Initial Treatment for Paget's Disease of Bone
Bisphosphonates are the first-line treatment for Paget's disease of bone, with intravenous zoledronic acid being the most effective option, achieving normalization of alkaline phosphatase in 89-96% of patients with a single 5 mg infusion. 1, 2
Primary Treatment Options
Zoledronic Acid (Preferred)
- A single 15-minute intravenous infusion of 5 mg zoledronic acid is the most effective therapy available, producing therapeutic response in 96% of patients compared to 74.3% with risedronate 2
- Normalizes serum alkaline phosphatase in 88.6-89% of patients 3, 2
- Provides more rapid response (median 64 days vs. 89 days for risedronate) and more sustained remission 2
- During follow-up (median 190 days), only 1 of 113 patients lost therapeutic response compared to 21 of 82 patients on risedronate 2
Oral Bisphosphonates (Alternative Options)
- Risedronate 30 mg daily for 60 days is effective but less potent than zoledronic acid, with contraindication in patients with GFR <30 mL/min/1.73 m² 1, 4
- Alendronate can be used but is not recommended in patients with GFR <35 mL/min/1.73 m² 1
- Pamidronate has sustained effects for months following a single injection 1
Treatment Indications
Bisphosphonate therapy is indicated for:
- Symptomatic patients with bone pain, joint pain, or neurological complications referable to pagetic sites 3
- Asymptomatic patients with active disease at sites susceptible to local progression and late complications 3
- Patients requiring elective surgery at an active pagetic site to reduce intraoperative blood loss 3
- Rare instances of immobilization hypercalcemia with polyostotic disease 3
Essential Supportive Therapy
All patients must receive calcium and vitamin D supplementation to prevent hypocalcemia, which is mandatory with potent anti-osteoclast therapies 3, 5
Important Contraindications and Precautions
Teriparatide (PTH 1-34) is Contraindicated
- Never use teriparatide in Paget's disease due to increased baseline risk of osteosarcoma 6
- This contraindication applies to patients with Paget's disease, open epiphyses, or prior skeletal radiation 6
Renal Impairment Considerations
- Risedronate: contraindicated if GFR <30 mL/min/1.73 m² 1, 4
- Alendronate: not recommended if GFR <35 mL/min/1.73 m² 1
- Dose adjustments or alternative agents needed based on renal function 1
Expected Adverse Effects
Zoledronic Acid
- Acute phase reaction with fever and flu-like symptoms may occur with first dose, primarily in bisphosphonate-naïve patients 3
- This is typically self-limited and occurs less frequently with subsequent doses
Oral Bisphosphonates
- Esophageal irritation occurs in a minority of patients with alendronate and risedronate 3
- Take on empty stomach with full glass of water, remain upright for 30 minutes
Clinical Outcomes
- Biochemical remission is achievable in the majority of patients with potent nitrogen-containing bisphosphonates 3
- Treatment improves bone pain in symptomatic patients, with zoledronic acid most likely to provide favorable pain response 7
- Quality of life scores (SF-36 physical component) improve significantly with zoledronic acid at 3 and 6 months 2
- Short-term studies demonstrate promotion of lamellar bone formation and improved radiographic appearances 7