绝经后骨质疏松患者血清SIK2,SMURF1表达水平及其与骨代谢、骨密度指标的相关性研究

Expression of Serum SIK2 and SMURF1 in Postmenopausal Osteoporosis Patients and Their Correlation with Bone Metabolism and Bone Mineral Density

目的探讨绝经后骨质疏松(postmenopausal osteoporosis,PMOP)患者血清盐诱导激酶2(salt-inducible kinase 2,SIK2)、Smad泛素化调节因子1(Smad ubiquitination regulatory factor 1,SMURF1)表达水平与骨代谢、骨密度的相关性。方法选取朝阳市第二医院2019年4月~2021年4月收治的154例绝经后骨质疏松患者作为研究组,另选取该院同期体检的绝经后健康女性150例作为对照组。用定量逆转录聚合酶链式反应(reverse transcription-polymerase chain reaction,RT-PCR)法检测两组血清SIK2和SMURF1相对表达水平;Pearson相关分析明确血清SIK2,SMURF1与骨代谢指标、骨密度的相关性;Logistic回归分析绝经后骨质疏松的影响因素;受试者工作特征(ROC)曲线分析血清SIK2和SMURF1对绝经后骨质疏松的预测价值。结果与对照组相比,研究组腰椎L1~4骨密度(0.71±0.20 g/cm^(3)vs 0.86±0.21 g/cm^(3))、25羟基维生素D[(25-hydroxyvitamin D,25-OH-D)(12.07±2.76 ng/ml vs 14.31±2.62 ng/ml)]和股骨颈骨密度(0.61±0.18 g/cm^(3)vs 0.82±0.19 g/cm^(3))水平均显著降低,差异均有统计学意义(t=6.378,7.254,9.895,均P<0.001);血清骨桥蛋白(osteopontin,OPN)(18.67±3.17 ng/ml vs 16.78±2.69 ng/ml)、甲状旁腺素(parathyroid hormone,PTH)(71.26±8.88 pg/ml vs 64.31±8.24 pg/ml)、SIK2(0.94±0.16 vs 0.79±0.17)、Ⅰ型胶原羧基端肽β特殊序列(bate C-terminal cross-linked telopeptids of typeⅠcollagen,β-CTx)(5.12±0.96 pg/ml vs 4.28±0.84 pg/ml)、骨钙素(osteocalcin,OC)(15.64±2.73 ng/ml vs 13.28±2.14 ng/ml)、Ⅰ型胶原氨基端前肽(N-terminal propeptide of typeⅠprocollagen,PINP)(41.28±4.68 ng/ml vs 36.47±4.62 ng/ml)及SMURF1(0.93±0.22 vs 0.66±0.16)水平显著升高,差异均有统计学意义(t=5.598~11.759,均P<0.001)。血清SIK2,SMURF1与OPN,OC,SMURF1,β-CTx,PINP均呈正相关(rSIK2=0.169~0.292,rSMURF1=0.194~0.246,均P<0.05);血清SIK2,SMURF1与25-OH-D,股骨颈骨密度呈负相关(rSIK2=-0.212,-0.210;rSMURF1=-0.285,-0.252,均P<0.05)。股骨颈骨密度(OR=0.002,P<0.05),OPN(OR=1.592,P<0.05),OC(OR=1.603,P<0.05),PINP(OR=1.675,P<0.05),SIK2(OR=310.221,P<0.001)和SMURF1(OR=1359.044,P<0.001)是绝经后骨质疏松的影响因素。二者联合预测绝经后骨质疏松ROC曲线下面积(AUC)显著大于SIK2单独预测的AUC(Z=3.339,P<0.001),与SMURF1单独预测的AUC差异无统计学意义(P>0.05)。结论绝经后骨质疏松患者血清SIK2和SMURF1水平均明显升高,二者均与患者骨代谢指标、骨密度密切相关。

Objective To investigate the correlation between the expression levels of serum Salt-inducible kinase 2(SIK2)and Smad ubiquitination regulator 1(SMURF1),and bone metabolism and bone mineral density in patients with postmenopausal osteoporosis.Methods A total of 154 patients with postmenopausal osteoporosis admitted to the Second Hospital of Chaoyang from April 2019 to April 2021 were selected as the study group,and 150 healthy postmenopausal women who underwent physical examination in the same period were selected as the control group.The relative expression levels of serum SIK2 and SMURF1 were detected by quantitative reverse transcription-polymerase chain reaction(RT-PCR).Pearson correlation analysis was used to determine the correlation between serum SIK2 and SMURF1 and bone metabolism index and bone mineral density.Logistic regression analysis was used to analyze the influencing factors of postmenopausal osteoporosis,and ROC curve was used to analyze the predictive value of serum SIK2 and SMURF1 for postmenopausal osteoporosis.Results Compared with the control group,the bone mineral density of lumbar L1-4(0.71±0.20 g/cm^(3) vs 0.86±0.21 g/cm^(3)),25-hydroxyvitamin D(25-OH-D,12.07±2.76 ng/ml vs 14.31±2.62 ng/ml)and femoral neck bone mineral density(0.61±0.18 g/cm^(3) vs 0.82±0.19 g/cm^(3))in the study group were significantly decreased,the differences were statistically significant(t=6.378,7.254,9.895,all P<0.001).Serum osteopontin(OPN,18.67±3.17 ng/ml vs 16.78±2.69 ng/ml),parathyroid hormone(PTH,71.26±8.88 pg/ml vs 64.31±8.24 pg/ml),SIK2(0.94±0.16 vs 0.79±0.17),β-CTx(5.12±0.96 pg/ml vs 4.28±0.84 pg/ml),osteocalcin(OC,15.64±2.73 ng/ml vs 13.28±2.14 ng/ml),N-terminal propeptide of type I procollagen(PINP,41.28±4.68 ng/ml vs 36.47±4.62 ng/ml)and SMURF1(0.93±0.22 vs 0.66±0.16)were significantly increased,the differences were statistically significant(t=5.598~11.759,all P<0.001).Serum SIK2 and SMURF1 was positively correlated with OPN,OC,SMURF1,β-CTx and PINP(rSIK2=0.169~0.292,rSMURF1=0.194~0.246,all P<0.05).Serum SIK2 and SMURF1 was negatively correlated with 25-OH-D and femoral neck bone mineral density(rSIK2=-0.212,-0.210,rSMURF1=-0.285,-0.252,all P<0.05).Femoral neck bone mineral density(OR=0.002,P<0.05),OPN(OR=1.592,P<0.05),OC(OR=1.603,P<0.05),PINP(OR=1.675,P<0.05),SIK2(OR=310.221,P<0.001),SMURF1(OR=1359.044,P<0.001)were the influencing factors of postmenopausal osteoporosis.The area under the ROC curve(AUC)of the combined prediction of postmenopausal osteoporosis was significantly larger than that of SIK2 alone(Z=3.339,P<0.001),and there was no significant difference between the combined prediction and SMURF1 alone(P>0.05).Conclusion The serum SIK2 and SMURF1 levels in postmenopausal osteoporosis patients were significantly increased,both of which were closely related to bone metabolism index and bone mineral density.