Bisphosphonates for Paget disease of bone

Bisphosphonates inhibit bone resorption and reduce the abnormal bone remodelling caused by Paget disease to normal or near-normal. For indications for bisphosphonate therapy and aims of treatment, see Principles of managing Paget disease of bone.

A single dose of an intravenous bisphosphonate or a short course of an oral bisphosphonate can produce prolonged clinical and biochemical remission that persists after withdrawal of therapy. A repeat course of therapy is occasionally required if serum total alkaline phosphatase remains elevated after the initial treatment, but continuous long-term treatment is not recommended—the long-term benefit of treating Paget disease with a bisphosphonate beyond 2 to 3 years is unknown.

Intravenous zoledronic acid appears to be the most effective bisphosphonate for Paget disease; the vast majority of patients achieve sustained remission following a single dose of zoledronic acid.

Use:

Intravenous administration of zoledronic acid in primary care is safe provided that:

• serum 25-hydroxyvitamin D concentration is greater than 50 nanomol/L
• serum total calcium concentration corrected for albumin is in the normal range (2.10 to 2.60 mmol/L)
• estimated glomerular filtration rate (eGFR) is greater than 35 mL/min/1.73 m²
• the patient is well hydrated.

Markers of bone resorption are suppressed quickly following antipagetic treatment, while the serum total alkaline phosphatase concentration can take more than 3 months to reach its nadir. Measure the serum total alkaline phosphatase concentration 3 to 6 months after giving zoledronic acid. A single dose of zoledronic acid is usually effective. Persistent elevation of serum total alkaline phosphatase concentration following zoledronic acid should prompt consideration of an alternative cause (eg osteosarcoma, bony metastasis).

If zoledronic acid is not appropriate, use:

Measure the serum total alkaline phosphatase concentration 3 months after completing the course of therapy, to determine whether the patient has achieved biochemical remission. If the serum total alkaline phosphatase concentration remains elevated or if the patient still has symptoms, consider a repeat course of treatment after 6 to 12 months. If a patient does not respond to repeat therapy, review the diagnosis of Paget disease.

In a patient with a progressive rise in serum total alkaline phosphatase concentration or atypical bone pain with neuropathic complications, investigate the possibility of malignancy; osteogenic sarcoma is an exceedingly rare complication of Paget disease.

In refractory Paget disease, consider trialling an alternative bisphosphonate (eg change from oral to intravenous bisphosphonate). Resistance to pamidronate can occur, particularly following repeated infusions.