Denosumab to Prevent High-Turnover Bone Loss After Bariatric Surgery

NCT ID: NCT04087096

Last Updated: 2025-10-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-24
• Study Completion Date: 2024-08-06

Brief Summary

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

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.

Conditions

Bariatric Surgery Candidate; Bone Loss

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Denosumab

Denosumab 60mg subcutaneous injection every 6 months

Group Type: EXPERIMENTAL

Denosumab

Intervention Type: DRUG

Denosumab will be administered at postoperative months 1, 7, and 13

Zoledronic Acid

Intervention Type: DRUG

Zoledronic Acid 5mg will be administered intravenously at postoperative month 19

Placebo

Placebo subcutaneous injection every 6 months

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo will be administered at postoperative months 1, 7, and 13

Zoledronic Acid

Intervention Type: DRUG

Zoledronic Acid 5mg will be administered intravenously at postoperative month 19

Interventions

Denosumab

Denosumab will be administered at postoperative months 1, 7, and 13

Intervention Type: DRUG

Placebo

Placebo will be administered at postoperative months 1, 7, and 13

Intervention Type: DRUG

Zoledronic Acid

Zoledronic Acid 5mg will be administered intravenously at postoperative month 19

Intervention Type: DRUG

Other Intervention Names

Prolia; Reclast

Eligibility Criteria

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

• Minimum Eligible Age: 25 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of California, San Francisco

OTHER

Sponsor Role: collaborator

San Francisco VA Health Care System

FED

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Elaine W. Yu

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University of California, San Francisco

San Francisco, California, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Countries

United States

References

Tabira T. [Immunological abnormalities in multiple sclerosis]. No To Shinkei. 1983 Jun;35(6):535-41. No abstract available. Japanese.

Reference Type: BACKGROUND

PMID: 6194805 (View on PubMed)

Ramirez-Lassepas M, Quinones MR. Heparin therapy for stroke: hemorrhagic complications and risk factors for intracerebral hemorrhage. Neurology. 1984 Jan;34(1):114-7. doi: 10.1212/wnl.34.1.114.

Reference Type: BACKGROUND

PMID: 6537834 (View on PubMed)

Marina Fiol C. [Treatment of the hepatic repercussions of cholelithiasis]. Minerva Med. 1966 Jul 14;57(56):2550-2. No abstract available. Italian.

Reference Type: BACKGROUND

PMID: 6002877 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

20187525

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

20187525

Identifier Type: -

Identifier Source: org_study_id