Bariatric Surgery Candidate, Bone Loss
Conditions
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.
Interventions
DRUGDenosumab
Denosumab will be administered at postoperative months 1, 7, and 13
DRUGPlacebo
Placebo will be administered at postoperative months 1, 7, and 13
DRUGZoledronic Acid
Zoledronic Acid 5mg will be administered intravenously at postoperative month 19
Sponsors
University of California, San Francisco
San Francisco VA Health Care System
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
25 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage Change in Total Hip Bone Mineral Density | Pre-operative baseline to post-operative month 19 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Denosumab Denosumab 60mg subcutaneous injection every 6 months
Denosumab: Denosumab will be administered at postoperative months 1, 7, and 13
Zoledronic Acid: Zoledronic Acid 5mg will be administered intravenously at postoperative month 19 | 24 |
| Placebo Placebo subcutaneous injection every 6 months
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 | 12 |
| Total | 36 |
Baseline characteristics
| Characteristic | Denosumab | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 56.71 years STANDARD_DEVIATION 5.03 | 56.58 years STANDARD_DEVIATION 10.04 | 56.67 years STANDARD_DEVIATION 6.95 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants | 10 Participants | 32 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Pre-Op Body Mass Index (BMI) | 43.9 kg/m2 STANDARD_DEVIATION 5.59 | 43.8 kg/m2 STANDARD_DEVIATION 6.36 | 43.87 kg/m2 STANDARD_DEVIATION 5.76 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 17 Participants | 11 Participants | 28 Participants |
| Region of Enrollment United States | 24 participants | 12 participants | 36 participants |
| Sex: Female, Male Female | 15 Participants | 9 Participants | 24 Participants |
| Sex: Female, Male Male | 9 Participants | 3 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 12 |
| other Total, other adverse events | 24 / 24 | 12 / 12 |
| serious Total, serious adverse events | 5 / 24 | 1 / 12 |
Outcome results
Primary
Percentage Change in Total Hip Bone Mineral Density
Time frame: Pre-operative baseline to post-operative month 19
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Denosumab | Percentage Change in Total Hip Bone Mineral Density | 0.60 percentage of change |
| Placebo | Percentage Change in Total Hip Bone Mineral Density | -6.44 percentage of change |