Abstract
BackgroundPhosphate 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.ResultsSprague 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 (β = -0.737; p < 0.001 and β = -0.526; p = 0.006, respectively). Serum parathyroid hormone levels independently correlated with bone formation rate (β = 0.714; p < 0.001) while collagen type I C-telopeptide levels correlated with osteoid parameter.ConclusionSerum FGF-23 levels independently correlated with bone volume parameters in rats with experimentally induced CKD.
Highlights
In chronic kidney disease, CKD-mineral and bone disorder (CKD-MBD) is a disturbance in mineral metabolism and bone remodeling
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; CKD was induced by partial nephrectomy
Our study demonstrated the relationship between Fibroblast growth factor23 (FGF-23), other biochemical markers, and bone histomorphometric parameters with the intention to provide a better understanding of bone metabolism in CKD
Summary
CKD-mineral and bone disorder (CKD-MBD) is a disturbance in mineral metabolism and bone remodeling. Fibroblast growth factor (FGF-23) is a regulator of phosphate metabolism and is elevated in patients with CKD [5]. The hormone FGF-23 is derived mainly from osteocytes in bone [6,7] and acts on proximal renal tubules to maintain serum phosphate homeostasis [8,9] by excreting excess phosphate through the kidney [10,11]. Disrupted phosphate homeostasis in patients with CKD induces secondary hyperparathyroidism, the elevation of serum FGF-23 occurs earlier than that of serum PTH levels [13,14]. 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). 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
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