■25-羟基维生素D(25(OH)D)和潜在的1,25-二羟基维生素D(1,25(OH)2D)抑制甲状旁腺激素(PTH)在甲状旁腺的主要细胞中的合成。显示(25(OH)D和PTH之间呈负相关的临床研究与基础科学研究中的这些发现非常吻合。然而,在这些研究中,用目前临床上使用的第二代或第三代完整PTH(iPTH)测定系统测量PTH。iPTH测定不能区分PTH的氧化形式和非氧化PTH。PTH的氧化形式是在肾功能受损的患者的循环中迄今为止最丰富的PTH形式。PTH的氧化导致PTH功能的丧失。鉴于迄今为止完成的临床研究是使用主要检测PTH氧化形式的PTH测定系统进行的,生物活性非氧化PTH与25(OH)D以及1,25(OH)2D之间的真实关系仍然未知。
■要解决此主题,我们首次比较了25(OH)D和1,25(OH)2D与iPTH的关系,在Charité中央临床实验室的531例稳定的肾移植受者中,oxPTH以及具有完全生物活性的n-oxPTH。直接(iPTH)或在使用抗人oxPTH单克隆抗体的柱去除oxPTH(n-oxPTH)后评估样品。将单克隆大鼠/小鼠甲状旁腺激素抗体(MAB)固定在具有500升血浆样品的柱上。采用Spearman相关分析和多元线性回归分析评价各变量之间的相关性。
■25(OH)D与所有形式的PTH呈负相关,包括oxPTH(iPTH:r=-0.197,p<0.0001;oxPTH:r=-0.203,p<0.0001;n-oxPTH:r=-0.146,p=0.001)。在1,25(OH)2D和所有形式的PTH之间没有观察到显著的相关性。考虑年龄的多元线性回归分析,PTH(iPTH,oxPTH和n-oxPTH),血清钙,血清荧光粉,血清肌酐,成纤维细胞生长因子23(FGF23),骨保护素(OPG),白蛋白,和硬化蛋白作为混杂因素证实了这些发现。亚组分析表明,我们的结果不受性别和年龄的影响。
■在我们的研究中,所有形式的PTH与25-羟基维生素D(25(OH)D)呈负相关。这一发现与甲状旁腺主要细胞中所有形式的PTH(生物活性的n-oxPTH和具有较小或没有生物活性的氧化形式的PTH)的合成受到抑制是一致的。
25-hydroxyvitamin D (25(OH)D) and potentially also 1,25-dihydroxyvitamin D (1,25(OH)2D) inhibits the synthesis of parathyroid hormone (PTH) in the chief cells of the parathyroid gland. Clinical studies showing a negative correlation between (25(OH)D and PTH are in good agreement with these findings in basic science studies. However, PTH was measured in these studies with the currently clinically used 2nd or 3rd generation intact PTH (iPTH) assay systems. iPTH assays cannot distinguish between oxidized forms of PTH and non-oxidized PTH. Oxidized forms of PTH are the by far most abundant form of PTH in the circulation of patients with impaired kidney function. Oxidation of PTH causes a loss of function of PTH. Given that the clinical studies done so far were performed with an PTH assay systems that mainly detect oxidized forms of PTH, the real relationship between bioactive non-oxidized PTH and 25(OH)D as well as 1,25(OH)2D is still unknown.
To address this topic, we compared for the first time the relationship between 25(OH)D as well as 1,25(OH)2D and iPTH, oxPTH as well as fully bioactive n-oxPTH in 531 stable kidney transplant recipients in the central clinical laboratories of the Charité. Samples were assessed either directly (iPTH) or after oxPTH (n-oxPTH) was removed using a column that used anti-human oxPTH monoclonal antibodies, a monoclonal rat/mouse parathyroid hormone antibody (MAB) was immobilized onto a column with 500 liters of plasma samples. Spearman correlation analysis and Multivariate linear regression were used to evaluate the correlations between the variables.
There was an inverse correlation between 25(OH)D and all forms of PTH, including oxPTH (iPTH: r=-0.197, p<0.0001; oxPTH: r=-0.203, p<0.0001; n-oxPTH: r=-0.146, p=0.001). No significant correlation was observed between 1,25(OH)2D and all forms of PTH. Multiple linear regression analysis considering age, PTH (iPTH, oxPTH and n-oxPTH), serum calcium, serum phosphor, serum creatinine, fibroblast growth factor 23 (FGF23), osteoprotegerin (OPG), albumin, and sclerostin as confounding factors confirmed these findings. Subgroup analysis showed that our results are not affected by sex and age.
In our study, all forms of PTH are inversely correlated with 25-hydroxyvitamin D (25(OH)D). This finding would be in line with an inhibition of the synthesis of all forms of PTH (bioactive n-oxPTH and oxidized forms of PTH with minor or no bioactivity) in the chief cells of the parathyroid glad.