Effects of Cycle Therapy vs Sequential Therapy With Romosozumab and Denosumab in Postmenopausal Osteoporosis Patients

NCT ID: NCT06938152

Last Updated: 2025-12-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

70 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-04-08

Study Completion Date

2029-12-31

Brief Summary

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This study is a prospective, randomized, controlled clinical trial comparing the efficacy of a 24-month cyclic therapy regimen (6 months of Romosozumab followed by 6 months of Denosumab, repeated for two years) versus a traditional sequential treatment regimen (12 months of Romosozumab followed by 12 months of Denosumab). The goal is to determine which approach yields better therapeutic outcomes and to optimize drug strategies for osteoporosis patients.

Detailed Description

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Osteoporosis is common in postmenopausal women and the elderly, and has been recognized by the World Health Organization as the second most prevalent metabolic bone disease worldwide. Most patients show no obvious symptoms, but a fall or sudden exertion can cause fragility fractures. Once fractures occur, complications such as acute pain, prolonged bed rest, and restricted mobility can significantly impact the quality of life and even increase mortality. Furthermore, managing these conditions requires substantial medical and social resources.

Currently, anti-osteoporosis medications are classified into two major categories: antiresorptive and anabolic agents. Studies have confirmed that both types can increase bone mineral density (BMD) and reduce fracture risk. However, each medication has usage limitations.

Denosumab is a potent antiresorptive drug, but long-term use can lead to rare side effects such as atypical femoral fractures (AFF) and medication-related osteonecrosis of the jaw (MRONJ). Additionally, stopping Denosumab can cause a severe rebound in bone resorption markers (CTX), leading to rapid BMD loss and an increased fracture risk. Managing drug discontinuation remains a major clinical challenge.

Conditions

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Osteoporosis Osteoporosis Postmenopausal

Keywords

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postmenopausal Romosozumab Denosumab cycle therapy Bone mineral density Bone turnover marker

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Sequential therapy group

Romosozumab followed by Denosumab

Group Type ACTIVE_COMPARATOR

Romosozumab followed by Denosumab

Intervention Type DRUG

Romosozumab 210mg/month for 12 months, then Denosumab 60mg/6months for 12 months

Cycle therapy group

Romosozumab and Denosumab Cycle Therapy

Group Type EXPERIMENTAL

Romosozumab and Denosumab Cycle Therapy

Intervention Type DRUG

Romosozumab 210mg/month for 6 months then followed by Denosumab 60mg/6months once, and then repeat one more time after 6 months

Interventions

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Romosozumab followed by Denosumab

Romosozumab 210mg/month for 12 months, then Denosumab 60mg/6months for 12 months

Intervention Type DRUG

Romosozumab and Denosumab Cycle Therapy

Romosozumab 210mg/month for 6 months then followed by Denosumab 60mg/6months once, and then repeat one more time after 6 months

Intervention Type DRUG

Other Intervention Names

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Sequential therapy group Cycle therapy group

Eligibility Criteria

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Inclusion Criteria

* 1\. Postmenopausal women aged 50-90 years
* 2\. BMD T-score ≤ -3.0 at any lumbar vertebra
* 3\. Physically and mentally capable of understanding and complying with the study protocol and follow-up
* 4\. Signed informed consent

Exclusion Criteria

* 1\. Previous osteoporosis treatment within the past two years, including Romosozumab, Teriparatide, Denosumab, Alendronate, Ibandronate, Zoledronic Acid, Risedronate, Raloxifene, or Bazedoxifene
* 2\. Allergy to Romosozumab or Denosumab
* 3\. Secondary osteoporosis
* 4\. Autoimmune disease
* 5\. Chronic steroid use (e.g., Chronic Obstruction Pulmonary Disease patients)
* 6\. Hypercalcemia or hypocalcemia
* 7\. Metabolic bone diseases
* 8\. Primary or metastatic bone tumors
* 9\. Cancer patients (except for in situ carcinoma and non-melanoma skin cancer, unless fully treated and in remission for five years)
* 10\. Planned dental procedures (e.g., extractions, implants) within the next year
* 11\. History of stent placement, myocardial infarction, stroke, or coronary artery disease
* 12\. Renal disease (Creatinine \> 1.5 mg/dL) or dialysis patients
* 13\. Smoking more than one pack per day (except for those who have quit for over ten years)
Minimum Eligible Age

50 Years

Maximum Eligible Age

90 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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National Taiwan University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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National Taiwan University Hospital

Taipei, , Taiwan

Site Status RECRUITING

Countries

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Taiwan

Central Contacts

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Fon-Yih Tsuang

Role: CONTACT

Phone: 886-2312-3456

Email: [email protected]

Facility Contacts

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Fon-Yih Tsuang

Role: primary

References

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Chandran M. The why and how of sequential and combination therapy in osteoporosis. A review of the current evidence. Arch Endocrinol Metab. 2022 Nov 11;66(5):724-738. doi: 10.20945/2359-3997000000564.

Reference Type RESULT
PMID: 36382762 (View on PubMed)

Gehrke B, Alves Coelho MC, Brasil d'Alva C, Madeira M. Long-term consequences of osteoporosis therapy with bisphosphonates. Arch Endocrinol Metab. 2023 Nov 10;68:e220334. doi: 10.20945/2359-4292-2022-0334.

Reference Type RESULT
PMID: 37948565 (View on PubMed)

McClung MR, Wagman RB, Miller PD, Wang A, Lewiecki EM. Observations following discontinuation of long-term denosumab therapy. Osteoporos Int. 2017 May;28(5):1723-1732. doi: 10.1007/s00198-017-3919-1. Epub 2017 Jan 31.

Reference Type RESULT
PMID: 28144701 (View on PubMed)

Cosman F, Huang S, McDermott M, Cummings SR. Multiple Vertebral Fractures After Denosumab Discontinuation: FREEDOM and FREEDOM Extension Trials Additional Post Hoc Analyses. J Bone Miner Res. 2022 Nov;37(11):2112-2120. doi: 10.1002/jbmr.4705. Epub 2022 Oct 12.

Reference Type RESULT
PMID: 36088628 (View on PubMed)

Reid IR, Billington EO. Drug therapy for osteoporosis in older adults. Lancet. 2022 Mar 12;399(10329):1080-1092. doi: 10.1016/S0140-6736(21)02646-5.

Reference Type RESULT
PMID: 35279261 (View on PubMed)

LeBoff MS, Greenspan SL, Insogna KL, Lewiecki EM, Saag KG, Singer AJ, Siris ES. The clinician's guide to prevention and treatment of osteoporosis. Osteoporos Int. 2022 Oct;33(10):2049-2102. doi: 10.1007/s00198-021-05900-y. Epub 2022 Apr 28.

Reference Type RESULT
PMID: 35478046 (View on PubMed)

Fogelman I, Blake GM. Different approaches to bone densitometry. J Nucl Med. 2000 Dec;41(12):2015-25.

Reference Type RESULT
PMID: 11138687 (View on PubMed)

Kobayakawa T, Miyazaki A, Takahashi J, Nakamura Y. Verification of efficacy and safety of ibandronate or denosumab for postmenopausal osteoporosis after 12-month treatment with romosozumab as sequential therapy: The prospective VICTOR study. Bone. 2022 Sep;162:116480. doi: 10.1016/j.bone.2022.116480. Epub 2022 Jul 1.

Reference Type RESULT
PMID: 35787482 (View on PubMed)

Hong N, Shin S, Kim H, Cho SJ, Park JA, Rhee Y. Romosozumab following denosumab improves lumbar spine bone mineral density and trabecular bone score greater than denosumab continuation in postmenopausal women. J Bone Miner Res. 2025 Feb 2;40(2):184-192. doi: 10.1093/jbmr/zjae179.

Reference Type RESULT
PMID: 39485918 (View on PubMed)

Cosman F, Crittenden DB, Adachi JD, Binkley N, Czerwinski E, Ferrari S, Hofbauer LC, Lau E, Lewiecki EM, Miyauchi A, Zerbini CA, Milmont CE, Chen L, Maddox J, Meisner PD, Libanati C, Grauer A. Romosozumab Treatment in Postmenopausal Women with Osteoporosis. N Engl J Med. 2016 Oct 20;375(16):1532-1543. doi: 10.1056/NEJMoa1607948. Epub 2016 Sep 18.

Reference Type RESULT
PMID: 27641143 (View on PubMed)

Wang CY, Wu CH, Chen HM, Lin JW, Hsu CC, Chang YF, Tai TW, Fu SH, Hwang JS. Cost and effectiveness analyses of the anti-osteoporosis medication in patients with hip fracture in Taiwan: A population-based national claims database analysis. J Formos Med Assoc. 2023;122 Suppl 1:S92-S100. doi: 10.1016/j.jfma.2023.07.018. Epub 2023 Aug 11.

Reference Type RESULT
PMID: 37574339 (View on PubMed)

Wang CY, Fu SH, Yang RS, Shen LJ, Wu FL, Hsiao FY. Age- and gender-specific epidemiology, treatment patterns, and economic burden of osteoporosis and associated fracture in Taiwan between 2009 and 2013. Arch Osteoporos. 2017 Oct 25;12(1):92. doi: 10.1007/s11657-017-0385-5.

Reference Type RESULT
PMID: 29067572 (View on PubMed)

Related Links

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https://www.niams.nih.gov/health-topics/osteoporosis

National Institute of Arthritis and Musculoskeletal and Skin Diseases. (2022.12)

Other Identifiers

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202501144MINE

Identifier Type: -

Identifier Source: org_study_id