54. Paget Disease

• Prevalence: second most prevalent skeletal disease after osteoporosis in individuals > 50 years of age [1]

• Sex: ♂ > ♀ (1.2:1)

• Age of onset: > 55 years [1]

• Idiopathic disease

• Associated with a high rate of bone remodeling: ↑ RANKL-RANK activity → ↑ NF-κB signaling → ↑ osteoclast activity → ↑ osteoblast activity → formation of disorganized (woven) bone

Bone remodeling in Paget disease occurs in three phases, followed by a quiescent stage: [2]

• Lytic phase: ↑ number of osteoclasts appear in bone → ↑ osteoclastic activity → ↑ rate of bone resorption

• Mixed lytic and blastic phase: ↑ osteoclastic activity is accompanied by an ↑ number of osteoblasts, which infiltrate the lacunae → ↑ rate of bone formation with haphazardly laid collagen fibers → formation of abnormal hypervascular woven bone

• Sclerotic phase: Osteoblastic activity overtakes osteoclastic activity, which leads to formation of dense, sclerotic bone.

• Quiescent stage: Both osteoclastic and osteoblastic activity cease (“quiet phase” of the disease).

The pelvis, skull, vertebral column, and long bones of the lower extremities are the most commonly affected sites.

• Monostotic PDB: affects only one bone (∼ ⅓ of cases)

• Polyostotic PDB: affects two or more bones (∼ ⅔ of cases)

• Approximately 70–90% of cases are asymptomatic.

• Bone pain, which may be associated with erythema and elevated skin temperature over the affected bones

• Pathological fractures: chalk-stick fractures of long bones [2]

• Bony deformities, e.g., bowing of legs (saber shin)

• Skull involvement (in ∼ 40% of cases)

  • Skull enlargement (increasing hat size)

  • Cranial nerve deficits

  • Impaired hearing: due to ankylosis of the ossicles and narrowing of the internal auditory meatus

  • Headache

  • Leonine facies

• Cauda equina syndrome, nerve root compression

This woman's face appears deeply furrowed and swollen, large coalescent nodules are visible.

Leonine facies (so termed after the ostensible resemblance to a lion's face) is characteristic of lepromatous leprosy. It can, however, also occur in conditions such as Paget disease of bone, fibrous dysplasia, or renal osteodystrophy.

• Blood work

  • Normal calcium, phosphate, and parathyroid hormone (PTH) levels

  • ↑↑ Serum alkaline phosphatase (ALP)

  • Hyperuricemia

• Urinalysis: ↑ markers of collagen degradation [3]

  • Deoxypyridinoline

  • N-telopeptide, C-telopeptide

  • Hydroxyproline

• X-ray

  • Deformed bones with both sclerotic and osteolytic lesions

    • Sclerotic lesion: focus/foci of ↑ density (usually the result of increased mineralization and/or thickening).

    • Osteolytic lesion: focus/foci of ↓ density (usually the result of decreased demineralization).

  • Thickened cortical bone

    • Coarsened trabeculae; expansion or enlargement of a region of the bone.

    • Skull x-ray: thickening of the diploe; osteoporosis circumscripta (cotton wool appearance).

    • Vertebral x-ray: thickening of the upper and lower plates of the vertebral body gives rise to a “picture frame” appearance; diffuse enlargement of the vertebrae (ivory vertebra)

    • Pelvic x-ray: disruption/fusion of sacroiliac joints; thickened iliopectineal line (brim sign)

• Bone scans (skeletal scintigraphy): to test for additional bony lesions

Paget disease of the skull

X-ray skull (lateral view)

The calvarium is markedly thickened (left right arrow), with widening of the diploic space. Numerous ill-defined lytic (examples indicated by green overlay) and sclerotic (examples indicated by red overlay) lesions are present.

The presence of multiple poorly marginated sclerotic lesions in Paget disease has been termed “cotton wool appearance.”

X-ray pelvis

Enlargement of the right hemipelvis is accompanied by coarsened trabeculation and areas of sclerosis compatible with abnormal remodeling in Paget disease (green overlay).

Paget disease of bone

Radionuclide bone scan

An increased uptake of radionuclide is visible in the calvaria.

Enhanced radionuclide uptake indicates an active Pagetic lesion and is caused by a localized increase in vascularity and bone remodeling.

Pelvic bone scan: increased enhancement, especially of the right pelvis

Paget disease of lower leg

X-ray right lower leg (left: AP view; right: lateral view)

The tibia is heterogeneous in appearance, with multiple lytic (examples indicated by green overlay) and sclerotic areas (example shown with S and black arrows), coarsened trabeculae, and cortical thickening characteristic of Paget disease. There is lesser involvement of the fibula. Anterior bowing of the tibia, as seen in this patient, is sometimes termed “saber shin deformity” or “saber tibia.”

Paget disease of bone

CT head (axial plane; bone window)

The diploic space of the calvarium is widened and the cortex is thickened. There are numerous ill-defined lucent and sclerotic areas (arrows), which may produce a characteristic cotton-wool appearance.

• Bone metastases

• Primary hyperparathyroidism

• Osteopetrosis (marble bone disease)

• Fibrous dysplasia

• First-line: bisphosphonates

  • Bisphosphonates induce apoptosis of osteoclasts

    • Oral bisphosphonates: tiludronate, alendronate, risedronate

    • IV bisphosphonates: zoledronate, pamidronate

• Second-line: calcitonin therapy [7]

  • Less effective than bisphosphonate therapy

  • May be used when bisphosphonates are poorly tolerated by patients

  • Administered as a subcutaneous injection

  • Side effects include facial flushing, nausea, and tachyphylaxis.

• Supportive therapy

  • Vitamin D3 (cholecalciferol) and calcium

  • NSAIDs may be used in addition to bisphosphonates to treat pain.

• Bone deformities

• Pathological fractures

• Osteoarthritis

• Malignant degeneration into osteosarcoma (very rare: < 1% of cases)

• High-output cardiac failure (due to the formation of arteriovenous shunts within the bone, which leads to an increased overall blood flow)