强直性脊柱炎中与骨质增生和骨质疏松相关的骨代谢生物标志物。

Biomarkers of bone metabolism in ankylosing spondylitis in relation to osteoproliferation and osteoporosis.

作者信息

Klingberg Eva, Nurkkala Merja, Carlsten Hans, Forsblad-d'Elia Helena

机构信息

From the Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Sweden.E. Klingberg, MD, PhD; M. Nurkkala, PhD; H. Carlsten, MD, PhD, Professor; H. Forsblad-d'Elia, MD, PhD, Associate professor, Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at the University of Gothenburg.

出版信息

J Rheumatol. 2014 Jul;41(7):1349-56. doi: 10.3899/jrheum.131199.

DOI:10.3899/jrheum.131199

PMID:24931960

Abstract

OBJECTIVE

To identify biomarkers for bone metabolism in patients with ankylosing spondylitis (AS) and to determine the relationship between these biomarkers and disease activity, back mobility, osteoproliferation, and bone mineral density (BMD).

METHODS

Serum levels of Wingless protein (Wnt-3a), Dickkopf-1 (DKK-1), sclerostin, soluble receptor activator of nuclear factor-κB ligand (sRANKL), and osteoprotegerin were assessed using ELISA. Ankylosing Spondylitis Disease Activity Score-C reactive protein, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis patient global score, and C-reactive protein (CRP) were used as disease activity measures, and Bath Ankylosing Spondylitis Metrology Index (BASMI) as a measure of spinal mobility. Lateral spine radiographs were scored for chronic AS-related changes (mSASSS). BMD was measured with dual-energy x-ray absorptiometry.

RESULTS

Two hundred four patients with AS (NY criteria; 57% men), with a mean age of 50 ± 13 years and disease duration 15 ± 11 years, and 80 age and sex-matched controls were included. The patients with AS had significantly higher serum levels of Wnt-3a (p < 0.001) and lower levels of sclerostin (p = 0.014) and sRANKL (p = 0.047) compared with the controls. High CRP was associated with low sclerostin (r(S) = -0.21, p = 0.003) and DKK-1 (r(S) = -0.14, p = 0.045). In multiple linear regression analyses, increasing BASMI and mSASSS were independently associated with older age, male sex, high CRP, and elevated serum levels of Wnt-3a. In addition, mSASSS remained associated with a high number of smoking pack-years after adjusting for age. Low BMD of femoral neck was associated with high mSASSS after adjusting for age.

CONCLUSION

Serum levels of Wnt-3a are elevated in AS and associated with increased BASMI and mSASSS, independent of age, indicating that Wnt-3a could be a biomarker for the osteoproliferative process.

摘要

目的

确定强直性脊柱炎（AS）患者骨代谢的生物标志物，并确定这些生物标志物与疾病活动度、脊柱活动度、骨质增生及骨密度（BMD）之间的关系。

方法

采用酶联免疫吸附测定法（ELISA）评估血清中无翅蛋白（Wnt-3a）、Dickkopf-1（DKK-1）、硬化蛋白、核因子κB受体活化因子配体可溶性受体（sRANKL）及骨保护素的水平。使用强直性脊柱炎疾病活动评分- C反应蛋白、巴斯强直性脊柱炎疾病活动指数、巴斯强直性脊柱炎患者整体评分及C反应蛋白（CRP）作为疾病活动度指标，采用巴斯强直性脊柱炎测量指数（BASMI）作为脊柱活动度指标。对脊柱侧位X线片进行慢性AS相关改变评分（mSASSS）。采用双能X线吸收法测量骨密度。

结果

纳入204例AS患者（纽约标准；57%为男性），平均年龄50±13岁，病程15±11年，以及80例年龄和性别匹配的对照者。与对照组相比，AS患者血清Wnt-3a水平显著升高（p<0.001），硬化蛋白（p = 0.014）和sRANKL（p = 0.047）水平降低。高CRP与低硬化蛋白（r(S)= -0.21，p = 0.003）及DKK-1（r(S)= -0.14，p = 0.045）相关。在多元线性回归分析中，BASMI和mSASSS升高分别独立与年龄较大、男性、高CRP及血清Wnt-3a水平升高相关。此外，校正年龄后，mSASSS仍与吸烟包年数较多相关。校正年龄后，股骨颈低骨密度与高mSASSS相关。