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抑制炎症和对强直性脊柱炎新骨形成的影响:疾病修饰治疗机会窗口的证据。

Suppression of inflammation and effects on new bone formation in ankylosing spondylitis: evidence for a window of opportunity in disease modification.

机构信息

Department of Medicine,University of Alberta, Edmonton,Canada.

出版信息

Ann Rheum Dis. 2013 Jan;72(1):23-8. doi: 10.1136/annrheumdis-2011-200859. Epub 2012 May 5.

Abstract

OBJECTIVES

Although MRI data supports a link between spinal inflammation and formation of new bone in ankylosing spondylitis, anti-tumour necrosis factor α therapies have not been shown to prevent new bone formation. The authors aimed to demonstrate that while acute lesions resolve completely, more advanced lesions, characterised by evidence of reparation, are associated with new bone formation.

METHODS

MRI scans were performed at baseline, 12 and 52 weeks in 76 ankylosing spondylitis patients recruited to a placebo-controlled trial of adalimumab therapy. New syndesmophytes were assessed on lateral radiographs of the cervical and lumbar spine at baseline and 104 weeks. Anonymised MRI scans were read independently by two readers who recorded the presence/absence of acute (type A) and advanced (type B) vertebral corner inflammatory lesions (CIL) and fat lesions. The authors used generalised linear latent and mixed models analysis to adjust for the extent of syndesmophytes/ankylosis at baseline.

RESULTS

New syndesmophytes developed significantly more frequently from type B CIL (16.7%) compared with type A CIL (2.9%) (p=0.002) or no CIL (2.5%) (p<0.0001). This was also observed for both baseline and new vertebral corner fat lesions evolving over 52 weeks (11.1% (p<0.001) and 6.8% (p=0.03), respectively). The association with type B CIL (OR (95% CI 3.88, 1.20 to -12.57) and fat (OR 95% CI 4.83, 2.38- to 9.80), p<0.0001) was significant after adjustment for the extent of syndesmophytes/ankylosis at baseline.

CONCLUSIONS

Our data supports the hypothesis that new bone formation is more likely in advanced inflammatory lesions and proceeds through a process of fat metaplasia, supporting a window of opportunity for disease modification.

摘要

目的

尽管 MRI 数据支持强直性脊柱炎脊柱炎症与新骨形成之间存在关联,但抗肿瘤坏死因子 α 治疗并未显示可预防新骨形成。作者旨在证明,虽然急性病变完全消退,但更严重的病变,表现为修复证据,与新骨形成有关。

方法

76 例强直性脊柱炎患者入组阿达木单抗治疗安慰剂对照试验,分别在基线、12 周和 52 周进行 MRI 扫描。在基线和 104 周时,对颈椎和腰椎的侧位 X 线片进行新的脊柱融合评估。对匿名 MRI 扫描进行了两位读者的独立阅读,记录了急性(A 型)和晚期(B 型)脊柱角炎症病变(CIL)和脂肪病变的存在/缺失。作者使用广义线性潜在和混合模型分析来调整基线时脊柱融合/强直的程度。

结果

与 A 型 CIL(2.9%)或无 CIL(2.5%)相比,B 型 CIL (16.7%)中明显更频繁地出现新的脊柱融合(p=0.002)。在 52 周时,基线和新的脊柱角脂肪病变也有类似的观察结果(分别为 11.1%(p<0.001)和 6.8%(p=0.03))。B 型 CIL(OR(95%CI 3.88,1.20 至-12.57)和脂肪(OR 95%CI 4.83,2.38 至-9.80)与 B 型 CIL 的相关性在调整基线时脊柱融合/强直的程度后仍具有统计学意义(p<0.0001)。

结论

我们的数据支持这样一种假设,即新骨形成更可能发生在晚期炎症病变中,并通过脂肪化生过程进行,这为疾病修饰提供了一个机会窗口。

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