The Link Between Alpha-Klotho Level and Iron Status Among Children with Iron Deficiency Anemia.

Abstract

Background: Iron deficiency anemia (IDA) is the most common nutritional deficiency worldwide, particularly affecting children during critical periods of growth and skeletal development. Alpha-Klotho (α-Klotho) is an essential regulator of mineral metabolism and bone health, acting as a co-receptor for fibroblast growth factor 23 (FGF23). However, the relationship between iron status and Klotho expression in pediatric populations remains poorly understood.
Objective: This study aimed to assess serum α-Klotho levels in children with IDA and examine their association with iron status and fracture history.
Methods: A cross-sectional study was conducted on 77 children aged 9–15 years (39 with IDA and 38 controls). Clinical assessment, anthropometric measurements, complete blood count, iron profile (serum iron, ferritin, total iron-binding capacity, transferrin saturation), and serum α-Klotho levels were performed. Fracture history was recorded as a surrogate marker of bone health.
Results: Children with IDA had significantly lower serum α-Klotho levels compared to controls (median 2.4 vs. 3.7 ng/mL, p = 0.018). Within the IDA group, Klotho correlated positively with serum iron (ρ = 0.447, p = 0.004) and ferritin (ρ = 0.349, p = 0.036), and inversely with age (ρ = -0.322, p = 0.045). Multiple regression analysis identified IDA (B = -1.655, p = 0.015) and ferritin (B = 0.040, p = 0.013) as independent predictors of Klotho levels. Children with fracture history had significantly lower Klotho levels (median 2.2 vs. 3.4, p = 0.009), with ROC analysis showing moderate discriminatory ability (AUC = 0.701).
Conclusion: IDA is independently associated with reduced serum α-Klotho levels in children, with ferritin emerging as the strongest predictor. These findings suggest that iron deficiency may impair Klotho-mediated mineral metabolism during critical periods of skeletal growth, supporting early detection and treatment of IDA for optimal bone health.