AfterDmab: Zoledronic Acid to Maintain Bone Mass After Denosumab Discontinuation

Sponsor

424 General Military Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT02499237

Collaborator

251 Hellenic Air Force & VA General Hospital (Other), Leiden University Medical Center (Other)

Enrollment

Locations

Arms

40.9

Actual Duration (Months)

28.5

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

In contrast with bisphosphonates,discontinuation of denosumab results in gradual loss of bone mineral density gains. The investigators aim to evaluate whether in patients treated with denosumab, a single zoledronic acid infusion would prevent the anticipated bone loss.

Condition or Disease	Intervention/Treatment	Phase
Postmenopausal Osteoporosis	Drug: Denosumab Drug: Zoledronic acid	Phase 4

Detailed Description

Discontinuation of denosumab results in a rebound rise of bone turnover markers and gradual loss of the achieved bone mineral density gains. In contrast, bisphosphonates, such as zoledronic acid, remain within the skeleton acting for several months or even years after discontinuation while maintaining bone mineral density despite the cessation of treatment. In this study, the investigators aim to evaluate changes in bone mineral density of the lumbar spine and the femoral neck, as well as in bone turnover markers one year after treatment discontinuation both in denosumab-treated women and in denosumab-treated women who switched to zoledronic acid infusion one year before treatment discontinuation.

Study Design

Study Type:

Interventional

Actual Enrollment :

57 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

The Effect of Zoledronic Acid Infusion in the Bone Loss Observed Following Denosumab Discontinuation in Postmenopausal Women With Low Bone Mass

Actual Study Start Date :

Jul 1, 2015

Actual Primary Completion Date :

Nov 1, 2018

Actual Study Completion Date :

Nov 26, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Denosumab Patients with low bone mass, being treated only with denosumab in the past, who will receive another year of treatment with denosumab and subsequently discontinue treatment for one year	Drug: Denosumab Treatment of low bone mass with subcutaneous injections of denosumab 60 mg every 6 months for one year Other Names: Prolia
Experimental: Denosumab plus zoledronic acid Patients with low bone mass, being treated only with denosumab in the past, who will receive a single infusion of zoledronic acid and subsequently discontinue treatment for another year	Drug: Zoledronic acid Treatment of low bone mass with a single infusion of zoledronic acid 5 mg for one year Other Names: Aclasta

Arm

Intervention/Treatment

Active Comparator: Denosumab

Patients with low bone mass, being treated only with denosumab in the past, who will receive another year of treatment with denosumab and subsequently discontinue treatment for one year

Drug: Denosumab

Treatment of low bone mass with subcutaneous injections of denosumab 60 mg every 6 months for one year

Other Names:

Prolia

Experimental: Denosumab plus zoledronic acid

Patients with low bone mass, being treated only with denosumab in the past, who will receive a single infusion of zoledronic acid and subsequently discontinue treatment for another year

Drug: Zoledronic acid

Treatment of low bone mass with a single infusion of zoledronic acid 5 mg for one year

Other Names:

Aclasta

Outcome Measures

Primary Outcome Measures

bone mineral density of the lumbar spine [from 12 to 24 months]
differences between the 2 arms in the changes of lumbar spine bone mineral density measured by dual-energy X-ray absorptiometry

Secondary Outcome Measures

bone mineral density of the femoral neck [from 12 to 24 months]
differences between the 2 arms in the changes of femoral neck bone mineral density measured by dual-energy X-ray absorptiometry
C-terminal telopeptide of type I collagen [from 12 to 15, 18, 24 months]
differences between the 2 arms in the changes of C-terminal telopeptide of type I collagen
propeptide of procollagen type I [from 12 to 15, 18, 24 months]
differences between the 2 arms in the changes of propeptide of procollagen type I
bone mineral density of the lumbar spine [from baseline to 12 months]
differences between the 2 arms in the changes of lumbar spine bone mineral density measured by dual-energy X-ray absorptiometry
bone mineral density of the femoral neck [from baseline to 12 months]
differences between the 2 arms in the changes of femoral neck bone mineral density measured by dual-energy X-ray absorptiometry

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

postmenopausal women
osteopenic (T-score > -2.5 but < -1.0) after treatment with denosumab

Exclusion Criteria:

secondary osteoporosis;
diseases that could affect bone metabolism;
medications that could affect bone metabolism;
history of any antiosteoporotic treatment other than denosumab prior to randomization
severe liver or kidney disease (creatinine clearance < 60ml/min/1.73m2)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	251 Airforce & VA General Hospital	Athens		Greece	11525
2	424 General Military Hospital	Thessaloniki		Greece	56429

Sponsors and Collaborators

424 General Military Hospital
251 Hellenic Air Force & VA General Hospital
Leiden University Medical Center

Investigators

Principal Investigator: Athanasios D Anastasilakis, PhD, 424 General Military Hospital, Thessaloniki, Greece
Principal Investigator: Polyzois Makras, PhD, 251 Airforce and VA General Hospital