Paget Disease

General Considerations

• Multifocal chronic skeletal disease due to chronic paramyxoviral infection
• Prevalence
• 3% of individuals >40 years
• 10% of persons >80 years
• Unusual <40 years
• M:F = 2:1
• Histology
• Increased resorption and increased bone formation
• Newly formed bone is abnormally soft with disorganized trabecular pattern
• Active or Osteolytic phase
• Aggressive bone resorption with lytic lesions
• Replacement of hematopoietic bone marrow by fibrous connective tissue with numerous large vascular channels
• Inactive or Quiescent phase
• Decreased bone turnover with skeletal sclerosis and thickening of the cortex
• Mixed pattern
• Lytic and sclerotic phases frequently coexist

Clinical findings

• Asymptomatic (1/5)
• When symptomatic, symptoms may include
• Fatigue
• Enlarged hat size
• Peripheral nerve compression
• Neurologic disorders from compression of brainstem (basilar invagination)
• Hearing loss, blindness
• Facial palsy (narrowing of neural foramina) - rare
• Pain from(a)primary disease process is rare so think of
• Pathologic fracture
• Malignant transformation
• Secondary degenerative joint disease aggravated by skeletal deformity
• High-output congestive heart failure from markedly increased perfusion (rare)
• Increased alkaline phosphatase (increased bone formation)
• Hydroxyproline increased (increased bone resorption)
• Normal serum calcium + phosphorus

Sites of involvement

• Usually polyostotic and asymmetric
• Pelvis (75%) most common, followed by
• Lumbar spine
• Thoracic spine
• Proximal femur
• Calvarium
• Scapula
• Distal femur
• Proximal tibia
• Proximal humerus

Imaging Findings

• Classical triad
• Thickening of the cortex
• Accentuation of the trabecular pattern
• Increased size of bone
• Cyst-like areas
• Skull (involvement in 29-65%)
• Inner and outer table involved
• Leads to diploic widening
• Osteoporosis circumscripta is well-defined lysis, most commonly in frontal bone producing well-defined geographic lytic lesion in skull
• Represents early destructive phase of disease active stage)
  
  

Osteoporosis circumscripta of frontal bone in lytic phase of Paget's disease

Paget Skull, "Cotton-Wool" appearance: There is a thickened calvarium with mixed lytic and blastic areas lending an appearance likened to "cotton-wool."

• "Cotton wool" appearance represents mixed lytic and blastic pattern of thickened calvarium (later stage)
• Basilar invagination with encroachment on foramen magnum
• Deossification and sclerosis in maxilla
• Sclerosis of skull base
• Long bones (almost invariably starts at end of bone)
• "Candle flame" or "blade of grass" pattern of lysis is the advancing tip of V-shaped lytic defect in diaphysis of long bone originating in subarticular site
• Lateral curvature of femur
• Anterior curvature of tibia (commonly resulting in fracture)
• Pelvis
• Thickened trabeculae in sacrum, ilium
• Rarefaction in central portion of ilium (looks like a large lytic lesion)
• Thickening of iliopectineal line
• Acetabular protrusio with secondary degenerative joint disease
• Spine (upper cervical, low dorsal, midlumbar most common sites)
• Coarse trabeculations at periphery of bone
• "Picture-frame vertebra" mimics bone-within-bone appearance
• Enlarged vertebral body with reinforced peripheral trabeculae and more lucent center, typically in lumbar spine
• "Ivory vertebra" is a blastic vertebra with increased density
• Ossification of spinal ligaments, paravertebral soft tissue, disk spaces can occur

Bone scan

• Sensitivity
• Scintography and radiography (60%)
• Scintography only (27%)
• Radiography only (13%)
• Usually markedly increased uptake (symptomatic lesions strikingly positive)
• Normal scan may occur in some burned-out lesions
• Marginal uptake can be seen in lytic lesions

Bone marrow scan

• Sulfur colloid bone marrow uptake is decreased (marrow replacement by cellular fibrovascular tissue)

MRI Findings

• Hypointense area / area of signal void on T1WI + T2WI (cortical thickening, coarse trabeculation)
• Widening of bone
• Reduction in size and signal intensity of medullary cavity due to replacement of high-signal-intensity fatty marrow by medullary bone formation
• Focal areas of higher signal intensity than fatty marrow (from cyst-like fat-filled marrow spaces)
• Areas of decreased signal intensity within marrow on T1WI and increased intensity on T2WI (= fibrovascular tissue resembling granulation tissue)

Complications

• Associated neoplasia (0.7-20%)
• Sarcomatous transformation into osteosarcoma (22-90%), fibrosarcoma /malignant fibrous histiocytoma (29-51%), chondrosarcoma (1-15%)
• Sarcomas are usually osteolytic in pelvis, femur, humerus
• Giant cell tumor occurs in 3-10%
• Lytic expansile lesion in skull, facial bones
• Lymphoma or plasma cell myeloma are reported
• Fracture
• "Banana fracture" = tiny horizontal cortical infractions (“Looser lines”)on convex surfaces of lower extremity long bones (lateral bowing of femur, anterior bowing of tibia)
• Compression fractures of vertebrae
• Early-onset osteoarthritis

Treatment

• Calcitonin, diphosphonate, mithramycin
• Detection of recurrence:
• In 1/3 detected by bone scan
• In 1/3 detected by biomarkers (alkaline phosphatase, urine hydroxyproline)
• In 1/3 by scan and biomarkers simultaneously

DDx

• Depends on the bone in which it occurs
• Skull
• Osteolytic or osteoblastic metastases
• Long bones
• Metastases
• Chronic osteomyelitis (thickened cortex)
• Old trauma (thickened cortex)
• Hodgkin’s disease
• Spine
• Hemangioma
• Metastases