Effects of Cycle Therapy With Romosozumab and Denosumab 2 Years vs 1 Year Romosozumab Followed by 1 Year Denosumab in Postmenopausal Osteoporosis Patients-A Randomized Control Trial
Related Papers Related Patents Related Grants Related Experts
All trials for Osteoporosis All trials for Osteoporosis Postmenopausal All trials of Romosozumab followed by Denosumab All trials of Romosozumab and Denosumab Cycle Therapy
-Summary
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.
Expand all sections · Collapse all
+Detailed description
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.
+Arms and interventions
| Arm | Type | Interventions | Description |
|---|
| Sequential therapy group | Active comparator | Drug: Romosozumab followed by Denosumab | Romosozumab followed by Denosumab |
| Cycle therapy group | Experimental | Drug: Romosozumab and Denosumab Cycle Therapy | Romosozumab and Denosumab Cycle Therapy |
- Romosozumab followed by Denosumab (Drug), also known as Sequential therapy group: Romosozumab 210mg/month for 12 months, then Denosumab 60mg/6months for 12 months
- Romosozumab and Denosumab Cycle Therapy (Drug), also known as Cycle therapy group: Romosozumab 210mg/month for 6 months then followed by Denosumab 60mg/6months once, and then repeat one more time after 6 months
+Outcome measures
Primary outcomes
- Change in bone mineral density (BMD) [Participants will undergo baseline assessments, followed by evaluations at 6, 12, 18 and 24 months.]: Change in BMD at lumbar spine, femoral neck and total hip at 24 months
Secondary outcomes
- Change in bone turnover makers (BTM) level [Participants will undergo baseline assessments, followed by evaluations at 3, 6, 9, 12, 13, 15, 18, 21, and 24 months.]: Changes in BTM, including bone formation (P1NP) and resorption markers (CTX)
- Change in visual Analogue Scale (VAS) score [Participants will undergo baseline assessments, followed by evaluations at 3, 6, 9, 12, 15, 18, 21, and 24 months.]: The Visual Analogue Scale (VAS) for pain will be used to assess participants' self-reported pain intensity. The VAS score ranges from 0 to 10, higher scores indicate worse pain intensity, and lower scores indicate less pain.
- Oswestry Disability Index (ODI) score change [Participants will undergo baseline assessments, followed by evaluations at 6, 12, 18 and 24 months.]: The Oswestry Disability Index (ODI) will be used to assess the level of disability related to lower back pain. The ODI score ranges from 0 to 100, higher scores reflect worse functional disability and lower scores reflect better functional status.
- New fracture [During the intervention period, up to 24 months.]: Any new fracture within 24 months
- Adverse Events [During the intervention period, up to 24 months.]: Any adverse events
+Eligibility
Sex: Female, ages: 50 Years to 90 Years
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)
+Locations (1)
| Facility | City | Country | Status |
|---|
| National Taiwan University Hospital | Taipei | Taiwan | Recruiting |
+Publications
- Results publication: 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. PMID 35787482
- Results publication: 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. PMID 39485918
- Results publication: 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. PMID 27641143
- Results publication: 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. PMID 36382762
- Results publication: 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. PMID 37948565
- Results publication: 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. PMID 28144701
- Results publication: 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. PMID 36088628
- Results publication: 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. PMID 35279261
- Results publication: 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. PMID 35478046
- Results publication: Fogelman I, Blake GM. Different approaches to bone densitometry. J Nucl Med. 2000 Dec;41(12):2015-25. PMID 11138687
- Results publication: 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. PMID 37574339
- Results publication: 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. PMID 29067572