TY - JOUR
T1 - Biochemical and radiologic improvement in Paget's disease of bone treated with alendronate
T2 - A randomized, placebo-controlled trial
AU - Reid, Ian R.
AU - Nicholson, Geoffrey C.
AU - Weinstein, Robert S.
AU - Hosking, David J.
AU - Cundy, Tim
AU - Kotowicz, Mark A.
AU - Murphy, William A.
AU - Yeap, Swan
AU - Dufresne, Suzanne
AU - Lombardi, Antonio
AU - Musliner, Thomas A.
AU - Thompson, Desmond E.
AU - Yates, A. John
N1 - Funding Information:
From the University of Auckland (IRR, TC), Auckland, New Zealand; University of Melbourne (GCN, MAK), Geelong Hospital, Geelong, Victoria, Australia: Universitv of Arkansas for Medical Sciences (RSW), Little Rock, Arkansas; NottinghBm City Hospital [DJH, SY), Nottingham, United Kingdom; University of Texas-MD Anderson Cancer Center (WAM), Houston, Texas; and Merck Research Laboratories (SD, AL, TAM, DET, AJY), Rah-way, New Jersey. This study was supported by grants from Merck Research Laboratories. Requests for reprints should be addressed to IR Reid, Department of Medicine, University of Auckland, Auckland, New Zealand. Manuscript submitted March 4, 1996 and accepted in revised form July 5, 1996.
PY - 1996/10
Y1 - 1996/10
N2 - PURPOSE: The potent bisphosphonates offer great promise in the management of Paget's 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 lyric bone lesions characteristic of this condition. Alendronate is a potent new oral aminobisphosphonate that has shown promising effects on Paget's 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 Paget'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 Paget's disease and results in healing of lyric bone lesions.
AB - PURPOSE: The potent bisphosphonates offer great promise in the management of Paget's 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 lyric bone lesions characteristic of this condition. Alendronate is a potent new oral aminobisphosphonate that has shown promising effects on Paget's 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 Paget'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 Paget's disease and results in healing of lyric bone lesions.
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U2 - 10.1016/S0002-9343(96)00227-6
DO - 10.1016/S0002-9343(96)00227-6
M3 - Article
C2 - 8873503
AN - SCOPUS:10544223736
SN - 0002-9343
VL - 101
SP - 341
EP - 348
JO - American Journal of Medicine
JF - American Journal of Medicine
IS - 4
ER -