Bariatric Surgery Candidate, Bone Loss, Bone Resorption
Conditions
Brief summary
One in three adults in the United States suffers from obesity. Bariatric surgery is an increasingly utilized and effective treatment for obesity and obesity-related comorbidities, however, the massive weight loss associated with bariatric surgery adversely affects bone leads to an increased risk of fracture. Bisphosphonate medications, such as zoledronic acid, are used to treat bone loss in patients with osteoporosis, and this study investigates whether this medication can prevent bone loss associated with surgical weight loss procedures.
Detailed description
One in three adults in the United States suffers from obesity. Bariatric surgery is an increasingly utilized and effective treatment for obesity and obesity-related comorbidities, however, the massive weight loss associated with bariatric surgery adversely affects bone metabolism. Significant decreases in bone mineral density lead to an increased risk of fracture and subsequent reduction in physical function among bariatric surgery patients. Bisphosphonate medications, such as zoledronic acid, have been evaluated for safety and efficacy in combating bone loss in patients with osteoporosis, but their use in bariatric surgery-induced bone loss has not been explored. The primary goal of this study is to investigate whether bisphosphonate therapies are able to combat bone loss associated with surgical weight loss procedures. This research proposal is a 1-year, pilot randomized controlled trial (RCT) involving 30 adult sleeve gastrectomy patients randomized to receive either a one-time zoledronic acid infusion or placebo (n=15 per group). The investigators hypothesize that zoledronic acid, a standard treatment for low bone density, will be an effective intervention to reduce sleeve gastrectomy-induced bone loss. Bone loss is an unintended consequence of an otherwise life-saving procedure, with declining bone health potentially contributing to major morbidity in those undergoing a bariatric procedure. Identifying effective interventions to minimize bone loss is crucial for comprehensive treatment of patients who undergo bariatric surgery. Specific Aim 1: To determine the efficacy of zoledronic acid in preventing bone loss associated with sleeve gastrectomy (SG). Bone mineral density (BMD) and bone turnover markers will be measured at baseline and 9 months. The primary outcome is change in BMD as measured by Dual-energy x-ray absorptiometry (DXA). Secondary outcomes are change in BMD as measured by Quantitative Computed Tomography (QCT) and change in the serum bone turnover markers, urinary collagen type 1 cross-linked N-telopeptide (CTX; bone formation marker), serum type 1 procollagen N-terminal (P1NP; bone resorption marker), sclerostin, and osteocalcin. Specific Aim 2: To evaluate the feasibility of this trial in those who have undergone SG surgery. The feasibility will be assessed by documenting adverse events and compliance rates of the intervention at each study time point.
Interventions
Zoledronic acid infusion
DRUGPlacebos
Saline infusion
Sponsors
University of Nebraska
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The research pharmacist will deliver the drug pr placebo to the treatment nurse in an unlabeled 100 ml saline bag for infusion.
Intervention model description
In this randomized controlled trial each subject will be randomized (1:1, block randomization with a block size of 10) to one treatment group (Active or Inactive treatment) and will be considered part of the intent-to-treat (ITT) cohort. The research pharmacist will be responsible for completing the randomization process, and will hold the group assignment data. All other study personnel will be blinded to group assignment.
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Subjects planning a sleeve gastrectomy procedure at the University of Nebraska Medical Center (UNMC) Bariatric Center * Agreement to all study procedures and assessments * Women must be postmenopausal (FSH blood level \> 30 mIU/m), or incapable of child-bearing
Exclusion criteria
* Prior bariatric surgery * \< 19 years of age * Weight ≥ 350lbs * Liver or renal disease * Hypercalcemia, hypocalcemia, or hypomagnesemia * Serum 25-OH vitamin D \< 20 ng/mL * History of bone-modifying disorders * Use of bone-active medications * Known sensitivity to bisphosphonates * Extensive dental work involving extraction or dental implant within the past 2 months or planned in the upcoming 6 months * Current diagnosis of type 1 diabetes * Current malignancy * Autoimmune disease impacting bone (ex: Rheumatoid Arthritis)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hip Bone Mineral Density (BMD) | baseline and 10 months post-surgery | Change in hip bone mineral density (BMD) measured by dual-energy x-ray absorptiometry (DXA) - g/cm2 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Lumbar Spine Bone Mineral Density (BMD) | baseline and 10 months post-surgery | Change in lumbar spine bone mineral density (BMD) measured by dual-energy x-ray absorptiometry (DXA)/cm2 of L1-L4 lumbar vertebrae |
| Change in Trunk Lean Mass | baseline and 9 months post-surgery | Change in trunk lean mass, measured in kg |
| Change in Trunk Fat Mass | baseline and 9 months post-surgery | Change in Trunk fat mass, measured in kg |
| Change in Weight | baseline and 9 months post-surgery | Change in weight, measured in kgs |
Other
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Completing 9 Month Study Visit Requirements | 9 Months | Feasibility assessment: proportion of participants completing 9 Month study visit requirements |
| Tolerance: Total Number of Adverse Events Reported by Participants in the Active and In-active Arms | 9 Months | Comparison of the total number of adverse events reported by participants in the active and in-active arms |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active Infusion At 6 weeks post surgery, 5 mg of zoledronic acid in 100 ml of saline will be infused intravenously over a 15 minute time period.
Zoledronic Acid 5 mg/Bag 100 ml Inj: Zoledronic acid infusion | 3 |
| Non-active Infusion At 6 weeks post surgery, 100 ml of saline will be infused intravenously over a 15 minute time period.
Placebos: Saline infusion | 7 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 1 | 0 |
Baseline characteristics
| Characteristic | Active Infusion | Non-active Infusion | Total |
|---|---|---|---|
| Age, Continuous | 49.8 years | 43.1 years | 44.4 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 7 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Hip BMD | 1.2 g/cm2 | 1.2 g/cm2 | 1.2 g/cm2 |
| 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 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 | 3 Participants | 7 Participants | 10 Participants |
| Region of Enrollment United States | 3 participants | 7 participants | 10 participants |
| Sex: Female, Male Female | 2 Participants | 7 Participants | 9 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 7 |
| other Total, other adverse events | 0 / 3 | 0 / 7 |
| serious Total, serious adverse events | 1 / 3 | 0 / 7 |
Outcome results
Primary
Change in Hip Bone Mineral Density (BMD)
Change in hip bone mineral density (BMD) measured by dual-energy x-ray absorptiometry (DXA) - g/cm2
Time frame: baseline and 10 months post-surgery
Population: Study participants who completed the study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Active Infusion | Change in Hip Bone Mineral Density (BMD) | 0 g/cm2 |
| Non-active Infusion | Change in Hip Bone Mineral Density (BMD) | -.03 g/cm2 |
Secondary
Change in Lumbar Spine Bone Mineral Density (BMD)
Change in lumbar spine bone mineral density (BMD) measured by dual-energy x-ray absorptiometry (DXA)/cm2 of L1-L4 lumbar vertebrae
Time frame: baseline and 10 months post-surgery
Population: Participants who completed the study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Active Infusion | Change in Lumbar Spine Bone Mineral Density (BMD) | .06 g/cm2 |
| Non-active Infusion | Change in Lumbar Spine Bone Mineral Density (BMD) | .06 g/cm2 |
Secondary
Change in Trunk Fat Mass
Change in Trunk fat mass, measured in kg
Time frame: baseline and 9 months post-surgery
Population: Participants who completed the study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Active Infusion | Change in Trunk Fat Mass | -1.0 kg |
| Non-active Infusion | Change in Trunk Fat Mass | -5.4 kg |
Secondary
Change in Trunk Lean Mass
Change in trunk lean mass, measured in kg
Time frame: baseline and 9 months post-surgery
Population: Participants who completed the study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Active Infusion | Change in Trunk Lean Mass | -2.7 kg |
| Non-active Infusion | Change in Trunk Lean Mass | -3.3 kg |
Secondary
Change in Weight
Change in weight, measured in kgs
Time frame: baseline and 9 months post-surgery
Population: participants who completed the study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Active Infusion | Change in Weight | -10.9 kg |
| Non-active Infusion | Change in Weight | -22.7 kg |
Other Pre-specified
Proportion of Participants Completing 9 Month Study Visit Requirements
Feasibility assessment: proportion of participants completing 9 Month study visit requirements
Time frame: 9 Months
Other Pre-specified
Tolerance: Total Number of Adverse Events Reported by Participants in the Active and In-active Arms
Comparison of the total number of adverse events reported by participants in the active and in-active arms
Time frame: 9 Months