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血清肿瘤坏死因子 α 水平升高与假体周围骨溶解患者:一项病例对照研究。

Elevation of serum tumor necrosis factor α in patients with periprosthetic osteolysis: a case-control study.

机构信息

Division of Rheumatology, University of California, San Francisco, 400 Parnassus Avenue, Box 0326, San Francisco, CA, 94143, USA,

出版信息

Clin Orthop Relat Res. 2014 Feb;472(2):584-9. doi: 10.1007/s11999-013-3235-9.

Abstract

BACKGROUND

Periprosthetic osteolysis is the leading reason for THA revision. The relationship of serum biomarkers with severe radiographic periprosthetic osteolysis has not been defined but may be important to direct future research and clinical therapeutics.

QUESTIONS/PURPOSES: We determined whether there was an association between measurable inflammatory markers (high-sensitivity C-reactive protein [hsCRP]) or inflammatory mediators (tumor necrosis factor α [TNF-α], IL-1β, IL-6, receptor activator of nuclear factor κB ligand [RANKL], and osteoprotegerin [OPG]) and periprosthetic osteolysis.

METHODS

We identified 15 patients with THAs scheduled for revision surgery because of severe periprosthetic osteolysis. For each study patient, a nonosteolytic, pain-free control patient with THAs was identified and matched for age, sex, time since initial THA, acetabular and femoral component prosthesis material, and prosthesis wear within 1.0 mm/year using a manual wear analysis technique. Overall, the study and control patients had a mean wear rate of 0.25 mm/year since index THA. There were no differences in baseline characteristics between study and control patients in age, sex, BMI, Charlson Comorbidity Index, time since initial THA, UCLA activity score, and acetabular and femoral component type. Serum hsCRP, IL-1β, IL-6, TNF-α, RANKL, and OPG were measured by ELISA in duplicate assays. Differences in values were assessed using the Wilcoxon rank-sum test.

RESULTS

Median TNF-α levels were higher in study patients than in controls (7.1 pg/mL [SD, 11.6 pg/mL] versus 1.5 pg/mL [SD, 1.3 pg/mL]) (p < 0.01). Median IL-6 levels tended to be higher in study patients than in controls (8.9 pg/mL [SD, 13.2 pg/mL] versus 3.5 pg/mL [SD, 0.7 pg/mL]) (p = 0.09). The other serum inflammatory proteins and mediators of bone turnover were not different between groups.

CONCLUSIONS

TNF-α is elevated in patients with osteolysis compared to matched controls. The role of TNF-α and its potential as a target of nonsurgical therapy to prevent osteolysis warrant further investigation in larger, prospective studies.

摘要

背景

假体周围骨溶解是髋关节置换术翻修的主要原因。血清生物标志物与严重影像学假体周围骨溶解之间的关系尚未确定,但对于指导未来的研究和临床治疗可能很重要。

问题/目的:我们确定了可测量的炎症标志物(高敏 C 反应蛋白[hsCRP])或炎症介质(肿瘤坏死因子-α[TNF-α]、白细胞介素-1β[IL-1β]、白细胞介素-6[IL-6]、核因子κB 受体激活剂配体[RANKL]和骨保护素[OPG])与假体周围骨溶解之间是否存在关联。

方法

我们确定了 15 例因严重假体周围骨溶解而计划接受髋关节翻修手术的患者。对于每位研究患者,我们都确定了一位无骨溶解且无痛的、接受髋关节置换术的对照患者,并根据年龄、性别、初次髋关节置换术的时间、髋臼和股骨组件假体材料以及使用手动磨损分析技术在 1.0 毫米/年内的假体磨损情况进行匹配。总体而言,研究患者和对照患者在初次髋关节置换术后的平均磨损率为 0.25 毫米/年。在年龄、性别、BMI、Charlson 合并症指数、初次髋关节置换术的时间、UCLA 活动评分以及髋臼和股骨组件类型方面,研究患者和对照患者之间无基线特征差异。通过酶联免疫吸附试验(ELISA)双检测法测量血清 hsCRP、IL-1β、IL-6、TNF-α、RANKL 和 OPG。使用 Wilcoxon 秩和检验评估值的差异。

结果

研究患者的 TNF-α 中位数高于对照组(7.1 pg/mL [标准差,11.6 pg/mL] 与 1.5 pg/mL [标准差,1.3 pg/mL])(p < 0.01)。研究患者的 IL-6 中位数水平高于对照组(8.9 pg/mL [标准差,13.2 pg/mL] 与 3.5 pg/mL [标准差,0.7 pg/mL])(p = 0.09)。两组之间其他血清炎症蛋白和骨转换的介体没有差异。

结论

与匹配的对照组相比,骨溶解患者的 TNF-α 水平升高。TNF-α 的作用及其作为预防骨溶解的非手术治疗靶点的潜力需要在更大的前瞻性研究中进一步研究。

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