血友病患者骨质减少的发病机制初探

A Preliminary Exploration on the Pathogenesis of Osteopenia in Patients with Hemophilia

目的:探讨血友病患者骨质减少的影响因素及其发病机制。方法:2015年3月至8月于华北理工大学附属医院血液科就诊的血友病患者23例,其中重型13例,轻中型10例。所有患者均接受了血清人Ⅰ型胶原交联N末端肽(NTXⅠ)、人骨保护素(OPG)、人骨碱性磷酸酶(BALP)、人碱性成纤维细胞生长因子(b FGF)、人类胰岛素样生长因子(IGF)和人转化生长因子β1(TGF-β1)水平检测,并根据美国疾控中心2002年发布的简易活动能力评分表,对21例进行了骨密度检测。依据世界卫生组织(WHO)定义,应用测量Z值水平评估骨密度(BMD)的临床意义。结果:本组研究中,Z值>-2组10例,Z值≤--2组11例;Z值≤-2组体重指数(BMI)及反映骨形成的血清人骨源性碱性磷酸酶(BALP)水平均低于Z值>-2组(P<0.05);BALP(r=0.489,P=0.024)、胰岛素样生长因子(IGF)(r=0.538,P=0.012)及BMI(r=0.572,P=0.007)与BMD均呈正相关且具有显著性(P<0.05);血清中促进骨形成的人碱性成纤维细胞生长因子(b FGF)(r=0.570,P=0.007)、人骨保护素(OPG)(r=0.505,P=0.02),与反应骨破坏的标志物人I型胶原N末端肽(NTXⅠ)水平呈正相关且具有显著性(P<0.05);重型患者(13例)活动能力评分明显低于轻中型患者(10例)(P<0.01),BMD在两组中并无统计学差异(P>0.05)。结论:BM D与血友病临床分型无关;低体重指数可能是骨质流失的危险因素;血友病患者骨质流失的机制可能与成骨细胞活性降低有关;IGF在血友病患者中起着阻止骨质流失的作用;b FGF和OPG可促进血友病患者骨代谢。

Objective: To investigate the influencing factors and pathogenesis of osteopenia in the patients w ith hemophilia. Methods: Tw enty- three patients w ith hemophilia w ere admitted in the hospital affiliated to North China University of Science and technology from M arch to August 2015,including 13 severe cases,10 mild and moderate cases. All the patients accepted the detection of serum I collagen cross-linking N terminal peptide( NTX I),osteoprotegerin( OPG),bone alkaline phosphatase( BALP),basic fibroblast grow th factor( b FGF),insulin-like grow th factor( IGF) and transforming grow th factor-β1( TGF-β1),the score scale of activity ability w as recorded according to the criteria published by the U. S. Center for disease prevention and control in 2002,and 21 patients received the measurement of bone mineral density. According to the World Health Organization( WHO) definition,the clinical significance of bone mineral density( BM D) w as assessed by measuring the Z level. Results: Z level >- 2 w as recorded in 10 cases,Z≤- 2 w as recorded in 11 cases; the levels of body mass index( BM I) and human bone alkaline phosphatase( BALP) reflecting bone formation in 11 cases( Z≤- 2) w ere low er than there in 10 cases( Z >- 2)( P <0. 05); the levels of BALP( r = 0. 489,P < 0. 05),IGF( r = 0. 538,P < 0. 05) and BM I( r = 0. 572,P < 0. 01) positively correlated significantly w ith BM D( P < 0. 05); the levels of b FGF( r = 0. 570,P < 0. 01) and OPG( r = 0. 505,P < 0. 05)positively correlated w ith NTXⅠ,indicating bone destruction( P < 0. 05); the score of activity ability of severe patients w as significantly low er than that of mild and moderate cases( P < 0. 05),BM D levels of these 2 groups w ere not statistically different( P > 0. 05). Conclusion: The BM D level does not correlate w ith the clinial grouping of hemophilia,the low body mass index may be a risk factor for bone lose; the mechanism of hemophilia patient' s bone lose may be related w ith the decrease of osteogenic activity,the IGF can prevent bone lose in hemophilia,the b FGF and OPG can promote bone metabolism of the patients w ith hemophilia.