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骨硬化蛋白:另一种血管钙化抑制剂?

Sclerostin: Another vascular calcification inhibitor?

机构信息

Department of Nephrology, University Hospitals Leuven, Herestraat 49, B-3000 Leuven, Belgium.

出版信息

J Clin Endocrinol Metab. 2013 Aug;98(8):3221-8. doi: 10.1210/jc.2013-1521. Epub 2013 Jun 20.

DOI:10.1210/jc.2013-1521
PMID:23788689
Abstract

CONTEXT

Sclerostin, a Wnt antagonist produced by osteocytes, regulates osteoblast activity and is a well-established key player in bone turnover. Recent data indicate that the Wnt pathway may also be involved in vascular calcification.

OBJECTIVE

The present study tests the hypothesis that serum sclerostin levels are associated with vascular calcification in patients with chronic kidney disease (CKD) not yet receiving dialysis.

DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: We performed a cross-sectional analysis in 154 patients with CKD. Aortic calcification (AC) was assessed by lumbar X-ray and scored with a maximum score of 24. In addition to traditional and nontraditional cardiovascular (CV) risk factors, serum sclerostin levels were assessed (ELISA). Regression analysis was performed to identify determinants of serum sclerostin and AC.

RESULTS

AC was present in 59% of patients. Older age (P < .0001), male sex (P = .006), lower estimated glomerular rate (eGFR) (P = .0008), lower bone-specific alkaline phosphatase (P = .03), and the absence of AC (P = .006) were identified as independent determinants of higher serum sclerostin levels. In univariate logistic regression, higher age, diabetes, CV history, higher body mass index, higher serum C-reactive protein and sclerostin levels and lower estimated glomerular rate were all associated with the presence of AC. In multivariate analysis, lower, not higher, sclerostin levels (P = .04, odds ratio [OR] per ng/mL of 0.24), higher age (P < .0001, OR per year of 1.17) and CV history (P = .02, OR for a positive CV history of 3.83) were identified as independent determinants of AC.

CONCLUSIONS

In this cohort of patients with CKD, we found that patients with aortic calcifications (ACs) had higher sclerostin levels. However, in multivariate analysis, the association became inverse. Additional clinical and experimental studies are urgently required to clarify whether or not sclerostin protects against progression of vascular calcification.

摘要

背景

骨钙素是一种由骨细胞产生的 Wnt 拮抗剂,调节成骨细胞活性,是骨转换的一个重要因子。最近的数据表明 Wnt 途径也可能参与血管钙化。

目的

本研究旨在检验骨钙素水平与尚未接受透析的慢性肾脏病(CKD)患者血管钙化之间存在相关性的假说。

设计、地点、参与者和测量:我们对 154 例 CKD 患者进行了横断面分析。通过腰椎 X 射线评估主动脉钙化(AC),并采用最大 24 分的评分系统进行评分。除了传统和非传统心血管(CV)危险因素外,还通过 ELISA 检测血清骨钙素水平。进行回归分析以确定血清骨钙素和 AC 的决定因素。

结果

59%的患者存在 AC。年龄较大(P<0.0001)、男性(P=0.006)、估算肾小球滤过率(eGFR)较低(P=0.0008)、骨特异性碱性磷酸酶较低(P=0.03)和无 AC(P=0.006)被确定为血清骨钙素水平较高的独立决定因素。在单变量逻辑回归中,较高的年龄、糖尿病、CV 病史、较高的体重指数、较高的血清 C 反应蛋白和骨钙素水平以及较低的 eGFR 均与 AC 存在相关。在多变量分析中,较低而非较高的骨钙素水平(P=0.04,每 ng/mL 骨钙素的 OR 为 0.24)、较高的年龄(P<0.0001,每年的 OR 为 1.17)和 CV 病史(P=0.02,CV 病史阳性的 OR 为 3.83)被确定为 AC 的独立决定因素。

结论

在本队列的 CKD 患者中,我们发现主动脉钙化(ACs)患者的骨钙素水平较高。然而,在多变量分析中,两者之间的关系变为负相关。需要进一步进行临床和实验研究,以明确骨钙素是否能防止血管钙化的进展。

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