重组人生长激素治疗无追赶性生长的小于胎龄儿骨代谢指标的变化
|
摘要
目的探讨青春前期无追赶性生长的小于胎龄儿(SGA)应用重组人生长激素(rhGH)治疗前后骨代谢相关指标的变化及在随访中的临床意义。方法选取SGA患儿44例为SGA组,健康儿童52例对照组。SGA组患儿予以rhGH 0.15IU/(kg·d),每日皮下注射,分别于治疗前、治疗3个月、治疗6个月测定胰岛素样生长因子(IGF-1)、胰岛素样生长因子结合蛋白-3(IGFBP3)、骨形成指标Ⅰ型前胶原氨基端前肽(PINP)及骨吸收指标Ⅰ型胶原交联羧基末端肽(β-CTX),同时记录身高、体重、体重指数(BMI)、生长速度、骨龄、身高标准差积分(HtSDS)。结果治疗前SGA组PINP水平低于健康对照组[(478. 82±133. 91)μg/L比(650. 72±211. 84)μg/L],β-CTX水平高于对照组[(0. 82±0. 31)比(0. 54±0. 17)μg/L],两者差异均有显著性(t=2. 266、-2. 711,P<0. 05)。SGA组rhGH治疗前后PINP及β-CTX在性别间差异无显著性(P>0.05);SGA组应用rhGH治疗3个月后PINP水平[(735.51±155.95)μg/L]及β-CTX水平[(1. 10±0. 28)μg/L]均较治疗前升高(t=4.763、2.479,P<0.05),其中PINP升高更显著,HtSDS与治疗前比较[(-2.68±0.54)比(-2.96±0.47)],差异有显著性(t=2.716,P<0.05);治疗6个月与3个月比较,PINP水平[(860.95±255.19)μg/L]、β-CTX水平[(0. 96±0. 34)μg/L]及HtSDS [(-2. 50±0. 52)]无明显变化(t=1.363、-0.833、1.611,P>0.05)。成骨指标PINP与IGF-1、IGFBP3呈正相关性(r=0.638、0.675,P<0.05),与破骨指标β-CTX无相关性(r=0. 338,P>0.05),PINP、β-CTX与HtSDS呈正相关(r=0. 656、0. 783,P<0.05)。结论骨代谢指标PINP、β-CTX可作为rhGH治疗SGA早期疗效的指标之一。
引文
[1][1] Lee PA, Chernausek SD, Hokken-Koelega AC, et al. International Small for Gestational Age Advisory Board consensus development conference statement:management of short children born small for gestational age, April 24-October 1,2001[J]. Pediatrics,2003,111(6 Pt 1):1253-1261.
[2] Chen Y, Wu L, Zou L, et al. Lpdate on the birth weight standard and its diagnostic value in small for gestational age(SGA)infants in China[J]. J Matern Fetal Neonatal Med,2016,30(7):801-807.
[3]郑靖阳,林锋,瞿尔力,等.生长激素治疗小于胎龄矮小患儿的疗效与血清胰岛素样生长因子1、胰岛素样生长因子结合蛋白3水平的相关性研究[J].中华内分泌代谢杂志,2015, 31(11):974-976.
[4]尉建霞,周莉.1747例低体重孕妇妊娠结局及孕期体重增长情况分析[J].中国医刊,2018,53(2):213-216.
[5] Dai Z, Wang R,Ang LW, et al. Bone turnover biomarkers and risk of osteoporotic hip fracture in an Asian population[J]. Bone, 2016(83):171-177.
[6] Garnero P. New developments in biological markers of bone metabolism in osteoporosis.[J]. Bone, 2014, 66(9):46-55.
[7]李辉,季成叶,宗心南,等.中国0~18岁儿童、青少年身高、体重的标准化生长曲线[J].中华儿科杂志,2009, 47(7):487-492.
[8] Pecoraro V,Roli L, Germagnoli L, et al. The prognostic role of bone turnover markers in multiple myeloma patients:The impact of their assay. A systematic review and meta-analysis.[J]. Crit Rev Oncol Hematol,2015,96(1):54-66.
[9] Navlor KE, Jacques RM, Paggiosi M, et al. Response of bone turnover markers to three oral bisphosphonate therapies in postmenopausal osteoporosis:the TRIO study[J]. Osteoporos Int, 2016,27(1):21-31.
[10] Bayer M. Reference values of osteocalcin and procollagen typeⅠNpropeptide plasma levels in a healthy Central European population aged 0-18 years[J]. Osteoporos Int,2014,25(2):729-736.
[11] Andersson B, Swolin-Eide D, Magnusson P, et al. Short-term changes in bone formation markers following growth hormone(GH)treatment in short prepubertal children with a broad range of GH secretion[J]. Clin Endocrinol(Oxf),2015,82(1):91.
[12]刘安宁,张高生,黄晶,等.150例矮身材儿童临床相关因素分析[J].中国临床医生杂志,2017,45(1):90-92.
[13] Jung H, Land C, Blum WF, et al. Early differentiation between good and poor response to growth hormone therapy in short children born small for gestational age(SGA)to improve the outcome of poor responders[J]. J Pediatr Endocrinol Metab,2014,27(3-4):229-235.
[14] Yakar S,Isaksson 0. Regulation of skeletal growth and mineral acquisition by the GH/IGF-1 axis:Lessons from mouse models[J].Growth Horm IGF Res,2016(28):26-42.
[15] L eland T, Cristina ON, Jorgensen AP, et al. Increased serum and bone matrix levels of the secreted Wnt antagonist DKK-1 in patients with GH deficiency in response to GH treatment[J]. J Clin Endocrinol Metab,2015,100(2):736-743.
[16] Fujita K,Nagasaka M,Iwatani S,et al. Prevalence of small for gestational age(SGA)and short stature in children born SGA who qualify for growth hormone treatment at 3years of age:Populationbased study[J]. Pediatr Int,2016,58(5):372-376.
[17]王斐,朱志颖,刘庆旭,等.生长激素治疗特发性矮小症前后骨转换指标变化的意义[J].中华实用儿科临床杂志,2016,31(20):1541-1545.
[2] Chen Y, Wu L, Zou L, et al. Lpdate on the birth weight standard and its diagnostic value in small for gestational age(SGA)infants in China[J]. J Matern Fetal Neonatal Med,2016,30(7):801-807.
[3]郑靖阳,林锋,瞿尔力,等.生长激素治疗小于胎龄矮小患儿的疗效与血清胰岛素样生长因子1、胰岛素样生长因子结合蛋白3水平的相关性研究[J].中华内分泌代谢杂志,2015, 31(11):974-976.
[4]尉建霞,周莉.1747例低体重孕妇妊娠结局及孕期体重增长情况分析[J].中国医刊,2018,53(2):213-216.
[5] Dai Z, Wang R,Ang LW, et al. Bone turnover biomarkers and risk of osteoporotic hip fracture in an Asian population[J]. Bone, 2016(83):171-177.
[6] Garnero P. New developments in biological markers of bone metabolism in osteoporosis.[J]. Bone, 2014, 66(9):46-55.
[7]李辉,季成叶,宗心南,等.中国0~18岁儿童、青少年身高、体重的标准化生长曲线[J].中华儿科杂志,2009, 47(7):487-492.
[8] Pecoraro V,Roli L, Germagnoli L, et al. The prognostic role of bone turnover markers in multiple myeloma patients:The impact of their assay. A systematic review and meta-analysis.[J]. Crit Rev Oncol Hematol,2015,96(1):54-66.
[9] Navlor KE, Jacques RM, Paggiosi M, et al. Response of bone turnover markers to three oral bisphosphonate therapies in postmenopausal osteoporosis:the TRIO study[J]. Osteoporos Int, 2016,27(1):21-31.
[10] Bayer M. Reference values of osteocalcin and procollagen typeⅠNpropeptide plasma levels in a healthy Central European population aged 0-18 years[J]. Osteoporos Int,2014,25(2):729-736.
[11] Andersson B, Swolin-Eide D, Magnusson P, et al. Short-term changes in bone formation markers following growth hormone(GH)treatment in short prepubertal children with a broad range of GH secretion[J]. Clin Endocrinol(Oxf),2015,82(1):91.
[12]刘安宁,张高生,黄晶,等.150例矮身材儿童临床相关因素分析[J].中国临床医生杂志,2017,45(1):90-92.
[13] Jung H, Land C, Blum WF, et al. Early differentiation between good and poor response to growth hormone therapy in short children born small for gestational age(SGA)to improve the outcome of poor responders[J]. J Pediatr Endocrinol Metab,2014,27(3-4):229-235.
[14] Yakar S,Isaksson 0. Regulation of skeletal growth and mineral acquisition by the GH/IGF-1 axis:Lessons from mouse models[J].Growth Horm IGF Res,2016(28):26-42.
[15] L eland T, Cristina ON, Jorgensen AP, et al. Increased serum and bone matrix levels of the secreted Wnt antagonist DKK-1 in patients with GH deficiency in response to GH treatment[J]. J Clin Endocrinol Metab,2015,100(2):736-743.
[16] Fujita K,Nagasaka M,Iwatani S,et al. Prevalence of small for gestational age(SGA)and short stature in children born SGA who qualify for growth hormone treatment at 3years of age:Populationbased study[J]. Pediatr Int,2016,58(5):372-376.
[17]王斐,朱志颖,刘庆旭,等.生长激素治疗特发性矮小症前后骨转换指标变化的意义[J].中华实用儿科临床杂志,2016,31(20):1541-1545.