Etiology of Paget's disease and osteoclast abnormalities

Journal of Cellular Biochemistry
Sakamuri V Reddy

Abstract

Paget's disease of bone is a chronic focal skeletal disorder that affects up to 2-3% of the population over the age of 60 years. Paget's disease is primarily a disease of the osteoclast. The pathologic abnormality in patients with Paget's disease involves increased bone resorption by the osteoclasts, followed by abundant new bone formation that is of poor quality. Genetic linkage analysis indicated that 40% of patients with Paget's disease have an affected first degree relative and 1% of patients develop osteosarcoma. Paget's disease is an autosomal dominant trait with genetic heterogeneity. Recurrent mutations in the ubiquitin-associated (UBA) domain of sequestosome 1 (SQSTM1/p62) are identified in patients with Paget's disease. Osteoclasts and osteoclast precursors from patients with Paget's disease contain paramyxoviral transcripts and appear hyperresponsive to 1,25-(OH)2D3 and RANK ligand (RANKL). It has been suggested that the enhanced sensitivity of osteoclast precursors for 1,25-(OH)2D3 in Paget's disease results from increased expression of coactivators of vitamin D receptor (VDR). However, a cause and effect relationship for the paramyxoviral infection and SQSTM1/p62 gene mutations associated with this disease and oste...Continue Reading

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Citations

Apr 18, 2007·Skeletal Radiology·Benjamin HochDempsey Springfield
Sep 1, 2011·Endocrinology·Kumaran SundaramSakamuri V Reddy
Jun 27, 2009·Molecular Endocrinology·Kumaran SundaramSakamuri V Reddy
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Feb 19, 2021·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Zhe WeiHua Yue
Aug 8, 2021·International Journal of Molecular Sciences·Liberato GiardulloFrancesco Paolo Cantatore

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