Intact parathyroid hormone overestimates the presence and severity of parathyroid-mediated osseous abnormalities in uremia.
Intact parathyroid hormone overestimates the presence and severity of parathyroid-mediated osseous abnormalities in uremia.
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DOI：
10.1210/jcem.75.1.1619003
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发表时间：
1992-07
期刊：
影响因子：
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通讯作者：
L. Quarles;Bruce Lobaugh;G. Murphy
中科院分区：
文献类型：
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作者：
L. Quarles;Bruce Lobaugh;G. Murphy
为了研究尿毒症改变生物活性甲状旁腺激素血清浓度与其骨性终末器官反应之间关系的可能性，我们评估了39例不同严重程度甲状旁腺功能亢进性骨病终末期肾病患者循环完整甲状旁腺激素与骨转换之间的关系。我们从分析中排除矿化共存缺陷的患者，以确保骨重塑指标主要反映甲状旁腺激素的影响。血清甲状旁腺激素水平分布范围从正常到显著升高。两位点免疫放射测定的循环完整甲状旁腺激素浓度与髂骨活检定量骨组织分析测定的甲状旁腺功能异常骨性指标之间的回归分析显示，生物活性血清甲状旁腺激素水平与骨形成（r = 0.836）、编织类骨体积（r = 0.718）和骨髓纤维化（r = 0.856）呈线性相关，与骨吸收参数呈非线性相关（r = 0.760）。从这些功能关系中，我们发现平均血清完整甲状旁腺激素水平约为165 pg/mL，超过非尿毒症患者完整甲状旁腺激素上限（65 pg/mL） 2.5倍，定义了尿毒症患者骨转换的正常上限。事实上，在尿毒症患者出现严重甲状旁腺功能亢进的组织学证据之前，平均血清甲状旁腺激素浓度达到500 pg/mL。这些发现表明，在尿毒症患者中，PTH浓度的升高对于维持正常的骨重塑是必要的。因此，可能没有必要达到正常的血清完整甲状旁腺激素水平来控制尿毒症患者甲状旁腺激素过量的骨骼表现。
To examine the possibility that uremia alters the relationship between bioactive PTH serum concentrations and its osseous end-organ response, we evaluated the relationship between circulating intact PTH and bone turnover in 39 end-stage renal disease patients with hyperparathyroid-mediated bone disease of varying severity. We excluded from analysis patients with coexistent defects in mineralization to insure that bone remodeling indices primarily reflected the effects of PTH. The distribution of serum PTH levels ranged from normal to markedly elevated. Regression analysis between circulating intact PTH concentrations, measured by a two-site immunoradiometric assay, and osseous indices of hyperparathyroidism, determined by quantitative bone histological analysis of iliac crest bone biopsies, showed that bioactive serum PTH levels correlated linearly with bone formation (r = 0.836), woven osteoid volume (r = 0.718), and marrow fibrosis (r = 0.856), and nonlinearly with parameters of bone resorption (r = 0.760). From these functional relationships, we found that the average serum intact PTH level of approximately 165 pg/mL, a value that exceeds the upper limit of intact PTH in nonuremic subjects (65 pg/mL) by 2.5-fold, defines the upper normal limit of bone turnover in uremic subjects. Indeed, the average serum PTH concentrations reached 500 pg/mL before histological evidence of severe hyperparathyroidism developed in uremic subjects. These findings demonstrate that elevated PTH concentrations are necessary to maintain normal bone remodeling in the uremic setting. Consequently, it may not be necessary to attain normal serum intact PTH levels to control the osseous manifestations of PTH excess in uremic subjects.