Alendronate for Osteonecrosis in Sickle Cell Disease

Overseen By Leyla Y Teos, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, Davis

Disqualifiers: Pregnancy, Minors, Prisoners, Recent hospitalization, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if alendronate, a pill typically used to treat weak bones, can benefit adults with sickle cell disease who also have osteonecrosis, a condition where bones begin to die due to poor blood flow. The study focuses on whether this medication can improve bone health in these patients. It is a single-arm study, meaning all participants will receive alendronate to assess its effects. Individuals with sickle cell disease and a diagnosis of osteonecrosis may be suitable candidates for this trial. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that alendronate is likely to be safe for humans?

Research has shown that alendronate is usually well-tolerated by adults with sickle cell disease (SCD) and osteoporosis. One study found that bone strength improved after 6 and 12 months of treatment, suggesting the treatment is safe for these patients during this period. Although this study focuses on alendronate for bone damage in SCD, its previous use for similar issues provides some confidence about its safety. As this study is in an early phase, researchers will closely monitor safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for osteonecrosis in sickle cell disease?

Most treatments for osteonecrosis in sickle cell disease focus on managing symptoms and pain relief, often using pain medications, physical therapy, or surgery. But Alendronate works differently by targeting bone metabolism as a bisphosphonate. It helps to slow down bone loss and potentially improve bone density. Researchers are excited about Alendronate because it offers a new approach by addressing the underlying bone damage rather than just alleviating symptoms. This could lead to better long-term outcomes for patients with sickle cell disease experiencing osteonecrosis.

What evidence suggests that alendronate might be an effective treatment for osteonecrosis in sickle cell disease?

Research has shown that alendronate, which participants in this trial will receive, may help treat bone damage in adults with sickle cell disease. Studies have found that patients who took alendronate developed stronger and thicker bones, with bone strength improving after 6 and 12 months of treatment. Another study demonstrated that alendronate significantly reduced pain, with patients experiencing less pain after just 6 weeks. This suggests that alendronate could help manage symptoms and slow down bone damage in people with sickle cell disease. ^{1 2 4 5 6}

Who Is on the Research Team?

Oyebimpe O Adesina, MD, MS

Principal Investigator

UC Davis School of Medicine

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 with Sickle Cell Disease (SCD) of any genotype, confirmed by specific blood tests. Participants must be able to consent, lay on a DXA scanner for bone density measurements, and women capable of becoming pregnant must have a negative pregnancy test.

Inclusion Criteria

Ability to provide written informed consent

Negative urine pregnancy test for anyone of childbearing potential at study entry

I can lay on a DXA scanner.

Exclusion Criteria

Prisoners

I have not been hospitalized for any reason in the last 2 weeks.

Pregnant women

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral alendronate 70 mg once a week for 24 weeks

24 weeks

Weekly visits for medication administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Alendronate

Trial Overview The study is testing the effects of an oral medication called Alendronate Sodium in adults with SCD who are experiencing osteonecrosis, which is bone tissue death due to reduced blood flow.

How Is the Trial Designed?

Group I: Alendronate group Experimental Treatment 1 Intervention

Single-arm prospective cohort of 30 adult with SCD

Alendronate is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Fosamax for:

• Prevention and treatment of osteoporosis in postmenopausal women
• Treatment of osteoporosis in men

Approved in European Union as Fosamax for:

• Treatment of osteoporosis in postmenopausal women at risk of fracture
• Treatment of osteoporosis in men at risk of fracture

Approved in Canada as Fosamax for:

• Treatment of osteoporosis in postmenopausal women
• Treatment of osteoporosis in men

Who Is Running the Clinical Trial?

University of California, Davis

Lead Sponsor

Trials

958

Recruited

4,816,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Doris Duke Charitable Foundation

Collaborator

Trials

65

Recruited

264,000+

Published Research Related to This Trial

In a study of 186 women with postmenopausal osteoporosis, generic alendronate showed significantly lower increases in bone mineral density (BMD) compared to branded alendronate (Fosamax®) and branded risedronate (Actonel®) after one year, suggesting that the generic may be less effective.

Patients taking generic alendronate also had lower treatment persistence (68%) compared to those on branded medications (84% for Fosamax® and 94% for Actonel®), which may be linked to a higher incidence of gastrointestinal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differences in persistence, safety and efficacy of generic and original branded once weekly bisphosphonates in patients with postmenopausal osteoporosis: 1-year results of a retrospective patient chart review analysis. Ringe, JD., Möller, G.[2021]

In a study of a population of 900,000 in south-east Scotland, the incidence of alendronate-associated osteonecrosis of the jaws (AONJ) was found to be less than 0.004% for patients treated for age-related or hormone-related osteoporosis.

However, the incidence increased to over 0.1% when alendronate was used as a preventive treatment for glucocorticosteroid-induced osteoporosis, indicating a higher risk associated with this specific use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An epidemiological study of alendronate-related osteonecrosis of the jaws. A case series from the south-east of Scotland with attention given to case definition and prevalence. Malden, N., Lopes, V.[2022]

A patient taking alendronate (Fosamax) experienced low phosphate and calcium levels after using Fleet Phospho-Soda for bowel preparation, indicating a potential risk for those on bone metabolism medications.

The case suggests that patients on these medications may have an impaired ability to respond to situations that cause low calcium levels, highlighting the need for careful monitoring in similar cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postoperative hypocalcemic tetany caused by fleet phospho-soda preparation in a patient taking alendronate sodium: report of a case. Campisi, P., Badhwar, V., Morin, S., et al.[2022]

Alendronate is an effective treatment for osteoporosis in postmenopausal women, significantly reducing the risk of vertebral and nonvertebral fractures, as shown in large randomized controlled trials lasting up to 3 years.

The drug works by inhibiting osteoclast activity, which helps prevent bone loss without increasing the risk of osteomalacia, making it a safe option for increasing bone mass in women with osteoporosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Drug clinics. The drug of the month. Alendronate (Fosamax)]. Scheen, AJ.[2015]

Alendronate, a bisphosphonate, effectively inhibits bone resorption and shows promise in managing osteoporosis, with studies indicating it can decrease bone loss and potentially increase bone mass over time.

While alendronate has demonstrated biological efficacy and low toxicity in treating conditions like Paget's disease and malignancy-related bone disease, further long-term studies are necessary to confirm its effects on bone mass and fracture reduction in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale for the use of alendronate in osteoporosis. Kanis, JA., Gertz, BJ., Singer, F., et al.[2020]

A 71-year-old woman developed extensive osteonecrosis of the mandible after a dental extraction while taking alendronic acid for osteoporosis, highlighting a potential risk associated with bisphosphonate use.

The case suggests that bone affected by medication-related osteonecrosis of the jaw (MRONJ) can be treated and regenerated using non-vascularised autologous grafts and endosseous implants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful long-term mandibular reconstruction and rehabilitation using non-vascularised autologous bone graft and recombinant human BMP-7 with subsequent endosseous implant in a patient with bisphosphonate-related osteonecrosis of the jaw. Rahim, I., Salt, S., Heliotis, M.[2018]

In a study involving 20 rabbits and 79 dental implants, systemic administration of alendronate did not significantly affect the osseointegration of dental implants, as measured by torque-removal values after 6 weeks.

While alendronate did not show an impact on implant stability, there was a notable difference in torque removal values between the femur and tibia sites, indicating that the location of the implant may influence osseointegration outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of alendronate on endosseous implant integration: an in vivo study in rabbits. Chacon, GE., Stine, EA., Larsen, PE., et al.[2022]

In a study of 40 early postmenopausal women, alendronate sodium significantly reduced bone turnover markers, indicating its effectiveness in decreasing bone resorption and improving bone mass over three months.

The treatment was well tolerated, with no significant increase in adverse effects compared to the placebo group, making alendronate a safe option for managing postmenopausal osteoporosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of alendronate on bone turnover markers in early postmenopausal women. Yang, TS., Tsan, SH., Chen, CR., et al.[2015]

Oral bisphosphonates, commonly used for osteoporosis, can cause various adverse events including gastrointestinal issues, musculoskeletal pain, and osteonecrosis of the jaw, while intravenous bisphosphonates are linked to similar issues but with added risks of renal toxicity.

The severity and frequency of adverse events from bisphosphonates are often related to the dosage and potency of the medication, highlighting the need for careful management in their use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bisphosphonate-associated adverse events. Papapetrou, PD.[2022]

Alendronate (Fosamax) has been shown to significantly increase bone mineral density in postmenopausal women and reduce the risk of new vertebral and hip fractures by about 50%, based on evidence from six randomized controlled trials involving 3854 participants.

The treatment is well tolerated with no adverse effects on bone mineralization or microstructure, making alendronate a safe and effective nonhormonal therapy for osteoporosis in postmenopausal women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alendronate for osteoporosis. Safe and efficacious nonhormonal therapy. Adachi, JD.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06016634?intr=G-704650&aggFilters=studyType:int&viewType=Table&rank=6

Alendronate for Osteonecrosis in Adults With Sickle Cell ... To measure the safety, tolerability, and preliminary efficacy of oral alendronate in adults with SCD-related osteonecrosis over a 6-month treatment duration; To ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9568449/

Sickle cell bone disease and response to intravenous ... Another group demonstrated improved BMD T-scores at 6 and 12 months after treatment of alendronate in adults with SCD and osteoporosis [23].

3. journals.lww.com journals.lww.com/jbjsoa/fulltext/2021/12000/a_paradigm_shift_in_osteonecrosis_treatment_with.26.aspx

A Paradigm Shift in Osteonecrosis Treatment with... Patients in the combination treatment group had a significantly better improvement in VAS score at 6 weeks (from 7.10 to 3.66) compared with patients in the ...

4. cdek.pharmacy.purdue.edu cdek.pharmacy.purdue.edu/trial/NCT06016634/

Trial | NCT06016634 A prospective, single-arm, intervention study of oral alendronate in adults with sickle cell disease and osteonecrosis. Detailed Description.

5. josr-online.biomedcentral.com josr-online.biomedcentral.com/articles/10.1186/s13018-019-1152-7

Bisphosphonate combination therapy for non-femoral ... Bisphosphonates have been shown to prevent disease progression, bone collapse, and the requirement for surgery in avascular necrosis of femoral head.

6. clinicaltrial.be clinicaltrial.be/en/details/444509?per_page=100&only_recruiting=0&only_eligible=0&only_active=0

Alendronate for Osteonecrosis in Adults With Sickle Cell... The study endpoints are summarized below: To determine the recruitment and retention rates of adults with SCD and osteonecrosis enrolled in this ...