An 80-year-old man presents with slowly progressive enlargement of his head circumference, deformities of long bones and spine, and chronic pain of the affected skeletal segments. Laboratory studies show elevated serum alkaline phosphatase and high urine hydroxyproline. X-ray findings are consistent with Paget disease. Which of the following is the most likely pathogenetic mechanism of this condition?
Paget disease, also known as osteitis deformans, is a frequent bone condition affecting middle-aged to elderly persons. Usually polyostotic, it affects the axial skeleton, including the spine, pelvis, proximal femur, and head. Often, it presents with gradual enlargement of the head and chronic bone pain. Affected bone is thickened and coarse, with disorderly osteoblastic and osteoclastic activity. Paget himself proposed a viral hypothesis for the pathogenesis of this condition, but only recent immunologic and molecular techniques have allowed identification of paramyxoviruses (measles and respiratory syncytial virus) in osteoclasts of affected bones. In most cases, the diagnosis can be made by radiologic investigations. Generalized reduction in bone mass is the defining feature of osteoporosis. In its most common form, the condition affects elderly persons, especially women after menopause. It characteristically causes compression fractures of veebral bones or pathologic fractures of the femoral neck. Genetic deficiency of carbonic anhydrase II is one cause of the rare hereditary disorders collectively known as osteopetrosis, which are due to osteoclast dysfunction. This condition manifests in infancy or childhood with bone fragility and recurrent fractures. The bone has a stony hard consistency, but is brittle. Monoclonal proliferation of plasma cells is the underlying cause of multiple myeloma, the most frequent primary bone neoplasm. Multiple myeloma results in multifocal accumulation of neoplastic plasma cells in bones, manifesting with punched-out osteolytic lesions on x-ray films. Veebrae, skull, ribs and pelvic bones are most frequently affected.
Generalized reduction in bone mass
Genetic deficiency of carbonic anhydrase II
Monoclonal proliferation of plasma cells
Paramyxovirus infection of osteoclasts