Denosumab to Prevent High-Turnover Bone Loss After Bariatric Surgery

Study Overview
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Brief Summary
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Bariatric surgery leads to bone loss and increases fracture risk. This study evaluates whether denosumab can prevent the high-turnover bone loss that occurs after Roux-en-Y Gastric Bypass (RYGB) and sleeve gastrectomy (SG) surgery.

Detailed Description
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Bariatric surgery is a highly effective weight loss treatment, but one of the unintended side effects of these procedures is high-turnover bone loss and metabolic bone disease. Denosumab is a monoclonal antibody to RANKL that acts as a potent inhibitor of bone resorption. The investigators are conducting a randomized placebo-controlled trial to evaluate the ability of denosumab to prevent bone loss after RYGB or SG surgery in older adults. At the conclusion of the study, all participants will be given zoledronic acid.

Official Title
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Denosumab to Prevent High-Turnover Bone Loss After Bariatric Surgery

Conditions
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Bariatric Surgery Candidate, Bone Loss

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


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Postmenopausal women who are planning RYGB or SG surgery Men aged ≥ 50 years who are planning RYGB or SG surgery Exclusion criteria: Prior bariatric surgery Weight = 400 lbs (due to limitations of bone imaging equipment) Renal disease Hypercalcemia or hypocalcemia Hypomagnesemia Serum 25-OH vitamin D (25OHD) < 20 ng/mL Hyperparathyroidism Liver disease (AST or ALT > 2 x upper normal limit) HCT < 32% History of malignancy (except basal cell carcinoma) in the past 1 year Significant cardiopulmonary disease Major psychiatric disease History of celiac disease or inflammatory bowel disease Excessive alcohol or substance abuse Paget's disease, primary hyperparathyroidism, or any other known congenital or acquired bone disease other than osteoporosis Current hyperthyroidism or use of levothyroxine with TSH < 0.1 uIU/mL Current use of loop diuretics Current use or use in the past 12 months of oral bisphosphonates or DMAB Current use or use within the past 3 months of SERMs or calcitonin Current use or use within the past 3 months of estrogen Use of testosterone therapy if dose has changed within the last 3 months, or if dose change or discontinuation is planned in the upcoming 18 months Any current or previous use of teriparatide, strontium, or any parenteral bisphosphonate Use of oral or parenteral glucocorticoids for more than 14 days within the past 6 months Extensive dental work involving extraction or dental implant within the past 2 months or planned in the upcoming 18 months DXA BMD T-score of < -3.0 at PA spine, total hip, or femoral neck Current use of anti-VEGF drug

Ages Eligible for Study
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Minimum Age: 25 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Denosumab<br>Denosumab 60mg subcutaneous injection every 6 months | Drug: Denosumab<br>* Denosumab will be administered at postoperative months 1, 7, and 13<br>* Other names: Prolia;Drug: Zoledronic Acid<br>* Zoledronic Acid 5mg will be administered intravenously at postoperative month 19<br>* Other names: Reclast;|
| Placebo Comparator: Placebo<br>Placebo subcutaneous injection every 6 months | Drug: Placebo<br>* Placebo will be administered at postoperative months 1, 7, and 13<br>Drug: Zoledronic Acid<br>* Zoledronic Acid 5mg will be administered intravenously at postoperative month 19<br>* Other names: Reclast;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change in total hip bone mineral density |  | Pre-operative baseline to post-operative month 19 |