Paget’s Disease of Bone (Osteitis Deformans)
Paget’s Disease of Bone (Osteitis Deformans) 1. Cause and Etiology Paget's disease of bone (PDB) is a chronic, focal disorder of bone remodeling characterized by excessive and disorganized bone turnover. The etiology of PDB remains partially elucidated, with evidence supporting both genetic and environmental contributions. 1.1 Genetic Factors Paget’s disease exhibits a strong familial aggregation, with an autosomal dominant inheritance pattern seen in some families. Up to 40% of affected individuals have a first-degree relative with the disease. Several genes have been implicated: · SQSTM1 (Sequestosome 1) : Mutations in this gene, especially affecting the ubiquitin-associated (UBA) domain, are the most well-established genetic cause. SQSTM1 encodes p62, a scaffold protein involved in NF-κB signaling, which regulates osteoclastogenesis and survival. Mutations lead to enhanced NF-κB activity and increased osteoclast activity...