尿毒症患者桡动脉钙化与骨密度及血清骨代谢指标的关系

Association of radial arterial calcification damage with bone mineral density and bone metabolism biomarkers in uremia patients

目的观察尿毒症患者桡动脉钙化情况并分析其与骨密度及血清骨代谢指标改变的关系。方法以67例尿毒症患者为对象，取内瘘手术切除的桡动脉段，vonKossa染色及透射电镜检测血管钙化情况；检测Scr、血钙、磷、甲状旁腺素（iPTH）；测定腰椎、股骨颈骨密度（BMD）；放射免疫法测定血清25羟维生素D3（250HD）、1，25羟维生素D3[1，25（OH）2D]；ELISA法测定成纤维生长因子（FGF）23、骨特异性碱性磷酸酶（BAP）、骨钙素（BGP）与I型胶原吡啶交联物（ICTP）。以23例健康体检者为对照，仅接受血清及骨密度检查。结果vonKossa染色见24例（35．8％）尿毒症患者桡动脉中膜明显钙沉积；电镜发现中膜平滑肌细胞由收缩型向分泌型转化，胞内有较多含钙囊泡，基质胶原明显增加伴钙磷结晶附着，程度与钙化评分一致。与对照组比较，尿毒症患者血磷、iPTH、FGF23、BGP、ICTP显著增加（均P〈0．05），血钙、250HD、1，25（OH）2D显著降低（均P〈0．01），腰椎、股骨颈BMD也显著降低（均P〈0．01）。相关分析显示，桡动脉钙化与糖尿病、股骨颈及腰椎骨密度z值、ICTP、FGF23相关（r=0．62、-0．43、-0．25、0．34、0．86，P：0．000、0．012、0．001、0．018、0．000），与iPTH无相关（r=-0．08，P=0．306）。按iPTH水平分层后，低iPTH（〈150ng／L）组、高iPTH（〉300ng／L）组患者iPTH与钙化相关（r=-0．41、0．31，P=0．044、0．023）。多元回归分析显示，股骨颈骨密度Z值、ICTP、FGF23是桡动脉钙化的独立危险因素（β=-0．221、0．181、0．260，P=0．021、0．024、0．036）。结论尿毒症桡动脉钙化与平滑肌细胞合成和分泌较多的含钙基质有关，骨密度降低、骨转化率异常、骨吸收增加、血清FGF23水平增加是其危险因素。

Objective To investigate the association of radial arterial calcification damage with bone mineral density （BMD） and bone metabolism biomarkers in uremia patients. Methods Sixty-seven incident hemodialysis patients were recruited into uremic group. Serum creatinine, calcium, phosphorus, lumbar spine and femoral neck BMD were measured. Parathyroid hormone （iPTH）, 25OHD, 1,25（OH）2D, fibroblast growth factor （FGF） 23, bone specific alkaline phosphates （BAP） and osteocalcin （BGP）, type I collagen pyridine crosslinked C- telopcptidc （ICTP） were detected. Radial artery calcification was analyzed by yon Kossa staining and transmission electron microscopy. Arterial type I collagen （Col I ） expression was examined. Twenty- three healthy cases received serum and BMD examination only as control. Results Uremic patients presented higher serum phosphate, iPTH, FGF23, lower serum calcium, 25OHD, 1,25 （OH）2D （all P 〈 0.05）, and lower lumbar spine and femoral neck BMD （all P 〈 0.01） compared to controls. Significant calcium deposit was observed in radial arteries in 24 uremic cases （35.8%）, including 10 cases of diabetes. Immunohistochemistric assay confirmed that Col I expression increased around calcification site and electron microscope revealed that more calcium and phosphorus plaque attached among collagen fibers. No correlation was showed between iPTH and radial artery calcification （r = -0.08, P = 0.306）, but after stratified by iPTH levels, correlation of iPTH and calcification was found in low iPTH （ 〈 150 ng/L） group and high iPTH group （〉 300 ng/L） （r=-0.41, 0.31, P= 0.044, 0.023）. Diabetes, lumbar spine and femoral neck BMD, ICTP, FGF23 were correlated with arterial calcification （r = 0.62,-0.25,-0.43, 0.34, 0.86, P = 0.000, 0.001, 0.012, 0.018, 0.000）. Multiple regression analysis showed femoral neck BMD, ICTP, FGF23 levels were independently associated with radial arterial calcification （β =-0.221, 0.181, 0.260, P = 0.021, 0.024, 0.036）. Conclusion In uremic patients, reduced BMD, abnormal bone turnover rate, especially accelerated bone reabsorption, and increased serum FGF23 level are independently associated with radial artery calcification.