122 Paget’s Disease

Paget’s Disease

George Nomikos, Hema N. Choudur, Anthony G. Ryan, Peter L. Munk, and Mark Murphey

Clinical Presentation

A 74-year-old man presented with right leg pain.

Figure 122A

A plain radiograph of the right femur (Fig. 122A) shows gross deformity and diffuse expansion. Mixed sclerotic and lucent areas are interspersed in the deformed bone, with loss of the normal trabecular pattern.

Diagnosis

Paget’s disease (mixed phase).

Differential Diagnosis

Osseous metastases
Chronic osteomyelitis

Discussion

Background

Paget’s disease of bone (osteitis deformans) is a common nonhormonal metabolic bone disorder characterized by progressive skeletal deformation due to abnormal bone resorption and remodeling, resulting in osseous overgrowth and weakening. It occurs more frequently in the axial than in the appendicular skeleton. The relative frequency of involvement is, from most involved to least, pelvis, femur, skull, tibia, and vertebrae.

It is most common in Great Britain and in countries colonized by the British, such as the United States, New Zealand, and Australia. It is also common in continental Europe, but it is uncommon in Asia and Africa.

Paget’s disease affects 3 to 4% of the population over 40 years old and 10 to 11% of the population over age 80; there is an overall mild male predominance (1.8:1 male:female ratio). It is uncommon in patients younger than 40 years old.

Etiology

Although the etiology is still uncertain, two entities have been implicated, one, a virus and the other, a genetic predisposition. The viral theory is favored by those authorities pointing to the presence of intranuclear inclusions in the osteoclasts of pagetic bone and the presence of giant osteoclasts. The genetic theory is prevalent, as the condition is known to occur in families.

Pathophysiology

At the outset, there is abnormal resorption of bone due to uncontrolled osteoclastic activity. This is followed by fibrous tissue formation, with disorderly trabeculae being laid down by the osteoblasts; however, the matrix is undermineralized and therefore structurally soft. As the disease progresses, more dense bone is laid down in a haphazard manner.

Clinical Findings

Symptoms of Paget’s disease are variable, and many patients are initially asymptomatic. Common musculoskeletal symptoms include pain, tenderness, warmth (secondary to hypervascularity), osseous enlargement, bowing deformities, and kyphosis. Exacerbation of the pain at rest and at night is typical. Patients may present with a pathological fracture or an increasing bone or soft-tissue mass secondary to malignant transformation (osteosarcomas, chondrosarcomas, malignant fibrous histiocytoma, and giant cell tumors have all been reported in patients with Paget’s disease).

Osseous expansion may lead to nerve compression syndromes, particularly involving the cranial nerves, producing deafness and visual disturbances. Skull deformity and enlargement can lead to increased intracranial pressure and hydrocephalus. Vertebral body enlargement can lead to narrowing of the spinal canal and consequent neurologic deficit, including weakness and incontinence or cranial nerve deficits.

High-output congestive heart failure has been associated with Paget’s disease because of the hypervascularity of the abnormal bone. Aortic stenosis, heart block, and bundle branch block have also been associated with Paget’s disease.

Laboratory values mirror the increased turnover of bone associated with this condition. During the lytic phase, serum and urine levels of hydroxyproline are increased and can be used to assess the degree of bone resorption. Serum alkaline phosphatase is elevated during the mixed and sclerotic phases due to increased bone formation during these phases. Serum calcium and phosphorus are normal.

Figure 122B Multiple fractures are evident on the convex side of the bone, which is bowed with gross cortical thickening.

Stages of Disease

Lytic phase Characterized by bone resorption due to excessive osteoclastic activity
Mixed phase A phase of simultaneous resorption and bone formation
Blastic phase Characterized by erratic bone formation

Complications

Deformity and bowing secondary to osseous weakening

Scoliosis

Anterior bowing of the femur or tibia

Acetabuli protrusio

Fractures, which usually develop on the convex side of the involved bone and may progress to become complete (Fig. 122B)
Secondary osteoarthritis owing to abnormal mechanics, most commonly involving the hip and knee
Gout, calcium pyrophosphate dehydrate deposition disease, and rheumatoid arthritis have also been associated with Paget’s disease.
Neurologic complications secondary to osseous expansion causing nerve compression, including spinal stenosis and compression of cranial nerves. Paget’s occurs in the skull in about 30% of cases.
In the spine, cord compression may occur due to the enlargement of the vertebral bodies, intraspinal soft-tissue overgrowth, ossification of epidural fat, platybasia, bleeding, sarcomatous degeneration, vertebral fracture, or subluxation.
Spinal ischemia can occur when blood is diverted due to a steal phenomenon.
Recrudescence of the lytic phase, which may be associated with trauma to pagetic bone or after restriction of weight bearing, may simulate a malignant process.
Sarcomatous transformation (< 1% with long duration of disease, but up to 5 to 10% in those with extensive polyostotic disease), most commonly in the proximal femur, pelvis (Fig. 122C), and shoulder

Figure 122C Transaxial T2-weighted image at the level of the sacral ala shows low signal intensity cortical thickening and a large right-sided multilobular mass, subsequently demonstrated to be sarcomatous transformation within pagetic bone.
Sarcomatous transformation is most commonly to osteosarcoma, followed by malignant fibrous histiocytoma/fibrosarcoma, and chondrosarcoma.
There is an association between giant cell tumors (both solitary and multiple) and Paget’s disease.
Giant cell tumors of the skull and facial bones are almost always associated with Paget’s disease.
Metastatic disease, myeloma, and lymphoma may all occur in pagetic bone, although whether or not there is an increased or decreased incidence of metastatic disease in pagetic bone remains controversial.