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

NCT06414616 | Completed DMC

• 1 other identifier: 2022/343
• Study Type: observational
• Target: 210
• Locations: 1 country
• Sites: 1

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.

Conditions

Osteoporosis

Keywords

Denosumab; Fragility fracture; Rebound fracture; Discontinuation; Osteoporosis

Outcome Measures

Primary Outcomes (1)

• Number of new fragility fractures

  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 Outcomes (1)

• Denosumab adherence rate and factors that may play a role in Denosumab adherence/non-adherence

  Through study completion, an average of 2 years

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• \. Patients who had received at least two consecutive doses of Denosumab ,with a gap of fewer than 8 months, with the diagnosis of osteoporosis.
• \. Patients who had at least one radiological image before the initiation of Denosumab therapy in which the lumbar and thoracic spine could be visualised
• \. 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.

You may not qualify if:

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

Sponsors & Collaborators

• Trakya University: lead

Study Sites (1)

Trakya University Medical Faculty

Edirne, 22030, Turkey (Türkiye)

Location

Related Publications (12)

• Lyu H, Jundi B, Xu C, Tedeschi SK, Yoshida K, Zhao S, Nigwekar SU, Leder BZ, Solomon DH. Comparison of Denosumab and Bisphosphonates in Patients With Osteoporosis: A Meta-Analysis of Randomized Controlled Trials. J Clin Endocrinol Metab. 2019 May 1;104(5):1753-1765. doi: 10.1210/jc.2018-02236.

  PMID: 30535289 BACKGROUND

• Brown JP, Roux C, Torring O, Ho PR, Beck Jensen JE, Gilchrist N, Recknor C, Austin M, Wang A, Grauer A, Wagman RB. Discontinuation of denosumab and associated fracture incidence: analysis from the Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) trial. J Bone Miner Res. 2013 Apr;28(4):746-52. doi: 10.1002/jbmr.1808.

  PMID: 23109251 BACKGROUND

• Black DM, Schwartz AV, Ensrud KE, Cauley JA, Levis S, Quandt SA, Satterfield S, Wallace RB, Bauer DC, Palermo L, Wehren LE, Lombardi A, Santora AC, Cummings SR; FLEX Research Group. Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial. JAMA. 2006 Dec 27;296(24):2927-38. doi: 10.1001/jama.296.24.2927.

  PMID: 17190893 BACKGROUND

• Sosa-Henriquez M, Torregrosa O, Deniz A, Saavedra P, Ortego N, Turrion A, Perez Castrillon JL, Diaz-Curiel M, Gomez-Alonso C, Martinez G, Antonio Blazquez J, Olmos-Martinez JM, Etxebarria I, Caeiro JR, Mora-Pena D. Multiple vertebral fractures after suspension of denosumab. A series of 56 cases. Int J Clin Pract. 2021 Oct;75(10):e14550. doi: 10.1111/ijcp.14550. Epub 2021 Jun 30.

  PMID: 34145944 BACKGROUND

• Anastasilakis AD, Evangelatos G, Makras P, Iliopoulos A. Rebound-associated vertebral fractures may occur in sequential time points following denosumab discontinuation: need for prompt treatment re-initiation. Bone Rep. 2020 Apr 22;12:100267. doi: 10.1016/j.bonr.2020.100267. eCollection 2020 Jun.

  PMID: 32373677 BACKGROUND

• Aubry-Rozier B, Gonzalez-Rodriguez E, Stoll D, Lamy O. Severe spontaneous vertebral fractures after denosumab discontinuation: three case reports. Osteoporos Int. 2016 May;27(5):1923-5. doi: 10.1007/s00198-015-3380-y. Epub 2015 Oct 28.

  PMID: 26510845 BACKGROUND

• Niimi R, Kono T, Nishihara A, Hasegawa M, Kono T, Sudo A. Second rebound-associated vertebral fractures after denosumab discontinuation. Arch Osteoporos. 2020 Jan 2;15(1):7. doi: 10.1007/s11657-019-0676-0.

  PMID: 31898803 BACKGROUND

• Fu SH, Wang CY, Hung CC, Lee CC, Yang RS, Huang CC, Farn CJ, Lin WH, Chen HM, Hsiao FY, Lin JW, Li CY. Increased fracture risk after discontinuation of anti-osteoporosis medications among hip fracture patients: A population-based cohort study. J Intern Med. 2021 Dec;290(6):1194-1205. doi: 10.1111/joim.13354. Epub 2021 Aug 2.

  PMID: 34237171 BACKGROUND

• Cramer JA, Amonkar MM, Hebborn A, Altman R. Compliance and persistence with bisphosphonate dosing regimens among women with postmenopausal osteoporosis. Curr Med Res Opin. 2005 Sep;21(9):1453-60. doi: 10.1185/030079905X61875.

  PMID: 16197664 BACKGROUND

• Chandran M, Hao Y, Kwee AK, Cheen MHH, Chin YA, Ng VYT. Adherence to dosing schedule of denosumab therapy for osteoporosis during COVID-19 lockdown: an electronic medical record and pharmacy claims database study from Asia. Osteoporos Int. 2022 Jan;33(1):251-261. doi: 10.1007/s00198-021-06085-0. Epub 2021 Aug 21.

  PMID: 34417842 BACKGROUND

• Siris ES, Harris ST, Rosen CJ, Barr CE, Arvesen JN, Abbott TA, Silverman S. Adherence to bisphosphonate therapy and fracture rates in osteoporotic women: relationship to vertebral and nonvertebral fractures from 2 US claims databases. Mayo Clin Proc. 2006 Aug;81(8):1013-22. doi: 10.4065/81.8.1013.

  PMID: 16901023 BACKGROUND

• Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, Cosman F, Lakatos P, Leung PC, Man Z, Mautalen C, Mesenbrink P, Hu H, Caminis J, Tong K, Rosario-Jansen T, Krasnow J, Hue TF, Sellmeyer D, Eriksen EF, Cummings SR; HORIZON Pivotal Fracture Trial. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007 May 3;356(18):1809-22. doi: 10.1056/NEJMoa067312.

  PMID: 17476007 BACKGROUND

MeSH Terms

Conditions

Osteoporosis

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Hande Özdemir, MD

  Trakya University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assoc. Prof.

Study Record Dates

• First Submitted: December 6, 2022
• First Posted: May 16, 2024
• Study Start: October 1, 2022
• Primary Completion: May 1, 2023
• Study Completion: March 1, 2024
• Last Updated: May 16, 2024

Record last verified: 2024-05

Locations

TU (1)