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CompletedNCT01732770Updated Mar 10, 2020Results posted

Safety and Efficacy Study to Evaluate Denosumab Compared With Zoledronic Acid in Postmenopausal Women With Osteoporosis

A Phase 4 interventional study of Denosumab and Zoledronic Acid in Post Menopausal Osteoporosis, sponsored by Amgen. Completed at 45 sites in 7 countries. Open to female participants aged 55 Years and older. Per ClinicalTrials.gov, last updated 2020-03-10.

Sponsored by Amgen · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
643
Allocation
Randomized
Ages
55 Years and older
Sex
Female
01

Study summary

This study will compare the effectiveness of denosumab treatment every 6 months with once yearly zoledronic acid treatment on bone mineral density (BMD) at various skeletal sites.

02

Conditions studied

  • Post Menopausal Osteoporosis
03

In context

Osteoporosis, Postmenopausal

337 studies on the registry are indexed under Osteoporosis, Postmenopausal; 29 are open to participants now.

This study's enrollment of 643 is above the median of 110 across 265 interventional studies indexed under Osteoporosis, Postmenopausal.

Browse Osteoporosis, Postmenopausal studies →

Lead sponsor

Amgen is the lead sponsor of 1,044 studies on the registry; 51 are open to participants now.

Of its 246 completed or terminated interventional studies of FDA-regulated products, 164 (67%) have results posted.

Browse Amgen studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
55 Years and older
Sexes eligible
Female
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Ambulatory postmenopausal women.
  • Age 55 years or older
  • Subject has provided informed consent prior to any study specific procedures
  • Received oral bisphosphonate therapy for osteoporosis at least 2 years prior to screening visit
  • Screening BMD (g/cm²) values at the lumbar spine, total hip or femoral neck values of equal to or less than those listed in the protocol.
  • At least 2 lumbar vertebrae and one hip must be evaluable by dual energy x-ray absorptiometry (DXA) at the screening visit

Exclusion criteria

Exclusion Criteria:

  • Received other osteoporosis treatment or bone active treatment

  • Evidence of history of any of the following:

    • hyperthyroidism (stable on antithyroid therapy is allowed)
    • hypothyroidism (stable on thyroid replacement therapy is allowed)
    • hypo- or hyperparathyroidism
    • hypo- or hypercalcemia based on the central laboratory reference ranges
    • Recent tooth extraction (within 6 months of screening visit)
    • Paget disease of bone (subject report or chart review)
    • other bone diseases which affect bone metabolism (eg, osteopetrosis, osteogenesis imperfecta) (chart review)

  • Abnormalities of the following per central laboratory reference ranges:

    • vitamin D deficiency (25[OH] vitamin D level \< 20 ng/mL), repletion will be allowed and subjects may be re-screened
    • hypercalcemia
    • elevated transaminases ≥ 2.0 x upper limits of normal (ULN)
  • History of any solid organ or bone marrow transplant
  • Malignancy (except nonmelanoma skin cancers, cervical or breast ductal carcinoma in situ) within the last 5 years
  • Known intolerance to calcium or vitamin D supplements
  • Self-reported alcohol or drug abuse within 12 months prior to screening
  • Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(s)
  • History or evidence of any other clinically significant disorder, condition or disease that in the opinion of the Investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion
05

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
643 participants (actual)

Study arms

  • Experimental
    Denosumab 60 mg

    Participants received denosumab 60 mg subcutaneous injection once every 6 months for 12 months and placebo to zoledronic acid by intravenous infusion on Day 1.

    Biological: Denosumab · Drug: Placebo to Zoledronic Acid

  • Active comparator
    Zoledronic Acid 5 mg

    Participants received zoledronic acid 5 mg by intravenous infusion on Day 1 and placebo to denosumab by subcutaneous injection on Day 1 and at Month 6.

    Drug: Zoledronic Acid · Drug: Placebo to Denosumab

Interventions

  • BiologicalDenosumab

    Denosumab 60 mg administered by subcutaneous injection once every 6 months.

    Also known as: Prolia®, AMG 162

  • DrugZoledronic Acid

    Zoledronic acid 5 mg administered by intravenous infusion once a year

    Also known as: Reclast, Aclasta

  • DrugPlacebo to Denosumab

    Administered by subcutaneous injection once every 6 months

  • DrugPlacebo to Zoledronic Acid

    Administered by intravenous infusion once a year

06

What researchers measure

Primary outcomes

  1. Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 12 - Non-inferiority Analysis

    Bone mineral density (BMD) of the lumbar spine was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging facility.

    Time frame: Baseline and Month 12

Secondary outcomes

  1. Percent Change From Baseline in Total Hip BMD at Month 12 - Non-inferiority Analysis

    BMD of the hip was measured by DXA. DXA scans were analyzed by a central imaging facility.

    Time frame: Baseline and Month 12

  2. Percent Change From Baseline in Lumbar Spine BMD at Month 12 - Superiority Analysis

    Time frame: Baseline and Month 12

  3. Percent Change From Baseline in Total Hip BMD at Month 12 - Superiority Analysis

    Time frame: Baseline and Month 12

07

Results

Posted Jan 25, 2016

Participant flow

This study was conducted at 37 centers in Belgium, Denmark, Poland, Spain, Canada, United States of America, and Australia. The first participant enrolled on 07 November 2012 and the last participant enrolled on 15 January 2014.

Participant flow — Overall Study
MilestoneZoledronic Acid 5 mg Q12MDenosumab 60 mg Q6M
Started322321
Received study treatment320320
Completed312313
Not completed108
Withdrew: Lost to follow-up23
Withdrew: Withdrawal by subject53
Withdrew: Decision by sponsor22
Withdrew: Death10

Outcome measures

PrimaryPercent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 12 - Non-inferiority Analysis

Bone mineral density (BMD) of the lumbar spine was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging facility.

Time frame:
Baseline and Month 12
Reported as:
Least squares mean · percent change
Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 12 - Non-inferiority Analysis
percent changeZoledronic Acid 5 mg Q12MDenosumab 60 mg Q6M
Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 12 - Non-inferiority Analysis1.1 (0.7 to 1.5)3.2 (2.8 to 3.6)
Statistical analysis
  • Zoledronic Acid 5 mg Q12M vs Denosumab 60 mg Q6M · ANCOVA · p = <0.0001 · Treatment difference: 2.1 · 95% CI 1.6 to 2.6Treatment difference = denosumab - zoledronic acid
SecondaryPercent Change From Baseline in Total Hip BMD at Month 12 - Non-inferiority Analysis

BMD of the hip was measured by DXA. DXA scans were analyzed by a central imaging facility.

Time frame:
Baseline and Month 12
Reported as:
Least squares mean · percent change
Percent Change From Baseline in Total Hip BMD at Month 12 - Non-inferiority Analysis
percent changeZoledronic Acid 5 mg Q12MDenosumab 60 mg Q6M
Percent Change From Baseline in Total Hip BMD at Month 12 - Non-inferiority Analysis0.6 (0.3 to 0.8)1.9 (1.7 to 2.2)
Statistical analysis
  • Zoledronic Acid 5 mg Q12M vs Denosumab 60 mg Q6M · ANCOVA · p = <0.0001 · Treatment difference: 1.4 · 95% CI 1.0 to 1.7Treatment difference = denosumab - zoledronic acid
SecondaryPercent Change From Baseline in Lumbar Spine BMD at Month 12 - Superiority Analysis
Time frame:
Baseline and Month 12
Reported as:
Least squares mean · percent change
Percent Change From Baseline in Lumbar Spine BMD at Month 12 - Superiority Analysis
percent changeZoledronic Acid 5 mg Q12MDenosumab 60 mg Q6M
Percent Change From Baseline in Lumbar Spine BMD at Month 12 - Superiority Analysis1.1 (0.7 to 1.5)3.2 (2.8 to 3.6)
Statistical analysis
  • Zoledronic Acid 5 mg Q12M vs Denosumab 60 mg Q6M · ANCOVA · p = <0.0001 · Treatment difference: 2.1 · 95% CI 1.6 to 2.6Treatment difference = denosumab - zoledronic acid
SecondaryPercent Change From Baseline in Total Hip BMD at Month 12 - Superiority Analysis
Time frame:
Baseline and Month 12
Reported as:
Least squares mean · percent change
Percent Change From Baseline in Total Hip BMD at Month 12 - Superiority Analysis
percent changeZoledronic Acid 5 mg Q12MDenosumab 60 mg Q6M
Percent Change From Baseline in Total Hip BMD at Month 12 - Superiority Analysis0.6 (0.3 to 0.8)1.9 (1.7 to 2.2)
Statistical analysis
  • Zoledronic Acid 5 mg Q12M vs Denosumab 60 mg Q6M · ANCOVA · p = <0.0001 · Treatment difference: 1.4 · 95% CI 1.0 to 1.7Treatment difference = denosumab - zoledronic acid

Adverse events

Collected over 12 months. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Zoledronic Acid 5 mg Q12M—29/320 (9.1%)22/320 (6.9%)
Denosumab 60 mg Q6M—25/320 (7.8%)15/320 (4.7%)
Most frequent serious events
Showing 10 of 60
Most frequent serious events
EventZoledronic Acid 5 mg Q12MDenosumab 60 mg Q6M
Urinary tract infectionInfections and infestations2/3201/320
Femur fractureInjury, poisoning and procedural complications2/3202/320
Cerebrovascular accidentNervous system disorders1/3202/320
Febrile neutropeniaBlood and lymphatic system disorders0/3201/320
Acute myocardial infarctionCardiac disorders1/3200/320
Atrial fibrillationCardiac disorders0/3201/320
Atrial flutterCardiac disorders0/3201/320
Coronary artery diseaseCardiac disorders0/3201/320
Myocardial infarctionCardiac disorders0/3201/320
GoitreEndocrine disorders0/3201/320
Most frequent other events
Most frequent other events
EventZoledronic Acid 5 mg Q12MDenosumab 60 mg Q6M
ArthralgiaMusculoskeletal and connective tissue disorders22/32015/320

Baseline characteristics

Age, Continuous
Age, Continuous(years)Zoledronic Acid 5 mg Q12MDenosumab 60 mg Q6MTotal
Mean69.5 ± 7.768.5 ± 7.169.0 ± 7.4
Sex: Female, Male
Sex: Female, Male(Participants)Zoledronic Acid 5 mg Q12MDenosumab 60 mg Q6MTotal
Female322321643
Male000
Race/Ethnicity, Customized
Race/Ethnicity, Customized(participants)Zoledronic Acid 5 mg Q12MDenosumab 60 mg Q6MTotal
White314309623
Asian459
Other246
Native Hawaiian or Other Pacific Islander123
Black or African American011
Multiple101
Screening serum CTX
Screening serum CTX(participants)Zoledronic Acid 5 mg Q12MDenosumab 60 mg Q6MTotal
< 0.3 ng/mL242239481
≥ 0.3 ng/mL7882160
Missing202
Lumbar Spine Bone Mineral Density (BMD) T-score
Lumbar Spine Bone Mineral Density (BMD) T-score(T-score)Zoledronic Acid 5 mg Q12MDenosumab 60 mg Q6MTotal
Mean-2.64 ± 0.86-2.74 ± 0.83-2.69 ± 0.84
Total Hip BMD T-score
Total Hip BMD T-score(T-score)Zoledronic Acid 5 mg Q12MDenosumab 60 mg Q6MTotal
Mean-1.93 ± 0.80-1.93 ± 0.74-1.93 ± 0.77
Femoral Neck BMD T-score
Femoral Neck BMD T-score(T-score)Zoledronic Acid 5 mg Q12MDenosumab 60 mg Q6MTotal
Mean-2.17 ± 0.68-2.17 ± 0.66-2.17 ± 0.67
Prior Oral Bisphosphonate Duration
Prior Oral Bisphosphonate Duration(years)Zoledronic Acid 5 mg Q12MDenosumab 60 mg Q6MTotal
Mean6.35 ± 3.686.21 ± 3.846.28 ± 3.76

2 further baseline measures are reported on the registry.

08

Study locations

45 sites
  • Research Site
    Santa Monica, California 90404, United States
  • Research Site
    Lakewood, Colorado 80227, United States
  • Research Site
    Longmont, Colorado 80501, United States
  • Research Site
    Washington D.C., District of Columbia 20007, United States
  • Research Site
    Bethesda, Maryland 20817, United States
  • Research Site
    Hagerstown, Maryland 21740, United States
  • Research Site
    Detroit, Michigan 48236, United States
  • Research Site
    West Haverstraw, New York 10993, United States
  • Research Site
    Houston, Texas 77074, United States
  • Research Site
    Maroubra, New South Wales 2035, Australia
  • Research Site
    Penrith, New South Wales 2750, Australia
  • Research Site
    St Leonards, New South Wales 2065, Australia
  • Research Site
    Box Hill, Victoria 3128, Australia
  • Research Site
    Geelong, Victoria 3220, Australia
  • Research Site
    Parkville, Victoria 3050, Australia
  • Research Site
    Brussels, 1000, Belgium
  • Research Site
    Brussels, 1020, Belgium
  • Research Site
    Brussels, 1050, Belgium
  • Research Site
    Brussels, 1090, Belgium
  • Research Site
    Genk, 3600, Belgium
  • Research Site
    Leuven, 3000, Belgium
  • Research Site
    Liège, 4020, Belgium
  • Research Site
    Merksem, 2170, Belgium
  • Research Site
    Tessenderlo, 3980, Belgium
  • Research Site
    Wilrijk, 2610, Belgium
  • Research Site
    Yvoir, 5530, Belgium
  • Research Site
    Calgary, Alberta T2N 4Z6, Canada
  • Research Site
    Vancouver, British Columbia V5Z 4E1, Canada
  • Research Site
    Halifax, Nova Scotia B3H 2Y9, Canada
  • Research Site
    Toronto, Ontario M5C 2T2, Canada
  • Research Site
    Toronto, Ontario M5G 2C4, Canada
  • Research Site
    Toronto, Ontario M9W 4L6, Canada
  • Research Site
    Québec, Quebec G1V 3M7, Canada
  • Research Site
    Aalborg, 9000, Denmark
  • Research Site
    Ballerup Municipality, 2750, Denmark
  • Research Site
    Vejle, 7100, Denmark
  • Research Site
    Bialystok, 15-879, Poland
  • Research Site
    Krakow, 31-501, Poland
  • Research Site
    Torun, 87-100, Poland
  • Research Site
    Warsaw, 01-192, Poland
  • Research Site
    Granada, Andalusia 18012, Spain
  • Research Site
    Barcelona, Catalonia 08036, Spain
  • Research Site
    Barcelona, Catalonia 08041, Spain
  • Research Site
    Madrid, 28009, Spain
  • Research Site
    Madrid, 28040, Spain
09

References and documents

Publications

  • Miller PD, Pannacciulli N, Brown JP, Czerwinski E, Nedergaard BS, Bolognese MA, Malouf J, Bone HG, Reginster JY, Singer A, Wang C, Wagman RB, Cummings SR. Denosumab or Zoledronic Acid in Postmenopausal Women With Osteoporosis Previously Treated With Oral Bisphosphonates. J Clin Endocrinol Metab. 2016 Aug;101(8):3163-70. doi: 10.1210/jc.2016-1801. Epub 2016 Jun 6. PubMed 27270237 ↗
  • Miller PD, Pannacciulli N, Malouf-Sierra J, Singer A, Czerwinski E, Bone HG, Wang C, Huang S, Chines A, Lems W, Brown JP. Efficacy and safety of denosumab vs. bisphosphonates in postmenopausal women previously treated with oral bisphosphonates. Osteoporos Int. 2020 Jan;31(1):181-191. doi: 10.1007/s00198-019-05233-x. Epub 2019 Nov 28. PubMed 31776637 ↗
  • Chotiyarnwong P, McCloskey E, Eastell R, McClung MR, Gielen E, Gostage J, McDermott M, Chines A, Huang S, Cummings SR. A Pooled Analysis of Fall Incidence From Placebo-Controlled Trials of Denosumab. J Bone Miner Res. 2020 Jun;35(6):1014-1021. doi: 10.1002/jbmr.3972. Epub 2020 Apr 2. PubMed 31999376 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 10, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01732770
Lead sponsor
Amgen
Responsible party
Sponsor
First posted
Nov 26, 2012
Start date
Nov 7, 2012
Primary completion
Jan 7, 2015
Completion
Jan 7, 2015
Results posted
Jan 25, 2016
Last update
Mar 10, 2020

Study contacts

MD
study director · Amgen

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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