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

Official title

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

Overview

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

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.

Interventions

• Drug Romosozumab followed by Denosumab
  Romosozumab 210mg/month for 12 months, then Denosumab 60mg/6months for 12 months
• 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

Primary outcome measures

• Change in bone mineral density (BMD) [Time frame: Participants will undergo baseline assessments, followed by evaluations at 6, 12, 18 and 24 months.]

Secondary outcome measures (5)

• Change in bone turnover makers (BTM) level [Time frame: Participants will undergo baseline assessments, followed by evaluations at 3, 6, 9, 12, 13, 15, 18, 21, and 24 months.]
• Change in visual Analogue Scale (VAS) score [Time frame: Participants will undergo baseline assessments, followed by evaluations at 3, 6, 9, 12, 15, 18, 21, and 24 months.]
• Oswestry Disability Index (ODI) score change [Time frame: Participants will undergo baseline assessments, followed by evaluations at 6, 12, 18 and 24 months.]
• New fracture [Time frame: During the intervention period, up to 24 months.]
• Adverse Events [Time frame: During the intervention period, up to 24 months.]

Eligibility criteria

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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Taiwan · 1 center

• National Taiwan University Hospital — Taipei

Publications

• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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

Identifiers

NCT: NCT06938152 · 202501144MINE

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗