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Osteoporosis International

, Volume 25, Issue 7, pp 1953–1961 | Cite as

Denosumab significantly increases bone mineral density and reduces bone turnover compared with monthly oral ibandronate and risedronate in postmenopausal women who remained at higher risk for fracture despite previous suboptimal treatment with an oral bisphosphonate

  • J. P. BrownEmail author
  • C. Roux
  • P. R. Ho
  • M. A. Bolognese
  • J. Hall
  • H. G. Bone
  • S. Bonnick
  • J. P. van den Bergh
  • I. Ferreira
  • P. Dakin
  • R. B. Wagman
  • C. Recknor
Original Article

Abstract

Summary

Managing osteoporotic patients suboptimally adherent to bisphosphonates (BPs) is difficult. Such patients who remained at higher risk for fracture (≥1 risk factor) were transitioned to denosumab or a monthly oral BP. Denosumab-treated subjects had significantly greater increases in bone mineral density and decreases in bone turnover in this 12-month study.

Introduction

A clinical need exists to manage patients who are suboptimally adherent to oral BPs and remain at higher risk for fracture. Here, we compare the effects on bone mineral density (BMD) and bone turnover of transitioning such patients to denosumab or monthly oral BP (ibandronate or risedronate).

Methods

In two previous multicenter, open-label studies, postmenopausal women ≥55 years previously treated with, though suboptimally adherent to, a daily or weekly BP were randomized to denosumab 60 mg subcutaneously every 6 months (N = 852) or oral BP 150 mg monthly (N = 851) for 12 months. In this combined post-hoc analysis, a subset of higher risk subjects was identified, and the percentage changes from baseline in BMD and serum C-telopeptide of type I collagen (sCTX-1) were assessed.

Results

In the overall population, denosumab was associated with greater gains in BMD at 12 months than monthly oral BP at the total hip, femoral neck, and lumbar spine (p < 0.0001 for all). In higher risk subjects, denosumab led to greater gains in BMD than oral BPs at the total hip (2.2 vs 0.8 %), femoral neck (1.8 vs 0.3 %), and lumbar spine (3.7 vs 1.4 %) (p < 0.0001 for all). Denosumab also led to greater decreases in sCTX-1 in the overall population and higher risk subjects at months 1 and 6 (p < 0.0001 for both). Adverse events and serious adverse events were generally similar between treatment groups.

Conclusions

Transitioning to denosumab was well tolerated and more effective in increasing BMD and reducing bone turnover than cycling to a monthly oral BP treatment in subjects who remained at higher fracture risk despite suboptimal BP treatment.

Keywords

Adherence Bone mineral density Bone turnover Denosumab Postmenopausal osteoporosis Oral bisphosphonate 

Notes

Acknowledgments

This study was sponsored by Amgen Inc. Erica Rockabrand, PhD, an employee of Amgen Inc., and Mary G. Royer, MS, a paid consultant of Amgen Inc., provided medical writing support.

Conflicts of interest

J.P. Brown received research grants and/or consulting or speaking fees from Amgen Inc., Eli Lilly, Merck, Novartis, and Warner Chilcott.

M.A. Bolognese also received research grants from Amgen Inc., Lilly, MSD, and Genentech, and is part of the advisory board or board of directors for NOF, Lilly, and Vivus.

P.R. Ho, J. Hall, I. Ferreira, P. Dakin, and R.B. Wagman are employees of Amgen Inc. and may own stock and/or stock options in Amgen Inc.

C. Roux received research grants and/or consulting or speaking fees from Amgen Inc., Bongrain, Lilly, MSD, Novartis, Roche, and Servier.

H.G. Bone received research grants from Amgen Inc., Lilly, Merck, Novartis, and Tarsa; part of the advisory board for Amgen Inc. and Merck; and received consulting fees from Amgen Inc., Merck, Novartis, and Tarsa.

S. Bonnick received research grants from Amgen Inc. and Merck.

J.P. van den Bergh received speaker fees from Amgen Inc., Eli Lilly, MSD, and Will Pharma, and part of the advisory board or board of directors for Amgen Inc. and MSD.

C. Recknor received research grants from Medi; received consulting and/or speaking fees from Amgen Inc., Eli Lilly, Novartis, and Warner Chilcott; and is shareholder in Ion Med Systems.

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Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2014

Authors and Affiliations

  • J. P. Brown
    • 1
    Email author
  • C. Roux
    • 2
  • P. R. Ho
    • 3
  • M. A. Bolognese
    • 4
  • J. Hall
    • 3
  • H. G. Bone
    • 5
  • S. Bonnick
    • 6
  • J. P. van den Bergh
    • 7
  • I. Ferreira
    • 8
  • P. Dakin
    • 3
  • R. B. Wagman
    • 3
  • C. Recknor
    • 9
  1. 1.CHU de Québec Research Centre and Laval UniversityQuebec CityCanada
  2. 2.Paris Descartes UniversityParisFrance
  3. 3.Amgen Inc.Thousand OaksUSA
  4. 4.Bethesda Health Research CenterBethesdaUSA
  5. 5.Michigan Bone and Mineral ClinicDetroitUSA
  6. 6.Clinical Research Center of North TexasDentonUSA
  7. 7.VieCuri Medical Centre and Maastricht UniversityMaastrichtThe Netherlands
  8. 8.Amgen Inc.CambridgeUK
  9. 9.United Osteoporosis CentersGainesvilleUSA

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