The pathogenesis of osteodystrophy after renal transplantation as detected by early alterations in bone remodeling
The pathogenesis of osteodystrophy after renal transplantation as detected by early alterations in bone remodeling
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DOI：
10.1046/j.1523-1755.2003.00938.x
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发表时间：
2003-05-01
影响因子：
19.6
通讯作者：
Bellorin-Font, E
中科院分区：
文献类型：
--
作者：
Rojas, E;Carlini, RG;Bellorin-Font, E
背景。移植后骨量损失在移植后早期就开始出现，并且可能持续数年，即使对于肾功能正常的患者也是如此。虽然这些异常的发病机制仍不清楚，但一些研究表明，先前存在的骨病、糖皮质激素治疗和磷酸盐代谢的改变可能发挥重要作用。最近的研究表明，成骨细胞凋亡和成骨细胞生成受损在糖皮质激素诱导的骨质疏松症的发病机制中发挥着重要作用。 目的。检查肾移植后期间成骨细胞数量和表面的早期变化。方法。 20 名平均年龄为 36.5 +/- 12 岁的患者在肾移植后 22 至 160 天进行了骨活检。在移植当天对 12 名患者进行了对照活检。使用免疫过氧化物酶和直接免疫荧光技术，通过末端脱氧核苷酸转移酶介导的尿苷三磷酸缺口末端标记（TUNEL）的方法，通过组织形态计量分析和细胞DNA片段化来评估骨切片。结果。移植后活检的主要变化是类骨和成骨细胞表面减少、骨形成率调整和矿化滞后时间延长。小梁周纤维化明显减少。移植前活检均未显示成骨细胞凋亡。相比之下，在 9 例移植后活检中观察到类骨质接缝附近或髓腔内有 TUNEL 阳性细胞，其中 4 例患有混合性骨病，2 例患有动态性骨病，1 例患有骨软化症，1 例患有纤维性骨炎，1 例患有轻度甲状旁腺功能亢进性骨病。与没有凋亡的移植后活检相比，有凋亡的移植后活检中的成骨细胞数量较低。此外，它们中的大多数表现出从活跃成骨细胞的立方体形态明显转向静止状态。显示成骨细胞凋亡的患者血清磷水平较低，与成骨细胞数量呈正相关，与凋亡成骨细胞数量呈负相关。此外，移植后成骨细胞表面与甲状旁腺激素（PTH）水平呈正相关，与糖皮质激素累积剂量呈负相关。结论。数据表明，成骨细胞生成受损和早期成骨细胞凋亡可能在移植后骨质疏松症的发病机制中发挥重要作用。这些改变的发病机制涉及的可能机制包括移植后低磷血症、糖皮质激素的使用和先前存在的骨疾病。 PTH 似乎通过保持成骨细胞存活而具有保护作用。
Background. Loss of bone mass after transplantation begins in the early periods after transplantations and may persist for several years, even in patients with normal renal function. While the pathogenesis of these abnormalities is still unclear, several studies suggest that preexisting bone disease, glucocorticoid therapy, and alterations in phosphate metabolism may play important roles. Recent studies indicate that osteoblast apoptosis and impaired osteoblastogenesis play important roles in the pathogenesis of glucocorticoid-induced osteoporosis.Objectives. To examine the early alterations in osteoblast number and surfaces during the period following renal transplantation.Methods. Twenty patients with a mean age of 36.5 +/- 12 years were subjected to bone biopsy 22 to 160 days after renal transplantation. In 12 patients, a control biopsy was performed on the day of transplantation. Bone sections were evaluated by histomorphometric analysis and cell DNA fragmentation by the methods of terminal deoxynucleotidyl transferase-mediated uridine triphosphate nick end labeling (TUNEL), using immunoperoxidase and direct immunofluorescence techniques.Results. The main alterations in posttransplant biopsies were a decrease in osteoid and osteoblast surfaces, adjusted bone formation rate, and prolonged mineralization lag time. Peritrabecular fibrosis was markedly decreased. None of the pretransplant biopsies revealed osteoblast apoptosis. In contrast, TUNEL-positive cells in the proximity of osteoid seams or in the medullary space were observed in nine posttransplant biopsies of which four had mixed bone disease, two had adynamic bone disease, one had osteomalacia, one had osteitis fibrosa, and one had mild hyperparathyroid bone disease. Osteoblast number in posttransplant biopsies with apoptosis was lower as compared with posttransplant biopsies without apoptosis. In addition, most of them showed a marked shift toward quiescence from the cuboidal morphology of active osteoblasts. Serum phosphorus levels were lower in patients showing osteoblast apoptosis and correlated positively with osteoblast number and negatively with the number of apoptotic osteoblasts. In addition, posttransplant osteoblast surface correlated positively with parathyroid hormone (PTH) levels and negatively with glucocorticoid cumulative dose.Conclusion. The data suggest that impaired osteoblastogenesis and early osteoblast apoptosis may play important roles in the pathogenesis of posttransplant osteoporosis. The possible mechanisms involved in the pathogenesis of theses alterations include posttransplant hypophosphatemia, the use of glucocorticoids, and the preexisting bone disease. PTH seems to have a protective effect by preserving osteoblast survival.