Denosumab to Prevent High-Turnover Bone Loss After Bariatric Surgery

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.

Study Overview

• Status: Completed
• Conditions: Bone Loss; Bariatric Surgery Candidate
• Intervention / Treatment: Drug: Denosumab; Drug: Zoledronic Acid; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California, San Francisco
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage Change in Total Hip Bone Mineral Density	Pre-operative baseline to post-operative month 19

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: University of California, San Francisco; San Francisco VA Health Care System

Publications and helpful links

General Publications

• Tabira T. [Immunological abnormalities in multiple sclerosis]. No To Shinkei. 1983 Jun;35(6):535-41. No abstract available. Japanese.
• 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.
• Marina Fiol C. [Treatment of the hepatic repercussions of cholelithiasis]. Minerva Med. 1966 Jul 14;57(56):2550-2. No abstract available. Italian.

Study record dates

Study Major Dates

• Study Start (Actual): August 24, 2020
• Primary Completion (Actual): August 6, 2024
• Study Completion (Actual): August 6, 2024

Study Registration Dates

• First Submitted: September 10, 2019
• First Submitted That Met QC Criteria: September 10, 2019
• First Posted (Actual): September 12, 2019

Study Record Updates

• Last Update Posted (Estimated): October 29, 2025
• Last Update Submitted That Met QC Criteria: October 1, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Bone Diseases, Metabolic; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Imidazoles; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Organophosphorus Compounds; Organophosphonates; Diphosphonates; Zoledronic Acid; Denosumab
• Other Study ID Numbers: 20187525 (Other Grant/Funding Number: Amgen - Investigator Sponsored Study)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No