Zoledronic Acid to Maintain Bone Mass After Denosumab Discontinuation

Study Overview
=================
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.

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.

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

Conditions
-----------------
Postmenopausal Osteoporosis

Intervention / Treatment
-----------------
* Drug: Denosumab
* Drug: Zoledronic acid


Participation Criteria
=================
Eligibility Criteria
-----------------
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)

Ages Eligible for Study
-----------------
Minimum Age: 50 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Denosumab<br>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<br>* Treatment of low bone mass with subcutaneous injections of denosumab 60 mg every 6 months for one year<br>* Other names: Prolia;|
| Experimental: Denosumab plus zoledronic acid<br>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<br>* Treatment of low bone mass with a single infusion of zoledronic acid 5 mg for one year<br>* Other names: Aclasta;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| bone mineral density of the lumbar spine | differences between the 2 arms in the changes of lumbar spine bone mineral density measured by dual-energy X-ray absorptiometry | from 12 to 24 months | 

Secondary Outcome Measures

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

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
osteoporosis, denosumab, zoledronic acid, bone mineral density, bone markers