维生素D和骨形态发生蛋白-2水平与生长激素缺乏症儿童成骨细胞功能的相关性研究

Research on the correlation among vitamin D,bone morphogenetic protein-2 and osteoblast function in growth hormone deficiency children

目的研究维生素D及骨形态发生蛋白-2(BMP-2)与生长激素缺乏症(GHD)患儿成骨细胞功能的相关性,以期为矮小症的辅助治疗提供理论依据。方法收集2012年3月—2013年12月确诊为GHD患儿83例作为病例组,同期随机选取健康儿童40例作为对照组,按年龄及Turner分期分为青春期前组和青春期组。测定其身高、身高标准差得分(HtSDS)、骨龄等一般指标。用酶联法分别检测并比较病例组及对照组儿童血清25(OH)D3、BMP-2、骨钙素(OC)、Ⅰ型前胶原氨基端前肽(PINP)水平。用Pearson相关性分析法分析25(OH)D3、BMP-2与OC、PINP、HtSDS、生长激素(GH)峰值、骨龄与年龄差值的相关性。结果青春期前GHD组和青春期GHD组患儿血清25(OH)D3、BMP-2、OC、PINP均显著低于对照组水平(t=4.282、7.162、3.940、4.832,P<0.05);经Pearson相关性分析,病例组25(OH)D3与OC(r=0.481)、PINP(r=0.473)、BMP-2(r=0.324)及GH峰值(r=0.545)存在显著正相关性(P<0.05);BMP-2与OC(r=0.322)、PINP(r=0.415)及GH峰值(r=0.619)存在显著正相关性(P<0.05);25(OH)D3、BMP-2与HtSDS及骨龄和年龄的差值之间无相关性(P>0.05)。结论 GHD患儿骨形成处于低水平状态。GHD患儿骨形成标志物OC、PINP水平降低与其体内低维生素D、BMP-2水平密切相关。GH的分泌状态影响维生素D、BMP-2的水平。

Objective To clarify the correlation among vitamin D,bone morphogenetic protein-2(BMP-2) and osteoblast function in children with growth hormone deficiency(GHD),in order to provide theoretical reference for the complementary treatment of short stature in children. Methods A total of 83 GHD children and 40 normal children admitted in the Pediatrics Department of the Second Affiliated Hospital of Xi′an Jiaotong University from March 2012 to March 2013 were enrolled in this study. According to the Tanner staging and age, GHD children were divided into 2 sub-groups, prepuberty group and puberty group. Their body height, body height standard deviation(HtSDS),bone age were measured. Serum levels of 25(OH)D3,BMP-2,osteocalcin(OC) and procollagen Ⅰ N-terminal propeptide(PINP) were tested by enzyme linked immunosorbent assay(ELISA) in GHD children, and the results were compared with healthy control. The relationship among 25(OH)D3,BMP-2,OC,PINP,GH,HtSDS,the difference between bone age and age were analyzed by Pearson correlation analysis. Results The prepubertal GHD and the pubertal GHD children had significant lower levels of 25(OH)D3,BMP-2,OC and PINP than the controls(t=4.282,7.162,3.940,4.832,P<0.05). It was significant in the correlation between 25(OH)D3 and bone formation markers(OC,PINP,BMP-2 and GH) in GHD children(r=0.481,0.473,0.324,0.545, P<0.05),as well as the correlation between BMP-2 and bone formation markers(OC,PINP and GH) in GHD children(r=0.322,0.415,0.619, P<0.05).But the correlation among 25(OH)D3,BMP-2 and HtSDS and the difference between bone age and age were not significant in GHD children(P>0.05). Conclusions Bone formation in GHD children is lower than healthy controls. The low levels of osteogenic markers in GHD children, like OC and PINP,are related to its low vitamin D and BMP-2 levels. The low level of GH has an impact on the levels of vitamin D and BMP-2.