= OSTEITIS DEFORMANS

[Sir James Paget, 1st. Baronet (1814–1899), professor of anatomy & surgery at the Royal College of Surgeons at St. Bartholomew Hospital, London]

= multifocal chronic skeletal disease characterized by disordered and exaggerated bone remodeling

Etiology: ? chronic paramyxoviral infection

Prevalence: 3% of individuals >40 years; 10% of persons >80 years; higher prevalence in northern latitudes; 2^nd most common disease (after osteoporosis) affecting older individuals

Age: Caucasian of Northern European descent >55 years (in 3%); >85 years (in 10%); unusual <40 years; M÷F = 2÷1

Histo: increased resorption + increased bone formation; newly formed bone is abnormally soft with disorganized trabecular pattern (“mosaic pattern”) causing deformity

1. ACTIVE PHASE = OSTEOLYTIC PHASE
   = intense osteoclastic activity = aggressive bone resorption with lytic lesions
   Path: replacement of hematopoietic bone marrow by fibrous connective tissue with numerous large vascular channels
   • osteoporosis circumscripta of skull
   • flame-shaped radiolucency extending from end of long bone into diaphysis
2. MIDDLE / MIXED / BLASTIC PHASE (common)
   = decreased osteoclastic activity + increased osteoblastic activity
   Location: polyostotic in axial skeleton: skull, pelvis, spine
   • coexistence of lytic + sclerotic phases
   • osseous sclerosis → coarse trabecular + cortical thickening + bone enlargement
3. INACTIVE / LATE PHASE = QUIESCENT PHASE
   = diminished osteoblastic activity with decreased bone turnover
   Path: loss of excessive vascularity
   • osteosclerosis + cortical accretion (eg, ivory vertebral body)

• asymptomatic (⅕–¾)
• 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
  1. primary disease process – rare
  2. pathologic fracture
  3. malignant transformation
  4. degenerative joint disease / rheumatic disorder aggravated by skeletal deformity
• local hyperthermia of overlying skin
• 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: usually polyostotic + asymmetric; pelvis (75%) >lumbar spine >thoracic spine >proximal femur >calvarium >scapula >distal femur >proximal tibia >proximal humerus

Sensitivity: scintigraphy + radiography (60%) scintigraphy only (27–94%) radiography only (13–74%)

• osseous expansion
• trabecular coarsening
• cortical thickening
• cystlike areas (fat-filled marrow cavity / blood-filled sinusoids / liquefactive degeneration + necrosis of proliferating fibrous tissue)
• Skull (involvement in 29–65%)
  • inner + outer table involved
  • diploic widening
  • osteoporosis circumscripta = well-defined lysis, most commonly in calvarium anteriorly, occasionally in long bones (destructive active stage)
  • “cotton wool” appearance = mixed lytic + blastic pattern of thickened calvarium (late stage)
  • basilar impression with encroachment on foramen magnum
  • deossification + sclerosis in maxilla
  • sclerosis of base of skull
• Long bones (almost invariable at end of bone; rarely in diaphysis)
  • “candle flame” / “blade of grass” lysis = advancing tip of V-shaped lytic defect in diaphysis of long bone originating in subarticular site (CHARACTERISTIC)
  • lateral curvature of femur, anterior curvature of tibia (commonly resulting in fracture)
• Ribs (involvement in 1–4%)
• Small / flat bones
  • bubbly destruction + periosteal successive layering
• Pelvis
  • thickened trabeculae in sacrum, ilium; rarefaction in central portion of ilium
  • thickening of iliopectineal line
  • acetabular protrusion (DDx: metastatic disease not deforming) + secondary degenerative joint disease
• Spine (upper cervical, low dorsal, midlumbar)
  • expansion of vertebra
  • lytic / coarse trabeculations at periphery of bone
  • “picture-frame vertebra” = bone-within-bone appearance = enlarged square vertebral body with reinforced peripheral trabeculae + central osteopenia, typically in lumbar spine
  • “ivory vertebra” = blastic vertebra with increased density
  • isolated posterior arch involvement
  • ossification of spinal ligaments, paravertebral soft tissue, disk spaces

Bone scan (94% sensitive):

• usually markedly increased uptake (symptomatic lesions strikingly positive ← increased blood flow + osteoblastic activity)
• normal scan in some sclerotic burned-out lesions
• marginal uptake in lytic lesions
• enlargement + deformity of bones

Bone marrow scan:

• sulfur colloid bone marrow uptake is decreased ← marrow replacement by cellular fibrovascular tissue

MR:

Indications: imaging of complications (spinal stenosis, basilar impression, sarcoma staging)

• areas of decreased SI within marrow on T1WI + increased intensity on T2WI (= fibrovascular tissue resembling granulation tissue)
• hypointense area / area of signal void on T1WI + T2WI (cortical thickening, coarse trabeculation)
• reduction in size + SI of medullary cavity (= replacement of high-SI fatty marrow by ↑ medullary bone formation)
• focal areas of higher SI than fatty marrow (= cystlike fat-filled marrow spaces)
• widening of bone

Cx:

1. Associated neoplasia (0.7–1–20%)
   1. sarcomatous transformation into osteosarcoma (22–90%), fibrosarcoma / malignant fibrous histiocytoma (29–51%), chondrosarcoma (1–15%)
      • osteolysis in pelvis, femur, humerus
      
      Prognosis:<10% 5-year survival
   2. multicentric giant cell tumor (3–10%)
      • lytic expansile lesion in skull, facial bones
   3. lymphoma, plasma cell myeloma
2. Insufficiency fracture
   1. “banana fracture” = tiny horizontal cortical infractions on convex surfaces of lower extremity long bones (lateral bowing of femur, anterior bowing of tibia)
   2. compression fracture of vertebra (soft bone despite increased density)
3. Neurologic entrapment
   1. basilar impression with obstructive hydrocephalus + brainstem compression + syringomyelia
   2. spinal stenosis with extradural spinal block (osseous expansion / osteosarcoma / vertebral retropulsion ← compression fracture)
4. Early-onset osteoarthritis
   Pathogenesis: altered biomechanics across affected articulations

Cx: sarcomatous degeneration: most commonly osteo- / chondrosarcoma / malignant fibrous histiocytoma

Rx: calcitonin, biphosphonates, mithramycin

Detection of recurrence:

1. in ⅓ detected by bone scan
2. in ⅓ detected by biomarkers (alkaline phosphatase, urine hydroxyproline)
3. in ⅓ by bone scan + biomarkers simultaneously
   • diffuse (most common) / focal increase in tracer uptake
   • extension of uptake beyond boundaries of initial lesion

DDx: osteosclerotic metastasis, osteolytic metastasis, Hodgkin disease, vertebral hemangioma