非透析慢性肾脏病3~5期患者髋关节骨质丢失的影响因素分析

非透析慢性肾脏病3~5期患者髋关节骨质丢失的影响因素分析

邱莉1, 梁玉枫1, 丘美蓉1, 张声灿2, 黄彬三1, 丘美兰1, 蓝梅金1, 卢娟1, 陈勇平1, 梁兴澜1

【作者机构】 1福建省龙岩市第二医院肾内科; 2龙岩市疾病预防控制中心检验科
【分 类 号】 R589.9
【基    金】 福建省龙岩市科技计划项目(2022LYF17048)
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非透析慢性肾脏病3~5期患者髋关节骨质丢失的影响因素分析

非透析慢性肾脏病3~5期患者髋关节骨质丢失的影响因素分析

邱莉1,梁玉枫1,丘美蓉1,张声灿2,黄彬三1,丘美兰1,蓝梅金1,卢娟1,陈勇平1,梁兴澜1

1.福建省龙岩市第二医院肾内科,福建龙岩 364000;2.龙岩市疾病预防控制中心检验科,福建龙岩 364000

[摘要] 目的 探讨非透析慢性肾脏病(chronic kidney disease,CKD)3~5期患者髋关节骨质丢失的影响因素,为临床早期识别和干预提供参考。方法 选取2022年9月30日至2023年9月30日龙岩市第二医院收治的250例CKD 3~5期非透析患者作为研究对象。根据髋关节骨密度(bone mineral density,BMD)中位数分为低BMD(low bone mineral density,L-BMD)组和高BMD (high bone mineral density,H-BMD)组。采用二元逻辑回归分析髋关节骨质丢失的影响因素,受试者操作特征曲线(receiver operating characteristic curve,ROC曲线)评估各指标诊断价值。结果 L-BMD组患者的体质量指数(body mass index,BMI)、血红蛋白、甘油三酯、血清镁、血清白蛋白水平均显著低于H-BMD组,且L-BMD组患者年龄更大,女性比例更高(P<0.05)。多因素二元逻辑回归分析显示年龄和碱性磷酸酶是髋关节骨质丢失的独立危险因素,BMI和血清镁是保护因素。ROC曲线分析显示年龄、碱性磷酸酶、BMI、血清镁诊断髋关节骨质丢失的曲线下面积分别为0.681、0.610、0.655、0.648,最佳截断值分别为59.5岁、84.5U/L、23.7 kg/m2、0.895mmol/L,这些指标联合应用可提高骨质丢失的诊断效能。结论 年龄和碱性磷酸酶是髋关节骨质丢失危险因素,BMI和血清镁是髋关节骨质丢失的保护因素,多指标联合评估有助于早期识别高危患者。

[关键词] 慢性肾脏病;骨密度下降;影响因素;髋关节

骨密度(bone mineral density,BMD)下降是慢性肾脏病(chronic kidney disease,CKD)患者常见并发症,CKD 3~5期患者的矿物质和骨代谢异常(chronic kidney disease-mineral and bone disorder,CKD-MBD)不仅增加骨折风险,而且影响患者预后[1]。CKD患者BMD下降的发病机制复杂,除传统危险因素外,CKD特异性因素包括矿物质代谢紊乱、维生素D代谢异常等也起着重要作用[2]。血清镁和成纤维细胞生长因子23等新型因素在骨代谢中亦可能发挥重要作用[3];这提示需全面评估BMD的影响因素。既往研究多聚焦于透析患者,对非透析CKD患者相关研究匮乏[4-5]。本研究旨在探讨非透析CKD患者的血清镁与BMD相关性及各指标的诊断价值。

1 对象与方法

1.1 研究对象

选取2022年9月30日至2023年9月30日龙岩市第二医院收治的250例CKD 3~5期非透析患者作为研究对象。其中男141例,女109例,中位年龄60(49,71)岁,高血压患者占比75.6%,糖尿病患者占比29.6%,原发性肾炎患者占比15.5%。根据髋关节BMD中位数分为低BMD(low bone mineral density,L-BMD)组(BMD≤0.788mmol/L)和高BMD (high bone mineral density,H-BMD)组(BMD>0.788mmol/L)。纳入标准:①年龄≥18周岁;②肾小球滤过率(estimated glomerular filtration rate,eGFR) <60ml/min/1.73m2,即CKD3~5期非透析患者;③已行BMD检查。排除标准:①使用影响骨代谢或血清镁水平的药物;②有透析或肾移植史;③重度营养不良者;④骨肿瘤或先天骨发育异常者;⑤原发性甲状旁腺功能亢进、多发性骨髓瘤及使用糖皮质激素≥3个月者;⑥妊娠及哺乳期妇女;⑦近期有严重感染者。所有患者均签署知情同意书,本研究经龙岩市第二医院医学伦理委员会批准(伦理审批号:LYEY2022LSK-003)。

1.2 研究方法

评估非透析CKD 3~5期患者传统和新型危险因素对BMD的影响。研究对象于入院第1天空腹抽血,采用美国General Electric公司的Prodigy型双能X线吸收骨密度仪(dual-energy X-ray absorptiometry,DXA)测量髋关节BMD。收集患者的血红蛋白(hemoglobin,Hb)、血肌酐、血清尿素氮、血尿酸(uric acid,UA)、血清白蛋白(albumin,Alb)、血清钙(calcium,Ca)、血清磷(phosphate,P)、血清镁(magnesium,Mg)、碱性磷酸酶(alkaline phosphatase,ALP)、总胆固醇(total cholesterol,TC)、甘油三酯(triglycerides,TG)、全段甲状旁腺激素(intact para thyroid hormone,iPTH)等指标数据。血清校正钙(corrected serum calcium,CsCa)公式:CsCa(mmol/L)=Ca(mmol/L)+[40-Alb(g/L)]×0.02。基于DXA检测的BMD T值,T值<–1定义为骨质丢失。

1.3 统计学方法

采用SPSS 25.0统计学软件对数据进行处理分析,符合正态分布的计量资料以均数±标准差表示,组间比较采用t检验。不符合正态分布的数据以中位数(四分位数间距)[MQ1Q3)]表示,组间比较采用秩和检验。计数资料以例数(百分率)[n(%)]表示,组间比较采用χ2检验。采用Logistic回归分析影响因素,采用受试者操作特征曲线(receiver operating characteristic curve,ROC曲线)分析预测价值。P<0.05为差异有统计学意义。

2 结果

2.1 两组患者的基线资料比较

本研究CKD患者的骨质丢失发生率为58%。L-BMD组年龄更大,女性比例更高,BMI、Hb、TG、Mg、Alb均较低(P<0.05),见表1。

表1 两组患者的基线资料比较

项目L-BMD组(n=125)H-BMD组(n=125)χ2/ZP性别[n(%)]11.86<0.001男57(45.6)84(67.2)女68(54.4)41(32.8)合并高血压[n(%)]0.1950.659是93(74.4)96(76.8)否32(25.6)29(23.2)年龄[M(Q1,Q3),岁]67(56,74)55(45,64.5)–5.416<0.001 BMI[M(Q1,Q3),kg/m2]21.8(19.9,23.7)23.6(20.9,27.0)–4.338<0.001髋关节BMD[M(Q1,Q3),g/cm2]0.66(0.58,0.74)0.89(0.83,0.99)–13.666<0.001 Hb[M(Q1,Q3),g/L]106.0(94.5,121.5)113.0(98.0,127.5)–2.2640.024 TG[M(Q1,Q3),mmol/L]1.22(0.94,1.84)1.63(1.07,2.88)–3.0100.003 CsCa[M(Q1,Q3),mmol/L]2.30(2.20,2.36)2.30(2.21,2.37)–0.7510.452 Mg[M(Q1,Q3),mmol/L]0.84(0.76,0.96)0.93(0.81,1.07)–3.879<0.001 P[M(Q1,Q3),mmol/L]1.38(1.15,1.68)1.42(1.21,2.04)–1.3510.452 iPTH[M(Q1,Q3),ng/L]100.0(50.0,232.0)122.3(43.9,288.4)–0.5840.559 Alb[M(Q1,Q3),g/L]34.8(31.2,38.6)37.7(33.1,40.9)–2.5690.010 eGFR[M(Q1,Q3),ml/(min·1.73m2)]13.2(6.4,43.8)13.0(5.5,46.8)–0.1570.876

2.2 髋关节骨质丢失的危险因素分析

单因素二元逻辑回归分析结果显示年龄、BMI、ALP、Alb、TG、Mg均是髋关节BMD下降的影响因素。多因素二元逻辑回归分析结果显示年龄和ALP是髋关节BMD下降的危险因素,BMI、Mg是髋关节骨质丢失的保护因素,见表2。

表2 髋关节BMD下降危险因素分析

因素单因素分析多因素分析OR(95%CI)βPOR(95%CI)βP女性1.126(0.678~1.871)0.1190.6460.833(0.454~1.527)–0.1830.554年龄1.049(1.028~1.069)0.048<0.0011.049(1.026~1.074)0.048<0.001 BMI0.841(0.777~0.909)–0.174<0.0010.830(0.757~0.911)–0.186<0.001 ALP1.008(1.002~1.015)0.0080.0171.009(1.001~1.017)0.0090.036 Alb0.957(0.919~0.997)–0.0440.0330.978(0.935~1.022)–0.0230.322 TG0.818(0.686~0.977)–0.2000.0260.931(0.497~1.144)–0.0710.497 Mg0.055(0.012~0.248)–2.896<0.0010.037(0.005~0.294)–3.2850.002

2.3 髋关节骨质丢失的ROC曲线分析

ROC曲线分析结果显示,年龄诊断骨质丢失的曲线下面积(area under the curve,AUC)为0.681,最佳截断值59.5岁,敏感度66.2%,特异性63.8%;ALP诊断骨质丢失的AUC为0.610,最佳截断值84.5U/L,敏感度51.0%,特异性67.6%;联合年龄与ALP诊断骨质丢失的AUC为0.710,敏感度71.0%,特异性65.7%,见图1、表3。BMI诊断骨质丢失的AUC为0.655,最佳截断值23.7kg/m2,敏感度75.1%,特异性51.5%;Mg诊断骨质丢失的AUC为0.648,最佳截断值0.895mmol/L,敏感度62.8%,特异性60.0%。BMI联合Mg诊断骨质丢失的AUC为0.714,敏感度71.0%,特异性65.7%,见图2、表3。

图1 年龄、ALP诊断髋关节骨质丢失的ROC曲线分析

图2 BMI、Mg诊断髋关节骨质丢失的ROC曲线分析

表3 各项指标诊断髋关节骨质丢失的诊断效能

影响AUC95%CIP年龄0.6810.614~0.748<0.001 ALP0.6100.540~0.6810.003年龄+ALP0.7100.646~0.775<0.001 Mg0.6480.580~0.717<0.001 BMI+Mg0.7140.649~0.779<0.001危险因素保护因素BMI0.6550.585~0.724<0.001

3 讨论

本研究中年龄和ALP是髋关节骨质丢失的独立危险因素,BMI和Mg是保护因素。其他传统CKD-MBD标志物(Ca、P、iPTH)与BMD无显著相关性。本研究中CKD患者骨质丢失发生率为58%,显著高于一般人群,与既往研究结果基本一致[6-7]。本研究中传统CKD-MBD标志物如CsCa、P、iPTH在两组间差异无统计学意义,提示传统标志物在预测骨质丢失方面可能存在局限性[8],可能原因:①部分CKD3~5期患者矿物质代谢紊乱可能尚未达到显著影响BMD的程度,且iPTH对骨骼的影响比较滞后[9]。②现有的实验室检测存在局限性,可能无法完全反映骨组织水平的矿物质代谢状态[10];③CKD骨病的发病机制比传统认识更为复杂[2]。有研究证实男性P与BMD无关[11],且CKD患者存在iPTH低反应性,单纯依赖iPTH等传统标志物可能导致骨病诊断的误判[12]。这提示临床需重新审视CKD骨病的诊断和管理策略,单纯依赖传统指标可能不足以准确评估骨健康状态。

年龄是CKD患者髋关节骨质丢失的重要危险因素,本研究ROC曲线表明有良好的诊断价值。随着年龄增长,CKD患者中骨形成减少而骨吸收增加,且可能因维生素D缺乏、慢性炎症等进一步加剧[13]。本研究确定的最佳截断值为59.5岁,≥60岁的CKD患者应被视为骨质丢失的高危人群。

ALP为骨转换标志物,在本研究中是CKD患者髋关节骨质丢失的独立危险因素。ALP升高反映骨转换活跃,在CKD患者中通常表现为继发性甲状旁腺功能亢进导致的高转换性骨病。Chen等[14]的研究证实CKD患者中ALP升高与BMD下降及骨质疏松风险增加相关。ALP检测与其他骨转换标志物如I型胶原交联C端肽等相比,更简便易得,成本较低,ALP最佳截断值为84.5U/L。

BMI是髋关节骨质丢失的保护因素,符合骨代谢研究中的“肥胖悖论”概念[15]。分析原因:①适当的体质量负荷对骨骼产生机械性刺激,根据Wolff定律,机械负荷可促进骨形成,增加BMD[16];且脂肪组织分泌的瘦素、脂联素等多种激素和细胞因子对骨代谢具有调节作用[17];②较高的BMI通常伴随着更好的营养状态,有利于骨基质合成,Kim等[18]证实骨骼肌含量与BMD呈正相关。而在CKD患者中,因存在营养不良与体质量下降问题,可通过肌肉量减少、胰岛素样生长因子-1 水平降低、促炎细胞因子增多等多重机制加剧骨质丢失[19]。因此,维持适当的BMI和良好的营养状态对CKD患者的骨健康具有重要意义。

本研究结果表明Mg是髋关节骨质丢失的保护因素。Mg在骨代谢中发挥重要作用,约67%的体内Mg储存在骨骼中,是羟基磷灰石晶体结构的重要组成部分,参与骨基质形成[20];且调节成骨细胞和破骨细胞功能[19]。此外,Mg缺乏还导致BMD降低和骨微结构恶化[19]。CKD患者由于肾脏排泄功能受损、药物影响及饮食限制,Mg代谢异常较常见。研究表明透析患者Mg水平与骨折风险呈负相关[21]。不过,即便在正常Mg浓度的人群中,也可能出现低镁血症[22],目前尚无研究明确指出CKD患者适宜的Mg浓度区间[23]。本研究结果提示维持适当Mg水平对预防CKD患者骨质丢失意义重大,建议常规监测Mg,对Mg<0.895mmol/L患者适当补Mg。

本研究存在一定局限性:①本研究为横断面研究,无法确定因果关系;②未纳入骨活检等金标准,可能无法完全反映骨质的变化。综上,本研究确定的危险因素和保护因素为非透析CKD患者骨健康管理提供实用工具。Mg、年龄、ALP和BMI联合构建的预测模型具有良好诊断效能,未来研究应聚焦于前瞻性验证这些预测因子的长期价值,探索基于多因素风险模型的个体化干预策略。

利益冲突:所有作者均声明不存在利益冲突。

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Analysis of influencing factors of hip bone loss in non-dialysis chronic kidney disease stages 3-5 patients

QIU Li1, LIANG Yufeng1, QIU Meirong1, ZHANG Shengcan2, HUANG Binsan1, QIU Meilan1, LAN Meijin1, LU Juan1,CHEN Yongping1, LIANG Xinglan1

1.Department of Nephrology, the Second Hospital of Longyan, Longyan 364000, Fujian, China; 2.Department of Laboratory Medicine, Longyan Center for Disease Control and Prevention, Longyan 364000, Fujian, China

[Abstract] Objective To investigate the influencing factors of hip bone loss in non-dialysis chronic kidney disease (CKD)stage 3-5 patients and provide evidence for early clinical identification and intervention. Methods A total of 250 non-dialysis patients with CKD stages 3-5 admitted to the Second Hospital of Longyan from September 30,2022, to September 30,2023 were selected as study subjects. Based on the median hip joint bone mineral density (BMD), patients were divided into low BMD (low bone mineral density L-BMD) group and high BMD (H-BMD) group. Binary Logistic regression analysis was employed to identify factors influencing hip joint bone loss, and receiver operating characteristic (ROC) curves were used to evaluate the diagnostic value of each indicator. Results Compared to the H-BMD group, body mass index (BMI), hemoglobin,triglycerides, serum magnesium, and albumin levels with older age and higher proportion of females were significantly lower in L-BMD group(P<0.05). Multivariate binary Logistic regression analysis showed that age and alkaline phosphatase were independent risk factors, while BMI and serum magnesium were protective factors. ROC analysis showed that area under the curves for age, alkaline phosphatase, BMI, and serum magnesium in diagnosing hip bone loss were 0.681,0.610, 0.655, and 0.648, respectively, with optimal cutoff values of 59.5 years, 84.5U/L, 23.7kg/m2, and 0.895mmol/L, respectively. Combined indicators improved predictive efficacy. Conclusion Age and alkaline phosphatase are risk factors of hip bone loss,while BMI and serum magnesium are protective factors. Combined multi-indicator assessment helps early identification of high-risk patients.

[Key words] Chronic kidney disease; Bone mineral density; Influencing factors; Hip joint

[中图分类号] R589.9

[文献标识码] A

[DOI] 10.3969/j.issn.1673-9701.2026.14.001

基金项目:福建省龙岩市科技计划项目(2022LYF17048)

通信作者:梁玉枫,电子信箱:liangyufeng@fjmu.edu.cn

(收稿日期:2026–02–06)

(修回日期:2026–04–11)

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