Paget's disease of bone

Abstract

Paget's disease of bone is a common disorder characterized by increased but disorganized bone remodelling. Some patients are asymptomatic but others present with bone pain or other complications such as fracture and deformity. Major advances have been made in understanding the pathophysiology of Paget's disease in recent years and highly effective agents are now available with which to suppress the abnormal bone turnover that causes the disease. Here we review recent advances in the epidemiology, pathogenesis, clinical features and management of Paget's disease. We also reflect upon the future challenges that remain to be overcome to explain the unusual distribution of the disease and to favourably alter the natural history and prevent the development of complications.

p62/sequestosome 1 deficiency accelerates osteoclastogenesis in vitro and leads to Paget’s disease–like bone phenotypes in mice

“…Paget's disease of bone (PDB), 3 which was first described by Sir James Paget as osteitis deformans in 1877 (1), is a severe condition of pathological bone abnormalities that affects about 2-5% of the Caucasian population over 55 years (2). PDB is characterized by elevated number, size, and nucleation of osteoclasts (OCs) (3).…”

“…Paget's disease of bone (PDB), 3 which was first described by Sir James Paget as osteitis deformans in 1877 (1), is a severe condition of pathological bone abnormalities that affects about 2-5% of the Caucasian population over 55 years (2). PDB is characterized by elevated number, size, and nucleation of osteoclasts (OCs) (3). Bone turnover rates are abnormal as a consequence of increased OC-related bone resorption, which is coupled with intensive formation of unstable and woven bone material characterized by irregular collagen fibers (2,3).…”

“…PDB is characterized by elevated number, size, and nucleation of osteoclasts (OCs) (3). Bone turnover rates are abnormal as a consequence of increased OC-related bone resorption, which is coupled with intensive formation of unstable and woven bone material characterized by irregular collagen fibers (2,3). PDB risk factors include environmental and genetic components (4).…”

Unusual presentation of Paget's disease of bone

“…It usually presents after the age of 55 years and the highest prevalence has been reported from the UK. The SQSTM1 (sequestosome-1 encoder) gene has been shown to be associated with this disease 1. Bone pain, deformities, fractures and neurological complications such as headache, hearing loss and nerve palsies have been reported as the manifestations of PDB.…”

The dynamics of adult haematopoiesis in the bone and bone marrow environment

“…Certain mutations in osteoclasts have enhanced bone resorption capabilities in the diseased state [e.g. Paget disease (Tan & Ralston, )] with normal blood parameters except for markers of bone turnover. Where the signalling changes in osteoclasts does not impact their function, haematopoietic parameters are not affected [e.g.…”