Serum levels of biomarkers of bone and cartilage destruction and new bone formation in different cohorts of patients with axial spondyloarthritis with and without tumor necrosis factor-alpha blocker treatment
Serum levels of biomarkers of bone and cartilage destruction and new bone formation in different cohorts of patients with axial spondyloarthritis with and without tumor necrosis factor-alpha blocker treatment
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DOI：
10.1186/ar2537
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发表时间：
2008-01-01
影响因子：
4.9
通讯作者：
Sieper, Joachim
中科院分区：
文献类型：
--
作者：
Appel, Heiner;Janssen, Louise;Sieper, Joachim
简介 关于强直性脊柱炎 (AS) 患者使用肿瘤坏死因子-α (TNF-α) 阻滞剂治疗期间的放射学进展的最新数据，引发了关于炎症/骨破坏与新骨形成之间的联系以及事件顺序的深入讨论。因此，我们分析了接受和未接受 TNF-α 阻滞剂治疗的中轴型脊柱关节炎患者的不同队列中的软骨退化、新生血管生成和新骨形成的参数。方法 对未接受 TNF-α 阻滞剂治疗的 AS 患者进行了金属蛋白酶 3 (MMP-3) (n = 71)、血管内皮生长因子 (VEGF) (n = 50) 和骨特异性碱性磷酸酶血清水平的调查(BALP) (n = 71) 在基线以及 1 和 2 年后。将此结果与 34 名接受阿达木单抗治疗的中轴型脊柱关节炎患者（22 名 AS 和 12 名非放射学中轴型脊柱关节炎患者）在治疗 36 至 52 周前后进行比较。 结果 在一个大队列中，血清 MMP-3 (P > 0.05)、VEGF (P > 0.05) 和 BALP (P > 0.05) 水平没有显着变化。未使用 TNF-α 阻滞剂的 AS 患者接受了 2 年的随访。相比之下，接受阿达木单抗治疗的脊柱关节炎（AS 和非放射学中轴型脊柱关节炎）患者在治疗 36 至 52 周后 VEGF (P < 0.001) 和 MMP-3 (P = 0.022) 显着下降。最有趣的是，治疗 36 至 52 周后，BALP 水平显着升高（P < 0.001）。血清 MMP-3 水平的降低与 BALP 的升高显着相关（r = -0.398，P = 0.02）。 VEGF 呈负相关，但无显着性（r = -0.214，P > 0.05）。 结论 在接受 TNF-α 阻滞剂治疗的脊柱关节炎患者中，BALP 水平升高以及 MMP-3 和 BALP 之间的负相关表明，如果炎症得到成功治疗，AS 中会出现新骨形成，并且可能是愈合过程的一部分。
Introduction Recent data about radiographic progression during treatment with tumor necrosis factor-alpha (TNF-alpha) blocker agents in patients with ankylosing spondylitis (AS) have prompted an intensive discussion about the link between inflammation/bone destruction and new bone formation and the order of events. Therefore, we analysed parameters of cartilage degradation, neoangiogenesis, and new bone formation in different cohorts of patients with axial spondyloarthritis with and without treatment with TNF-alpha blocker agents.Method TNF-alpha blocker-naive AS patients were investigated for serum levels of metalloproteinase-3 (MMP-3) (n = 71), vasoendothelial growth factor (VEGF) (n = 50), and bone-specific alkaline phosphatase (BALP) (n = 71) at baseline and after 1 and 2 years. This was compared with 34 adalimumab-treated patients with axial spondyloarthritis (22 AS and 12 non-radiographic axial spondyloarthritis patients) before and after 36 to 52 weeks of treatment.Results There were no significant changes in serum levels of MMP-3 (P > 0.05), VEGF (P > 0.05), and BALP (P > 0.05) in a large cohort of TNF-alpha blocker-naive AS patients followed for 2 years. In contrast, adalimumab-treated spondyloarthritis (AS and non-radiographic axial spondyloarthritis) patients had a significant decrease of VEGF (P < 0.001) and MMP-3 (P = 0.022) after 36 to 52 weeks of therapy. Most interestingly, the level of BALP increased significantly after 36 to 52 weeks of therapy (P < 0.001). A decrease in MMP-3 serum levels correlated significantly to an increase of BALP (r = -0.398, P = 0.02). In the case of VEGF, there was a negative correlation without significance (r = -0.214, P > 0.05).Conclusions Rising levels of BALP and the negative correlation between MMP-3 and BALP in spondyloarthritis patients with TNF-alpha blocker treatment indicate that new bone formation in AS occurs if inflammation is successfully treated and might be part of a healing process.