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

Trial Summary

What is the purpose of this trial?

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).

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.

What data supports the effectiveness of the drug Risedronate for preventing bone loss after bariatric surgery?

The pilot study suggests that using Risedronate, a type of bisphosphonate, is feasible and well-tolerated for preventing bone loss after sleeve gastrectomy, a common type of bariatric surgery. Bisphosphonates are known to reduce fracture risk in osteoporosis, which supports their potential use in minimizing bone loss after bariatric surgery. ^{1 2 3 4 5}

Is risedronate safe for humans?

Risedronate is generally well-tolerated and has a safety profile similar to a placebo in clinical studies, even in patients with a history of gastrointestinal issues. It has been used safely in treating osteoporosis and preventing bone loss in various conditions. ^{6 7 8 9 10}

How is the drug Risedronate unique for treating bone loss after bariatric surgery?

Risedronate is a potent bisphosphonate that works by inhibiting osteoclasts (cells that break down bone), which helps preserve bone density and reduce fracture risk. It is unique because it acts quickly, showing significant effects within 6 months, and has a lower risk of causing stomach ulcers compared to similar drugs like alendronate. ^{6 7 8 9 11}

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

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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, 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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Risedronate to Prevent Bone Loss After Sleeve Gastrectomy: Study Design and Feasibility Report of a Pilot Randomized Controlled Trial. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Zoledronic acid for prevention of bone loss in patients receiving bariatric surgery. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Strategies to reduce the onset of sleeve gastrectomy associated bone loss (STRONG BONES): Trial design and methods. [2023]

4. England pubmed.ncbi.nlm.nih.gov

MANAGEMENT OF ENDOCRINE DISEASE: Bone complications of bariatric surgery: updates on sleeve gastrectomy, fractures, and interventions. [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

Vitamin D status and supplementation before and after Bariatric Surgery: Recommendations based on a systematic review and meta-analysis. [2023]

6. Croatia pubmed.ncbi.nlm.nih.gov

[Treatment of osteoporosis by risedronate-- speed, efficacy and safety]. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

History of risedronate. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Review of risedronate in the treatment of osteoporosis. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Bisphosphonate treatment of osteoporosis. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Extemporaneous procedures for dissolving risedronate tablets for oral administration and for feeding tubes. [2018]

11. United States pubmed.ncbi.nlm.nih.gov

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