Uncoupling of type II collagen synthesis and degradation predicts progression of joint damage in patients with knee osteoarthritis
Uncoupling of type II collagen synthesis and degradation predicts progression of joint damage in patients with knee osteoarthritis
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DOI：
10.1002/art.10576
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发表时间：
2002-10-01
影响因子：
--
通讯作者：
Delmas, PD
中科院分区：
文献类型：
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作者：
Garnero, P;Ayral, X;Delmas, PD
Objective.骨关节炎（OA）的标志是关节软骨的丧失。这种损失是由于在可变的时间段内软骨合成和软骨降解之间的不平衡引起的。本研究的目的是调查使用两种新的分子标记物的膝关节OA患者的这些过程的发生率，并调查这些标记物的联合使用是否可以预测关节损伤的进展，通过关节的X线摄影和关节镜检查评估在1年的时间内。对75例内侧膝关节OA患者（51例女性，24例男性;平均+/- SD年龄63 8岁，平均+/- SD病程4. 8 +/-5. 2年）进行了前瞻性研究。在基线时，我们分别测定了作为II型胶原合成和降解标志物的IIA型前胶原N-前肽（PIIANP）和II型胶原C-末端交联端肽（CTX-II）的尿排泄水平。在基线时测量所有患者的关节间隙宽度（JSW），在关节镜检查时测量内侧软骨病（使用100 mm视觉模拟量表[VAS]评估），在1年时测量52例患者的关节间隙宽度（JSW）。关节破坏的进展定义为在基线和1年评估之间，X线片上JSW减少大于或等于0.5分钟，软骨病增加（VAS评分增加>8.0单位）。基线时，与58名年龄和性别匹配的健康对照组相比，膝关节OA患者血清PIIANP水平降低（20 ng/ml vs 29 ng/ml; P < 0.001），尿CTX-II排泄增加（618 ng/mmole肌酐[Cr] vs 367 ng/mmole Cr; P < 0.001）。OA患者和对照组之间的最高区分度通过在解偶联指数（Z评分CTX-II - Z评分PIIANP）中组合PIIANP和CTX-II获得，其产生平均Z评分2.9（P < 0.0001）。通过JSW（r =-0.46，P = 0.0016）或VAS评分（r = 0.36，P = 0.014）评估，解偶联指数基线值增加与关节损伤进展加快相关。PIIANP水平均较低的患者（对照组小于或等于平均-1SD）和高水平的CTX-II（大于或等于对照组的平均值+1 SD）的关节损伤进展速度是其他患者的8倍（P = 0.012和P < 0.0001，通过X线摄影和关节镜评估，X线片和关节镜检查的进展相对危险度分别为2.9（95%CI 0.80-11.1）和9.3（95%CI 2.2-39）。膝关节OA患者的特征在于II型胶原合成和降解的解偶联，其可通过血清PIIANP和尿CTX-II的测定来检测。这两种新标记物的组合可能有助于识别关节损伤快速进展的高风险膝关节OA患者。
Objective. The hallmark of osteoarthritis (OA) is the loss of articular cartilage. This loss arises from an imbalance between cartilage synthesis and cartilage degradation over a variable period of time. The aims of this study were to investigate the rates of these processes in patients with knee OA using two new molecular markers and to investigate whether the combined use of these markers could predict the progression of joint damage evaluated by both radiography and arthroscopy of the joints during a period of 1 year.Methods. Seventy-five patients with medial knee OA (51 women, 24 men; mean +/- SD age 63 8 years, mean +/- SD disease duration 4.8 +/- 5.2 years) were studied prospectively. At baseline, we measured serum levels of N-propeptide of type IIA procollagen (PIIANP) and urinary excretion of C-terminal crosslinking telopeptide of type II collagen (CTX-II) as markers of type II collagen synthesis and degradation, respectively. Joint space width (JSW) on radiography and medial chondropathy at arthroscopy (assessed using a 100-mm visual analog scale [VAS]) were measured in all patients at baseline and in 52 patients at 1 year. Progression of joint destruction was defined as a decrease of greater than or equal to0.5 min in JSW on radiography and as increased chondropathy (an increase in the VAS score of >8.0 units) between the baseline and 1-year evaluations.Results. At baseline, compared with 58 healthy age- and sex-matched controls, patients with knee OA had decreased serum levels of PIIANP (20 ng/ml versus 29 ng/ml; P < 0.001) and increased urinary excretion of CTX-II (618 ng/mmole creatinine [Cr] versus 367 ng/mmole Cr; P < 0.001). The highest discrimination between OA patients and controls was obtained by combining PIIANP and CTX-II in an uncoupling index (Z score CTX-II - Z score PIIANP), which yielded a mean Z score of 2.9 (P < 0.0001). Increased baseline values in the uncoupling index were associated with greater progression of joint damage evaluated either by changes in JSW (r = -0.46, P = 0.0016) or by VAS score (r = 0.36, P = 0.014). Patients with both low levels of PIIANP (less than or equal to the mean - 1 SD in controls) and high levels of CTX-II (greater than or equal to the mean + 1 SD in controls) had an 8-fold more rapid progression of joint damage than other patients (P = 0.012 and P < 0.0001 as assessed by radiography and arthroscopy, respectively) and had relative risks of progression of 2.9 (95% confidence interval [95% CI] 0.80-11.1) and 9.3 (95% CI 2.2-39) by radiography and arthroscopy, respectively.Conclusion. Patients with knee OA are characterized by an uncoupling of type II collagen synthesis and degradation which can be detected by assays for serum PIIANP and urinary CTX-II. The combination of these two new markers could be useful for identifying knee OA patients at high risk for rapid progression of joint damage.