Bisphosphonate Use to Mitigate Bone Loss Secondary to Bariatric Surgery

NCT ID: NCT04922333

Last Updated: 2025-12-18

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-03-28
• Study Completion Date: 2028-04-30

Brief Summary

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).

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.

Conditions

Bone Loss

Keywords

bariatric surgery; bisphosphonate; mitigate bone loss

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Bisphosphonate

Participants in this arm will receive six months of 150 mg once monthly oral risedronate

Group Type: EXPERIMENTAL

Risedronate

Intervention Type: DRUG

150mg over-encapsulated risedronate

Placebo

Participants in this arm will receive six months of placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Capsules containing placebo tablets

Interventions

Risedronate

150mg over-encapsulated risedronate

Intervention Type: DRUG

Placebo

Capsules containing placebo tablets

Intervention Type: DRUG

Other Intervention Names

Actonel; Atelvia

Eligibility Criteria

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.

• Minimum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

NIH

Sponsor Role: collaborator

Wake Forest University Health Sciences

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kristen Beavers, PhD, MPH, RD

Role: PRINCIPAL_INVESTIGATOR

Wake Forest University Health Sciences

Jamy Ard, MD

Role: PRINCIPAL_INVESTIGATOR

Wake Forest University Health Sciences

Locations

Wake Forest School of Medicine

Winston-Salem, North Carolina, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Kristen Beavers, PhD, MPH, RD

Role: CONTACT

Phone: 336-758-5855

Email: beaverkm@wfu.edu

Facility Contacts

Kristen Beavers, PhD, MPH, RD

Role: primary

Lori Cogdill, MS

Role: backup

Other Identifiers

U01AR080969

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB00074763

Identifier Type: -

Identifier Source: org_study_id