Risedronate for Bone Loss After Bariatric Surgery

(WE RISE U01 Trial)

Overseen By Kristen M Beavers, PhD, MPH, RD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Wake Forest University Health Sciences

Must not be taking: Growth hormones, Oral steroids

Disqualifiers: Weight > 450 lbs, Allergies, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 6 months

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether risedronate can prevent bone and muscle loss after bariatric surgery. Already approved for treating osteoporosis, researchers aim to determine if it is effective in this new context. Participants will take either the medication or a placebo for six months and attend several follow-up visits. This trial suits individuals who have undergone a sleeve gastrectomy and are not taking certain other medications, such as oral steroids. As a Phase 3 trial, it represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you regularly use growth hormones, oral steroids, or prescription osteoporosis medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that risedronate is generally safe for use. The FDA has already approved it for treating osteoporosis, a condition where bones become weak, indicating it has been tested for safety in individuals with that condition.

Studies suggest that risedronate might help reduce bone loss after weight-loss surgeries, such as vertical sleeve gastrectomy. These surgeries can weaken bones, making this potential benefit significant. While the studies primarily assess risedronate's effectiveness, they also report few serious side effects among participants.

Like any medication, risedronate can cause side effects, but they are usually mild, such as an upset stomach or joint pain. Its testing in a later phase of trials suggests that earlier studies have not revealed any major safety concerns. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for bone loss?

Most treatments for bone loss after bariatric surgery focus on calcium and vitamin D supplementation. However, risedronate stands out because it is a bisphosphonate that helps by directly inhibiting bone resorption, which is the process where bone is broken down and its minerals are released into the bloodstream. Unlike traditional treatments that mainly focus on bone formation, risedronate works at the cellular level to prevent bone loss. Researchers are excited about risedronate because it offers a targeted approach that could more effectively maintain bone health in patients who have undergone bariatric surgery.

What evidence suggests that risedronate might be an effective treatment for bone loss after bariatric surgery?

In this trial, participants will receive either risedronate or a placebo to study its effects on bone loss after bariatric surgery. Research has shown that risedronate, a type of medication, can help reduce bone loss. Studies have found it effectively lowers the risk of fractures in people with osteoporosis and may also help prevent bone loss after weight-loss surgery. Specifically, a study found that taking risedronate for 6 months reduced bone loss after sleeve gastrectomy compared to a placebo. This suggests that risedronate could be helpful in managing bone health after bariatric surgery. ^{1 2 3 4 6}

Who Is on the Research Team?

Jamy Ard, MD

Principal Investigator

Wake Forest University Health Sciences

Kristen M Beavers, PhD, MPH, RD

Principal Investigator

Wake Forest University Health Sciences

Are You a Good Fit for This Trial?

This trial is for individuals who have undergone sleeve gastrectomy and are willing to follow the study procedures. They must be able to get themselves to study visits, weigh less than 450 lbs, and not require assistance with positioning on a scanner. Participants should not be in another research study or regularly use certain medications like growth hormones, steroids, or osteoporosis drugs.

Inclusion Criteria

Willing to provide informed consent

Agree to all study procedures and assessments.

I have had a sleeve gastrectomy.

Exclusion Criteria

I need help to position myself on a medical scanner.

You weigh more than 450 pounds.

Current participation in other research study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

2 visits (in-person)

Treatment

Participants receive six monthly doses of risedronate or placebo

6 months

Monthly contacts (virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

4 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Risedronate

Trial Overview The trial is testing if risedronate can prevent bone and muscle loss after bariatric surgery. Over one year, participants will take either risedronate or a placebo pill monthly while being monitored through six visits and regular check-ins by the study team.

How Is the Trial Designed?

Group I: Bisphosphonate Experimental Treatment 1 Intervention

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

Group II: Placebo Placebo Group 1 Intervention

Participants in this arm will receive six months of placebo

Risedronate is already approved in United States for the following indications:

Approved in United States as Actonel for:

• Postmenopausal osteoporosis
• Glucocorticoid-induced osteoporosis
• Male osteoporosis
• Paget disease

Who Is Running the Clinical Trial?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

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

Collaborator

Trials

508

Recruited

1,090,000+

Published Research Related to This Trial

Risedronate, a potent bisphosphonate, was shown to significantly reduce serum alkaline phosphatase levels and clinical symptoms in patients with Paget's disease, leading to its approval for this condition in 1998.

In large Phase 3 studies, a daily dose of 5 mg of risedronate was effective in increasing bone mineral density for treating postmenopausal and glucocorticoid-induced osteoporosis, resulting in the discontinuation of the lower 2.5 mg dose in most studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

History of risedronate. McClung, MR., Ebetino, FH.[2021]

This pilot randomized controlled trial involving 24 older patients who underwent sleeve gastrectomy demonstrated that using risedronate, a bisphosphonate, to prevent bone loss is feasible and well-tolerated, with a low adverse event rate of 3.7%.

The study achieved high participant satisfaction and retention rates, indicating that further research on bisphosphonates for preserving bone density in post-bariatric surgery patients is warranted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risedronate to Prevent Bone Loss After Sleeve Gastrectomy: Study Design and Feasibility Report of a Pilot Randomized Controlled Trial. Swafford, AA., Ard, JD., Beavers, DP., et al.[2022]

Bisphosphonates are the preferred treatment for osteoporosis, effectively increasing bone mineral density (BMD) and significantly reducing the risk of vertebral and hip fractures, with effects seen as early as 6 months to 1 year after starting treatment.

Both alendronate and risedronate are FDA-approved for treating osteoporosis in postmenopausal women and men, and while combining bisphosphonates with other antiresorptive agents may increase bone mass, it is not recommended due to lack of evidence for reduced fracture risk and potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bisphosphonate treatment of osteoporosis. Watts, NB.[2022]

Risedronate is a highly effective bisphosphonate that significantly reduces bone resorption and preserves bone formation, showing a 62% reduction in vertebral fracture risk within the first year of treatment for postmenopausal osteoporosis.

In large clinical studies involving over 15,000 patients, risedronate demonstrated excellent tolerability and safety, with a lower incidence of gastrointestinal issues compared to alendronate, making it a preferred first-line treatment for osteoporosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of osteoporosis by risedronate-- speed, efficacy and safety]. Giljević, Z., Vlak, T.[2018]

Risedronate is an effective treatment for postmenopausal osteoporosis, significantly reducing the risk of vertebral fractures by up to 49% and non-vertebral fractures by up to 39% over 3 years, with benefits seen as early as the first year.

The safety profile of risedronate is comparable to placebo, showing no significant gastrointestinal issues or acute-phase reactions, making it a well-tolerated option for patients, including those with a history of upper GI illness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of risedronate in the treatment of osteoporosis. Geusens, P., McClung, M.[2019]

The STRONG BONES trial aims to evaluate the effectiveness of the bisphosphonate risedronate in preventing bone loss in approximately 120 middle-aged and older patients who have undergone sleeve gastrectomy, a procedure linked to 3-7% axial bone loss in the year following surgery.

The primary outcome will be the change in total hip bone mineral density over 12 months, which could provide crucial insights into how bisphosphonates may help reduce fracture risk and improve bone health in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Strategies to reduce the onset of sleeve gastrectomy associated bone loss (STRONG BONES): Trial design and methods. Stapleton, JR., Ard, JD., Beavers, DP., et al.[2023]

All four approved bisphosphonates (alendronate, risedronate, ibandronate, and zoledronic acid) significantly reduce the risk of new vertebral fractures in women with postmenopausal osteoporosis, demonstrating their efficacy in fracture prevention.

Long-term studies (up to 10 years for alendronate and 7 years for risedronate) confirm that the effectiveness of these bisphosphonates in increasing bone mineral density and reducing fracture risk is maintained over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of bisphosphonates in reducing fracture risk in postmenopausal osteoporosis. Bilezikian, JP.[2018]

Bariatric surgery, particularly sleeve gastrectomy, is associated with significant bone loss, raising concerns about skeletal health in patients undergoing this procedure.

There is emerging evidence linking bariatric surgery to an increased risk of fractures, highlighting the need for intervention strategies to prevent bone loss in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MANAGEMENT OF ENDOCRINE DISEASE: Bone complications of bariatric surgery: updates on sleeve gastrectomy, fractures, and interventions. Beavers, KM., Greene, KA., Yu, EW.[2023]

In a pilot study involving 4 postmenopausal women undergoing Roux-en-Y gastric bypass (RYGB), a single dose of zoledronic acid (ZOL) showed a transient effect in reducing bone turnover markers but did not fully prevent bone loss at the hip after 24 weeks.

While ZOL did not prevent significant bone mineral density loss at the hip, there was a suggestion that it might help preserve bone density at the trabecular spine, indicating potential benefits that warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zoledronic acid for prevention of bone loss in patients receiving bariatric surgery. Liu, Y., Côté, MM., Cheney, MC., et al.[2022]

A reliable method for dissolving risedronate tablets in water was developed, allowing for accurate preparation of a liquid formulation for oral or feeding tube administration.

The drug recovery rates were high, with 95.7% to 100.5% recovery from cups and 98.3% to 101.9% from feeding tubes, indicating that the dissolution process is effective and maintains the medication's integrity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extemporaneous procedures for dissolving risedronate tablets for oral administration and for feeding tubes. Dansereau, RJ., Crail, DJ.[2018]

A systematic review of 18 studies involving 2,869 patients found that 85% of bariatric surgery candidates had vitamin D insufficiency before surgery, highlighting a significant need for preoperative assessment and management of vitamin D levels.

Post-surgery, a review of 39 studies with 5,296 patients indicated that those receiving high-dose vitamin D supplementation (≥2,000 IU daily) had better vitamin D levels and lower rates of insufficiency, suggesting that high-dose supplementation is crucial for postoperative care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin D status and supplementation before and after Bariatric Surgery: Recommendations based on a systematic review and meta-analysis. Giustina, A., di Filippo, L., Facciorusso, A., et al.[2023]

Citations

1. link.springer.com link.springer.com/article/10.1007/s11914-025-00902-9

Management of Adverse Skeletal Effects Following ... This review will address new developments in the prevention and treatment of adverse skeletal effects following bariatric surgery in people living with obesity ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8563448/

Risedronate use to attenuate bone loss following sleeve ... Bisphosphonate therapy reduces osteoporotic fracture risk and may be effective in minimizing bone loss associated with bariatric surgery. What does your study ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7574708/

Risedronate to Prevent Bone Loss After Sleeve Gastrectomy Bisphosphonate therapy reduces osteoporotic fracture risk and may be effective in minimizing bone loss associated with bariatric surgery. The ...

4. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/abs/10.1002/jbm4.10407

Risedronate to Prevent Bone Loss After Sleeve ... Bisphosphonate therapy reduces osteoporotic fracture risk and may be effective in minimizing bone loss associated with bariatric surgery.

5. sciencedirect.com sciencedirect.com/science/article/pii/S2451865423001278

Strategies to reduce the onset of sleeve gastrectomy ... 6-months of risedronate treatment is feasible and likely effective in reducing SG-associated bone loss and resorption, as compared to placebo.

6. bariatrictimes.com bariatrictimes.com/therapeutic-treatment-options-for-osteoporosis-in-the-surgical-weight-loss-population/

Therapeutic Treatment Options for Osteoporosis in the ... Bariatric surgical intervention may accentuate the excessive bone demineralization by decreasing calcium absorption in the bypassed anatomy, ...