What is the typical management of Paget's disease of bone?

Management of Paget's Disease of Bone

Bisphosphonates are the mainstay of treatment for Paget's disease of bone, with alendronate 40 mg once daily for six months being the recommended treatment regimen for symptomatic patients. 1

Diagnosis and Clinical Features

• Paget's disease is a common destructive condition affecting 1-2% of the population over age 55, characterized by focal increased bone remodeling activity resulting in sclerotic or lytic lesions 2
• Most cases are diagnosed incidentally on radiographs or as an isolated elevation of serum alkaline phosphatase 2
• Symptomatic patients present with bone pain, fractures, arthritis, and features of compression neuropathy 2
• Diagnosis is made based on typical radiological features on plain films, while radionuclide bone scan may be used to assess the extent of disease 3

Treatment Indications

Treatment is indicated in the following situations:

• Patients who are symptomatic with bone pain, joint pain, or neurological complications 4
• Prior to elective surgery at an active pagetic site to reduce intraoperative blood loss 4
• Management of rare instances of immobilization hypercalcemia with polyostotic disease 4
• Patients with alkaline phosphatase at least two times the upper limit of normal 1
• Patients who are at risk for future complications from their disease 1

First-Line Treatment: Bisphosphonates

Oral Alendronate

• The FDA-approved regimen for Paget's disease is alendronate 40 mg once daily for six months 1
• Re-treatment may be considered following a six-month post-treatment evaluation period in patients who have relapsed, based on increases in serum alkaline phosphatase 1
• Response (defined as either normalization of serum alkaline phosphatase or decrease from baseline ≥60%) occurs in approximately 85% of patients treated with alendronate 1

Administration Instructions

• Take alendronate at least 30 minutes before the first food, beverage, or medication of the day with plain water only 1
• Patients should not lie down for at least 30 minutes and until after their first food of the day 1
• Calcium and vitamin D supplementation should be provided if dietary intake is inadequate 1

Alternative Bisphosphonates

• Zoledronic acid (5 mg intravenous infusion) is currently considered the most effective agent, with a single infusion leading to normalization of serum alkaline phosphatase in 89% of patients and providing prolonged biochemical remission 4, 3
• Pamidronate has sustained effects for months following a single injection in Paget's disease 5, 6
• Risedronate is also effective but contraindicated in patients with GFR less than 30 ml/min/1.73 m² 6

Treatment Considerations

• Bisphosphonates should be reserved for symptomatic patients, as treatment with these agents has been associated with increased fracture rates in asymptomatic patients 2
• A randomized trial comparing intensive bisphosphonate therapy versus symptomatic management found that striving to maintain normal alkaline phosphatase levels with intensive therapy conferred no clinical advantage over symptom-driven management 7
• For patients with renal impairment, dose adjustments or alternative agents may be needed based on GFR, with alendronate not recommended in patients with GFR less than 35 ml/min/1.73 m² 6

Monitoring and Follow-up

• Monitor serum alkaline phosphatase periodically to assess treatment response and determine need for re-treatment 1
• Re-treatment with alendronate may be considered following a six-month post-treatment evaluation period in patients who have relapsed 1
• Bone histology evaluations in patients with Paget's disease treated with alendronate 40 mg/day for 6 months showed that normal lamellar bone was produced during treatment, even where preexisting bone was woven and disorganized 1

Clinical Pitfalls to Avoid

• Treating asymptomatic patients without clear indications, as bisphosphonate therapy has been associated with increased fracture rates in asymptomatic patients 2
• Using bisphosphonates in patients with significant renal impairment without appropriate dose adjustments 6
• Failing to provide adequate calcium and vitamin D supplementation during bisphosphonate therapy, which can lead to hypocalcemia 4
• Discontinuing therapy abruptly without considering the potential for disease relapse 1