Effect of denosumab on bone mineral density in women receiving adjuvant aromatase inhibitors for non-metastatic breast cancer: subgroup analyses of a phase 3 study

  • Georgiana K. Ellis
  • Henry G. Bone
  • Rowan Chlebowski
  • Devchand Paul
  • Silvana Spadafora
  • Michelle Fan
  • Dennis Kim
Clinical Trial


Denosumab increased lumbar spine bone mineral density (BMD) versus placebo in a 2-year, randomized, placebo-controlled, phase 3 study of patients with hormone-receptor-positive, non-metastatic breast cancer and low bone mass who were receiving adjuvant aromatase inhibitor therapy. In subgroup analyses at 12 and 24 months, we evaluated factors (duration and type of aromatase inhibitor, tamoxifen use, age, time since menopause, body mass index, T-score) that might influence BMD at the lumbar spine, total hip, femoral neck, and 1/3 radius. Patients were randomized to receive placebo (= 125) or 60 mg denosumab (= 127) subcutaneously every 6 months. In all subgroups, 12 or 24 months’ treatment with denosumab was associated with larger BMD gains than placebo across multiple skeletal sites. Most increases were statistically significant (< 0.05). Twice-yearly administration of denosumab, regardless of patient subgroup or skeletal site, resulted in consistent increases in BMD versus placebo at 12 and 24 months.


RANKL Denosumab Clinical trial Cancer treatment-induced bone loss Breast cancer 



This study was funded by Amgen Inc., Thousand Oaks, CA. This study is registered with with the identifier NCT00089661. GK Ellis is an investigator in this study and has received research grants from Amgen, Abraxis, and Roche, and has been a speaker for Novartis. HG Bone is an investigator for Amgen, Merck, Zelos, Eli Lilly, Novartis, and Nordic Bioscience, and has been a consultant for Amgen, Osteologix, Nordic Bioscience, Merck, Zelos, Pfizer, Novartis, and GlaxoSmithKline; he has received speaker’s honoraria from Novartis. R. Chlebowski has been a consultant for AstraZeneca, Novartis, Genentech, Pfizer, Lilly, and Wyeth; he has received speaker’s honoraria from AstraZeneca, Abraxis, and Novartis. D. Paul and S. Spadafora have no conflicts of interest to disclose. M. Fan and D. Kim are employees of Amgen Inc. We thank Christine Gatchalian, PhD, of Amgen Inc., and Linda Melvin, BA, for writing assistance.


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Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Georgiana K. Ellis
    • 1
  • Henry G. Bone
    • 2
  • Rowan Chlebowski
    • 3
  • Devchand Paul
    • 4
    • 5
  • Silvana Spadafora
    • 6
  • Michelle Fan
    • 7
  • Dennis Kim
    • 7
  1. 1.Seattle Cancer Care AllianceSeattleUSA
  2. 2.Michigan Bone & Mineral ClinicDetroitUSA
  3. 3.UCLA Medical CenterTorranceUSA
  4. 4.US OncologyHoustonUSA
  5. 5.Rocky Mountain Cancer CentersDenverUSA
  6. 6.Algoma Regional Cancer ProgramSault Ste. MarieCanada
  7. 7.Amgen Inc.Thousand OaksUSA

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