• Clinical science

Paget disease of bone (Osteitis deformans)

Abstract

Paget disease of bone (PDB, or osteitis deformans) is a slowly progressive monostotic or polyostotic skeletal disease. It is characterized by increased bone turnover, which causes normal lamellar bone to be replaced by weak woven bone. The cause of this common yet underdiagnosed skeletal disease is not known. It predominantly affects individuals over the age of 55 and is characterized by localized pain and bony deformities (such as bowing of long bones). Skeletal x-ray, bone scans, and serum alkaline phosphatase are important tests for diagnosing and monitoring the progression of PDB. Treatment is mainly supportive and involves the use of bisphosphonates to inhibit osteoclastic function.

Paget disease of the bone should not be confused with Paget disease of the nipple (see breast carcinoma) or Paget disease of the vulva (see vulval carcinoma), which are named after the same physician.

Epidemiology

  • Second most prevalent skeletal disease after osteoporosis
  • Sex: > (1.2:1)
  • Age of onset: > 55 years


References:[1][2][3]

Epidemiological data refers to the US, unless otherwise specified.

Pathophysiology

  • PDB is an idiopathic disease.
  • PDB is associated with a high rate of bone remodeling.
    • RANKL-RANK activityNF-κB signalingosteoclast activityosteoblast activity → formation of disorganized (woven) bone
  • Bone remodeling in Paget disease occurs in three phases:
    1. Lytic phase: increased number of osteoclasts, which are larger than usual and have more than the usual number of nuclei, appear in bone → increased osteoclastic activity → increased rate of bone resorption
    2. Mixed lytic and blastic phase: increased osteoclastic activity is accompanied by an increased number of osteoblasts, which retain a normal morphology → increased rate of bone formation with haphazardly laid collagen fibers → abnormal woven bone that is hypervascular
    3. Sclerotic phase (quiescent phase): Osteoclastic activity and osteoblastic activity eventually cease.
  • Disease localization: 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)


References:[1][2][4]

Clinical features


References:[1][2]

Diagnostics

  • Laboratory tests
  • Conventional x-ray
    • Deformed bones with both sclerotic and osteolytic lesions Sclerotic lesions are generally associated with slow-growing bony lesions and reflect an attempt by the bone to wall off and limit the pathology. Osteolytic lesions are usually the result of rapidly progressive lesions and are evidence of local bone destruction or removal of diseased bone tissue by the osteoclasts.
    • 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 spots).
      • 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 should be considered in an asymptomatic patient who presents with isolated ALP elevation that cannot be explained by any other means (e.g., cholestasis or bone metastases)!

References:[5][2][6][7][8]

Differential diagnoses

Osteopetrosis

Fibrous dysplasia

The 3 P's of McCune-Albright syndrome: Polyostotic fibrous dysplasia, Pigmentation (cafe au lait spots), Precocious puberty

References:[5][9][10][11][12][13][14]

The differential diagnoses listed here are not exhaustive.

Treatment

Medical therapy

Medical therapy should be initiated among all patients with active disease (raised ALP levels or active disease foci on skeletal scintigraphy).

Surgical therapy

Surgical therapy may be indicated in patients with bone deformities and/or pathological fractures.

References:[5][2][15][16][17]

Complications

References:[5][1][2]

We list the most important complications. The selection is not exhaustive.