Bone Mineral Density, FGF-23/Klotho Axis, and Adipokine Profile in Children with Obesity

Background/Objectives: Obesity may adversely affect skeletal development during childhood, but the mechanisms linking bone metabolism, phosphorus homeostasis, and adipokines remain incompletely understood. This study investigated bone turnover markers, the fibroblast growth factor-23/Klotho (FGF-23/Klotho) axis, and pro- and anti-inflammatory adipokines in prepubertal children with obesity according to bone mineral density (BMD) status. Methods: Children with obesity (n = 60; aged 5-10 years) were stratified into subgroups according to their total body less head (TBLH)-BMD Z-score (>1 or −1 to 1). Fifty healthy, normal-weight children served as controls. Serum levels of bone formation, bone resorption, and bone regulatory markers, a panel of adipokines, intact and C-terminal FGF-23 (iFGF-23 and cFGF-23), and α-Klotho levels were measured using ELISAs. Densitometric and dietary assessments were performed. Results: The subgroup with obesity and TBLH-BMD Z-score >1 had lower osteoprotegerin (OPG) levels than both the Z-score −1 to 1 subgroup (p = 0.040) and controls (p = 0.016). This subgroup also exhibited higher periostin, iFGF-23, cFGF-23, leptin, and resistin concentrations, together with lower high-molecular-weight adiponectin levels compared with controls (all p < 0.001). In the whole group with obesity, OPG was negatively associated with TBLH-BMD (rpartial = -0.266, p = 0.041) and iFGF-23 (rpartial = -0.306, p = 0.018), and positively associated with bone alkaline phosphatase (rpartial = 0.297, p = 0.023). α-Klotho was inversely associated with leptin concentrations (β = -14.129, p = 0.038). Conclusions: Higher TBLH-BMD values in prepubertal obesity was accompanied by reduced OPG levels, disturbances of the FGF-23/Klotho axis, and an unfavorable adipokine profile. These alterations may reflect impaired bone quality despite increased bone mass and could contribute to adverse skeletal outcomes later in life.