Review Question - QID 4441

The clinical presentation and imaging studies are consistent with Paget's disease. Observation with evaluation for bisphosphonate therapy is the most appropriate treatment.

Paget's disease is a benign condition characterized by abnormal bone remodeling where osseous tissue is reconstructed through active interplay between excessive bone resorption and abnormal new bone formation. Increased osteoclastic bone resorption is the primary cellular abnormality. The cause is thought to be a slow viral infection (intra-nuclear nucleocapsid-like structure). Malignant transformation to Paget's sarcoma occurs in 1% of patients.

Friedrichs et al. review the molecular biology of Paget's disease. They address the long-standing debate of whether a virus is responsible for Paget's disease. Their findings are consistent with the presence of a chronic MV infection in affected sites from these patients with Paget's disease.

Ralston et al. report that genetic factors play an important role in Paget's disease, and mutations have been identified in four genes that cause Paget's disease and related syndromes. The most important of these is Sequestosome 1 (SQSTM1), which is a scaffold protein in the nuclear factor kappaB (NFkappaB) signaling pathway. Patients with SQSTM1 mutations have severe Paget's disease of bone and a high degree of penetrance with increasing age. Environmental factors also contribute. Most research has focused on paramyxovirus infection as a possible trigger, but evidence for this notion is conflicting.

Figure A shows the typical radiographic features of Paget's, which include osseous expansion, coarsened trabeculae, thickened cortices, and increased density. Figures C and D show histology consistent with Paget's disease. Notice the woven bone and irregular broad trabeculae with disorganized cement lines in a mosaic pattern.

Incorrect Answers:
Answers 1, 2, 3, 4: These treatments are not indicated for Paget's disease.