A Clinical Trial to Evaluate Efficacy of Once or Twice ZOledronic Acid After Different Duration of denOsumMab Administration in Postmenopausal Women With Osteoporosis (ZOOM Study)

NCT05361408 | Completed Phase 4 DMC

• 1 other identifier: 4-2021-1023
• Study Type: interventional
• Target: 114
• Locations: 1 country
• Sites: 1

Brief Summary

Denosumab(Dmab) is a monoclonal antibody that inhibits the receptor-activator of nuclear factor kappa-B ligand. It improves bone density and reduces fractures by inhibiting osteoclast recruitment and differentiation. Although the FREEDOM trial showed Dmab increase bone mineral density for ten years, the effect was reversible. When Dmab is discontinued, the rebound phenomenon, the bone mineral density returns to the pre-treatment value, and multiple vertebral fractures may occur. Recently, a guideline to administer bisphosphonates sequentially when Dmab is discontinued has been published. In several studies, Zoledronic acid prevented bone loss after denosumab discontinuation with a single administration in Dmab short-term(less than 2.5years) users, but in Dmab long-term(more than 2.5years) users, zoledronic acid did not fully prevent loss of BMD. Our study tried to evaluate that ZOL administration twice for six months apart in long-term Dmab users is not inferior to a single administration of ZOL in Dmab short-term users.

Conditions

Osteoporosis

Outcome Measures

Primary Outcomes (1)

• BMD lumbar spine

  Change in lumbar spine BMD from baseline to one year after the zoledronic acid infusion

  One year

Secondary Outcomes (3)

• BMD Femoral neck and total hip

  One year

• Bone turnover marker

  One year

• Vertebral fracture

  One year

Study Arms (2)

Denosumab short-term user

ACTIVE COMPARATOR

Denosumab injection less than 5 times

Drug: Zoledronic acid, once

Denosumab long-term user

ACTIVE COMPARATOR

Denosumab injection more than 5 times

Drug: Zoledronic acid, twice

Interventions

Zoledronic acid, once DRUG

Intravenous infusion of 5mg zoledronic acid, once

Also known as: Zoledronate

Denosumab short-term user

Zoledronic acid, twice DRUG

Intravenous infusion of 5mg zoledronic acid for 6month interval, twice

Also known as: Zoledronate

Denosumab long-term user

Eligibility Criteria

• Age: 50 Years+
• Gender Eligibility Details: Women
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Postmenopausal women (defined as no menstruation for more than 48 weeks prior to screening and no other pathological or physiological causes. If in doubt, a serum follicle-stimulating hormone (FSH) test may be performed at screening)
• Patients diagnosed with osteoporosis, osteoporotic fractures, received at least two doses of denosumab, and who have osteopenia in follow-up DXA

You may not qualify if:

• Secondary osteoporosis (Systemic glucocorticoid use, aromatase inhibitor, thyrotoxicosis, hypeparathyroidism, etc)
• Active cancer treatment
• Inflammatory bowel disease
• History of medication related osteonecrosis of jaw(MRONJ)
• low-energy fracture within the last 12months
• Estimated glomerular filtration rate (eGFR) \< 35 mL/min
• Hepatic dysfunction (aspartate transaminase (AST)/alanine transferase (ALT) \> 3 x upper normal limit)
• Contraindication for zoledronic acid according to the SPC
• Allergic to zoledronic acid

Sponsors & Collaborators

• Yonsei University: lead

Study Sites (1)

Yonsei University Health System, Severance Hospital

Seoul, South Korea

Location

Related Publications (2)

• Tsourdi E, Zillikens MC, Meier C, Body JJ, Gonzalez Rodriguez E, Anastasilakis AD, Abrahamsen B, McCloskey E, Hofbauer LC, Guanabens N, Obermayer-Pietsch B, Ralston SH, Eastell R, Pepe J, Palermo A, Langdahl B. Fracture risk and management of discontinuation of denosumab therapy: a systematic review and position statement by ECTS. J Clin Endocrinol Metab. 2020 Oct 26:dgaa756. doi: 10.1210/clinem/dgaa756. Online ahead of print.

  PMID: 33103722 BACKGROUND

• Solling AS, Harslof T, Langdahl B. Treatment With Zoledronate Subsequent to Denosumab in Osteoporosis: A 2-Year Randomized Study. J Bone Miner Res. 2021 Jul;36(7):1245-1254. doi: 10.1002/jbmr.4305. Epub 2021 Apr 20.

  PMID: 33813753 BACKGROUND

MeSH Terms

Conditions

Osteoporosis

Interventions

Zoledronic Acid

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2022
• First Posted: May 4, 2022
• Study Start: February 11, 2022
• Primary Completion: February 13, 2024
• Study Completion: February 13, 2024
• Last Updated: March 7, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)