Relationship between Fibroblast Growth Factor 23 and Biochemical and Bone Histomorphometric Alterations in a Chronic Kidney Disease Rat Model Undergoing Parathyroidectomy

doi:10.1371/journal.pone.0133278

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Title:	Relationship between Fibroblast Growth Factor 23 and Biochemical and Bone Histomorphometric Alterations in a Chronic Kidney Disease Rat Model Undergoing Parathyroidectomy
Authors:	Liao, Hung-Wei Hung, Peir-Haur Hsiao, Chih-Yen Liou, Hung-Hsiang Lin, Hsin-Shih Huang, Tsang-Hai Jou, I-Ming Tsai, Kuen-Jer
Contributors:	生活應用與保健系
Keywords:	in-vivo Secondary hyperparathyroidism Renal hyperparathyroidism Circulating levels gene-expression Oral phosphate Mousemodel Hormone fgf23 fgf-23
Date:	2015-07
Issue Date:	2016-04-19 19:05:59 (UTC+8)
Publisher:	Public Library Science
Abstract:	Background Phosphate burden in chronic kidney disease (CKD) leads to elevated serum fibroblast factor-23 (FGF-23) levels, secondary hyperparathyroidism and chronic kidney disease-mineral bone disorder (CKD-MBD). However dissociated hyperphosphatemia and low serum FGF-23 concentrations have been observed in experimentally parathyoridectomized rats. The relationships between serum mineral, hormone, and bone metabolism may be altered in the presence of CKD. The aim of our study was to investigate whether a consistent relationship existed between serum FGF-23 levels, specific serum biochemical markers, and histomorphometric parameters of bone metabolism in a parathyroidectomized CKD animal model. Results Sprague Dawley rats were divided into 3 groups: parathyroidectomy (PTX) and CKD (PTX+CKD, 9 rats), CKD without PTX (CKD, 9 rats), and neither PTX nor CKD (sham-operated control, 8 rats); CKD was induced by partial nephrectomy. At 8 weeks after partial nephrectomy, serum biomarkers were measured. Bone histomorphometries of the distal femoral metaphyseal bone were analyzed. The mean serum FGF-23 levels and mean bone formation rate were the highest in the CKD group and the lowest in the PTX+CKD group. Bone volume parameters increased significantly in the PTX+CKD group. Pearson's correlation revealed that serum FGF-23 levels associated with those of intact parathyroid hormone, phosphate, collagen type I C-telopeptide, and calcium. Univariate linear regression showed that serum FGF-23 values correlated with bone formation rate, bone volume, and osteoid parameters. Stepwise multivariate regression analysis revealed that circulating FGF-23 values were independently associated with bone volume and thickness (beta = -0.737; p < 0.001 and beta = -0.526; p = 0.006, respectively). Serum parathyroid hormone levels independently correlated with bone formation rate (beta = 0.714; p < 0.001) while collagen type I C-telopeptide levels correlated with osteoid parameter. Conclusion Serum FGF-23 levels independently correlated with bone volume parameters in rats with experimentally induced CKD.
Relation:	Plos One, v.10 n.7, Article ID e0133278
Appears in Collections:	[Dept. of Life and Health Science] Periodical Articles

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