Pharmacotherapy of Paget's Disease of Bone: Focus on Zoledronic Acid

Paget’s disease of bone (PDB) affects 1%–3% of the population and is associated with increased risk for bone fracture and deformity. Increased osteoclastic activity is the principal characteristic of PDB. Bisphosphonates inhibit osteoclastic activity and represent the mainstay of treatment of PDB. Zoledronic acid, a potent member of this class, normalizes serum alkaline phosphatase (ALP) levels in the majority of patients with PDB and induces sustained disease remissions. It appears to be more effective than both risedronate and pamidronate. However, it is not clear whether bisphosphonates, including zoledronic acid, improve the clinical outcome of patients with PDB. Zoledronic acid was associated with increased risk for atrial fi brillation and osteonecrosis of the jaw in some studies in patients with osteoporosis and cancer, respectively, but not in patients with PDB. Until we have data on the effects of bisphosphonates on clinical outcomes in PDB such as fracture, deformity and osteosarcoma, we must base therapeutic decisions on the data regarding the effects of these agents on disease activity markers (such as serum ALP levels) and bone pain.