骨质疏松合并压缩性胸腰椎骨折患者血清中IGF-1、IGFBP3含量与骨代谢活力的相关性研究
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摘要
目的探讨骨质疏松合并压缩性胸腰椎骨折患者血清中胰岛素样生长因子-1(IGF-1)、IGF结合蛋白3(IGFBP3)含量与骨代谢标志物的相关性。方法选择2014年6月一2017年6月在青海省人民医院骨科诊断为骨质疏松的患者106例,并根据有无胸腰椎压缩性骨折分为合并压缩性骨折组(A组)、未发生压缩性骨折组(B组),另纳入同期健康体检者60例作为健康对照组。采集血清并测定IGF-1、IGFBP3及骨代谢标志物(包括骨形成标志物和骨吸收标志物)的含量,并分析各指标间的相关性。结果 A组和B组患者血清中IGF-1、IGFBP3、骨保护素(OPG)、骨碱性磷酸酶(BALP)、骨钙素(BGP)、I型前胶原氨基端原肽(PINP)的含量均显著低于健康对照组(F=24.594、18.387、14.239、11.283、9.938、9.233,P<0.01),核因子KB受体活化因子配体(RANKL)、抗酒石酸酸性磷酸酶(TRACP-5b)、基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)、β-胶原降解产物(β-CTX)的含量均显著高于健康对照组(F=13.489、10.282、9.384、15.675、13.485<0.01);A组患者血清中IGF-1、IGFBP3、OPG、BALP、BGP、PINP的含量均显著低于B组患者(P均<0.05),RANKL、TRACP-5b、MMP-2、MMP-9、β-CTX的含量均显著高于B组患者(P均<0.05);骨质疏松合并压缩性骨折患者血清中IGF-1、IGFBP3的含量与OPG、BALP、BGP、PINP的含量呈正相关(IGF-1:r=0.674、0.624、0.681、0.597,P=0.011、0.002、0.015、0.021、0.008;IGFBP3:r=0.594、0.657、0.652,0.624,P=0.018、0.014、0.018、0.021),与RANKL、TRACP-5b、MMP-2、MMP-9、β-CTX的含量呈负相关(IGF-1:r=-0.629、-0.681、-0.649、-0.718、-0.628,P=0.008、0.014、0.002、0.009、0.019;IGFBP3:-0.658、-0.619、-0.725、-0.641、-0.595,P=0.013、0.004、0.019、0.027、0.018)。结论骨质疏松合并压缩性骨折患者血清中IGF-1、IGFBP3含量的降低能够影响骨代谢过程。
Objective To study the correlation of serum insulin like growth factor 1(IGF-1) and IGF binding protein3(IGFBP3) contents with bone metabolic markers in osteoporotic patients with compression fracture. Methods Patients diagnosed as osteoporosis in hospital during June 2014 to June 2017 were selected and divided into complicated with thoracolumbar compression fracture(group A) and without thoracolumbar compression fracture( group B). Serum were collected and IGF-1,IGFBP3, bone metabolism markers(including bone formation markers and bone resorption markers contents were determined.Results The serum IGF-1, IGFBP3, Osteoprotegerin(OPG), bone alkaline phosphatase(BALP), osteocalcin(BGP) and type I procollagen amino terminal propeptide(PINP) contents of A group and B group were significantly lower than the control group, nuclear factor kappa B receptor activator ligand(RANKL), tartaric acid phosphatase(TRACP-5 b), matrix metalloproteinase 2(MMP-2), matrix metalloproteinase 9(MMP-9), βcollagen degradation product(β-CTX) contents were significantly higher than the control group; serum IGF-1, IGFBP3, OPG, BALP, BGP and PINP contents of A group were significantly lower than the B group(t =24. 594,t= 18.387,t=14.239,t= 11.283, t=9.938, t =9.233, all P =0.000),RANKL, TRACP-5 b, MMP-2, MMP-9 and β-CTX contents were significantly higher than the B group(t= 13.489, t =10.282, t=9.384, t= 15.675, t= 13.485, all P=0.000); serum IGF-1, IGFBP3 contents of osteoporosis and compression fracture patients were positively correlated with OPG, BALP, BGP and PINP contents(IGF-1 : r = 0. 674, r = 0. 624, r =0.681, r =0.597, P = 0.011, P =0.002, P =0.015, P = 0.021, P =0.008; IGFBP3 :r = 0. 594, r =0.657, r = 0.652,r = 0.624,P = 0.018, P = 0.014, P =0.018,P= 0.021), negatively correlated with RANKL, TRACP-5 b, MMP-2, MMP-9 and βCTX contents(IGFl:r=-0.629, r =0.681, r =0.649, r =0.718, r =0.628, P =0.008, P =0.014, P =0.002,P=0.009, P=0.019; IGFBP3:r=-0.658, r=-0.619, r=-0.725, r=-0.641, r =-0.595, P = 0.013, P =0.004, P = 0.019, P = 0.027, P =0.018). Conclusion The decrease of the content of IGF-1 and IGFBP3 in the serum of osteoporotic patients with compression fracture can affect the process of bone metabolism.
Objective To study the correlation of serum insulin like growth factor 1(IGF-1) and IGF binding protein3(IGFBP3) contents with bone metabolic markers in osteoporotic patients with compression fracture. Methods Patients diagnosed as osteoporosis in hospital during June 2014 to June 2017 were selected and divided into complicated with thoracolumbar compression fracture(group A) and without thoracolumbar compression fracture( group B). Serum were collected and IGF-1,IGFBP3, bone metabolism markers(including bone formation markers and bone resorption markers contents were determined.Results The serum IGF-1, IGFBP3, Osteoprotegerin(OPG), bone alkaline phosphatase(BALP), osteocalcin(BGP) and type I procollagen amino terminal propeptide(PINP) contents of A group and B group were significantly lower than the control group, nuclear factor kappa B receptor activator ligand(RANKL), tartaric acid phosphatase(TRACP-5 b), matrix metalloproteinase 2(MMP-2), matrix metalloproteinase 9(MMP-9), βcollagen degradation product(β-CTX) contents were significantly higher than the control group; serum IGF-1, IGFBP3, OPG, BALP, BGP and PINP contents of A group were significantly lower than the B group(t =24. 594,t= 18.387,t=14.239,t= 11.283, t=9.938, t =9.233, all P =0.000),RANKL, TRACP-5 b, MMP-2, MMP-9 and β-CTX contents were significantly higher than the B group(t= 13.489, t =10.282, t=9.384, t= 15.675, t= 13.485, all P=0.000); serum IGF-1, IGFBP3 contents of osteoporosis and compression fracture patients were positively correlated with OPG, BALP, BGP and PINP contents(IGF-1 : r = 0. 674, r = 0. 624, r =0.681, r =0.597, P = 0.011, P =0.002, P =0.015, P = 0.021, P =0.008; IGFBP3 :r = 0. 594, r =0.657, r = 0.652,r = 0.624,P = 0.018, P = 0.014, P =0.018,P= 0.021), negatively correlated with RANKL, TRACP-5 b, MMP-2, MMP-9 and βCTX contents(IGFl:r=-0.629, r =0.681, r =0.649, r =0.718, r =0.628, P =0.008, P =0.014, P =0.002,P=0.009, P=0.019; IGFBP3:r=-0.658, r=-0.619, r=-0.725, r=-0.641, r =-0.595, P = 0.013, P =0.004, P = 0.019, P = 0.027, P =0.018). Conclusion The decrease of the content of IGF-1 and IGFBP3 in the serum of osteoporotic patients with compression fracture can affect the process of bone metabolism.
引文
[1]Sabo A,Hatgis J,Granville M,et al.Multilevel Contiguous Osteo-porotic Lumbar Compression Fractures:The Relationship of Scoliosis to the Development of Cascading Fractures[J].Cureus,2017,9(12):e1962.DOI:10.7759/cureus.1962.
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[3]张楠,周永焘,刘金煜,等.老年男性骨质疏松患者血清瘦素、胰岛素样生长因子-1和胰岛素样生长因子结合蛋白-3表达的临床意义[J].中国老年学杂志,2016,36(9):2142-2144.DOI:10.3969/j.issn.1005-9202.2016.09.042.
[4]中华医学会编著.临床诊疗指南·骨质疏松症和骨矿盐疾病分册[M].北京:人民卫生出版社,2006:1-7.
[5]Kim HJ,Park S,Park SH,et al.Prevalence of Frailty in Patients with Osteoporotic Vertebral Compression Fracture and Its Association with Numbers of Fractures[J].Yonsei Med J,2018,59(2):317-324.DOI:10.3349/ymj.2018.59.2.317.
[6]Miyake H,Kanazawa I,Sugimoto T.Decreased Serum Insulin-like Growth Factor-I is a Risk Factor for Non-vertebral Fractures in Diabetic Postmenopausal Women[J].Intern Med,2017,56(3):269-273.DOI:10.2169/internalmedicine.56.7416.
[7]Matar M,Al-Shaar L,Maalouf J,et al.The Relationship Between Calciotropic Hormones,IGF-1,and Bone Mass Across Pubertal Stages[J].J Clin Endocrinol Metab,2016,101(12):4860-4870.DOI:10.1210/jc.2016-3071.
[8]Teumer A,Qi Q,Nethander M,et al.Genomewide meta-analysis identifies loci associated with IGF-I and IGFBP-3 levels with impact on age-related traits[J].Aging Cell,2016,15(5):811-824.DOI:10.1111/acel.12490.
[9]黄斌,秦汉兴,吕波,等.骨质疏松性骨折与OPG/RANK/RANKL的相关性研究[J].实用临床医药杂志,2016,20(19):51-54.DOI:10.7619/jcmp.201619015.
[10]黄泳标,卓海燕,朱建国.血清BGP、BALP、TRACP-5b在老年骨质疏松性骨折病人中的水平及意义[J].实用老年医学,2017,31(3):237-238.
[11]Krege JH,Lane NE,Harris JM,Miller PD.PINP as a biological response marker during teriparatide treatment for osteoporosis[J].Osteoporos Int,2014,25(9):2159-2171.DOI:10.1007/s00198-014-2646-0.
[12]Piemontese M,Xiong J,Fujiwara Y,et al.Cortical bone loss caused by glucocorticoid excess requires RANKL production by osteocytes and is associated with reduced OPG expression in mice[J].Am J Physiol Endocrinol Metab,2016,311(3):587-593.DOI:10.1152/ajpendo.00219.2016.
[13]潘奇,陈黔,钱黎·绝经后骨质疏松症患者血清TRACP-56、Hey、BAP水平变化及诊断效能[J].山东医药,2017,57(35):58-60.DOI:10.3969/j.issn.1002-266X.2017.35.019.
[14]Sun B,Sun J,Han X,et al.Immunolocalization of MMP 2,9 and13 in prednisolone induced osteoporosis in mice[J].Histol Histopathol,2016,31(6):647-656.DOI:10.14670/HH-11-702.
[15]Baerts L,Glorie L,Maho W,et al.Potential impact of sitagliptin on collagen-derived dipeptides in diabetic osteoporosis[J].Pharmacol Res,2015,100(4):336-340.DOI:10.1016/j.phrs.2015.08.023.
[2]Kao FC,Hsu YC,Liu PH,et al.Osteoporotic sacral insufficiency fracture:An easily neglected disease in elderly palients[J].Medicine(Baltimore),2017,96(51):e9100.DOI:10.1097/MD.0000000000009100.
[3]张楠,周永焘,刘金煜,等.老年男性骨质疏松患者血清瘦素、胰岛素样生长因子-1和胰岛素样生长因子结合蛋白-3表达的临床意义[J].中国老年学杂志,2016,36(9):2142-2144.DOI:10.3969/j.issn.1005-9202.2016.09.042.
[4]中华医学会编著.临床诊疗指南·骨质疏松症和骨矿盐疾病分册[M].北京:人民卫生出版社,2006:1-7.
[5]Kim HJ,Park S,Park SH,et al.Prevalence of Frailty in Patients with Osteoporotic Vertebral Compression Fracture and Its Association with Numbers of Fractures[J].Yonsei Med J,2018,59(2):317-324.DOI:10.3349/ymj.2018.59.2.317.
[6]Miyake H,Kanazawa I,Sugimoto T.Decreased Serum Insulin-like Growth Factor-I is a Risk Factor for Non-vertebral Fractures in Diabetic Postmenopausal Women[J].Intern Med,2017,56(3):269-273.DOI:10.2169/internalmedicine.56.7416.
[7]Matar M,Al-Shaar L,Maalouf J,et al.The Relationship Between Calciotropic Hormones,IGF-1,and Bone Mass Across Pubertal Stages[J].J Clin Endocrinol Metab,2016,101(12):4860-4870.DOI:10.1210/jc.2016-3071.
[8]Teumer A,Qi Q,Nethander M,et al.Genomewide meta-analysis identifies loci associated with IGF-I and IGFBP-3 levels with impact on age-related traits[J].Aging Cell,2016,15(5):811-824.DOI:10.1111/acel.12490.
[9]黄斌,秦汉兴,吕波,等.骨质疏松性骨折与OPG/RANK/RANKL的相关性研究[J].实用临床医药杂志,2016,20(19):51-54.DOI:10.7619/jcmp.201619015.
[10]黄泳标,卓海燕,朱建国.血清BGP、BALP、TRACP-5b在老年骨质疏松性骨折病人中的水平及意义[J].实用老年医学,2017,31(3):237-238.
[11]Krege JH,Lane NE,Harris JM,Miller PD.PINP as a biological response marker during teriparatide treatment for osteoporosis[J].Osteoporos Int,2014,25(9):2159-2171.DOI:10.1007/s00198-014-2646-0.
[12]Piemontese M,Xiong J,Fujiwara Y,et al.Cortical bone loss caused by glucocorticoid excess requires RANKL production by osteocytes and is associated with reduced OPG expression in mice[J].Am J Physiol Endocrinol Metab,2016,311(3):587-593.DOI:10.1152/ajpendo.00219.2016.
[13]潘奇,陈黔,钱黎·绝经后骨质疏松症患者血清TRACP-56、Hey、BAP水平变化及诊断效能[J].山东医药,2017,57(35):58-60.DOI:10.3969/j.issn.1002-266X.2017.35.019.
[14]Sun B,Sun J,Han X,et al.Immunolocalization of MMP 2,9 and13 in prednisolone induced osteoporosis in mice[J].Histol Histopathol,2016,31(6):647-656.DOI:10.14670/HH-11-702.
[15]Baerts L,Glorie L,Maho W,et al.Potential impact of sitagliptin on collagen-derived dipeptides in diabetic osteoporosis[J].Pharmacol Res,2015,100(4):336-340.DOI:10.1016/j.phrs.2015.08.023.