Paget's Disease

Dimitrios Papaioannides, MD

,
Ch. Tatsis, MD

,
N. Akritides, MD

A 74-year-old man, who had been aware of a gradual increase in hat size over the past 3 years, complained of a mild headache and backache. His serum phosphatase level was 1,475 U/L (upper normal limit, 120 U/L). Skull films showed calvarial enlargement caused by thickening of the cortical tables, radiolucency in the frontal and occipital regions, and patchy osteosclerosis that produced a cotton-wool appearance.

A 74-year-old man, who had been aware of a gradual increase in hat size over the past 3 years, complained of a mild headache and backache. His serum phosphatase level was 1,475 U/L (upper normal limit, 120 U/L). Skull films showed calvarial enlargement caused by thickening of the cortical tables, radiolucency in the frontal and occipital regions, and patchy osteosclerosis that produced a cotton-wool appearance. Paget's disease was diagnosed.

Drs Dimitrios Papaioannides and Ch. Tatsis of Arta, Greece, and N. Akritides of Ioannina, Greece, remark that persons with Paget's disease generally have no or minimal symptoms; bone pain and skeletal deformity are the most common complaints. Extensive multifocal disease can be associated with considerable pain, deformity, and disability. The lumbosacral spine, skull, pelvis, femur, and tibia are affected most frequently by the disease.

The earliest phase of Paget's disease is characterized by an increase in osteoclastic bone resorption, which is seen on radiographs as a localized osteolytic area, often in the skull (osteoporosis circumscripta), or as a flame-shaped or “blade-of-grass” radiolucency in the ends of long bones.

In time, a compensatory increase in osteoblastic activity occurs, characterized by disorganized formation of new bone that lacks the normal trabecular pattern. In the mixed phase of the disease, expanded bones with cortical thickening, coarse trabecular markings, and both lytic and sclerotic areas are seen on radiographs.

Radionuclide bone scans offer the most sensitive surveys of pagetic sites. Biochemical markers of bone formation, such as serum alkaline phosphatase and osteocalcin levels, and bone resorption, as indicated by urinary excretion of hydroxyproline and pyridinolines, are increased in persons with active Paget's disease.

Complications of Paget's disease include pathologic fractures during the destructive phase of the disease, high output heart failure in extensive involvement of the skeleton, deafness, hyperuricemia and gout, urinary stone formation, and osteogenic sarcoma (in fewer than 1% of patients). Medical therapy focuses on specific inhibitors of osteoclast-mediated bone resorption, such as the bisphosphonates (eg, alendronate, etidronate, and pamidronate), calcitonins, mithramycin, and gallium nitrate.

A 6-month course of oral alendronate therapy was prescribed for this patient. After 4 months, his symptoms improved and the serum alkaline phosphatase level fell to 680 U/L.