What is the initial treatment for Paget's disease?

Initial Treatment for Paget's Disease of Bone

The initial treatment of choice for symptomatic Paget's disease of bone is a single 5 mg intravenous infusion of zoledronic acid, which provides the most rapid, complete, and sustained response compared to other bisphosphonates. 1

Diagnosis and Evaluation

Before initiating treatment, proper diagnosis and assessment should include:

• Laboratory tests:

  • Serum alkaline phosphatase (primary marker of disease activity)
  • Calcium, 25-hydroxy-vitamin D, parathyroid hormone levels, and phosphate 2
  • Complete blood count and renal function tests (for treatment safety assessment)

• Imaging:

  • Plain radiographs of affected areas showing characteristic mixed lytic and sclerotic changes
  • Bone scan to assess extent of disease involvement
  • MRI or CT may be needed in complex cases 2

Treatment Indications

Treatment is indicated for patients with:

1. Symptomatic disease (bone pain, joint pain, neurological complications)
2. Elevated alkaline phosphatase at least twice the upper limit of normal
3. Active disease at sites at risk for future complications
4. Planned surgery at an affected site to reduce bleeding risk 3

Treatment Algorithm

First-line Treatment:

• Zoledronic acid 5 mg IV as a single 15-minute infusion 1
  • Achieves normalization of alkaline phosphatase in 88.6% of patients
  • Provides faster response (median 64 days vs 89 days with risedronate)
  • Offers more sustained remission with minimal relapse rates

Alternative Options (if zoledronic acid is contraindicated):

1. Alendronate 40 mg daily for 6 months 4

   • FDA-approved regimen for Paget's disease
   • Response rate approximately 85%

2. Risedronate 30 mg daily for 2 months

   • Response rate approximately 74% 1

3. Pamidronate IV (less effective than zoledronic acid)

Second-line Options:

• Etidronate 5 mg/kg daily for 6 months 5
• Tiludronate (less potent than nitrogen-containing bisphosphonates) 3

Important Considerations

• Calcium and vitamin D supplementation is mandatory with bisphosphonate therapy to prevent hypocalcemia 3

• Potential side effects:

  • IV bisphosphonates (zoledronic acid, pamidronate): acute phase reaction with fever and flu-like symptoms after first dose
  • Oral bisphosphonates (alendronate, risedronate): esophageal irritation
  • All bisphosphonates: risk of hypocalcemia if calcium/vitamin D insufficient

• Treatment monitoring:

  • Measure serum alkaline phosphatase 3-6 months after treatment
  • Consider retreatment if alkaline phosphatase increases again or symptoms return 4

Important Pitfalls to Avoid

1. Treating asymptomatic patients with normal or mildly elevated alkaline phosphatase levels - The PRISM trial showed intensive bisphosphonate therapy aimed at normalizing alkaline phosphatase was no more effective than symptom-directed treatment in preventing complications 6

2. Failing to rule out other metabolic bone diseases that may mimic Paget's disease, including osteomalacia, hypophosphatasia, and fibrous dysplasia 2

3. Overlooking renal function - Bisphosphonates should be used with caution or avoided in patients with moderate to severe renal impairment 5

4. Inadequate calcium and vitamin D supplementation during treatment, which can lead to hypocalcemia 3

5. Routine bone biopsies are not recommended and should be reserved for cases with inconclusive imaging or suspicion of malignancy 2

By following this treatment approach, most patients with symptomatic Paget's disease will achieve biochemical remission and significant improvement in bone pain and quality of life.