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

Ian R. Reid, Geoffrey C. Nicholson, Robert S. Weinstein, David J. Hosking, Tim Cundy, Mark A. Kotowicz, William A. Murphy, Swan Yeap, Suzanne Dufresne, Antonio Lombardi, Thomas A. Musliner, Desmond E. Thompson, A. John Yates

Research output: Contribution to journalArticle

145 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)341-348
Number of pages8
JournalAmerican Journal of Medicine
Volume101
Issue number4
DOIs
StatePublished - Oct 1 1996

Fingerprint

Osteitis Deformans
Alendronate
Randomized Controlled Trials
Placebos
Alkaline Phosphatase
Bone and Bones
Osteolysis
Diphosphonates
Therapeutics
Physiologic Calcification
Bone Remodeling
Serum
Urine
Biopsy

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Reid, I. R., Nicholson, G. C., Weinstein, R. S., Hosking, D. J., Cundy, T., Kotowicz, M. A., ... Yates, A. J. (1996). Biochemical and radiologic improvement in Paget's disease of bone treated with alendronate: A randomized, placebo-controlled trial. American Journal of Medicine, 101(4), 341-348. https://doi.org/10.1016/S0002-9343(96)00227-6

Biochemical and radiologic improvement in Paget's disease of bone treated with alendronate : A randomized, placebo-controlled trial. / Reid, Ian R.; Nicholson, Geoffrey C.; Weinstein, Robert S.; Hosking, David J.; Cundy, Tim; Kotowicz, Mark A.; Murphy, William A.; Yeap, Swan; Dufresne, Suzanne; Lombardi, Antonio; Musliner, Thomas A.; Thompson, Desmond E.; Yates, A. John.

In: American Journal of Medicine, Vol. 101, No. 4, 01.10.1996, p. 341-348.

Research output: Contribution to journalArticle

Reid, IR, Nicholson, GC, Weinstein, RS, Hosking, DJ, Cundy, T, Kotowicz, MA, Murphy, WA, Yeap, S, Dufresne, S, Lombardi, A, Musliner, TA, Thompson, DE & Yates, AJ 1996, 'Biochemical and radiologic improvement in Paget's disease of bone treated with alendronate: A randomized, placebo-controlled trial', American Journal of Medicine, vol. 101, no. 4, pp. 341-348. https://doi.org/10.1016/S0002-9343(96)00227-6
Reid, Ian R. ; Nicholson, Geoffrey C. ; Weinstein, Robert S. ; Hosking, David J. ; Cundy, Tim ; Kotowicz, Mark A. ; Murphy, William A. ; Yeap, Swan ; Dufresne, Suzanne ; Lombardi, Antonio ; Musliner, Thomas A. ; Thompson, Desmond E. ; Yates, A. John. / Biochemical and radiologic improvement in Paget's disease of bone treated with alendronate : A randomized, placebo-controlled trial. In: American Journal of Medicine. 1996 ; Vol. 101, No. 4. pp. 341-348.
@article{e80344c9ebc94647869de60f1f44df90,
title = "Biochemical and radiologic improvement in Paget's disease of bone treated with alendronate: A randomized, placebo-controlled trial",
abstract = "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.",
author = "Reid, {Ian R.} and Nicholson, {Geoffrey C.} and Weinstein, {Robert S.} and Hosking, {David J.} and Tim Cundy and Kotowicz, {Mark A.} and Murphy, {William A.} and Swan Yeap and Suzanne Dufresne and Antonio Lombardi and Musliner, {Thomas A.} and Thompson, {Desmond E.} and Yates, {A. John}",
year = "1996",
month = "10",
day = "1",
doi = "10.1016/S0002-9343(96)00227-6",
language = "English (US)",
volume = "101",
pages = "341--348",
journal = "American Journal of Medicine",
issn = "0002-9343",
publisher = "Elsevier Inc.",
number = "4",

}

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

PY - 1996/10/1

Y1 - 1996/10/1

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.

UR - http://www.scopus.com/inward/record.url?scp=10544223736&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=10544223736&partnerID=8YFLogxK

U2 - 10.1016/S0002-9343(96)00227-6

DO - 10.1016/S0002-9343(96)00227-6

M3 - Article

C2 - 8873503

AN - SCOPUS:10544223736

VL - 101

SP - 341

EP - 348

JO - American Journal of Medicine

JF - American Journal of Medicine

SN - 0002-9343

IS - 4

ER -