Paget's Disease of Bone - Pathogenesis

Pathogenesis

The pathogenesis of Paget's disease is described in 4 stages:

1. Osteoclastic activity
   
2. Mixed osteoclastic - osteoblastic activity
   
3. Osteoblastic activity
   
4. Malignant degeneration
   

Initially, there is a marked increase in the rate of bone resorption at localized areas caused by large and numerous osteoclasts. These localized areas of osteolysis are seen radiologically as an advancing lytic wedge in long bones or osteoporosis circumscripta in the skull. The osteolysis is followed by a compensatory increase in bone formation induced by osteoblasts recruited to the area. This is associated with accelerated deposition of lamellar bone in a disorganized fashion. This intense cellular activity produces a chaotic picture of trabecular bone ("mosaic" pattern), rather than the normal linear lamellar pattern. The resorbed bone is replaced and the marrow spaces are filled by an excess of fibrous connective tissue with a marked increase in blood vessels, causing the bone to become hypervascular. The bone hypercellularity may then diminish, leaving a dense "pagetic bone," also known as burned-out Paget's disease.

Sir James Paget first suggested the disease was due to an inflammatory process. New evidence suggests he may have been correct and that a paramyxovirus infection is the underlying cause of Paget's disease. No infectious virus has yet been isolated as a causative agent, however, and other evidence suggests an intrinsic hyperresponsive reaction to vitamin D and RANK ligand is the cause. Further research is therefore necessary.