly due to inadequate trial design since efficacy demonstration requires disease progression in the placebo group. We investigated whether combinations of biochemical and magnetic resonance imaging (MRI)-based markers provided effective diagnostic and prognostic tools for identifying subjects with high risk of progression. Specifically, we investigated aggregate cartilage longevity markers combining markers of breakdown, quantity, and quality. The study included healthy individuals and subjects with radiographic osteoarthritis. In total, 159 subjects (48% female, age 56.0 ± 15.9 years, body mass index 26.1 ± 4.2 kg/m2) were recruited. At baseline and after 21 months, biochemical (urinary collagen type II C-telopeptide fragment, CTX-II) and MRI-based markers were quantified. MRI markers included cartilage volume, thickness, area, roughness, homogeneity, and curvature in the medial tibio-femoral compartment. Joint space width was measured from radiographs and at 21 months to assess progression of joint damage. Cartilage roughness had the highest diagnostic accuracy quantified as the area under the receiver-operator characteristics curve (AUC) of 0.80 (95% confidence interval: 0.69 to 0.91) among the individual markers (higher than all others, P < 0.05) to distinguish subjects with radiographic osteoarthritis from healthy controls. Diagnostically, cartilage longevity scored AUC 0.84 (0.77 to 0.92, higher than roughness: P = 0.03). For prediction of longitudinal radiographic progression based on baseline marker values, the individual prognostic marker with highest AUC was homogeneity at 0.71 (0.56 to 0.81). Prognostically, cartilage longevity scored AUC 0.77 (0.62 to 0.90, borderline higher than homogeneity: P = 0.12). When comparing patients in the highest quartile for the longevity score to lowest quartile, the odds ratio of progression was 20.0 (95% confidence interval: 6.4 to 62.1). Combination of biochemical and MRI-based biomarkers improved diagnosis and prognosis of knee osteoarthritis and may be useful to select high-risk patients for inclusion in DMOAD clinical trials.
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影响因子：
4.9
作者：
Krzeski, Piotr;Buckland-Wright, Chris;Spector, Tim D.
通讯作者：
Spector, Tim D.
影响因子：
10.6
作者：
Grau, V;Mewes, AUJ;Warfield, SK
通讯作者：
Warfield, SK
影响因子：
7
作者：
Altman, RD;Abadie, E;Reginster, JY
通讯作者：
Reginster, JY
影响因子：
5.5
作者：
Duddy, J;Kirwan, JR;Volkov, S
通讯作者：
Volkov, S
影响因子：
7
作者：
Blumenkrantz, G;Lindsey, CT;Majumdar, S
通讯作者：
Majumdar, S