Denosumab Sequential Therapy (DST)

National Taiwan University

Status and phase: Completed; Phase 4

Conditions: Osteoporosis

Treatments: Drug: Denosumab; Drug: Zoledronic Acid

Study type: Interventional

Funder types: Other

Identifiers

NCT03868033

201811067MIPC

Details and patient eligibility

About

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.

Full 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.

Enrollment: 101 patients

Sex: All

Ages: 50 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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101 participants in 4 patient groups

Continuous Denosumab

Experimental group

Description:

Continuous anti-resorptive therapy by Denosumab for 2 years

Treatment:

Drug: Denosumab

Zoledronic acid to Denosumab

Experimental group

Description:

treat with Zoledronic acid for one year and then shift to Denosumab for another one year

Treatment:

Drug: Zoledronic Acid

Drug: Denosumab

Continuous Zoledronic acid

Experimental group

Description:

Continuous anti-resorptive therapy by Zoledronic acid for 2 years

Treatment:

Drug: Zoledronic Acid

Zoledronic acid to observation

Experimental group

Description:

treat with Zoledronic acid for one year and then close follow up by bone turn over marker. resume another dose of Zoledronic acid if elevated CTX level above normal range

Treatment:

Drug: Zoledronic Acid