Zoledronic Acid for Prevention of Bone Loss After BAriatric Surgery (ZABAS)

Study Overview
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Brief Summary
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In a randomised placebo-controlled trial assess effects of zoledronic acid for prevention of bone and muscle loss after bariatric surgery.

Detailed Description
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In individuals with severe obesity, bariatric surgery effectively reduces body weight, improves obesity related diseases and lowers mortality. A loss of bone and muscle mass and an increase in bone fracture risk are however seen after surgery. In this study it is examined if treatment with zoledronic acid (a drug used to treat osteoporosis) can prevent the bone and muscle loss after bariatric surgery. A single infusion of zoledronic acid or placebo is given before surgery. The study is blinded and randomized for methodological reasons. Bone and muscle scans, tests of muscle strength and physical performance and blood samples (for analysis of markers related to bone and muscle metabolism) are performed at inclusion and 12 and 24 months after surgery. A total of 60 adult individuals will participate. Results will be important for the evidence-based care of patients undergoing bariatric surgery and zoledronic acid. Study design This is a single center randomized double-blind placebo-controlled study of zoledronic acid for prevention of bone and muscle loss after bariatric surgery. Routine bariatric surgery (RYGB or gastric sleeve) will be performed. The end of study is 24 months after surgery. Study Population Patients referred for bariatric surgery at The Hospital South West Jutland, Esbjerg will be invited to participate. Randomization After inclusion and baseline assessment, patients will be randomly assigned to either zoledronic acid or placebo with a 1:1 allocation. A randomization code stratifying an equal number of participants having RYGB or SG into each study arm will be applied.

Official Title
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Zoledronic Acid for Prevention of Bone Loss After BAriatric Surgery (ZABAS)

Conditions
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Bone Loss, Muscle Atrophy, Bariatric Surgery

Intervention / Treatment
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* Drug: Zoledronic Acid
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 35 years old or older Eligible for bariatric surgery (BMI>35 kg/m2 with obesity-related comorbidity) Exclusion Criteria: Pregnancy or breastfeeding. Chronic kidney disease with estimated GFR<45 ml/min. Hypocalcemia . Hypersensitivity to bisphosphonates, mannitol, sodium citrate or water. Metabolic bone disease (osteoporosis is allowed). Prior treatment with anti-osteoporotic agents. Treatment with oral glucocorticoids Other diseases with known effects on bone metabolism

Ages Eligible for Study
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Minimum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Zoledronic Acid<br>Active treatment | Drug: Zoledronic Acid<br>* A single treatment 21 days before bariatric surgery with Zoledronic acid 5 mg or placebo (an interval of 5 to 180 days is accepted) Pharmaceutical form: Solution for infusion (100 ml normal saline containing 5 mg zoledronic acid or placebo) Administration: slow intravenous infusion with a duration of at least 15 minutes<br>|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* as above<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantitative Computed Tomography (QCT) | Volumetric bone mineral density at the lumbar spine (L1 -L2) (Mindways QCT Pro software, Texas, USA). | Change from baseline to 12 and 24 months after bariatric surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| QCT | Volumetric BMD at the proximal femur (Mindways QCT Pro software, Texas, USA). | Change from baseline to 12 and 24 months after bariatric surgery | 
| Biochemical calcium-metabolic markers | Calcium, parathyroid hormone, vitamin D and markers of bone remodeling (CTX, P1NP). | Change from baseline to 12 and 24 months after bariatric surgery | 
| DEXA | Bone mineral density at the lumbar spine and total hip (Hologic Discovery, Waltham, MA, US). | Change from baseline to 12 and 24 months after bariatric surgery | 
| HR-pQCT | Radius and tibia bone microarchitecture (Scanco Medical AG, Brutisellen, Switzerland). | Change from baseline to 12 and 24 months after bariatric surgery | 
| Cortical bone stiffness | Cortical bone material strength index (BMSi) assessed using microindentation at the anterior surface of the mid-tibia diaphysis (OsteoProbe, Active Life Scientific, California, US). | Change from baseline to 12 and 24 months after bariatric surgery | 
| Muscle Strength | Upper and lower limb muscle strength assessed using dynamometers (foot, knee, shoulder, hand) | Change from baseline to 12 and 24 months after bariatric surgery | 
| Physical function | Short physical performance battery (SPPB), Stair Climb, 2 minute walking test | Change from baseline to 12 and 24 months after bariatric surgery |