Denosumab Sequential Therapy

Osteoporosis Clinical Trial

— DST  

Official title:

Department of Orthopedics, National Taiwan University Hospital

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03868033
• Other study ID #: 201811067MIPC
• Status: Completed
• Phase: Phase 4
• Start date: April 12, 2019
• Est. completion date: December 31, 2023

Study information

• Verified date: September 2023
• Source: National Taiwan University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Denosumab is a potent anti-resorptive agent and is now widely used in the treatment of osteoporosis. Although denosumab has excellent effect to increase bone mass and prevent fracture in FREEDOM study with very low complications, even up to ten years, it's effect is reversible. After holding the drug, circulating denosumab levels fall rapidly, and bone resorption reaching twice baseline levels for about 6 months. How to prevent bone loss after denosumab therapy is an important issue, especially when considering the compliance, persistence, or other comorbidities of the patient. We want to verify if zoledronic acid could be used as a sequential therapy after denosumab to prevent rapid bone loss by randomized clinical trial.

Description:

Denosumab is a monoclonal antibody directed against the protein RANK-L, the principal regulator of osteoclast development. Thus, it acts as a potent anti-resorptive agent and is now widely used in the treatment of osteoporosis. Because it's easily to be used with very low risk of complications, patient has better compliance and persistence of denosumab than bisphosphonates. It's market share increasing very rapidly in Taiwan.

Although denosumab has excellent effect to increase bone mass and prevent fracture in FREEDOM study with very low complications, even up to ten years, it's effect is reversible. After holding the drug, circulating denosumab levels fall rapidly, and bone resorption reaching twice baseline levels for about 6 months. Over the first 12 months off therapy, all the bone density gained on treatment is lost4. According to previous meta-analysis study, although the persistence of denosumab therapy is better than bisphosphonates, only 62% patients keep the treatment after two years. We could image how low the persistence is after five-year or ten-year treatment in the real world.

How to prevent bone loss after denosumab therapy is an important issue, especially when considering the compliance, persistence, or other comorbidities of the patient. There is only one randomized controlled trial dealing with this problem, although the primary goal of the study is designed to compare the compliance and persistence1. After switching from denosumab to alendronate for one year, bone mineral density does not decrease rapidly, although there is mild elevation of bone turn over marker.

We want to verify if zoledronic acid could be used as a sequential therapy after denosumab to prevent rapid bone loss by randomized clinical trial.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 101
• Est. completion date: December 31, 2023
• Est. primary completion date: July 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Postmenopausal women

2. Men >50-year-old

3. After Denosumab treatment = 2 years due to osteoporosis

Exclusion Criteria:

1. Patientshadeverusedantiosteoporosismedications other than Dmab

2. Estimated glomerular filtration rate <35 ml/min.

3. Malignancy

4. Continuous steroid treatment, hormone therapy or other medical treatment affecting bone metabolism

5. Secondary osteoporosis

6. Metabolic bone diseases

7. Contraindications to ZOL

8. Patients older than 80 years old

9. Hypocalcemia

Related Conditions & MeSH terms

• Osteoporosis

Intervention

Drug:
• Zoledronic Acid
Use Zoledronic acid as a sequential therapy after denosumab treatment for more than 2 years
• Denosumab
Continuous Denosumab treatment in arm 1 for two years or as a 2nd year treatment in arm 2 for one year

Locations

Country	Name	City	State
Taiwan	Department of Orthopedics, National Taiwan University Hospital	Taipei	N/A = Not Applicable

Sponsors (1)

Lead Sponsor	Collaborator
National Taiwan University Hospital

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes of lumbar spine, total hip and femoral neck bone mineral density	Changes of lumbar spine, total hip and femoral neck bone mineral density from baseline	baseline, 1 year, 2 year
Secondary	Change of bone turnover marker	Changes of bone turnover marker, including C-terminal telopeptide of type I collagen (CTX) and propeptide of procollagen type I (P1NP)	baseline, 6 months, 12 months, 15 months, 18 months, 24 months
Secondary	Clinical osteoporotic fracture	Incidence of clinical osteoporotic fracture	baseline, 1 year, 2 year