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甲状旁腺切除术对慢性肾脏病和继发性甲状旁腺功能亢进患者骨组织生物学的影响。

Effects of parathyroidectomy on the biology of bone tissue in patients with chronic kidney disease and secondary hyperparathyroidism.

机构信息

LIM 16 - Laboratorio de Fisiopatologia Renal, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.

Divisao de Nefrologia, Universidade Federal de Sao Paulo, Sao Paulo, SP, Brazil.

出版信息

Bone. 2019 Apr;121:277-283. doi: 10.1016/j.bone.2019.01.029. Epub 2019 Feb 6.

DOI:10.1016/j.bone.2019.01.029
PMID:30738215
Abstract

Secondary hyperparathyroidism is a complication of chronic kidney disease that compromises skeletal integrity. In patients with secondary hyperparathyroidism undergoing parathyroidectomy, parathyroid hormone levels dramatically decrease. The effects of parathyroidectomy on bone tissue are poorly understood, especially regarding the proteins expressed by osteocytes, such as fibroblast growth factor 23, dentin matrix protein 1, matrix extracellular phosphoglycoprotein, sclerostin, receptor activator of nuclear factor kappa B ligand (RANKL) and osteoprotegerin, which regulate bone turnover. The objective of this study was to characterize the bone expression of these proteins by immunohistochemistry and correlate these results with those of bone histomorphometry before and after parathyroidectomy. We studied bone biopsies that were obtained from 23 patients before and 12 months after parathyroidectomy. We observed an improvement in bone microarchitecture, but impaired mineralization after parathyroidectomy. We found significant increases in sclerostin and osteoprotegerin expression and a decrease in the RANKL/osteoprotegerin ratio after parathyroidectomy, suggesting that their expression is regulated by parathormone. These proteins correlated with structural and bone formation parameters. We conclude that after parathyroidectomy, significant changes occur in the bone expression of osteocyte proteins and that these proteins potentially regulate bone remodeling.

摘要

继发性甲状旁腺功能亢进是慢性肾脏病的一种并发症,会损害骨骼的完整性。在接受甲状旁腺切除术的继发性甲状旁腺功能亢进患者中,甲状旁腺激素水平会显著下降。甲状旁腺切除术对骨组织的影响尚未完全了解,特别是关于成骨细胞表达的蛋白,如成纤维细胞生长因子 23、牙本质基质蛋白 1、基质细胞外磷糖蛋白、硬骨素、核因子 kappa B 受体激活剂配体 (RANKL) 和骨保护素,这些蛋白调节骨转换。本研究的目的是通过免疫组织化学来描述这些蛋白在骨组织中的表达,并将这些结果与甲状旁腺切除术前和术后的骨组织形态计量学结果进行相关性分析。我们研究了 23 例患者在甲状旁腺切除术前和术后 12 个月时获得的骨活检。我们观察到骨微结构的改善,但甲状旁腺切除术后的矿化受损。我们发现硬骨素和骨保护素的表达显著增加,而 RANKL/骨保护素比值降低,提示它们的表达受甲状旁腺激素调节。这些蛋白与结构和骨形成参数相关。我们得出结论,甲状旁腺切除术后,成骨细胞蛋白在骨组织中的表达发生显著变化,这些蛋白可能调节骨重塑。

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