Alendronate for Osteonecrosis in Sickle Cell Disease
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: University of California, Davis
Disqualifiers: Pregnancy, Minors, Prisoners, Recent hospitalization, others
No Placebo Group
Prior Safety Data
Approved in 3 Jurisdictions
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.
12345Is 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.
16789How 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.
125810Eligibility 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.
+1 more
Exclusion Criteria
Prisoners
I have not been hospitalized for any reason in the last 2 weeks.
Pregnant women
+2 more
Trial 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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: Alendronate groupExperimental Treatment1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
UC Davis Comprehensive Cancer CenterSacramento, CA
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Who Is Running the Clinical Trial?
University of California, DavisLead Sponsor
National Heart, Lung, and Blood Institute (NHLBI)Collaborator
Doris Duke Charitable FoundationCollaborator
References
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]The objective of this study was to compare the changes on bone mineral density, and the effects on persistence and adverse events in patients treated for postmenopausal osteoporosis with generic alendronate or with branded alendronate (Fosamax®) or branded risedronate (Actonel®) once weekly. In this retrospective patient chart analysis, we reviewed the 1-year observational treatment results for 186 women (ITT population) with postmenopausal osteoporosis. Patients from our outpatient department, who had started with once-weekly bisphosphonate therapy between 36 and at least 12 months before this chart review, were included in this comparative three-arm study according to their treatment: A, Generic Alendonate 70 mg products; B, Branded Alendronate (Fosamax®) 70 mg once weekly and C, Branded Risedronate (Actonel®) 35 mg once weekly. All patients received basic therapy with 1,200 mg calcium and 800 IU vitamin D per day. Patient’s bone mineral density (BMD) at lumbar spine and total hip was below −2.5 T-score, and they were with or without prevalent vertebral and non-vertebral fractures. Data analysis regarding the 186 patients shows an average increase in LS-BMD after 12 months of 2.8, 5.2 and 4.8% for the groups A, B and C, respectively. The respective mean changes at total hip were 1.5, 2.9, and 3.1%. At both sites, the mean increases in BMD were not different between the two groups receiving branded bisphosphonates (B, C) but for both were significantly higher than for the group treated with generic alendronate (A). At 12 months, 68% of group A, 84% of group B and 94% of group C were still on bisphosphonate therapy. The persistence of patients treated with generic alendronate was significantly lower as compared to each of the two with branded bisphosphonate-treated groups. The total numbers of patients reporting gastrointestinal adverse events were 32, 15 and 9 for group A, group B, and group C, respectively. Significantly lower increases of lumbar spine and total hip BMD with generic alendronate once weekly as compared to the two branded bisphosphonate originals (Fosamax®, Actonel®) were observed. The reasons for the 40–50% lower BMD increase rates when using the generic compounds are not known yet. At least in part the lower efficacy can be explained by a significantly lower degree of persistence with generic alendronate, which could be related to a higher incidence of gastrointestinal adverse events. Other reasons could be lower bioavailability or potency of generic alendronate.
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]We describe a case of extensive osteonecrosis of the mandible after a dental extraction in a 71-year-old woman who was taking alendronic acid (Fosamax(®), Merck) for osteoporosis. Bone damaged by bisphosphonate-related osteonecrosis of the jaw (BRONJ), also now known as medication-related osteonecrosis of the jaw (MRONJ), can be regenerated and filled with endosseous implants using non-vascularised autologous grafts.
Alendronate for osteoporosis. Safe and efficacious nonhormonal therapy. [2018]To review the evidence concerning alendronate (Fosamax) therapy for postmenopausal osteoporosis.
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]A close case study series of alendronate-associated osteonecrosis of the jaws (AONJ) is presented. A consistency of case definition with a minimal reporting requirement was attempted as recommended by the task force of the American Society for Bone and Mineral Research. A hierarchy of evidence focussing on 7 categories of interest was included for each case. A further 7 categories were added by the authors and completed where possible. The patients were drawn from a discrete population of 900,000 from the south-east of Scotland. The prescribing of drugs to this population was monitored by a government agency, the Information Services Office of the National Health Service of Scotland. The daily or weekly standard doses of alendronate prescribed to this population were recorded, thus allowing a calculation of the drug patient years (DPYs). The number of cases of AONJ, when computed against the cumulative year-on-year DPYs for alendronate, suggests an incidence of AONJ per DPYs of 0.1% when alendronate was prescribed as a prophylaxis against glucocorticosteroid-induced osteoporosis.
Effect of alendronate on endosseous implant integration: an in vivo study in rabbits. [2022]Alendronate sodium (Fosamax; Merck, Whitehouse Station, NJ) is a second-generation bisphosphonate used widely in osteopenic individuals for decreasing bone resorption and increasing bone density. The ability of alendronate to affect systemic bone remodeling raises natural questions about the drug's influence on dental implant osseointegration. Current knowledge regarding the effect of systemic bisphosphonates, specifically alendronate, on all 3 phrases of osseointegration is incomplete and only a few studies have started to investigate peri-implant bone responses to alendronate-coated implants. The purpose of this study was to determine the effect of systemic alendronate therapy on osseointegration of dental implants based on torque-removal values in rabbits.
Rationale for the use of alendronate in osteoporosis. [2020]Bisphosphonates are being used in disorders associated with accelerated resorption of bone, particularly Paget's disease of bone and the bone disease of malignancy. Their undoubted biological efficacy and relatively low apparent toxicity make them attractive candidates for the management of osteoporosis. The bisphosphonate alendronate has many characteristics which suggest that it is suitable for use in osteoporosis. It is a potent inhibitor of osteoclast-mediated bone resorption with no adverse effect on the mineralization of bone. Earlier studies have shown it to be one of the most active bisphosphonates in Paget's disease and the hypercalcemia of malignancy. In common with other bisphosphonates tested thus far, alendronate appears to inhibit bone loss in a variety of experimental models of osteoporosis. Long-term studies are needed to determine its steady-state effects on bone mass in man. Most data indicate that alendronate is capable at least of decreasing the rate of bone loss, and might even induce increments in bone mass for many years. Since the experimental studies show that the increase in bone mass observed with alendronate is associated with an increase in bone strength, its use is likely to decrease the frequency of fractures. However, direct clinical evidence for this requires the outcome of well-designed long-term prospective studies.
Postoperative hypocalcemic tetany caused by fleet phospho-soda preparation in a patient taking alendronate sodium: report of a case. [2022]This case report describes a patient who was previously prescribed alendronate (Fosamax) and presented with postoperative hypophosphatemia and hypocalcemic tetany after bowel preparation with Fleet Phospho-Soda. This report suggests that patients taking bone metabolism regulators may not be able to respond appropriately to hypocalcemic stressors.
Effects of alendronate on bone turnover markers in early postmenopausal women. [2015]Alendronate sodium (Fosamax, Merck, Sharp & Dohme, Whitehouse Station, NJ, USA) is an aminobisphosphonate that can inhibit osteoclast-mediated bone resorption activity to reduce bone turnover rate and improve progressive gains in bone mass.
Bisphosphonate-associated adverse events. [2022]The adverse events of the nitrogen-containing bisphosphonates are reviewed. Oral bisphosphonates (alendronate, risedronate and ibandronate), mainly used for the treatment of osteoporosis, have been associated with adverse events from the upper gastrointestinal tract, acute phase response, hypocalcaemia and secondary hyperparathyroidism, musculoskeletal pain, osteonecrosis of the jaw and ocular events. Intravenous bisphosphonates (pamidronate, ibandronate and zoledronic acid), used in oncology and for the treatment of osteoporosis, have been associated with all the above adverse events, except those from the upper gastrointestinal tract. Moreover, pamidronate and zoledronic acid have been associated with renal toxicity. Association of bisphosphonates with atrial fibrillation and atypical fractures of the femoral diaphysis remains uncertain. There are a few case reports relating bisphosphonates to cutaneous reactions, oral ulcerations, hepatitis and esophageal cancer. Generally, intravenous are more potent than oral bisphosphonates and the frequency and severity of some of the bisphosphonate- associated adverse events are dose and potency dependent.
[Drug clinics. The drug of the month. Alendronate (Fosamax)]. [2015]Alendronate (Fosamax, Merck Sharp & Dohme) is an aminobisphosphonate which inhibits bone turnover by suppressing the activity of osteoclasts without increasing the risk of osteomalacia. Alendronate is highly effective at preventing bone loss associated to absence of endogenous estrogen and induces a sustained increase in bone mass. Fosamax is indicated and reimbursed in the treatment of osteoporosis in postmenopausal women, with either an history of bone fracture confirmed by X-ray exam or obvious osteoporosis assessed by bone mineral density measurement. The recommended dosage is 10 mg once daily, continuously. The drug should be absorbed after an overnight fast to improve its bioavailability and with a big glass of plain water to reduce the risk of oesophageal ulcerations. Large randomized controlled trials for up to 3 years have demonstrated that alendronate is able to reduce the risk and rate of occurrence of vertebral and nonvertebral fractures in postmenopausal women.