Use of volumetric computerized tomography as a primary outcome measure to evaluate drug efficacy in the prevention of peri-prosthetic osteolysis: a 1-year clinical pilot of etanercept vs. placebo
Use of volumetric computerized tomography as a primary outcome measure to evaluate drug efficacy in the prevention of peri-prosthetic osteolysis: a 1-year clinical pilot of etanercept vs. placebo
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DOI：
10.1016/s0736-0266(03)00093-7
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发表时间：
2003-11-01
影响因子：
2.8
通讯作者：
Looney, RJ
中科院分区：
文献类型：
--
作者：
Schwarz, EM;Campbell, D;Looney, RJ
尽管全髋关节置换术(THR)是迄今为止最成功和最有益的医疗手术之一，但长期结果仍然是假体周围骨溶解继发的无菌性松动。在过去的二十年中，广泛的研究阐明了骨溶解的一个核心机制，即种植体产生的磨屑刺激炎症细胞促进破骨细胞生成和骨吸收。细胞因子肿瘤坏死因子α(TNFpha)已被证明在这一过程中起中心作用，并被认为是干预的主要靶点。不幸的是，尽管FDA批准了肿瘤坏死因子拮抗剂(依那西普)，但目前还没有可靠的结果指标可以用来评估预防假体周围骨溶解的药物的疗效。为了制定有效的预后指标，我们使用一种新的体积计算机断层扫描(3D-CT)技术，评估了20名确诊为髋臼周围骨溶解(平均为29.99 cm(3)，范围为2.9-92.7 cm(3))的非骨水泥型原发THR患者1年内病变大小的进展情况。我们还评估了聚乙烯磨损、尿N-端肽和功能评估(WOMAC、SF-36和Harris Hip评分)以进行比较。在进入研究时，获得基线CT扫描，患者被随机分为依那西普(25 mg s.q，每周两次)和安慰剂，采用双盲方式。在6个月和12个月时进行CT扫描、尿液和功能评估。没有报道与药物有关的严重不良事件，但有一名患者由于无菌松动而不得不在研究完成前进行翻修手术。两组间无显著差异。然而，这项研究并没有看到显著的药物效应。来自19名患者的3D-CT数据被用来确定在48周内病变大小的平均增加，即3.19cm3(p<；0.0013)。对尿N-端肽和功能评估数据的分析未能确定与磨损或骨溶解有显著相关性。总而言之，体积CT能够测量一年中骨溶解的进展，从而提供了一种可用于治疗试验的技术。使用来自该试验的数据，我们为这样的试验提供了一个模型功率计算。(C)2003年骨科研究会。爱思唯尔有限公司出版。保留所有权利。
Although total hip replacement (THR) is amongst the most successful and beneficial medical procedures to date, long-term Outcomes continue to suffer from aseptic loosening secondary to peri-prosthetic osteolysis. Extensive research over the last two decades has elucidated a central mechanism for osteolysis in which wear debris generated from the implant stimulates inflammatory cells to promote osteoclastogenesis and bone resorption. The cytokine tumor necrosis factor alpha (TNFalpha) has been demonstrated to be central to this process and is considered to be a leading target for intervention. Unfortunately, even though FDA approved TNF antagonists are available (etanercept), currently there are no reliable outcome measures that can be used to evaluate the efficacy of a drug to prevent peri-prosthetic osteolysis. To the end of developing an effective outcome measure, we evaluated the progression of lesion size in 20 patients with established peri-acetabular osteolysis (mean = 29.99 cm(3), range = 2.9-92.7 cm(3)) of an uncemented primary THR over 1-year, using a novel volumetric computer tomography (3D-CT) technique. We also evaluated polyethylene wear, urine N-telopeptides and functional assessments (WOMAC, SF-36 and Harris Hip Score) for comparison. At the time of entry into the study baseline CT scans were obtained and the patients were randomized to etanercept (25 mg s.q., twice/week) and placebo in a double-blinded fashion. CT scans, urine and functional assessments were also obtained at 6 and 12 months. No serious adverse drug related events were reported, but one patient had to have revision surgery before completion of the study due to aseptic loosening. No remarkable differences between the groups were observed. However, the study was not powered to see significant drug effects. 3D-CT data from the 19 patients Was used to determine the mean increase in lesion size over 48 weeks, which was 3.19 cm(3) (p < 0.0013). Analysis of the urine N-telopeptides and functional assessment data failed to identify a significant correlation with wear or osteolysis. In conclusion, volumetric CT was able to measure progression of osteolysis over the course of a year, thus providing a technology that could be used in therapeutic trials. Using the data from this pilot we provide a model power calculation for such a trial. (C) 2003 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.