Pathogenesis of Paget's disease

Paget's disease of bone (osteitis deformans) is characterized by a focal increase of bone remodeling, starting with exaggerated resorption and reactively increased formation of insufficiently structured bone. The disease affects one or more sites throughout the whole skeleton. Concerning pathogenesis of the disorder, current concepts favour a critical role of genetic factors. Mutations identified to date in Paget's disease of bone and related disorders affect different genes (including SQSTM-1/p62, VCP/p97, RANK, OPG) which predominantly are associated with the NF kappa B-Pathway downstream the Receptor activator of NF kappa B (RANK). Geographical inhomogenities and temporal dynamics of incidence rates suggest a significant impact of environmental factors. Besides mechanical burden and noxious chemical substances, the relevance of chronic paramyxoviral infections is discussed controversially in this context. In summary current knowledge suggests that genetic alterations with relevance for bone remodeling increase susceptibility for the disease while environmental factors can be regarded as triggering factors for clinical manifestation.