Abstract
Background: Fibroblast growth factor-23 (FGF-23) is a hormone principally produced by osteocytes/osteoblasts. In patients with chronic kidney disease (CKD), FGF-23 levels are usually elevated and can reach up to 300 – 400 times the normal range. FGF-23 is regulated by local bone-related and systemic factors, but the relationship between circulating FGF-23 concentrations and bone remodeling and mineralization in CKD has not been well characterized. In the current study, we examined the relationship between FGF-23 levels and bone histomorphometry parameters in adult patients with renal osteodystrophy. Material and methods: 36 patients on dialysis (CKD-5D) underwent bone biopsies after tetracycline double labeling. Blood drawings were done at time of biopsy to determine serum levels of markers of bone and mineral metabolism. Results: Patients with high bone turnover had higher values of serum FGF-23 than patients with low bone turnover. FGF-23 levels correlated with activation frequency (ρ = 0.60, p < 0.01) and bone formation rate (ρ = 0.57, p < 0.01). Normal mineralization was observed in 90% of patients with FGF-23 levels above 2,000 pg/mL. Furthermore, FGF-23 correlated negatively with mineralization lag time (ρ = –0.69, p < 0.01) and osteoid maturation time (ρ = –0.46, p < 0.05) but not with osteoid thickness (ρ = 0.08, ns). Regression analysis showed that FGF-23 was the only independent predictor of mineralization lag time. FGF-23 correlated with cancellous bone volume (ρ = 0.38, p < 0.05) but did not predict it. Conclusion: Circulating FGF-23 concentrations may reflect alterations in ongoing bone formation along with active mineralization, but not exclusively in bone formation or mineralization. Abnormal mineralization lag time (> 100 days) was mainly seen in patients with FGF-23 levels less than 2,000 pg/mL, while very high levels of FGF-23 are associated with normal mineralization lag time.
Highlights
Fibroblast growth factor-23 (FGF-23) is produced mainly by osteocytes/osteoblasts in bone [1, 2] and is known to act on the kidney as a “phosphaturic hormone” by inhibiting renal phosphate reabsorption and 1,25-dihydroxyvitamin D (1,25D) production [3, 4, 5]
We examined the relationship between FGF-23 levels and bone histomorphometry parameters in adult patients with renal osteodystrophy
bone specific alkaline phosphatase (BSAP), tartrate-resistant acid phosphatase-5b (TRAP5b), and intact parathyroid hormone (iPTH) were in ranges expected for patients on chronic dialysis
Summary
Fibroblast growth factor-23 (FGF-23) is produced mainly by osteocytes/osteoblasts in bone [1, 2] and is known to act on the kidney as a “phosphaturic hormone” by inhibiting renal phosphate reabsorption and 1,25-dihydroxyvitamin D (1,25D) production [3, 4, 5]. Studies on human genetic and acquired diseases, as well as tissue culture and genetically modified animal models, have demonstrated that both extremely high and low serum FGF-23 levels are associated with skeletal abnormalities due to impaired mineralization [4, 6]. FGF-23 has been purported to have direct effects on osteoblasts in-vitro through activation of FGF receptors/soluble Klotho (s-Klotho) complexes [13] Both local (FGF receptor activation and bone turnover) and systemic factors (i.e., 1,25D, iron, parathyroid hormone (PTH) and calcium) regulate FGF-23 production by osteoblasts [3, 14, 15]. In patients with chronic kidney disease (CKD), FGF-23 levels are usually elevated and can reach up to 300 – 400 times the normal range. Abnormal mineralization lag time (> 100 days) was mainly seen in patients with FGF-23 levels less than 2,000 pg/mL, while very high levels of FGF23 are associated with normal mineralization lag time
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