Paget's disease of bone is characterised by focal increases in osteoclastic bone resorption coupled to increased but disorganised bone formation. It is a relatively rare disease affecting up to 1% of individuals in the United Kingdom, but many cases are not diagnosed clinically. The most common presentation is with musculoskeletal pain which in some cases is due to increased bone turnover, but which can also be due to complications such as bone deformity, nerve compression syndromes and osteoarthritis. Predisposition to Paget's disease is regulated by pathogenic variants in or close to genes that regulate osteoclast differentiation and function. The most important of these is SQSTM1 which encodes p62-a signalling protein in the NFκB pathway. Environmental factors also influence susceptibility to PDB and disease severity, but the mechanisms are not well understood. Medical management is based on the use of bisphosphonates to supress the abnormal bone turnover and are indicated for the treatment of bone pain associated with the disease. Of the bisphosphonates currently available, intravenous zoledronic acid is the treatment of choice. The diagnosis can usually be made by typical features on X-ray and radionuclide bone scan. Genetic testing for pathogenic variants in the SQSTM1 gene in people with a family history of Paget's disease has been used to detect people with early asymptomatic disease, and in these individuals, prophylactic treatment with zoledronic acid favourably affects disease progression.
Keywords: Paget's disease of bone; SQSTM1; osteoclast.
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