Effects of Endocrine Disruptors on the Molecular Regulation of Bone Metabolism: Wnt/β-Catenin Signaling Pathway

Bone is a highly dynamic tissue that undergoes continuous remodeling throughout life, a process tightly regulated by coordinated osteoblastic bone formation and osteoclastic bone resorption. Among the molecular mechanisms governing bone homeostasis, the Wnt/β-catenin signaling pathway plays a pivotal role in osteoblast differentiation, bone mass acquisition, and skeletal integrity. Increasing evidence indicates that endocrine-disrupting chemicals (EDCs), ubiquitous environmental contaminants capable of interfering with hormonal signaling, adversely affect bone metabolism. Recent experimental and clinical findings suggest that EDCs exert their skeletal effects not only through classical endocrine pathways but also by modulating Wnt/β-catenin signaling and its key inhibitors, including Dickkopf-1 and sclerostin. This review comprehensively summarizes current knowledge on the molecular regulation of bone metabolism, the role of Wnt/β-catenin signaling, and the mechanisms by which endocrine disruptors impair skeletal health. Emphasis is placed on experimental and epidemiological evidence linking EDC exposure to altered Wnt signaling, changes in bone turnover biomarkers, and increased risk of bone fragility. Understanding these interactions is essential for developing preventive strategies and targeted interventions to mitigate environmentally induced bone disorders.