Biochemical and radiologic improvement in Pagetʹs disease of bone treated with alendronate: A randomized, placebo-controlled trial

Purpose The potent bisphosphonates offer great promise in the management of Pagetʹs disease of bone, but are currently available only as parenteral preparations in most countries. There is a need for a well-tolerated, oral therapy. Furthermore, none of the currently available therapies have been rigorously demonstrated to heal the lytic bone lesions characteristic of this condition. Alendronate is a potent new oral aminobisphosphonate that has shown promising effects on Pagetʹs disease in preliminary studies. Methods We report a double-blind, randomized comparison of oral alendronate 40 mg/day and placebo over 6 months in 55 patients with Pagef s disease. Efficacy was determined from measurements of biochemical indices of bone turnover (serum alkaline phosphatase and urine N-telopeptide) and blinded radiologic assessment of lytic bone lesions. Results N-telopeptide excretion declined by 86% and serum alkaline phosphatase by 73% in patients receiving alendronate, but remained stable in patients receiving placebo (P< 0.001 between groups for both indices). Responses were similar whether or not patients had previously received bisphosphonate treatment. Alendronate treatment normalized alkaline phosphatase in 48% of patients. Forty-eight percent of alendronate-treated patients showed radiologic improvement in osteolysis whereas in the placebo group only 4% improved (P = 0.02 for between-groups comparison). No patient in either group showed worsening of osteolysis. Bone histomorphometry indicated that alendronate tended to normalize turnover indices. There was no evidence of abnormal mineralization in bone biopsies taken from 12 alendronate-treated subjects. The treatment was well tolerated. Conclusion Oral alendronate appears to be a safe and effective therapy for Pagetʹs disease and results in healing of lytic bone lesions.