维持性血液透析患者发生骨折与骨矿物质代谢紊乱的关系

Relationship between fracture and disturbances of bone mineral metabolism in patients on maintenance hemodialysis

目的 观察维持性血液透析（MHD）患者发生骨折与患者预后的关系以及骨代谢指标监测对临床的指导意义。方法 采用前瞻队列研究，从2010～2012年对中国中医科学院广安门医院血液净化中心行MＨD的158例患者进行随访，记录患者干体质量变化，陈旧及新发生骨折例数，新发骨折对患者生存以及心血管事件发生情况的影响，定期监测患者血钙、磷、碱性磷酸酶、全段甲状旁腺素（iPTH）、总维生素D（总VitD）、Ⅰ型胶原交联Ｃ末端肽，骨钙素，降钙素，比较新发生骨折者与未发生骨折者上述指标以及预后的差异。结果 研究开始时已存在陈旧骨折者27例，随访期内新发骨折21例，平均骨折发生率为：4．43／100个患者年，均为脆性骨折。与未发现骨折者比较，新发生骨折患者年龄更大，ALP水平较高，女性所占比例较高，体质指数较低，干体质量呈下降者更多（P〈０．05），规律使用骨化三醇或阿发骨化醇者比例较低（42．86％比72．26％，P〈０．05），随访期内死亡及心血管事件发生率较高，分别为：66．67％比18．98％和52．38％比10．95％（P〈0．05），2组患者其余矿物质及骨代谢相关指标均未见明显差异。发生骨折后未接受骨科固定治疗者1年内死亡率明显高于接受治疗者（70．59％比25．00％），寿命表生存分析显示新发骨折使MHD患者累计生存率较未骨折组明显降低（中位生存月15．75比36．00）。Logistic回归表明干体质量下降、女性是MHD患者发生骨折的独立危险因素，OR值分别为42．94（95％CI：9．31，196．34）和3．47（95％CI：1．11，10．84）。结论 老龄、女性、干体重下降、血ALP水平增高、未规律补充维生素D治疗可能与MHD者骨折风险增高有关；除ALP外，其余骨代谢指标对预测骨折风险意义有限。骨折与MHD患者死亡及心血管事件风险明显增高有关，一旦发生骨折需多学科合作尽快处理。

objective To observe the relationship between fresh bone fracture and its prognostic significance, and to assess clinical significance of bone mineral metabolism markers in maintenance hemodialysis （MHD） patients. Methods This was a perspective cohort study to follow up 158 MHD patients treated in our hemodialysis center from 2010 to 2012. Dry body weight changes, fresh and old fractures, impact of fresh fracture on survival and cardiovascular events were recorded. Serum calcium （Ca）, phosphorus （P）, alkaline phosphatase （ALP）, intact PTH （iPTH）, total vit D, cross-linked C telopeptide of collagen I, osteocalcin, and calcitonin were regularly measured. The laboratory markers and prognosis were compared between patients with fresh fracture and those without fracture. Results Twenty-seven patients had old bone fractures at beginning of the study and 21 patients had fresh fractures in the follow-up period, with the fracture incidence of 4.43/100 patients/year. All of them were brittle fractures. Compared with the patients without fracture, patients with fresh fracture had older age （average age 67.84±12.46 vs. 57.80±13.63, P〈0.05）, more females （80.95% vs. 55.47%, P〈0.05）, higher ALP level [97.33 （45.30～322.00） vs. 83.50 （42.00～272.70）; P〈0.01], lower body mass index （20.03 ±3.56 vs. 21.96 ±4.05; P〈0.05）, more decrease of dry body weight （90.48% vs.18.25%; P〈0.01）, infrequent use of Calcitriol or Alfacalcidol （42.86% vs. 72.26%）, higher mortality （66.67% vs. 18.98%）, and more cardiovascular events （52.38% vs. 18.98%）. The rest ofbone mineral metabolism markers were indifferent between the two groups. Patients treated the fracture without fixation had higher one-year mortality than those with fixation treatment （70.59% vs. 25.00%）. Life tables and survival analyses showed that fresh fracture would greatly reduce the accumulative survival rate （median survival time 15.75 vs. 36.00 months）. Logistic regression analyses revealed that decrease of dry body weight and female were the independent risk factors for fracture in MHD patients. The OR for decrease of dry body weight was 42.94 （95% CI： 9.31, 196.34） and that for female was 9.31 （95% CI： 1.11, 10.84）. Conclusion Older age, female, decrease of dry body weight, higher serum ALP, and iirregular Vitamin D supplementation are associated with a higher risk of fracture in MHD patients. Other bone mineral metabolism markers we tested have only limited clinical significance in prediction of fracture in MHD patients. Fracture is usually associated with high mortality and more cardiovascular events in MHD patients. Multidisciplinary treatments are urgently needed once fracture occurs in a MHD patient.