What is the primary management for Paget disease of bone?

Primary Management of Paget's Disease of Bone

Bisphosphonate therapy is the mainstay of treatment for symptomatic Paget's disease of bone, with zoledronic acid being the most effective agent currently available. A single 5 mg intravenous infusion of zoledronic acid leads to sustained reduction in bone pain and markers of bone turnover 1.

Diagnosis and Assessment

• Diagnosis is typically made through:

  • Radiographic findings showing characteristic sclerotic or lytic lesions
  • Elevated serum alkaline phosphatase (ALP) levels
  • Radionuclide bone scan to determine the extent of disease 1

• Most cases are discovered incidentally through:

  • Routine blood tests showing isolated elevation of ALP
  • Radiographs performed for other reasons 2

Indications for Treatment

Treatment is indicated for:

1. Symptomatic patients with:

   • Bone pain directly attributable to pagetic activity
   • Joint pain adjacent to pagetic sites
   • Neurological complications due to bone compression
   • Planned surgery at an active pagetic site 3

2. Asymptomatic patients with:

   • Disease at sites at risk for future complications (skull, spine, weight-bearing bones)
   • Immobilization hypercalcemia with polyostotic disease 3

Note: Bisphosphonates should be reserved for symptomatic patients, as treatment has been associated with increased fracture rates in asymptomatic Paget's disease 2.

Treatment Algorithm

1. First-line therapy: Nitrogen-containing bisphosphonates

   • Zoledronic acid: 5 mg IV as a single infusion (preferred)

     • Normalizes serum ALP in 89% of patients
     • Provides prolonged biochemical remission
     • Most effective at relieving bone pain 3, 4

   • Alternative options:

     • Alendronate: 40 mg daily for 6 months 5
     • Risedronate: 30 mg daily for 2 months
     • Pamidronate: 60-90 mg IV every 3 months

2. Second-line therapy (if first-line agents contraindicated):

   • Etidronate: 5 mg/kg daily for 6 months 6
   • Tiludronate: 400 mg daily for 3 months

3. Supportive measures:

   • Calcium and vitamin D supplementation (mandatory with bisphosphonate therapy)
   • Pain management as needed
   • Orthopedic consultation for fractures or spinal cord compression 7

Monitoring Treatment Response

• Measure serum ALP levels at 3-6 months after treatment
• Goal is normalization or significant reduction in ALP
• Consider retreatment if:
  • Symptoms recur
  • ALP rises to >25% above normal limit 1
  • At least 6 months have passed since initial treatment 5

Special Considerations

1. Before starting bisphosphonates:

   • Dental examination to reduce risk of osteonecrosis of the jaw 7
   • Ensure adequate renal function
   • Correct vitamin D deficiency

2. Side effects to monitor:

   • Acute phase reaction with IV bisphosphonates (fever, flu-like symptoms)
   • Esophageal irritation with oral agents
   • Hypocalcemia (preventable with calcium/vitamin D)
   • Osteonecrosis of the jaw (rare) 3

3. Acquired resistance:

   • Some patients develop resistance to etidronate or pamidronate
   • Switching to a different bisphosphonate typically restores response 3

Evidence Quality Assessment

The evidence supporting bisphosphonate use in Paget's disease is of moderate quality. While bisphosphonates clearly improve biochemical markers and bone pain (moderate-quality evidence), there is insufficient evidence regarding their effect on complications such as fractures, deformity, and hearing loss 8. The Cochrane review found that bisphosphonates tripled the proportion of patients whose bone pain disappeared compared to placebo (31% vs. 9%) 8.