What is the initial treatment for Paget's disease?

Initial Treatment for Paget's Disease of Bone

The recommended initial treatment for Paget's disease of bone is a single 5 mg intravenous infusion of zoledronic acid, which produces more rapid, complete, and sustained responses than other bisphosphonates. 1

Indications for Treatment

Treatment is indicated in patients with:

• Symptomatic disease (bone pain, joint pain, neurological complications)
• Alkaline phosphatase at least two times the upper limit of normal
• Active disease at sites susceptible to local progression and complications
• Planned surgery at an affected site 2, 3

First-Line Treatment Options

Zoledronic Acid (Preferred)

• Dosage: Single 5 mg IV infusion over 15 minutes
• Efficacy: 96% therapeutic response rate at 6 months with 88.6% normalization of alkaline phosphatase 1
• Advantages: Rapid onset of action (median 64 days to response), sustained remission (minimal relapse during follow-up), convenient single-dose administration 1, 4

Alternative Oral Bisphosphonates

If IV therapy is not feasible:

• Alendronate:

  • Dosage: 40 mg once daily for six months 3
  • Efficacy: Approximately 85% response rate 3
  • Re-treatment may be considered after six months if alkaline phosphatase increases or symptoms return 3

• Risedronate:

  • Dosage: 30 mg daily for 2 months
  • Efficacy: 74.3% therapeutic response rate at 6 months 1

Monitoring Treatment Response

• Measure serum alkaline phosphatase 3-6 months after treatment 2
• Consider retreatment if alkaline phosphatase increases again or symptoms return 2
• Response is defined as either normalization of serum alkaline phosphatase or decrease from baseline ≥60% 3

Important Considerations

• Calcium and vitamin D supplementation is mandatory with bisphosphonate therapy to avoid hypocalcemia 5
• Administration instructions for oral bisphosphonates:
  • Take at least 30 minutes before first food/beverage of the day with plain water only
  • Remain upright for at least 30 minutes after taking the medication 3

Potential Side Effects

• Zoledronic acid: Acute phase reaction with fever and flu-like symptoms with first dose, particularly in treatment-naïve patients 5
• Oral bisphosphonates: Esophageal irritation in some patients 5

Pitfalls to Avoid

• Failure to rule out other metabolic bone diseases that may mimic Paget's disease, including osteomalacia, hypophosphatasia, and fibrous dysplasia 2
• Overlooking renal function when prescribing bisphosphonates, as they should be used with caution or avoided in patients with moderate to severe renal impairment 2
• Performing unnecessary bone biopsies - these should be reserved for cases with inconclusive imaging or suspicion of malignancy 2

Zoledronic acid has emerged as the most effective therapy for Paget's disease, offering superior rates of normalization of bone turnover markers, longer-lasting remission, and greater convenience compared to oral bisphosphonates 1, 4, 6.