I 型胶原α C 端肽与软骨下骨转换有关，可预测骨关节炎关节间隙变窄和骨赘的进展。
Alpha C-telopeptide of type I collagen is associated with subchondral bone turnover and predicts progression of joint space narrowing and osteophytes in osteoarthritis.
机构信息
Duke University School of Medicine, Durham, North Carolina.
出版信息
Arthritis Rheumatol. 2014 Sep;66(9):2440-9. doi: 10.1002/art.38739.
OBJECTIVE
To evaluate joint tissue remodeling using the urinary collagen biomarkers urinary α-C-telopeptide of type I collagen (α-CTX) and urinary C-telopeptide of type II collagen (CTX-II) and to determine the association of these biomarkers with osteoarthritis (OA) severity, progression, and localized knee bone turnover.
METHODS
Participants (n = 149) with symptomatic and radiographic knee OA underwent fixed-flexion knee radiography at baseline and 3 years, and late-phase bone scintigraphy of both knees at baseline, which were scored semiquantitatively for osteophyte and joint space narrowing (JSN) severity and uptake intensity, with scores summed across knees. Urinary concentrations of α-CTX and CTX-II were determined by enzyme-linked immunosorbent assay. Immunohistochemical analysis of human OA knees was performed to localize the joint tissue origin of the biomarker epitopes.
RESULTS
Urinary α-CTX concentrations correlated strongly with the intensity of bone scintigraphic uptake and with JSN progression (risk ratio 13.2) and osteophyte progression (risk ratio 3). Urinary CTX-II concentrations were strongly associated with intensity of bone scintigraphic uptake, with JSN and osteophyte severity, and with OA progression based on osteophyte score. Urinary α-CTX localized primarily to high bone turnover areas in subchondral bone. CTX-II localized to the bone-cartilage interface, the tidemark, and damaged articular cartilage.
CONCLUSION
Baseline urinary α-CTX, which was localized to high turnover areas of subchondral bone, was associated with dynamic bone turnover of knees, as signified by scintigraphy, and progression of both osteophytes and JSN. Urinary CTX-II correlated with JSN and osteophyte severity and progression of osteophytes. To our knowledge, this represents the first report of serologic markers reflecting subchondral bone turnover. These collagen markers may be useful for noninvasive detection and quantification of active subchondral bone turnover and joint remodeling in knee OA.
目的
评估关节组织重塑，使用尿Ⅰ型胶原α-C-末端肽（α-CTX）和尿Ⅱ型胶原 C-末端肽（CTX-II）两种尿胶原生物标志物，并确定这些生物标志物与骨关节炎（OA）严重程度、进展和局部膝关节骨转换的关系。
方法
共纳入 149 例有症状和放射学膝关节 OA 的患者，他们在基线和 3 年时接受了固定弯曲膝关节放射摄影，并在基线时对双侧膝关节进行了后期相骨闪烁扫描，对骨赘和关节间隙狭窄（JSN）严重程度和摄取强度进行半定量评分，评分累加至双侧膝关节。通过酶联免疫吸附试验测定尿 α-CTX 和 CTX-II 浓度。对人 OA 膝关节进行免疫组织化学分析，以定位生物标志物表位的关节组织来源。
结果
尿 α-CTX 浓度与骨闪烁扫描摄取强度、JSN 进展（风险比 13.2）和骨赘进展（风险比 3）高度相关。尿 CTX-II 浓度与骨闪烁扫描摄取强度、JSN 和骨赘严重程度以及基于骨赘评分的 OA 进展密切相关。尿 α-CTX 主要定位于软骨下骨高转换区域。CTX-II 定位于骨-软骨界面、钙化带和受损的关节软骨。
结论
基线尿 α-CTX 主要定位于软骨下骨高转换区域，与闪烁扫描所示膝关节动态骨转换以及骨赘和 JSN 的进展有关。尿 CTX-II 与 JSN 和骨赘严重程度以及骨赘进展相关。据我们所知，这是首次报道反映软骨下骨转换的血清标志物。这些胶原标志物可能有助于非侵入性检测和定量膝关节 OA 中活跃的软骨下骨转换和关节重塑。
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