Bisphosphonates for Prevention of Post-Denosumab Bone Loss

April 16, 2024 updated by: Elizabeth Shane, Columbia University

Bisphosphonates for Prevention of Post-Denosumab Bone Loss in Premenopausal Women With Idiopathic Osteoporosis

The primary goal of the study is to assess the extent to which bisphosphonate therapy will prevent decreases in bone mass that may occur after cessation of denosumab in premenopausal women with idiopathic osteoporosis (IOP) enrolled in AAAN0161 (FD05114) "Denosumab for the prevention of post-teriparatide bone loss in premenopausal women with idiopathic osteoporosis".

In addition, the investigator will observe participants for a second year off bisphosphonate therapy to assess duration of response.

The hypothesis is that bisphosphonate therapy with alendronate or zoledronic acid, initiated after recovery of bone remodeling activity, will prevent significant bone loss after discontinuing denosumab.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Osteoporosis in premenopausal women with normal menstrual function and no specific cause is termed idiopathic osteoporosis (IOP). IOP is a rare disease with an estimated prevalence of <200,000 affected premenopausal women in the United States.

Women with IOP completing at least one year and up to three years of denosumab (Protocol AAAN0161) will be offered participation in this open-label study in which they would choose whether to take oral alendronate 70 mg weekly for 12 months or a single intravenous dose of zoledronic acid 5 mg. Subjects and study personnel will be blinded to BMD outcomes until 12 months.

Discontinuation of denosumab is followed by substantial increases in bone turnover markers to well above baseline, bone resorption reaching twice baseline levels for about 6 months. Over the first 12 months off therapy, all the bone density gained on treatment is lost. Studies done at the institution has demonstrated the occurrence of multiple vertebral fractures in some patients who have stopped denosumab. Based upon these new fracture data, the Prolia label is currently recommending that consideration should be given to transition to another antiresorptive drug in patients stopping denosumab. The main goals of this extension study are to determine rates of bone loss and incidence of radiographic vertebral fractures during one year of bisphosphonate therapy (oral alendronate or intravenous zoledronic acid) initiated after completing denosumab.

Study Type

Interventional

Enrollment (Actual)

24

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Nebraska
      • Omaha, Nebraska, United States, 68131
        • Creighton University
    • New York
      • New York, New York, United States, 10032
        • Columbia University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 51 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • All women completing at least 12 months of Forteo treatment and at least 12 months of denosumab under previous research studies who remain without a diagnosis of an excluded medical condition and medication exposures as detailed below, will be offered enrollment into this study.

Exclusion Criteria:

  • Known intolerance to calcium supplements

  • Contraindications to bisphosphonate treatment:

    1. Hypocalcemia
    2. Pregnancy
    3. Known hypersensitivity to bisphosphonates
  • History of osteomalacia
  • History of osteonecrosis of the jaw
  • History of dental extraction or other invasive dental surgery within the prior 4 weeks
  • Invasive dental work planned in the next 12 months
  • Any condition or illness (acute, chronic, or history), which in the opinion of the Investigator might interfere with the evaluation of efficacy and safety during the study or may otherwise compromise the safety of the subject
  • Self-reported or known alcohol or drug abuse within the previous 12 months
  • Current or recent (within 1 year of enrollment) inflammatory bowel disease or malabsorption

  • Abnormal laboratory tests performed during Visit 1

    1. Renal insufficiency or liver disease: estimated glomerular filtration rate (eGFR) < 35 ml/min, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) >50% above upper limit of normal
    2. Hypercalcemia, hypocalcemia
    3. Vitamin D deficiency: 25-Hydroxyvitamin D (25-OHD) < 30 ng/mL
  • Subjects must be willing to participate voluntarily. Specifically excluded are the following: 1) women less than 20 (or 35 in the case of those who wish to participate because they have low BMD); 2) protected individuals (institutionalized); 3) prisoners; 4) any other prospective participant who, for any reason, might not be able to give voluntary informed consent.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: alendronate
Subjects will receive oral alendronate
Drug: Alendronate
oral alendronate 70 mg weekly for 12 months will be given for the prevention of osteoporosis
Other Names:
  • fosamax
Active Comparator: zoledronic acid
Subjects will receive zoledronic acid
Drug: Zoledronic Acid
single intravenous dose of zoledronic acid 5 mg will be given for the prevention of osteoporosis
Other Names:
  • Reclast

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Difference in BMD at the Lumbar Spine (L1-4) Within Group
Time Frame: Baseline, 12 month
Within-group difference (percent change) in BMD at the lumbar spine (L1-4) will be measured by Dual-energy X-ray absorptiometry (DXA) and calculated.
Baseline, 12 month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Columbia University

Collaborators

Amgen

Investigators

  • Principal Investigator: Elizabeth Shane, MD, Columbia University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 29, 2018

Primary Completion (Actual)

June 9, 2023

Study Completion (Actual)

June 9, 2023

Study Registration Dates

First Submitted

January 5, 2018

First Submitted That Met QC Criteria

January 5, 2018

First Posted (Actual)

January 10, 2018

Study Record Updates

Last Update Posted (Actual)

May 8, 2024

Last Update Submitted That Met QC Criteria

April 16, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AAAR5220

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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