Real-World Evidence of Adherence to Denosumab Therapy and Fracture Risk Associated With Drug Withdrawal: A Cross-sectional Study

May 14, 2024 updated by: Hande Ozdemir, Trakya University

Are We Overly Concerned About Rebound Fractures? Real-World Evidence of Adherence to Denosumab Therapy and Fracture Risk Associated With Drug Withdrawal: A Cross-sectional Study

In the light of current literature data, it is not recommended to discontinue Denosumab therapy without initiating another antiresorptive therapy. It is known that there is a rebound increase in bone resorption markers and a rapid decrease in bone mineral density (BMD) when patients using Denosumab remain untreated for 1 year. The coronavirus disease (Covid-19) pandemic has caused an unprecedented disruption in the management of osteoporosis, as in many chronic diseases. This study aims to determine whether the risk of rebound-associated osteoporotic fracture development is increased in patients who discontinued Denosumab therapy due to any reason but especially due to hesitancy to come to hospitals or lack of access to treatment institutions during the pandemic period as well as to evaluate the factors affecting treatment compliance.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Detailed Description

With increased life expectancy and decreased physical activity osteoporosis related fractures are increasing day by day which place a huge health economic burden on societies. Since fragility fractures and related disabilities bring about considerable morbidity and even mortality, the main goal in osteoporosis treatment is to prevent fractures.

The facts that bisphosphonates can plateau after 3-4 years in the treatment response and Teriparatide cannot be used for more than 2 years, bring the use of Denosumab to the fore in patients with high fracture risk who need long term treatment. Denosumab is also preferred in patients with renal dysfunction since it is excreted by the reticuloendothelial system and not the kidney. However, there is a dilemma that publications in the literature mostly show that the risk of fracture development returns to a no-treatment status shortly after Denosumab withdrawal.

Therefore, in this study it is aimed to examine whether there is statistically significant difference in terms of the risk of osteoporotic fracture development and other secondary outcome measures between the patient group who discontinued injections for more than 2 months and the patient group who regularly received their injections.

In this study, patients who had commenced Denosumab in Trakya University Osteoporosis Polyclinic between 2015-2021 and had received at least 2 doses will be included. Demographic and clinical data will be retrospectively examined by the Physical Medicine and Rehabilitation physician at last date of follow-up through electronic medical records and patient files. Radiological images of the patients will also be examined whether there is radiological fracture before, under or after the treatment. The number of fractures and their localizations, if any, will be recorded. The number of Denosumab doses administered will be determined by review of the hospital's electronic prescription records. Adherence will be defined as being punctual (with an allowable delay of up to 8 weeks) with the 6 month scheduled doses. In addition, pre-treatment values of BMD as evaluated on dual energy x-ray absorptiometry (DXA), and Fracture Risk Assessment Tool (FRAX) scores will be recorded.

In the light of the data obtained, the parameters affecting compliance and the effect of treatment compliance on the risk of osteoporotic fracture development will be presented to the literature.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
210

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

  • Turkey
      • Edirne, Turkey, 22030
        • Trakya University Medical Faculty

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

Patients initiated on Denosumab therapy at Trakya University Pyhsical Medicine and Rehabilitation Osteoporosis Unit between 2015-2021 and had received at least 2 doses of injection.

Description

Inclusion Criteria:

  • 1. Patients who had received at least two consecutive doses of Denosumab ,with a gap of fewer than 8 months, with the diagnosis of osteoporosis.
  • 2. Patients who had at least one radiological image before the initiation of Denosumab therapy in which the lumbar and thoracic spine could be visualised
  • 3. Patients whose BMD and T-score values had been evaluated via DXA scan and FRAX scores had been calculated before the initiation of Denosumab therapy.

Exclusion Criteria:

  • 1. Patients missing any of the above mentioned data
  • 2. Patients who develop fractures due to cancer, trauma or Paget's disease.
  • 3. Patients receiving monthly Denosumab to prevent bone metastasis.

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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of new fragility fractures
Time Frame: Through study completion, an average of 2 years
The number of new fragility fractures among Denosumab adherent and non-adherent patient groups as assessed by radiological images
Through study completion, an average of 2 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Denosumab adherence rate and factors that may play a role in Denosumab adherence/non-adherence
Time Frame: Through study completion, an average of 2 years
The rate of Denosumab adherence and factors that may play a role in Denosumab adherence/non-adherence as assessed by restrospective examination of patient files which are age, sex, age of menopause, parity, marital status, occupation, height (cm), weight (kg), and body mass index (BMI) (kg/m2), family history of fragility fracture, presence of baseline fragility fractures before initiation of Denosumab treatment, comorbidities, use of steroids, smoking status, presence of secondary osteoporosis, tea/coffee/alcohol consumption status, consumption of dairy products, presence of any therapy before Denosumab, treatment agent before Denosumab, number of received Denosumab injections, duration of Denosumab withdrawal.
Through study completion, an average of 2 years

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Trakya University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Hande Özdemir, MD, Trakya 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

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 1, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 6, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 9, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 16, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 16, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 14, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2022/343

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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