Randomized trial of intensive bisphosphonate treatment versus symptomatic management in Paget's disease of bone

Bisphosphonates are widely regarded as the treatment of choice for Paget's disease of bone (PDB) because of their potent inhibitory effects on bone turnover, but the effects of bisphosphonate therapy on symptoms and complications of PDB have been little studied. Here we report the results of a randomized trial that compared the effects of symptomatic treatment with intensive bisphosphonate therapy in a cohort of 1324 patients with PDB who were followed up for a median of 3 years (range 2 to 5 years). The symptomatic treatment group was treated only if they had pagetic bone pain, for which they were first given analgesics or anti-inflammatory drugs, followed by bisphosphonates if they did not respond. The intensive group received repeat courses of bisphosphonates irrespective of symptoms with the aim of reducing and maintaining serum alkaline phosphatase (ALP) levels within the normal range. The endpoints were fracture, orthopedic surgery, quality of life, bone pain, and hearing thresholds. Serum ALP levels were significantly lower in the intensive treatment group than in with the symptomatic treatment group within 4 months of commencing treatment and remained lower throughout the study (p