Asymptomatic patients may require only clinical surveillance and no treatment. However, treatment with bisphosphonates should be considered for asymptomatic patients who have significant involvement of the skull, long bones, or vertebrae. Patients must be monitored carefully before, during, and after treatment with clinical examinations and serial serum alkaline phosphatase determinations.
Zoledronic acid is the treatment of choice. Administered intravenously as a single 5-mg dose, it normalizes the serum alkaline phosphatase in 89% of patients by 6 months and in 98% by 2 years.
Zoledronic acid should be administered prior to total arthroplasty for a Paget-involved joint in order to reduce the risk of intraoperative hemorrhaging and loosening of the prosthesis postoperatively. Zoledronic acid should also be administered before osteotomy for severe bowing of a lower extremity caused by Paget disease. For patients with paraplegia due to vertebral involvement, intravenous zoledronic acid should be given while neurosurgical consultation is obtained.
Patients frequently experience a paradoxical increase in pain at sites of disease soon after commencing bisphosphonate therapy; this is the “first dose effect” and the pain usually subsides with further treatment. Following intravenous zoledronic acid, patients frequently experience fever, fatigue, myalgia, bone pain, and ocular problems. Serious side effects are rare but include seizures, uveitis, and acute kidney disease. Asthma may occur in aspirin-sensitive patients. Hypocalcemia is common and may be severe, especially if intravenous bisphosphonates are given along with loop diuretics. Therefore, it is advisable to administer calcium and vitamin D supplements, especially during the first 2 weeks following treatment. Any vitamin D deficiency should be corrected before prescribing a bisphosphonate.
Oral bisphosphonate regimens are inferior to intravenous zoledronic acid for therapy of Paget disease. However, if they are given, to prevent esophageal complications, oral bisphosphonates should be taken with 8 oz of plain water only, and the patient must remain upright afterward. Oral bisphosphonates are relatively contraindicated in patients with a history of esophagitis, esophageal stricture, dysphagia, hiatal hernia, or achalasia. Patients who cannot tolerate bisphosphonates may be treated with calcitonin.