Denosumab to Prevent High-Turnover Bone Loss After Bariatric Surgery

Bariatric Surgery Candidate Clinical Trial

Official title:

Denosumab to Prevent High-Turnover Bone Loss After Bariatric Surgery

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04087096
• Other study ID #: 20187525
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: August 24, 2020
• Est. completion date: August 2024

Study information

• Verified date: October 2023
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 36
• Est. completion date: August 2024
• Est. primary completion date: August 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Bariatric Surgery Candidate
• Bone Diseases, Metabolic
• Bone Loss

Intervention

Drug:
• Denosumab
Denosumab will be administered at postoperative months 1, 7, and 13
• Placebo
Placebo will be administered at postoperative months 1, 7, and 13
• Zoledronic Acid
Zoledronic Acid 5mg will be administered intravenously at postoperative month 19

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of California, San Francisco	San Francisco	California

Sponsors (3)

Lead Sponsor	Collaborator
Massachusetts General Hospital	San Francisco VA Health Care System, University of California, San Francisco

Country where clinical trial is conducted

United States, 

References & Publications (3)

Lindeman KG, Greenblatt LB, Rourke C, Bouxsein ML, Finkelstein JS, Yu EW. Longitudinal 5-Year Evaluation of Bone Density and Microarchitecture After Roux-en-Y Gastric Bypass Surgery. J Clin Endocrinol Metab. 2018 Nov 1;103(11):4104-4112. doi: 10.1210/jc.2018-01496. — View Citation

Schafer AL, Kazakia GJ, Vittinghoff E, Stewart L, Rogers SJ, Kim TY, Carter JT, Posselt AM, Pasco C, Shoback DM, Black DM. Effects of Gastric Bypass Surgery on Bone Mass and Microarchitecture Occur Early and Particularly Impact Postmenopausal Women. J Bone Miner Res. 2018 Jun;33(6):975-986. doi: 10.1002/jbmr.3371. Epub 2018 Feb 5. — View Citation

Yu EW, Kim SC, Sturgeon DJ, Lindeman KG, Weissman JS. Fracture Risk After Roux-en-Y Gastric Bypass vs Adjustable Gastric Banding Among Medicare Beneficiaries. JAMA Surg. 2019 Aug 1;154(8):746-753. doi: 10.1001/jamasurg.2019.1157. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage change in total hip bone mineral density		Pre-operative baseline to post-operative month 19