What is Paget's disease?

Paget's Disease of Bone: Diagnosis and Management

Paget's disease of bone is a common skeletal disorder characterized by increased and disorganized bone remodeling, typically affecting people over 55 years of age, with bisphosphonate therapy being the mainstay of treatment for symptomatic patients. 1, 2

Clinical Presentation

Paget's disease of bone (PDB) has the following characteristics:

• Most patients (majority) are asymptomatic, with diagnosis often made incidentally through:

  • Abnormal radiographic findings
  • Isolated elevation of serum alkaline phosphatase 1, 3

• When symptomatic, common presentations include:

  • Bone pain (most common symptom)
  • Bone deformities (bowing of long bones, enlarged skull)
  • Fractures
  • Arthritis
  • Nerve compression syndromes
  • Hearing loss 1, 3

• Typical age of onset: Usually >50 years 4

• Distribution patterns:

  • Can be monostotic (single bone) or polyostotic (multiple bones)
  • Most commonly affects pelvis, femur, spine, tibia, skull, and humerus 5

Diagnostic Approach

Laboratory Testing

• Serum alkaline phosphatase (ALP): Key biomarker that correlates with disease activity 3
• Other tests may include:
  • Calcium levels (usually normal)
  • Vitamin D levels (to rule out other metabolic bone diseases) 2

Imaging Studies

• Plain radiographs: Show characteristic mixed osteolytic and osteosclerotic lesions 4
• Radionuclide bone scan: Most sensitive test for determining extent of disease 3, 6
• Consider whole-body imaging to map clinically silent lesions 4

Differential Diagnosis

Key conditions to consider in the differential diagnosis include:

• Malignant bone tumors
• Fibrous dysplasia
• Osteoarthritis (when near joints)
• Osteomalacia
• Hypophosphatasia 4

Treatment Algorithm

Indications for Treatment

1. Symptomatic patients:

   • Bone pain
   • Active disease at sites at risk for complications
   • Preparation for orthopedic surgery in affected bone
   • Neurologic complications 2, 6

2. Asymptomatic patients with:

   • Disease in weight-bearing bones
   • Disease adjacent to major joints
   • Vertebral involvement
   • Skull base involvement
   • Sites where progression could cause complications 2

First-Line Treatment

• Bisphosphonates are the mainstay of therapy:
  • Zoledronic acid (5 mg IV single infusion): Most effective agent, providing sustained reduction in bone pain and markers of bone turnover 1, 6
  • Alternative options:
    • Pamidronate (APD)
    • Alendronate
    • Risedronate 3

Special Considerations

• Bisphosphonates should be reserved for symptomatic patients or those at high risk of complications
• Caution: Treatment with bisphosphonates in asymptomatic patients has been associated with increased fracture rates 1
• Patients who cannot tolerate bisphosphonates may be treated with calcitonin 3

Monitoring and Follow-up

• Monitor serum alkaline phosphatase levels to assess treatment response
• Clinical evaluation for symptom improvement
• Follow-up imaging may be necessary to assess disease progression or response to therapy 2, 6

Common Pitfalls to Avoid

• Treating all asymptomatic patients without considering risk of complications
• Failing to monitor for treatment response
• Missing malignant transformation (rare but serious complication)
• Overlooking other metabolic bone diseases with similar presentations 5, 2

Paget's disease is a chronic condition that requires individualized management based on disease extent, symptoms, and risk of complications. The availability of effective treatments like zoledronic acid has significantly improved outcomes for patients with this condition.