目的 探讨骨标志物与维持性血液透析(maintenance hemodialysis,MHD)患者冠状动脉钙化(coronary artery calcification,CAC)的关系，探讨骨标志物的可能影响因素。 方法 选取温州市人民医院维持性血液透析患者88例，根据冠状动脉钙化积分分钙化组(n=59)和非钙化组(n=29)。收集患者基本资料和生化指标，炎症指标血清淀粉样蛋白A(serum amyloid A protein,SAA)、高敏C反应蛋白(hs-CRP)和白细胞介素-6(interleukin-6, IL-6)，检测骨标志物碱性磷酸酶(ALP)、N端-骨钙素(osteocalcin,N-MID)、β-异构C-端肽(type 1 collagen cross-linking β-C terminal peptide, β-CTX)和Ⅰ型原胶原N-端前肽(procollagen type 1 N-terminal propeptide,PINP)。比较2组数据，做骨标志物的相关性分析及冠状动脉钙化危险因素分析。 结果 ①钙化组骨标志物较非钙化组升高 [N-MID(t=2.182,P=0.034)、β-CTX(t=2.912,P=0.005)、ALP(t=2.480,P=0.017)]，提示钙化组存在高转化骨病。②PINP与炎症指标hs-CRP(r=0.438，P=0.001)、IL-6(r=0.357,P=0.028)、SAA(r=0.298,P =0.038)呈正相关；甲状旁腺激素(PTH)与β-CTX(r=0.588,P＜0.001)、N-MID(r=0.463,P=0.001)、PINP(r=0.369,P=0.007)、PINP/β-CTX(r=0.364,P=0.009)呈正相关；β2微球蛋白(β2-microglobulin,β2-MG)与N-MID(r=0.389,P=0.005)、PINP(r=0.360,P＜0.010)、PINP/β-CTX(r=0.383,P =0.006)呈正相关。LHR(low-/high-density lipoprotein ratio,低密度脂蛋白/高密度脂蛋白比值)与β-CTX(r=0.340，P =0.010)呈正相关。③二元Logistic回归分析提示：β-CTX是冠状动脉钙化的独立危险因素(OR=3.43,95% CI：1.51～7.78,P=0.003)。 结论 骨标志物参与血液透析患者冠状动脉钙化的发生，其中β-CTX可作为独立预测因子。炎症因子、PTH、LHR及β2-MG与骨标志物之间存在相关性，可能共同参与影响血液透析患者骨代谢继而影响冠状动脉钙化。
Objective To investigate the relationship between bone markers and coronary artery calcification (CAC) in patients on maintenance hemodialysis (MHD), and to explore the influencing factors for bone markers in these patients. Methods A total of 88 MHD patients treated in Wenzhou People's Hospital were recruited. They were divided into CAC group (n=59) and non-CAC group (n=29) based on the CAC score. General clinical data, biochemical results including the inflammation indicators of serum amyloid A protein (SAA), high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6), and the bone markers of alkaline phosphatase (ALP), N-terminal osteocalcin (N-MID), type 1 collagen cross-linking β-C terminal peptide (β-CTX) and procollagen type 1 N-terminal propeptide (PINP) were recorded. These biochemical parameters were compared between the two groups to evaluate the relationship between bone markers and CAC and the risk factors for CAC. Results ①The bone markers were higher in CAC group than in non-CAC group [N-MID: 174.34±88.44 vs. 120.59±76.32, t=2.182, P=0.034; β-CTX: 2.58±0.99 vs. 1.74±1.0, t=2.912, P=0.005; ALP: 95 (59.0~489.00) vs. 83.5 (47.0~129.0), t=2.480, P=0.017], suggesting the presence of higher turnover osteopathy in CAC group. ②Correlation analyses found that PINP was positively correlated with the inflammation indicators of hs-CRP (r=0.438, P=0.001), IL-6 (r=0.357, P=0.028) and SAA (r=0.298, P=0.038); parathyroid hormone (PTH) was positively correlated with β-CTX (r=0.588, P=0.000), N-MID (r=0.463, P=0.001), PINP (r=0.369, P=0.007), and PINP/β-CTX (r=0.364, P=0.009); β2-microglobulin (β2-MG) was positively correlated with N-MID (r=0.389, P=0.005), PINP (r=0.360, P＜0.010) and PINP/β-CTX (r=0.383, P=0.006); and low-/high-density lipoprotein ratio (LHR) was positively correlated with β-CTX (r=0.340, P=0.010). ③Binary logistic regression demonstrated that β-CTX was an independent risk factor for CAC (OR=3.433, 95% CI: 1.51~7.78, P=0.003). Conclusion Bone markers are implicated in the pathogenesis of CAC. The bone marker of β-CTX can be used as an independent factor for the prediction of CAC. Bone markers are correlated with inflammatory factors, PTH, LHR and β2-MG, and they may collectively participate in the formation of CAC through affecting bone metabolism in MHD patients.
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