绝经后骨质疏松症患者血清Hcy、ERα水平对骨折发生的预测价值

Predictive values of serum Hcy and ERα levels for fracture occurrence in patients with postmenopausal osteoporosis

摘要

目的 探究绝经后骨质疏松症(PMOP)患者血清中同型半胱氨酸(Hcy)、雌激素受体α(ERα)的水平,并分析其与骨代谢指标的相关性、剂量-反应关系及对骨折发生的预测价值。方法 选择2019年7月至2024年12月我院收治的308例PMOP患者,根据是否发生骨折分为骨折组(n=93)和非骨折组(n=215)。比较两组血清Hcy、ERα及骨代谢指标;采用线性回归分析Hcy、ERα与骨代谢指标的关联性;多因素Logistic回归分析PMOP患者发生骨折的独立影响因素;限制性立方样条(RCS)分析Hcy、ERα与骨折风险的剂量-反应关系;受试者工作特征(ROC)曲线评估各指标对骨折的预测效能。结果 骨折组患者Hcy及Ⅰ型胶原氨基端延长肽(PINP)、I型胶原羧基端肽β特殊序列(β-CTX)、骨钙素N端中分子(N-MID)和骨碱性磷酸酶(BALP)明显高于非骨折组患者(t分别为11.094、14.614、14.196、9.925、11.498,P均<0.05),而ERα、腰椎骨密度(BMD)、股骨颈BMD、全髋BMD和25-羟基维生素D[25-(OH)D]明显低于非骨折组患者(t分别为14.743、5.485、10.581、5.631、10.490,P均<0.05)。线性回归分析显示,Hcy与BMD、25-(OH)D呈负向关联(β<0,除腰椎BMD外),与骨转换指标PINP、β-CTX、N-MID及BALP呈正向关联(β>0),ERα则与之相反(P均<0.05)。校正混杂因素后,Hcy升高(OR=2.254,95%CI:1.755~2.899)与ERα降低(OR=0.013,95%CI:0.003~0.046)仍是PMOP患者骨折风险的独立影响因素(P均<0.05)。RCS分析显示,Hcy与骨折风险呈线性关联(P_线性<0.001,P_非线性=0.844),ERα与骨折风险呈非线性关联(P_非线性=0.004)。Hcy和ERα联合预测较单指标预测效能提升,联合预测AUC为0.924(95%CI:0.895~0.952)。结论 绝经后骨质疏松症骨折患者血清Hcy水平异常升高且ERα水平下调,二者均是骨折发生的独立风险因子。联合检测Hcy与ERα水平对绝经后骨质疏松症患者骨折风险具有较高的早期预警和预测价值。

Abstract

Objective To explore serum levels of homocysteine (Hcy) and estrogen receptor α (ERα) of patients with postmenopausal osteoporosis (PMOP),and to analyze correlation between Hcy,ERα and bone metabolism markers,dose-response relationship,and predictive values of them for occurrence of fracture. Methods A total of 308 PMOP patients who admitted to our hospital from July 2019 to December 2024 were enrolled.The PMOP patients were divided into fracture group (n=93) and non-fracture group (n=215) according to whether the patient had fracture.Serum levels of Hcy,ERα and bone metabolism markers of the patients were compared between the two groups.Linear regression was used to analyze associations of Hcy and ERα with bone metabolism markers.Multivariate Logistic regression was used to analyze independent risk factors for fracture in PMOP patients.Restricted cubic spline (RCS) was used to evaluate dose-response relationship between Hcy,ERα and fracture risk.Receiver operating characteristic (ROC) curve was used to evaluate predictive values of these indexes for fracture. Results The serum levels of Hcy,typeⅠcollagen amino terminal extender propeptide (PINP),type Ⅰ collagen carboxy terminal peptide β special sequence (β-CTX),osteocalcin N-terminus molecule (N-MID) and bone alkaline phosphatase (BALP) of the patients in the fracture group were significantly higher than those in the non-fracture group (t=11.094,14.614,14.196,9.925 and 11.498 respectively,all P<0.05),while the serum levels of ERα,lumbar bone mineral density (BMD),femoral neck BMD,total hip BMD and 25-Hydroxy vitamin D [25-(OH)D]of the patients in the fracture group were significantly lower than those in the non-fracture group (t=14.743,5.485,10.581,5.631 and 10.490 respectively,all P<0.05).Linear regression analysis showed that Hcy was negatively correlated with BMD and 25-(OH)D (all β<0,except for lumbar BMD),but positively correlated with bone turnover markers (all β>0),whereas ERα presented the opposite correlations with BMD,25-(OH)D and bone turnover markers (all P<0.05).After adjusting for confounding factors,elevated serum level of Hcy (OR=2.254,95%CI:1.755-2.899) and decreased serum level of ERα (OR=0.013,95%CI:0.003-0.046) remained independent influencing factors for fracture risk in PMOP patients (both P<0.05).RCS analysis revealed a linear association between Hcy and fracture risk (P_linearity<0.001,P_{non-linearity}=0.844) and a non-linear association between ERα and fracture risk (P_{non-linearity}=0.004).Combination of Hcy and ERα showed higher predictive value as compared with single indexes,with area under the curve (AUC) of 0.924 (95%CI:0.895-0.952). Conclusion Serum Hcy level significantly elevates and ERα level down-regulates in PMOP patients with fracture,both of which were independent risk factors for fracture.Combined detection of serum Hcy and ERα levels has high early warning and predictive value for fracture risk in PMOP patients.

关键词

绝经后骨质疏松症 / 同型半胱氨酸 / 雌激素受体α / 骨代谢指标 / 剂量-反应关系 / 预测价值

Key words

postmenopausal osteoporosis / homocysteine / estrogen receptor alpha / bone metabolic marker / dose-response relationship / predictive value

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基金资助

2021年四川省医学(青年创新)科研课题(S21051)