title: Relationship between Fibroblast Growth Factor 23 and Biochemical and Bone Histomorphometric Alterations in a Chronic Kidney Disease Rat Model Undergoing Parathyroidectomy.
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 (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.
  
  
  CONCLUSIONS
  Serum FGF-23 levels independently correlated with bone volume parameters in rats with experimentally induced CKD.
authors.affiliation: Jia-yi Clinic, Taoyuan, Taiwan.
authors.forename: Hung-Wei
authors.initials: HW
authors.lastname: Liao
authors.affiliation: Department of Internal Medicine, Ditmanson Medical Foundation Chia-yi Christian Hospital, Chiayi City, Taiwan; Department of Applied Life Science and Health, Chia-Nan University of Pharmacy and Science, Tainan, Taiwan.
authors.forename: Peir-Haur
authors.initials: PH
authors.lastname: Hung
authors.affiliation: Department of Internal Medicine, Ditmanson Medical Foundation Chia-yi Christian Hospital, Chiayi City, Taiwan.
authors.forename: Chih-Yen
authors.initials: CY
authors.lastname: Hsiao
authors.affiliation: Division of Nephrology, Department of Medicine, Hsin-Jen Hospital, New Taipei City, Taiwan.
authors.forename: Hung-Hsiang
authors.initials: HH
authors.lastname: Liou
authors.affiliation: Institute of Physical Education, Health and Leisure Studies, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Hsin-Shih
authors.initials: HS
authors.lastname: Lin
authors.affiliation: Institute of Physical Education, Health and Leisure Studies, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Tsang-Hai
authors.initials: TH
authors.lastname: Huang
authors.affiliation: Department of Orthopedics, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: I-Ming
authors.initials: IM
authors.lastname: Jou
authors.affiliation: Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Center of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Kuen-Jer
authors.initials: KJ
authors.lastname: Tsai
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D001842:Bone and Bones / Q000737:chemistry* / Q000473:pathology; D002118:Calcium / Q000097:blood; D024042:Collagen Type I / Q000097:blood; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D054559:Hyperphosphatemia / Q000097:blood*; D008297:Male; D015999:Multivariate Analysis; D010281:Parathyroid Hormone / Q000097:blood; D016105:Parathyroidectomy / Q000379:methods*; D010455:Peptides / Q000097:blood; D010710:Phosphates / Q000097:blood; D017207:Rats, Sprague-Dawley; D012044:Regression Analysis; D051436:Renal Insufficiency, Chronic / Q000097:blood*
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D010281:Parathyroid Hormone; D010455:Peptides; D010710:Phosphates; C052929:collagen type I trimeric cross-linked peptide; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D002118:Calcium