FGF23-klotho axis as predictive factors of fractures in type 2 diabetics with early chronic kidney disease

Abstract

Background: The aim of our study was to evaluate the relevance of FGF23-klotho axis in the predisposition for bone fractures in type 2 diabetic patients with early chronic kidney disease.

Methods: In a prospective study we included 126 type 2 diabetic patients with CKD stages 2-3 (from 2010 to 2017). We used descriptive statistics, ANOVA and chi-square test. Our population was divided into two groups according to the occurrence of a bone fracture event or not, and the groups were compared considering several biological and laboratorial parameters. We employed a multiple regression model to identify risk factors for bone fracture events and hazard ratios (HR) were calculated using a backward stepwise likelihood ratio (LR) Cox regression.

Results: Patients with a fracture event displayed higher levels of FGF-23, Phosphorus, PTH, TNF-α, OxLDL, HOMA-IR, calcium × phosphorus product and ACR and lower levels of Osteocalcin, α-Klotho, 25(OH)D3 and eGFR compared with patients without a fracture event (p < 0.001). The number of patients with a fracture event was higher than expected within inclining CKD stages (χ2, p = 0.06). The occurrence of fracture and the levels of TNF- α, klotho, 25(OH)D3 and OxLDL were found to predict patient entry into RRT (p < 0.05). Age, osteocalcin, α-Klotho and FGF-23 independently influenced the occurrence of bone fracture (p < 0.05).

Conclusions: α-Klotho and FGF-23 levels may have a good clinical use as biomarkers to predict the occurrence of fracture events.

Keywords: Bone fracture; Chronic kidney disease; Diabetes; FGF-23.