多因素分析显示脂肪沉积比炎症损害更能预测强直性脊柱炎患者的脊柱新骨形成

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Multivariate Analysis Indicates That Fat Lesions Dominate Over Inflammatory Lesions in Predicting New Bone Formation in the Spine of Patients with Ankylosing Spondylitis

 

 

Walter P. Maksymowych, Nathalie Morency, Barbara Conner-Spady and Robert GW Lambert, University of Alberta, Edmonton, AB

 

Presentation Number: 778

 

Background/Purpose:Recent prospective data indicates that as inflammatory lesions mature, they undergo a process of transformation into fat in the spine of patients with ankylosing spondylitis (AS)¹. It has been proposed that bone formation becomes uncoupled from inflammation in these complex inflammatory lesions characterized by: 1. Inflammation that has receded from the vertebral corner (VC) on STIR MRI 2.Fat infiltration at the same VC location on T1W MRI. Early inflammatory lesion may resolve completely without sequelae while resolution of complex inflammatory lesion may be accompanied by new bone formation². Consequently, the appearance of fat lesions may indicate an even greater propensity to new bone formation than inflammatory lesions. We tested this hypothesis in this prospective study.

Method: MRI scans were performed at baseline, 12, and 52 weeks while radiographs were done at baseline and 104 weeks in 76 AS patients randomized to receive either adalimumab (ADA) 40 mg every other week or placebo for 24 weeks in a, double-blind, Phase III study of active AS. After the week 12 assessment, patients were eligible for early escape therapy and after 24 weeks all patients received ADA. The anterior VC of the cervical and lumbar spine were examined for new syndesmophytes and ankylosis (baseline, 104 weeks) on lateral radiographs of the spine. Anonymized MR scans were read independently by 2 readers who recorded the presence/absence of inflammatory and fat lesions at the same anterior VC that were assessed by radiography. We used Generalized Linear Latent and Mixed Models (GLLAMM) multivariate analysis to adjust for within patient dependence in the total number of vertebral corners with syndesmophytes/ankylosis at baseline to determine which lesions were independently predictive of new bone.

Result:At the patient level, the mean (SD) number of VC inflammatory or fat lesions was significantly higher on baseline MRI in those who developed new bone compared to those who did not (p = 0.002 and 0.0003, respectively). New bone developed significantly more frequently from VC that demonstrated inflammatory lesions (13 of 220 (5.9%)) or fat lesions (20 of 179 (11.2%) on baseline MRI as compared to VC with neither (29 of 1138 (2.5%)) (p= 0.002 and <0.0001, respectively). New bone also developed significantly more frequently from VC with both inflammation and fat (7 of 52 (13.5%)) compared to VC with only inflammation (6 of 168 (3.6%), p = 0.015). GLAMM multivariate analysis that included inflammation, fat, and syndesmophytes/ankylosis showed that fat dominated over inflammation in predicting new bone.

	OR (95%CI)	P value
Inflammation	1.11 (0.48-2.59)	NS
Fat	4.39 (2.08-9.26)	P<0.0001
Syndesmophyte/ankylosis	1.18 (1.10-1.27)	P<0.0001

Conclusion: Our data supports the hypothesis that new bone formation is more likely in complex inflammatory lesions characterized by fat metaplasia where it may be uncoupled from inflammation.

1.     Chiowchanwisawakit P, et al. Ann Rheum Dis 2010; 69(suppl3):262

2.     Maksymowych et al. Ann Rheum Dis 2011;70(Suppl3):97

 

多因素分析显示脂肪沉积比炎症损害更能预测强直性脊柱炎患者的脊柱新骨形成

Walter P. Maksymowych, et al. ACR 2011.  Present No: 778

背景/目的:最近的前瞻性数据表明, 强直性脊柱炎(AS)患者的脊柱炎症损伤会最终转化成脂肪1。有人提出假设，这些复杂的炎症损害部位的骨形成与炎症不同步，特点为:1 .STIR MRI上炎症从椎体角(VC)消退 2. T1W MRI上相同的VC部位出现脂肪浸润。早期炎性损害可以不留痕迹地完全消失，但复杂的炎性病变的消退可能同时伴随新骨形成2。因此,脂肪病变的出现比炎性病变更能提示新骨的形成倾向。我们在这个前瞻性研究中检测了这个假设。

方法: 一项双盲、III期的活动AS研究中，76例AS患者随机分配接受阿达木单抗（ADA）40mg 两周一次或安慰剂对照治疗24周，在基线、12周和52周时分别进行MRI检查, 基线和104周时进行X线检查。完成12周的评价后,患者可以早期退出治疗， 24周后所有患者均接受ADA治疗。检测基线和104周时脊柱侧影像学上颈椎、腰椎的前缘是否有新骨赘形成和强直。2位阅片者独立评估，记录X片上相同VC的前缘是否存在炎症和脂肪病变。用广义线性混合模型和多变量分析(GLLAMM)对基线时骨赘／强直的椎体角总数的患者个体间因素进行校正，以确定预测新骨形成的独立损害。

结果:患者层面上, 有新骨形成的患者基线水平MRI上的VC炎症或脂肪病变的平均(SD)数量就明显高于无新骨形成患者 (p 值分别为 0.002和0.0003)。基线MRI存在炎症损害(13/220(5.9%))或脂肪损害(20/179 (11.2%))的VC 更容易出现新骨，相比基线无上述表现患者 (29/1138(2.5%)(p = 0.002,p < 0.0001),差异呈显著性。相比仅有炎症或脂肪沉积的VC(6/168 (3.6%),同时存在炎症和脂肪沉积的VC(7/52(13.5%)，新骨的形成也更加明显（ p = 0.015)。包括炎症、脂肪和骨赘 / 强直在内的GLAMM多变量分析表明,脂肪沉积相比炎症能更好地预示新骨形成。

 

	OR (95%CI)	P value
Inflammation	1.11 (0.48-2.59)	NS
Fat	4.39 (2.08-9.26)	P<0.0001
Syndesmophyte/ankylosis	1.18 (1.10-1.27)	P<0.0001

 

 

结论： 我们的数据提示，新骨形成更容易出现在以脂肪化生为特征的复合炎症损害部位，可能与炎症不同步。