Bisphosphonate Use to Mitigate Bone Loss Secondary to Bariatric Surgery

The purpose of this research study is to see whether receiving a bisphosphonate medication called risedronate can reduce bone and muscle loss following bariatric surgery. Participation will involve up to 6 study visits and last about 1 year. Risedronate is a medication that prevents bone breakdown and has been approved by the US Food and Drug Administration (FDA) for the prevention and treatment of osteoporosis in older men and women. However, risedronate has not been approved for the prevention of bone and muscle loss following vertical sleeve gastrectomy.

Participation in this study will involve completing two visits before beginning the intervention. Participants who qualify will be scheduled to begin the intervention program which will involve taking 6 monthly doses of a risedronate or placebo pill. Participants will then receive monthly contacts by study staff during this time to remind participants to take the intervention pill and ask about any adverse events. After the completion of intervention period, participants will complete up to 4 follow up study visits at 6 months (2 visits) and at 12 months (2 visits).

Study Overview

• Status: Recruiting
• Conditions: Bone Loss
• Intervention / Treatment: Drug: Risedronate; Drug: Placebo

Detailed Description

The main objective of the proposed study is to definitively test whether risedronate use can effectively counter SG associated bone loss. To do this, we propose to randomize 120 middle-aged and older (≥40 years) SG patients to six months of risedronate or placebo treatment, with musculoskeletal outcomes assessed at baseline, six, and 12 months. Due to its robust change following SG and clinical utility in predicting fracture, our primary outcome is change in total hip areal (a)BMD measured by dual energy x-ray absorptiometry (DXA). This will be complemented by DXA-acquired aBMD assessment at other skeletal sites and appendicular lean mass, as well as quantitative computed tomography (QCT) derived changes in bone (volumetric BMD, cortical thickness, and strength) and muscle (cross sectional area, fat infiltration) at the hip and spine, and high-resolution peripheral quantitative computed tomography (HR-pQCT) derived changes in bone microarchitecture, density, and strength at the tibia and radius - allowing for novel assessment of intervention effectiveness on several state-of-the-art bioimaging metrics. Select measures of muscle function (fast 400-m walk, stair climb, knee extensor strength) are also included as proxies of fall risk. Finally, biomarkers of bone turnover (CTX, P1NP), bone-muscle crosstalk (TGF-β, RANKL, myostatin), and gut hormones (ghrelin, PYY, GLP-1) will be assessed in a tertiary aim, providing mechanistic insight into intervention-related changes to the bone-muscle unit. Thus, we aim to:

Aim 1: Determine the effect of risedronate compared to placebo on 12-month change from baseline in total hip aBMD following SG. We hypothesize that participants assigned to risedronate will better preserve total hip aBMD than participants assigned to placebo.

Aim 2: Determine the effects of risedronate compared to placebo on 12-month change from baseline in DXA-acquired aBMD at additional skeletal sites (femoral neck, lumbar spine, distal radius) and appendicular lean mass; QCT-derived measures of bone (volumetric BMD, cortical thickness, and strength) and muscle (cross sectional area, density, fat infiltration) at the hip and spine; HR-pQCT derived measures of bone microarchitecture, density, and strength at the tibia and radius; and muscle function (fast 400-m walk, stair climb, knee extensor strength) following SG. We hypothesize that participants assigned to risedronate will yield greater preservation/improvement in all secondary metrics than participants assigned to placebo.

Aim 3: Investigate the impact of treatment group assignment on biomarkers of bone turnover, bone-muscle crosstalk, and gut hormones to elucidate mechanisms underlying change in bone and muscle quantity and quality.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Kristen Beavers, PhD, MPH, RD; Phone Number: 336-758-5855; Email: beaverkm@wfu.edu

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Recruiting
      • Wake Forest School of Medicine
      • Contact: Lori Cogdill, MS; Phone Number: 336-758-5044; Email: lcogdill@wfu.edu
      • Contact: Kristen Beavers, PhD, MPH, RD; Phone Number: 336-758-5855; Email: beaverkm@wfu.edu
      • Principal Investigator: Kristen Beavers, PhD, MPH, RD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subjects who have had sleeve gastrectomy
• Willing to provide informed consent
• Agree to all study procedures and assessments.

Exclusion Criteria:

• Weight greater than 450 lbs
• Regular use of growth hormones, oral steroids, or prescription osteoporosis medications;
• Known allergies to bisphosphonates
• Unstable gastric reflux requiring two or more additional doses per month of anti-reflux medication.
• Current participation in other research study
• Unable to provide own transportation to study visits
• Unable to position on scanner independently.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bisphosphonate; Participants in this arm will receive six months of 150 mg once monthly oral risedronate	Drug: Risedronate; 150mg over-encapsulated risedronate; Other Names: Actonel; Atelvia
Placebo Comparator: Placebo; Participants in this arm will receive six months of placebo	Drug: Placebo; Capsules containing placebo tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Total Hip Areal Bone Mineral Density (aBMD)	Acquired through DXA scans.	baseline through Month 6
Change in Total Hip Areal Bone Mineral Density (aBMD)	Acquired through DXA scans.	baseline through Month 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dual Energy X-Ray Absorptiometry (DXA)-acquired Femoral Neck Measurements		Baseline, Month 6, Month 12
DXA-acquired Lumbar Spine Measurements		Baseline, Month 6, Month 12
DXA-acquired Distal Radius Areal BMD Measurements		Baseline, Month 6, Month 12
DXA-acquired Appendicular Lean Mass Measurements		Baseline, Month 6, Month 12
Quantitative Computed Tomography (QCT) Acquired Compartmental Volumetric BMD (hip) Measurement		Baseline, Month 6, Month 12
QCT-acquired Compartmental Volumetric BMD (Spine) Measurement		Baseline, Month 6, Month 12
QCT-acquired Cortical Thickness (Hip) Measurement		Baseline, Month 6, Month 12
QCT-acquired Finite Element (FE) Strength (Hip) Measurement		Baseline, Month 6, Month 12
QCT-acquired Mid-Thigh Cross-Sectional Area (CSA) Measurement		Baseline, Month 6, Month 12
QCT-acquired Trunk Muscle Cross-Sectional Area (CSA) Measurement		Baseline, Month 6, Month 12
QCT-acquired Thigh Muscle Density Measurement		Baseline, Month 6, Month 12
QCT-acquired Thigh Fat Infiltration Measurement		Baseline, Month 6, Month 12
Physical Function Measurement (Fast Walk)	Fast-paced gait speed will be assessed using the fast 400 meter walk test. Participants will be asked to walk 10 laps of a 40 meter course (20 meters out and 20 meters back) as fast as possible and are given a maximum of 15 minutes to complete the test.	Baseline, Month 6, Month 12
Physical Function Measurement (Stair Climb)	Stair climbing ability will be assessed by using the participant's fastest time achieved to climb 12 steps in two trials. Both tests are sensitive to intensive weight loss and predictive of fall risk.	Baseline, Month 6, Month 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarkers of Bone Turnover, Metabolism, and Bone-Muscle Crosstalk	Blood drawn for collection of biomarkers.	Baseline, Month 6, Month 12
High Resolution peripheral Quantitative Computed Tomagraphy (HRpQCT)-Acquired Distal Tibia Failure Load		Baseline, Month 6, Month 12
HRpQCT-Acquired Distal Tibia Bones Stiffness		Baseline, Month 6, Month 12
HRpQCT-Acquired Distal Radius Failure Load		Baseline, Month 6, Month 12
HRpQCT-Acquired Distal Radius Bone Stiffness		Baseline, Month 6, Month 12
HRpQCT-Acquired Distal Tibia Trabecular Number		Baseline, Month 6, Month 12
HRpQCT-Acquired Distal Tibia Trabecular Thickness		Baseline, Month 6, Month 12
HRpQCT-Acquired Distal Tibia Trabecular Separation		Baseline, Month 6, Month 12
HRpQCT-Acquired Distal Tibia Cortical Thickness		Baseline, Month 6, Month 12
HRpQCT-Acquired Distal Tibia Cortical Porosity		Baseline, Month 6, Month 12
HRpQCT-Acquired Distal Tibia Cortical Volumetric Bone Mineral Density		Baseline, Month 6, Month 12
HRpQCT-Acquired Distal Tibia Trabecular Volumetric Bone Mineral Density		Baseline, Month 6, Month 12

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
• Investigators: Principal Investigator: Kristen Beavers, PhD, MPH, RD, Wake Forest University Health Sciences; Principal Investigator: Jamy Ard, MD, Wake Forest University Health Sciences

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2023
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: June 4, 2021
• First Submitted That Met QC Criteria: June 4, 2021
• First Posted (Actual): June 10, 2021

Study Record Updates

• Last Update Posted (Actual): March 1, 2024
• Last Update Submitted That Met QC Criteria: February 28, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: bariatric surgery; bisphosphonate; mitigate bone loss
• Additional Relevant MeSH Terms: Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Metabolic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Risedronic Acid
• Other Study ID Numbers: IRB00074763; U01AR080969 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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.: Yes