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Paget's disease of bone

Description

Paget’s disease of bone (PDB), also known as osteitis deformans, is a skeletal disorder characterized by focal accelerated bone remodeling. Although it is most often asymptomatic, PDB can lead to both skeletal complications (including bone pain, deformity, and fracture) and non-skeletal complications (including arthritis, hearing loss, and hypercalcemia).

Clinical manifestations

Asymptomatic PDB is often diagnosed following an elevated alkaline phosphatase on routine laboratory testing, or as a typical radiologic abnormality (see below) incidentally noted on a study done for another reason. PDB may affect a single site (monostotic) or multiple sites (polyostotic).  The most commonly affected sites are the pelvis, skull, vertebra, femur and tibia.

Symptoms of PDB may include:

  • Bone pain, often worse at night
  • Warmth of the skin over areas of involvement
  • Skeletal deformity, such as bowing of the long bones or cranial deformities
  • Fracture
  • Osteoarthritis of adjacent joints
  • Hearing loss, due to involvement of the otic capsule
  • Nerve compression
  • High-output congestive heart failure, due to increased blood flow in cases of extensive skeletal involvement
  • Hypercalcemia, due to increased bone turnover especially in the setting of immobilization
  • Osteosarcoma (rare, occurs in less than 1% of patients with PDB)

Red flags

Elevated alkaline phosphatase of bone origin should lead to further evaluation for skeletal disorders including PDB. Persistent and worsening bone pain in a patient with PDB should raise concern for the development of osteosarcoma.

Epidemiology

PDB is common in areas with populations of western European ancestry — prevalence in Great Britain and the United States, for example, is approximately 2% of the population over age 55. It is the second most common metabolic bone disease after osteoporosis. The vast majority of persons (approximately 95%) with PDB are asymptomatic.

Pathology and pathophysiology

PDB is initially associated with an increase in osteoclast activity and number, resulting in enhanced bone resorption. This is followed by increased osteoblast activity and bone formation. The resulting bone is poorly structured and is susceptible to bowing or fracture. Eventually, the bone becomes sclerotic as remodeling slows.

Differential diagnosis

  • Vitamin D deficiency can raise alkaline phosphatase levels; therefore, vitamin D levels should be assessed in patients with elevated alkaline phosphatase.
  • Immobilization of patients with PDB can result in hypercalcemia. Measurement of PTH is useful to differentiate primary hyperparathyroidism from PDB.

Etiology

The cause of PDB is uncertain. Between 5% and 40% of patients with PDB have a first degree relative with the disease, suggesting genetic and/or environmental components. Genetic studies have implicated mutations in the sequestosome1 (SQSTM1) gene in a portion of patients.  Viral infection with a paramyxovirus has also been hypothesized.

Radiographic and laboratory findings

Patients with PDB should have a bone scan to demonstrate the extent and distribution of the disease, as well as plain films of high-risk sites noted on the bone scan. Plain X-rays may demonstrate:

  • Wedge, V-shaped, or “blade of grass” osteolytic front
  • Cortical thickening
  • Osteosclerosis
  • Bowing of affected long bones

Aside from alkaline phosphatase, measurement of other markers of bone turnover is not usually necessary.

Risk factors and prevention

Patients with a first-degree relative with PDB are at increased risk of developing PDB.  There are no known primary prevention strategies for PDB, but some patients with PDB may benefit from secondary prevention strategies to reduce complications of PDB (see Treatment Options).

Treatment options

Most patients with PDB do not require treatment. The best evidence for treatment benefit is in the reduction of bone pain. Others who may benefit from treatment include symptomatic patients with headache due to skull involvement, bone deformities (especially facial), nerve compression, or hearing loss; in patients prior to elective surgery on Pagetic bone; in patients with hypercalcemia; or as a preventive strategy in patients with disease at “high-risk” sites such as weight-bearing bones, bones adjacent to major joints, or with extensive skull or vertebral involvement.

Current first-line medical therapy is a bisphosphonate, either orally or intravenously.nbsp; Calcitonin can be considered as second-line treatment. Surgical treatment of fracture, deformity or nerve compression is performed when indicated. Physical therapy, orthotics, or canes may benefit some patients.

Outcomes

Bisphosphonate treatment typically results in a decline of alkaline phosphatase in 3 to 6 months. Treatment may be repeated if there is a return of symptoms or a rise in alkaline phosphatase levels.

Holistic medicine

Avoidance of immobilization reduces the risk of hypercalcemia in patients with PDB

Miscellany

  • PDB does not typically “spread” — it is unusual for new sites of involvement to develop after the initial diagnosis of PDB.
  • In previous generations, patients with skull involvement of PDB presented with changes in hat size.

Key terms

Paget’s disease of bone, osteitis deformans

Skills and competencies

  • Recognize the symptoms, signs, and radiologic, and lab findings of Paget’s disease of bone.
  • Distinguish patients with PDB who do or do not require intervention, and describe what interventions may be appropriate.
Content

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