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

Completed

• Conditions: Osteoporosis

• Registration Number: NCT06414616
• Lead Sponsor: Trakya University

Brief Summary

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.

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 Timeline

• Study Start: 2022-10-01
• Study First Submitted: 2022-12-06
• Primary Completion: 2023-05-01
• Study Completion: 2024-03-01
• Status Verified: 2024-05
• Study First Submitted QC: 2024-05-09
• Last Update Submitted: 2024-05-14
• Study First Posted: 2024-05-16
• Last Update Posted: 2024-05-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 210

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Number of new fragility fractures	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

Secondary Outcome Measures

Name	Time	Method
Denosumab adherence rate and factors that may play a role in Denosumab adherence/non-adherence	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.

Trial Locations

Locations (1)

Trakya University Medical Faculty; 🇹🇷 Edirne, Turkey