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[慢性肾功能不全患儿的血清骨钙素]

[Serum osteocalcin in children with chronic renal insufficiency].

作者信息

Peco-Antić A, Nastić-Mirić D, Milikić V, Babić D, Pejcić I, Kostić M, Paripović V, Jovanović O, Kruscić D, Mancić J

机构信息

University Children's Hospital, Belgrade.

出版信息

Srp Arh Celok Lek. 1996 Sep-Oct;124(9-10):227-31.

PMID:9102853
Abstract

UNLABELLED

The research of the bone metabolism has undergone a long evolution which began with the use of radioisotopes in calcium kinetic studies and went through the determination of several humoral parameters like alkaline phosphatase (ALP), hydroxyproline and intact immunoreactive parathyroid hormone (iPTH) and finally to the assay of a new serum and urinary parameters of bone metabolism, like osteocalcine (OC) and procollagen and collagen metabolites. The X-ray study of the skeleton, densitometric techniques, computerized tomography, scintigraphy and NMR are used for visualization of bone changes, but bone biopsy and histomorphometry provide the most precise evaluation [1]. Disorders of bone and mineral metabolism in children with chronic renal failure (CRF) are an almost regular occurrence; so early discovery and treatment of these changes are very important [2]. The aim of this study was to measure the serum OC level in children with CRF and terminal renal failure (TRF), treated with chronic haemodialysis, and to evaluate the significance of OC compared to other humoral parameters of renal osteodistrophy, such as ALP and iPTH.

MATERIALS AND METHODS

We studied the fasting levels of OC in three different groups of children: group A consisted of 18 patients with TRF; group B consisted of 12 patients at different stages of CRF, and group C consisted of 32 healthy children, all of the approximately same age. Clinical characteristics of the examinded children are presented in Table 1. Of 30 patients, 26 were treated with calcium carbonate and 21 with vitamin D analogues. None were treated with aluminium hydroxide. Additional parameters included serum calcium, phosphate, ALP and body height, while serum concentrations of iPTH and ionized serum calcium were measured only in group A. Serum OC was measured by radioimmunoassay using OSTK PR RIA (CIS), while ELISA-PTH (CIS) radioimmunoassay was used to determine iPTH plasma levels. Statistical analyses were performed using Kolmogorov-Smirnov test to confirm normal distribution, the Pearson and Spearman rank sum test for correlation between variables of interest, while analysis of variance was used to compare the findings.

RESULTS

Serum OC levels were significantly different in all groups (p < 0.01); they were three times higher in group A than in group C. Similar increase was noticed in plasma iPTH, assuming that "normal" uremic iPTH was raised up to threefold above normal range (between 10 and 60 pg/ml) [2]. However, the total serum ALP activity was not sensitive as OC and iPTH, since ALP increases were less as compared to them. OC was age related only in group A (p < 0.01), with a positive correlation between OC and duration of haemodialysis (p < 0.05), as well as between OC and serum phosphate (p < 0.05), but there was no correlation between OC and growth retardation (expressed by SDS), bone age and current therapy for renal osteodistrophy. A direct correlation between OC and ALP was found only in healthy children (p < 0.01), while in groups A and B it was remarkable, although not statistically significant (p = 0.08) (Graphs 1, 2, 3). In group A, ALP and iPTH were directly correlated (p < 0.001), but the correlation of OC with iPTH was less significant (p = 0.06). In patients with CRF no correlation was found between glomerular filtration rate and OC.

DISCUSSION

OC is a bone-derived noncollagenous protein of low molecular weight (about 5800 D), containing residues of the vitamin K dependent amino acid gamma-carboxyglutamic acid and is synthesized by osteoblasts and odontoblasts. Calcitriol is a potent stimulator of OC synthesis, acting at the transcriptional level and increasing mRNA severalfold. OC is found mainly in bone, but nanomolar concentrations circulate in the blood. Its serum levels are an expression of the bone formation process and are age related (higher in the neonatal and adolescent period). ABSTRACT TRUNCATED.

摘要

未标注

骨代谢研究经历了漫长的发展历程,始于钙动力学研究中放射性同位素的应用,历经多种体液参数的测定,如碱性磷酸酶(ALP)、羟脯氨酸和完整免疫反应性甲状旁腺激素(iPTH),最终发展到骨代谢血清和尿液新参数的检测,如骨钙素(OC)、前胶原和胶原代谢产物。骨骼的X线检查、骨密度测量技术、计算机断层扫描、闪烁扫描和核磁共振用于观察骨变化,但骨活检和组织形态计量学提供了最精确的评估[1]。慢性肾衰竭(CRF)儿童的骨和矿物质代谢紊乱几乎是常有的情况;因此,早期发现和治疗这些变化非常重要[2]。本研究的目的是测量接受慢性血液透析治疗的CRF和终末期肾衰竭(TRF)儿童的血清OC水平,并评估OC与肾性骨营养不良的其他体液参数(如ALP和iPTH)相比的意义。

材料与方法

我们研究了三组不同儿童的空腹OC水平:A组由18例TRF患者组成;B组由12例处于CRF不同阶段的患者组成,C组由32例年龄大致相同的健康儿童组成。被检查儿童的临床特征见表1。30例患者中,26例接受碳酸钙治疗,21例接受维生素D类似物治疗。均未接受氢氧化铝治疗。其他参数包括血清钙、磷、ALP和身高,而仅在A组测量了iPTH和离子化血清钙的血清浓度。血清OC采用OSTK PR RIA(CIS)放射免疫法测量,而采用ELISA - PTH(CIS)放射免疫法测定iPTH血浆水平。使用Kolmogorov - Smirnov检验确认正态分布,使用Pearson和Spearman秩和检验分析感兴趣变量之间的相关性,同时使用方差分析比较研究结果。

结果

所有组的血清OC水平均有显著差异(p < 0.01);A组比C组高3倍。血浆iPTH也有类似升高,假设“正常”尿毒症iPTH升高至正常范围(10至60 pg/ml)以上3倍[2]。然而,血清总ALP活性不如OC和iPTH敏感,因为与它们相比,ALP升高幅度较小。OC仅在A组与年龄相关(p < 0.01),OC与血液透析持续时间呈正相关(p < 0.05),与血清磷也呈正相关(p < 0.05),但OC与生长迟缓(用SDS表示)、骨龄和当前肾性骨营养不良治疗之间无相关性。仅在健康儿童中发现OC与ALP呈直接相关(p < 0.01),而在A组和B组中虽显著但无统计学意义(p = 0.08)(图1、2、3)。在A组中,ALP与iPTH直接相关(p < 0.001),但OC与iPTH的相关性较弱(p = 0.06)。在CRF患者中,未发现肾小球滤过率与OC之间的相关性。

讨论

OC是一种低分子量(约5800 D)的骨源性非胶原蛋白,含有维生素K依赖的氨基酸γ - 羧基谷氨酸残基,由成骨细胞和成牙本质细胞合成。骨化三醇是OC合成的有效刺激剂,作用于转录水平,使mRNA增加数倍。OC主要存在于骨骼中,但血液中也有纳摩尔浓度的循环。其血清水平是骨形成过程的一种表达,与年龄相关(新生儿期和青春期较高)。摘要截断。

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