FGF-23 serum levels and bone histomorphometric results in adult patients with chronic kidney disease on dialysis.
FGF-23 serum levels and bone histomorphometric results in adult patients with chronic kidney disease on dialysis.
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DOI：
10.5414/cn108407
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发表时间：
2014-11
影响因子：
1.1
通讯作者：
Malluche HH
中科院分区：
文献类型：
--
作者：
Lima F;El-Husseini A;Monier-Faugere MC;David V;Mawad H;Quarles D;Malluche HH
背景：成纤维细胞生长因子-23（FGF-23）是一种主要由骨细胞/成骨细胞产生的激素。在慢性肾脏病（CKD）患者中，FGF-23水平通常升高，可达到正常范围的300 - 400倍。FGF-23受局部骨相关和全身因素的调节，但CKD患者循环FGF-23浓度与骨重塑和矿化之间的关系尚未得到很好的表征。在目前的研究中，我们研究了肾性骨营养不良成人患者FGF-23水平和骨组织形态计量学参数之间的关系。材料和方法：36例慢性肾脏病（CKD-5D）患者接受四环素双标记后进行骨活检。在活检时进行抽血，以确定骨和矿物质代谢标志物的血清水平。结果：高骨转换患者血清FGF-23水平高于低骨转换患者。FGF-23水平与活化频率（ρ = 0.60，p < 0.01）和骨形成率（ρ = 0.57，p < 0.01）相关。在FGF-23水平高于2，000 pg/mL的患者中观察到90%的正常矿化。此外，FGF-23与矿化滞后时间（ρ =-0.69，p < 0.01）和类骨质成熟时间（ρ =-0.46，p < 0.05）呈负相关，但与类骨质厚度（ρ = 0.08，ns）不相关。回归分析表明，FGF-23是矿化滞后时间的唯一独立预测因子。FGF-23与松质骨体积相关（ρ = 0.38，p < 0.05），但不能预测其变化。结论：循环FGF-23浓度可能反映了骨形成沿着活性矿化的变化，但不完全是骨形成或矿化的变化。异常矿化滞后时间（> 100天）主要见于FGF-23水平低于2,000 pg/mL的患者，而FGF-23水平非常高与正常矿化滞后时间相关。
Background: Fibroblast growth factor-23 (FGF-23) is a hormone principally produced by osteocytes/osteoblasts. In patients with chronic kidney disease (CKD), FGF-23 levels are usually elevated and can reach up to 300 – 400 times the normal range. FGF-23 is regulated by local bone-related and systemic factors, but the relationship between circulating FGF-23 concentrations and bone remodeling and mineralization in CKD has not been well characterized. In the current study, we examined the relationship between FGF-23 levels and bone histomorphometry parameters in adult patients with renal osteodystrophy. Material and methods: 36 patients on dialysis (CKD-5D) underwent bone biopsies after tetracycline double labeling. Blood drawings were done at time of biopsy to determine serum levels of markers of bone and mineral metabolism. Results: Patients with high bone turnover had higher values of serum FGF-23 than patients with low bone turnover. FGF-23 levels correlated with activation frequency (ρ = 0.60, p < 0.01) and bone formation rate (ρ = 0.57, p < 0.01). Normal mineralization was observed in 90% of patients with FGF-23 levels above 2,000 pg/mL. Furthermore, FGF-23 correlated negatively with mineralization lag time (ρ = –0.69, p < 0.01) and osteoid maturation time (ρ = –0.46, p < 0.05) but not with osteoid thickness (ρ = 0.08, ns). Regression analysis showed that FGF-23 was the only independent predictor of mineralization lag time. FGF-23 correlated with cancellous bone volume (ρ = 0.38, p < 0.05) but did not predict it. Conclusion: Circulating FGF-23 concentrations may reflect alterations in ongoing bone formation along with active mineralization, but not exclusively in bone formation or mineralization. Abnormal mineralization lag time (> 100 days) was mainly seen in patients with FGF-23 levels less than 2,000 pg/mL, while very high levels of FGF-23 are associated with normal mineralization lag time.