Paget's Disease of Bone: Evidence for Complex Pathogenetic Interactions

摘要: Objectives Paget's disease of bone (PDB), with a prevalence 2 to 5% in Caucasians >55 years, is the second most frequent metabolic disease, after osteoporosis. PDB characteristics are lesions an imbalanced remodeling, resulting disorganized and nonfully fledged new bone. etiology not completely understood. In this review, current views on etiology, clinical aspects, treatment summarized discussed. Methods The PubMed database was searched using keywords PDB, sequestosome1 (SQSTM1), valosin-containing protein (VCP), receptor activator nuclear factor-κB (RANK), osteoprotegerin (OPG), RANK ligand (RANKL), mutation, genetic variants, virus, osteosarcoma, bisphosphonates, denosumab. Results Environmental evidence (e.g. viruses) also risk factors have been found for PDB. Until now, SQSTM1 only PDB-causing gene identified. However, patients without mutations seem susceptibility polymorphisms regions containing CaSR , ESR1 TNFRSF11B TNFRSF11A CSF1 (M-CSF), OPTN TM7SF4 (DC-STAMP), VCP NUP205 RIN3 PML GOLGA6A genes, increased developing nature these genes indicates that regulation osteoclastogenesis key process pathogenesis. Furthermore, involvement autophagy forming aggregates, might indicate disturbance processes be factor. Conclusions Unraveling background instrumental understanding pathogenesis role slow viruses. it make early detection subsequently individuals possible.