碳酸镧对伴无动力骨病的糖尿病维持性血液透析患者骨密度和血管钙化的影响

Effect of lanthanum carbonate on vascular calcification and bone mineral density in maintenance hemodialysis patients with diabetes complicated with adynamic bone disease:a prospective pilot study

目的探讨长期应用碳酸镧对伴无动力骨病的糖尿病维持性血液透析(maintenance hemodialysis,MHD)患者骨密度和血管钙化的影响及可能的机制。方法 92例伴无动力骨病的糖尿病MHD患者随机分为碳酸镧组(LC组)和碳酸钙组(CC组)各46例,治疗12个月。以多层螺旋CT评价冠状动脉钙化积分(coronary artery calcification score,CACS),以双能x线骨密度仪评价骨密度。比较两组患者治疗前后CACS、骨密度、磷酸盐代谢、成纤维细胞生长因子(fibroblast growth factors,FGF-23)、基质Gla蛋白(matrix gla protein,MGP)、骨碱性磷酸酶(bone alkaline phosphate,BALP)、血清I型胶原N-端前肽(procollagen I N-terminal peptide,PINP)、I型胶原交联C-末端肽(C-terminal telopeptide of type I collagen,β-CTX)、微炎症等指标变化。结果与基线相比,第12个月末碳酸镧组血磷、FGF23、MGP明显降低,全段甲状旁腺激素(intact parathyroid hormone,iPTH)、BALP、PINP、β-CTX、骨密度T值、CACS明显升高而血钙无显著性变化[磷:t=52.948,P<0.001;FGF23:t=18.722,P<0.001;MGP:t=5.981,P<0.001;iPTH:=33.042,t P<0.001;BALP:t=19.812,P<0.001;PINP:t=35.278,P<0.001;β-CTX:t=20.491,P<0.001;骨密度T值(腰椎、股骨、前臂):t=27.152,21.451,15.601,P=0.001,0.002,0.002;CACS:t=20.602,P=0.001;钙:t=1.281,P=0.212];碳酸钙组血磷(t=47.712,P<0.001)、iPTH(t=12.601,P<0.001)、BALP(t=5.336,P<0.001)、PINP(t=2.033,P=0.041)、β-CTX(t=5.282,P=0.001)、MGP(t=21.479,P<0.001)明显降低,血钙(t=12.922,P<0.001)、骨密度T值(腰椎、股骨、前臂)(t=23.571,14.222,25.377,P=0.001,0.002,<0.001)、CACS(t=26.571,P<0.001)明显升高而FGF23无显著性变化(t=1.162,P=0.242);第12个月末,LC组血磷(t=5.693,P<0.001)、血钙(t=8.150,P<0.001)、FGF23(t=11.370,P<0.001)、CACS(t=18.304,P<0.001)明显低于CC组;而iPTH(t=25.402,P<0.001)、BALP(t=65.335,P<0.001)、PINP(t=47.231,P<0.001)、β-CTX(t=12.351,P<0.001)、骨密度T值(腰椎:t=17.872,P<0.001;股骨:t=9.874,P<0.001;前臂:t=5.625,P<0.001)明显高于CC组。pearson相关分析显示前臂骨密度T值与iPTH(r=0.363,P=0.021)、MGP(r=0.389,P=0.012)显著正相关,与CACS(r=-0.792,P=0.001)显著负相关;CACS与腰椎骨密度T值(r=-0.584,P=0.001)、股骨颈T值(r=-0.642,P=0.001)、MGP(r=-0.294,P=0.002)显著负相关,与FGF23(r=0.542,P=0.001)、血钙(r=0.244,P=0.002)、血磷(r=0.474,P=0.001)显著正相关。多元线性回归分析显示前臂骨密度T值变化(B=-134.372,P=0.001)、股骨颈骨密度T值变化(B=-72.211,P=0.001)、FGF23变化(B=55.01,P=0.002)是CACS变化的独立影响因素。结论碳酸镧使伴ABD的糖尿病MHD患者血管钙化进展延缓,骨转运改善,骨密度提高,可能与改善磷酸盐代谢、MGP代谢及镧元素的直接作用有关。

Objective To explore the effect of lanthanum carbonate on vascular calcification and bone mineral density in maintenance hemodialysis （MHD） patients with diabetes complicated with adynamic bone disease. Methods A total of 92 MHD cases were divided into calcium carbonate （CC） group and lanthanum carbonate （LC） group. We compared serum calcium, phosphate, FGF23, bone alkaline phosphate （BALP）, pro- collagen I N-terminal peptide （PINP）, C-terminal telopeptide （β-CTX）, matrix gla protein （MGP） and hsCRP,coronary artery calcification score （CACS） and bone mineral density at baseline and after 12 months between the two groups. SPSS 17.0 for Windows was used for statistical analyses. Results After the treatment for 12 months, serum levels of phosphate, FGF23 and MGP decreased significantly and serum levels of iPTH, BALP, PINP and β-CTX, CACS, and bone mineral density increased significantly in LC group, as compared with those at baseline （P〈0.05）. After the treatment for 12 months, serum levels of calcium, phosphate, FGF23 and MGP, and CACS were lower in LC group than in CC group, and serum levels of iPTH, BALP, PINP and β-CTX, and bone mineral density were higher in LC group than in CC group. Pearson＇ s correlation analyses revealed that bone mineral density in forearm correlated positively with iPTH and MGP and negative- ly with CACS, and that CACS correlated positively with serum calcium, phosphate and FGF23 and negatively with serum MGP. Multivariate linear regression revealed that the changes of bone mineral density in forearm and collum femoris and serum FGF23 were the independent influence factors for the change of CACS （P〈 0.05）. Conclusions Slower progression of coronary artery calcification, improved bone turnover and in- creased bone mineral density occurred in the LC group as compared with those in the CC group. These results may result from the effects that lanthanum carbonate improves phosphate and MGP metabolism and directly antagonizes vascular calcification.