Healthy Body, Healthy Bones After Bariatric Surgery Trial

Feasibility of Bisphosphonate Use on Sleeve Gastrectomy Associated Bone Loss: Healthy Body, Healthy Bones Trial

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.

Study Overview

• Status: Completed
• Conditions: Bone Loss; Bariatric Surgery Candidate; Bone Resorption
• Intervention / Treatment: Drug: Zoledronic Acid 5 mg/Bag 100 ml Inj; Drug: Placebos

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • Bariatric Center, Nebraska Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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)

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
Active Comparator: 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.	Drug: Zoledronic Acid 5 mg/Bag 100 ml Inj; Zoledronic acid infusion; Other Names: Reclast
Placebo Comparator: Non-active Infusion; At 6 weeks post surgery, 100 ml of saline will be infused intravenously over a 15 minute time period.	Drug: Placebos; Saline infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Hip Bone Mineral Density (BMD)	Change in hip bone mineral density (BMD) measured by dual-energy x-ray absorptiometry (DXA) - g/cm2	baseline and 10 months post-surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	baseline and 10 months post-surgery
Change in Trunk Lean Mass	Change in trunk lean mass, measured in kg	baseline and 9 months post-surgery
Change in Trunk Fat Mass	Change in Trunk fat mass, measured in kg	baseline and 9 months post-surgery
Change in Weight	Change in weight, measured in kgs	baseline and 9 months post-surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants Completing 9 Month Study Visit Requirements	Feasibility assessment: proportion of participants completing 9 Month study visit requirements	9 Months
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	9 Months

Collaborators and Investigators

• Sponsor: University of Nebraska
• Investigators: Principal Investigator: Laura D Bilek, PT, PhD, University of Nebraska

Publications and helpful links

General Publications

• Flores LE, Mack L, Wichman C, Weaver AA, Kothari V, Bilek LD. Protocol for a pilot randomised controlled trial of zoledronic acid to prevent bone loss following sleeve gastrectomy surgery. BMJ Open. 2021 Dec 9;11(12):e057483. doi: 10.1136/bmjopen-2021-057483.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2020
• Primary Completion (Actual): December 30, 2022
• Study Completion (Actual): December 30, 2022

Study Registration Dates

• First Submitted: January 31, 2020
• First Submitted That Met QC Criteria: February 18, 2020
• First Posted (Actual): February 21, 2020

Study Record Updates

• Last Update Posted (Actual): September 24, 2024
• Last Update Submitted That Met QC Criteria: August 29, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Bone Diseases; Bone Resorption; Physiological Effects of Drugs; Bone Density Conservation Agents; Zoledronic Acid
• Other Study ID Numbers: 0820-19-FB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Interested researchers should contact the study PI for potential access to the research.
• IPD Sharing Time Frame: 06/30/2024
• IPD Sharing Access Criteria: Approval from the PI
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

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