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Paget's disease

Background

Overview

Definition
Paget's disease is a chronic non-inflammatory skeletal disorder characterized by excessive and abnormal bone remodeling, resulting in deformed, enlarged, and biomechanically unstable bone.
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Pathophysiology
Paget's disease is caused by osteoclastic abnormalities due to genetic mutations (sequestosome 1 gene), with some evidence suggesting a role for chronic paramyxovirus infection.
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Epidemiology
In the US, the estimated prevalence of Paget's disease ranges from 0.9% to 3.9%.
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Disease course
In patients with Paget's disease, hyperosteoclastosis with associated fibrosis and disorganized bone deposition results in a mosaic of woven bone that is mechanically weak, and increases the risk of fracture and deformity. Platybasia, leontiasis, cranial neuropathy, radiculopathies, osteosarcomas, chondrosarcomas, and fibrosarcoma may develop as a consequence.
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Prognosis and risk of recurrence
Progression to osteosarcoma is associated with poor prognosis, even with aggressive operative management.
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Guidelines

Key sources

The following summarized guidelines for the evaluation and management of Paget's disease are prepared by our editorial team based on guidelines from the Paget's Association (PA 2019) and the Endocrine Society (ES 2014).
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Diagnostic investigations

Laboratory evaluation: as per PA 2019 guidelines, obtain serum total ALP (in conjunction with liver biochemical tests) as part of the initial laboratory evaluation for the presence of metabolically active Paget's disease.
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  • Plain radiographs

  • Radionuclide bone scan

  • MRI and CT

Medical management

Bisphosphonates: as per PA 2019 guidelines, initiate bisphosphonate therapy for the treatment of bone pain associated with Paget's disease. Use zoledronic acid as the bisphosphonate most likely to give a favorable pain response.
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  • Calcitonin

  • Denosumab

  • Treatment targets

  • Management of spinal cord dysfunction

Surgical interventions

Management of bone fractures
As per PA 2019 guidelines:
Perform surgery for fixation of fractures through affected bone in patients with Paget's disease, recognizing that the clinical outcome in femoral neck and subtrochanteric fractures is poor.
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Insufficient evidence to recommend one type of surgical treatment over another.
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  • Management of osteoarthritis

  • Management of spinal stenosis

Specific circumstances

Patients with hearing loss: as per PA 2019 guidelines, insufficient evidence to recommend bisphosphonate therapy to prevent progression of hearing loss in patients with Paget's disease.

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  • Patients with osteoarthritis

  • Patients undergoing orthopedic or spinal surgery

  • Patients with osteosarcoma

  • Patients with congestive HF

Patient education

Counseling on bisphosphonates: as per PA 2019 guidelines, inform patients undergoing treatment with bisphosphonates for Paget's disease that this class of medication has a favorable adverse event profile. Advise patients that a transient flu-like illness occurs commonly with intravenous zoledronic acid.
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Follow-up and surveillance

Post-treatment follow-up: as per ES 2014 guidelines, use biochemical markers as a more objective indicator of relapse than symptoms in patients with increased bone turnover.
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