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

24 Participants Needed

Trial Summary

What is the purpose of this trial?

A prospective, single-arm, intervention study of oral alendronate in adults with sickle cell disease and osteonecrosis

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.

What data supports the effectiveness of the drug Alendronate for treating osteonecrosis in sickle cell disease?

Alendronate, known for increasing bone density in osteoporosis, showed significant improvements in bone mineral density in patients with postmenopausal osteoporosis, suggesting its potential to strengthen bones in other conditions as well. ^{1 2 3 4 5}

Is alendronate generally safe for humans?

Alendronate, also known as Fosamax, is generally considered safe for humans, but it can cause side effects like stomach issues, low calcium levels, and jaw problems. It has been used for bone conditions like osteoporosis, and while it is effective, some people may experience more side effects with generic versions compared to branded ones. ^{1 6 7 8 9}

How does the drug Alendronate work for osteonecrosis in sickle cell disease?

Alendronate is unique because it is a bisphosphonate that works by inhibiting the activity of cells that break down bone, which can help increase bone density. While it is commonly used for osteoporosis, its use in osteonecrosis related to sickle cell disease is novel, as there are no standard treatments specifically for this condition. ^{1 2 5 8 10}

Research Team

Oyebimpe O Adesina, MD, MS

Principal Investigator

UC Davis School of Medicine

Eligibility Criteria

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 am between 18 and 80 years old with confirmed sickle cell disease.

Exclusion Criteria

Prisoners

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

Pregnant women

Timeline

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

Treatment Details

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.

Participant Groups

Group I: Alendronate group Experimental Treatment 1 Intervention

Single-arm prospective cohort of 24 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+

Findings from Research

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]

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]

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]

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]

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]

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 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]

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 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]

References

1. Germany 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. [2021]

2. Scotland 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. [2018]

3. Canada pubmed.ncbi.nlm.nih.gov

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

4. Japan 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. [2022]

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

Effect of alendronate on endosseous implant integration: an in vivo study in rabbits. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Rationale for the use of alendronate in osteoporosis. [2020]

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

Postoperative hypocalcemic tetany caused by fleet phospho-soda preparation in a patient taking alendronate sodium: report of a case. [2022]

8. China (Republic : 1949- ) pubmed.ncbi.nlm.nih.gov

Effects of alendronate on bone turnover markers in early postmenopausal women. [2015]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Bisphosphonate-associated adverse events. [2022]

10. Belgium pubmed.ncbi.nlm.nih.gov

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