Pagets Disease: Etiology and Pathogenesis
- Etiology: disease may be caused by a virus;
- paramyxovirus infection of osteoblasts may activate of the c-fos proto-oncogene, resulting in localized abnormal osteoclastic activity typical of Paget's disease;
- in Paget's disease, primary defect is in the remodeling system of isolated areas of skeleton;
- it is characterized by massive turnover of bone in the affected areas w/ marked increase in both bone resorption & bone formation;
- owing to rapid turnover, the bone formed is immature bone;
- in the bones affected, there may be either little change in the shape of the bone or very marked change in the bone contour resulting from both lack of appropriate remodeling & change in quality of bone;
- small increased risk of osteosarcoma;
- Hypervascular / Osteolytic Phase:
- initial phase of disorder involves bone resorption by osteoclasts;
- subsequently there is vigorous osteoblastic response, producing excessive, poorly organized, structurally weak, highly vascular woven bone;
- disease causes significant increase in blood flow of involved bones;
- this increase may be so extensive, due to small arteriovenous shunts, that cardiac output is significantly increased;
- degenerative arthritis is assoc w/ hypervascularity of ends of bones;
- after some time osteoclastic activity subsides & woven bone is replaced by lamellar bone as the osteoblastic action persists;
- Intermediate Phase:
- in this phase osteoblastic activity predominates, but osteolytic activity is also present and therefore, and bone structural changes and bone deformity are manifest;
- Quiescent stage:
- finally, osteoblastic activity diminishes & bone becomes quiescent, w/ bony sclerosis and no evidence of increased turnover of bone, and bone enlargment and widening;
- vascular fibrous tissue replaces the marrow;
- Haversian systems are absent
On the trail of paramyxoviruses in Paget's disease of bone.
Pathogenesis of Paget's disease based on viral etiology.
Critical evaluation of viral antigen data in Paget's disease of bone.
Original Text by Clifford R. Wheeless, III, MD.
Last updated by Data Trace Staff on Monday, August 20, 2012 7:02 pm