Paget Disease of Bone : Pathogenesis

Comments:
Pathogenesis of Paget Disease of Bone (PDB): PDB disrupts the normal cycle of bone remodeling/renewal causing bone to become weakened and deformed. Genetic factors, acting in conjunction with environmental factors, are thought to underlie the pathogenesis of PDB.

Genetic Factors: Several closely related genes that regulate osteoclast differentiation via NF-κB signaling pathway appear to be involved. The most well-studied is Sequestosome 1 gene (SQSTM1) which encodes p62 - a protein that plays a key role in regulating osteoclast activity. The genetics of PDH is discussed in next several images.

Environmental Factors (Viral Infection): Initial research into the etiology of PDB using electron microscopy revealed intranuclear inclusions resembling paramyxoviral nucleocapsids in lesional osteoclasts. This led to the hypothesis of viral etiology of PDB. Measles, respiratory syncytial virus, and canine distemper virus have all be implicated over the years. However, attempts to extract viral nucleic acids and/or proteins have yielded conflicting results. Besides, no evidence of enhanced immune response to paramyxoviruses has been found to date.

Other Environmental Factors: Low dietary calcium intake during early childhood, vitamin D deficiency, environmental toxins, and repetitive mechanical trauma may also play a role in some cases.

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