Читать книгу The SAGE Encyclopedia of Stem Cell Research - Группа авторов - Страница 175

Paget’s disease (osteitis deformans) is a primary disease caused by osteoclastic dysfunction. It usually begins in late adulthood and becomes progressively more common thereafter. It can be divided into three phases: (1) initial osteolytic stage, (2) a mixed osteoclastic-osteoblastic stage, and (3) a burnt-out quiescent osteosclerotic stage. The cause of Paget’s disease remains uncertain but evidence suggests both genetic and environmental factors being contributory. The risk of developing this disorder is approximately seven times greater in first-degree relatives of affected individuals. Mutations involving the SQSTM1 gene are found in approximately 40 to 50 percent of the cases of familial disease. The SQSTM1 mutations enhance NF-kB activation of RANK signaling, leading to increased osteoclast activity and an increased susceptibility to the disease. Mutations in the RANKL and RANK/OPG genes have also been linked to genetic conditions that resemble clinical features of Paget’s disease. The cases are usually mild and are discovered accidentally. The axial skeleton is involved in up to 80 percent of the cases, and although no bone is immune, involvement of the ribs, fibula, and small bones of the hands and feet is unusual.