BIOCHEMICAL AND RADIOLOGIC IMPROVEMENT IN PAGETS-DISEASE OF BONE TREATED WITH ALENDRONATE - A RANDOMIZED, PLACEBO-CONTROLLED TRIAL

PURPOSE: The potent bisphosphonates offer great promise in the managem ent of Paget's disease of bone, but are currently available only as pa renteral preparations in most countries. There is a need for a well-to lerated, oral therapy. Furthermore, none of the currently available th erapies have been rigorously demonstrated to heal the lytic bone lesio ns characteristic of this condition. Alendronate is a potent new oral aminobisphosphonate that has shown promising effects on Paget's diseas e in preliminary studies. METHODS: We report a double-blind, randomize d comparison of oral alendronate 40 mg/day and placebo over 6 months i n 55 patients with Paget's disease. Efficacy was determined from measu rements of biochemical indices of bone turnover (serum alkaline phosph atase and urine N-telopeptide) and blinded radiologic assessment of ly tic 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 gr oups for both indices). Responses were similar whether or not patients had previously received bisphosphonate treatment. Alendronate treatme nt normalized alkaline phosphatase in 48% of patients. Forty-eight per cent 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 worseni ng of osteolysis. Bone histomorphometry indicated that alendronate ten ded to normalize turnover indices. There was no evidence of abnormal m ineralization in bone biopsies taken from 12 alendronate-treated subje cts. The treatment was well tolerated. CONCLUSION: Oral alendronate ap pears to be a safe and effective therapy for Paget's disease and resul ts in healing of lytic bone lesions.