Current advances of bone homeostasis imbalance in the cause of hereditary metabolic bone diseases

Bone homeostasis, a dynamic equilibrium essential for skeletal development and repair, is coordinately regulated by osteoclasts, osteoblasts, and osteocytes. Hereditary metabolic bone diseases arise from genetic mutations that impair the function of these key bone cells, disrupting the homeostatic balance. This review specifically addresses four prevalent hereditary metabolic bone diseases: osteogenesis imperfecta, Paget's disease of bone, hypophosphatemic rickets, and osteopetrosis. Dysfunction in major signaling pathways - notably the Wnt/β-catenin, RANK/RANKL/OPG, and TGF-β/BMP pathways - plays a central role in the aberrant bone remodeling underlying these disorders. Elucidating the molecular mechanisms involving these cells and pathways is fundamental to understanding disease pathogenesis and is crucial for the development of novel therapeutic interventions, presenting significant promise for future research.