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Denis Poddubnyy 1, Kristina Conrad2, Gisela Ruiz-Heiland3, Uta Syrbe2, Hildrun Haibel2, Heiner Appel2, Martin Rudwaleit4, Georg Schett3 and Joachim Sieper2, 1Charité Medical University, Campus Benjamin Franklin, Berlin, Germany, 2Charité – Campus Benjamin Franklin, Berlin, Germany, 3University of Erlangen-Nuremberg, Erlangen, Germany, 4Ev. Krankenhaus Hagen-Haspe, Hagen, Germany Presentation Number: 1338 Background/Purpose: In the recent years several biomarkers have been found to be associated with radiographic spinal progression/syndesmophyte formation in ankylosing spondylitis (AS): matrix metalloproteinase 3 (MMP-3) and C-reactive protein (C-RP) (positive association), sclerostin (SOST), Dickkopf 1 (DKK1), and periostin, (negative association). However, it is not clear, whether these biomarkers are also able to predict new bone formation in AS patients who are at high risk of radiographic progression due to a presence of syndesmophytes at baseline. The objective of the study was to to investigate the association of biomarkers with radiographic progression (new syndesmophytes formation or growth of the existing syndesmophytes) in patients with AS with and without radiographic damage at baseline. Method: Altogether 97 patients with AS from the German Spondyloarthritis Inception Cohort (GESPIC) were included in this analysis. Radiographs of the lumbar and cervical spine performed at baseline and after 2 years of follow-up were scored independently by two trained readers according to the mSASSS scoring system. Three groups of patients were defined according to the scoring results: Group I (n=26): patients with syndesmophytes at baseline and new syndesmophyte or syndesmophytes growth after 2 years; Group II (n=38): patients with syndesmophytes at baseline but without radiographic progression after 2 years; Group III (n=33): patients without radiographic spinal damage at baseline and after 2 years. Serum levels of the following biomarkers were examined: MMP-3, CRP, SOST, DKK1, periostin, C-terminal cross-linked telopeptide of type II collagen (CTX-II), bone alkaline phosphatase, sRANKL, osteoprotegerin, N-terminal telopeptide of type I collagen, procollagen type I and II N-propeptide (PINP and PIINP), bone sialoprotein and cartilage oligomeric matrix protein. Result:
There was a statistically significant
difference between Group I and Group II in the serum levels of
MMP3, CRP and PIINP (table), indicating that higher serum levels of
these biomarkers might be associated with active progression of
spinal structural changes in the patients who are at high risk of
such a progression. At the same time, higher levels of
Conclusion: Higher levels of MMP-3, CRP and PINP may predict further radiographic spinal progression/new bone formation in patients with AS already having syndesmophytes, while higher levels of SOST, DKK-1, periostin and CTX-II might play a protective role. |
对中轴放射学进展高风险的AS患者有预测和保护作用的生物标记 Denis Poddubnyy , et al. ACR 2011. Present No:1338 背景/目的:近年发现数种生物标记与强直性脊柱炎(AS)放射学脊柱进展／骨赘形成有关：基质金属蛋白酶3(MMP-3)和C反应蛋白(C-RP)(正相关),硬化蛋白(SOST)、Dickkopf 1(DKK1)、periostin(负关联)。然而, 还不清楚这些生物标记物是否能预测放射学进展高风险AS患者的新骨形成，因为他们在基线水平已有骨赘形成。 本研究目的是探讨基线水平有或无放射学破坏的AS患者中，生物标记与影像学进展(新骨赘形成或原有骨赘进展)的相关性。 方法: 德国脊柱关节炎初始队列(GESPIC)中97例AS患者被纳入本研究。基线和随访2年时的腰椎和颈椎摄片由两个独立阅片根据mSASSS评分系统打分。根据积分结果将患者分成三组: 第I组(n = 26): 基线水平有骨赘，2年后有新骨形成或原骨赘进展; 第II组(n = 38): 基线水平有骨赘，但2年后没有放射学进展; 第III类(n = 33): 基线和2年后都没有脊柱损伤。 检测下类生物标记的血清浓度: MMP-3、CRP、SOST、DKK1、periostin、II型胶原蛋白C端交联端肽 (CTX-II)、骨碱性磷酸酶、sRANKL,骨素、I型胶原蛋白N端交联端肽、I型和II型原胶原N-末端肽(PINP和PIINP)、骨唾液酸蛋白和软骨低聚基质蛋白。 结果:第I组和第II组的血清MMP3,CRP和PIINP有显著差异(表),说明这些标记物的血清高水平与高风险患者中脊柱结构进行性破坏相关。与此同时,高水平的SOST,DKK-1,periostin,CTX-II可能在AS患者起影像学进展的保护作用，因为这些标记物在基线水平或2年时无放射学骨赘形成患者中浓度最高，无论这些患者是否有高水平CRP、MMP3和PIINP(表)。其它的标记物则都未发现与脊柱放射学进展相关。 结论:高水平的MMP-3、CRP和PINP可能预示已有骨赘形成的AS患者进一步影像学进展和新骨形成,而高水平的SOST,DKK-1,periostin和CTX-IIz则可能起到了一个保护的作用。 |
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