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Seminars in Cancer Biology Jan 2021Amino-bisphosphonates (N-BPs) have been commercially available for over four decades and are used for the treatment of osteoporosis, Paget's disease, hypercalcemia of... (Review)
Review
Amino-bisphosphonates (N-BPs) have been commercially available for over four decades and are used for the treatment of osteoporosis, Paget's disease, hypercalcemia of malignancy, and bone metastases derived from various cancer types. Zoledronate and alendronate, two of the most potent N-BPs, have demonstrated direct tumoricidal activity on tumor cells and immune modulatory effects on myeloid cells and T cells in vitro and in animal models of cancer. However, the rapid renal clearance and sequestration in mineral bone of these drugs in free form severely limit their systemic exposure and applications in cancer patients. Reformulation of N-BPs by encapsulation in liposomal nanoparticles addresses these pharmacokinetic barriers, and liposomal zoledronate and alendronate formulations have been found to increase the anticancer efficacy of cytotoxic chemotherapies and adoptive T cell immunotherapies in murine cancer models. Herein, we review the differences in pharmacology between N-BPs versus non-N-BPs (e.g., clodronate), free versus liposomal N-BP formulations, and targeted versus non-targeted liposomal N-BPs, and the clinical and preclinical evidence supporting a role for liposomal N-BPs in the treatment of cancer. We propose that pegylated liposomal alendronate (PLA) has the most potential for clinical translation based on favorable therapeutic index, ability to passively target and accumulate in tumors, proven biocompatibility of the liposome carrier, and preclinical anticancer efficacy.
Topics: Animals; Antineoplastic Agents; Diphosphonates; Drug Compounding; Drug Discovery; Drug Repositioning; Humans; Liposomes; Neoplasms
PubMed: 31874280
DOI: 10.1016/j.semcancer.2019.12.001 -
Biomedicine & Pharmacotherapy =... Jul 2023Glucocorticoid-induced osteoporosis (GIO) complicates the clinical management of patients subjected to long-term glucocorticoid use. This study explored the effects of... (Randomized Controlled Trial)
Randomized Controlled Trial
Glucocorticoid-induced osteoporosis (GIO) complicates the clinical management of patients subjected to long-term glucocorticoid use. This study explored the effects of genistein on bone loss in a randomized double-blind alendronate-controlled trial in postmenopausal women with GIO. 200 postmenopausal women (taking at least 5 mg of prednisone equivalents) since 3 months, or more, and expected to continue for at least other 12 months, were randomized to receive genistein (54 mg/day daily) or alendronate (70 mg once a week) for 24 months. Both groups received also Calcium and Vitamin D3 supplementation. Median bone mineral density (BMD) at the antero-posterior lumbar spine significantly increased from 0.75 g/cm at baseline to 0.77 g/cm at 1 year and 0.79 g/cm at 2 years in alendronate-treated patients and from 0.77 g/cm at baseline to 0.79 g/cm at 12 months and to 0.80 g/cm at 24 months in genistein recipients. No difference was observed between the two treatments. Median BMD at the femoral neck increased from 0.67 g/cm at baseline to 0.68 g/cm at 1 year and 0.69 g/cm at 2 years in alendronate-treated patients and from 0.68 g/cm at baseline to 0.70 g/cm at 12 months and to 0.71 g/cm at 24 months in genistein recipients. No difference was observed between alendronate and genistein groups in BMD. Regarding bone markers genistein and alendronate statistically decreased c-terminal telopeptide, while osteocalcin, bone-ALP, and sclerostin showed greater changes in genistein treated patients. This randomized clinical trial suggests that genistein aglycone represents an additional therapeutic option for patients with GIO.
Topics: Humans; Female; Alendronate; Glucocorticoids; Genistein; Bone Density Conservation Agents; Osteoporosis; Bone Density; Osteoporosis, Postmenopausal; Double-Blind Method
PubMed: 37167726
DOI: 10.1016/j.biopha.2023.114821 -
Osteoporosis International : a Journal... Jul 2024This study evaluated the cost-effectiveness of sequential treatment with romosozumab-to-alendronate compared to alendronate monotherapy and teriparatide-to-alendronate,...
UNLABELLED
This study evaluated the cost-effectiveness of sequential treatment with romosozumab-to-alendronate compared to alendronate monotherapy and teriparatide-to-alendronate, in postmenopausal osteoporotic women from a Belgian healthcare perspective. Romosozumab-to-alendronate was found to be cost-effective compared to alendronate monotherapy and dominant compared to teriparatide-to-alendronate for osteoporotic women at high risk of fracture in Belgium.
PURPOSE
This study aimed to evaluate the cost-effectiveness of sequential treatment with romosozumab followed by alendronate compared to alendronate monotherapy and teriparatide followed by alendronate, in postmenopausal osteoporotic women at high risk of fracture, from a Belgian healthcare perspective. Romosozumab is reimbursed in Belgium since December 2021.
METHODS
A Markov microsimulation model was used to evaluate the cost-effectiveness of romosozumab-to-alendronate compared to alendronate monotherapy and to teriparatide-to-alendronate over a lifetime horizon. Patients transition between five different health states every 6 months based on fracture risks or death. The model was populated with Belgium-specific epidemiological and cost data, where available. The fracture risk reduction of romosozumab treatment was collated from the ARCH study, and from a published network meta-analysis. Costs were included from a healthcare perspective (NIHDI). Cost-effectiveness was reported in terms of costs per quality-adjusted life year (QALY), reported in Euro (€) 2022. Deterministic (DSA) and probabilistic sensitivity analyses (PSA) were performed.
RESULTS
Romosozumab-to-alendronate was associated with 0.12 additional QALYs at an additional cost of €2314 compared to alendronate monotherapy, resulting in an ICER of €19,978. Compared to teriparatide-to-alendronate, romosozumab-to-alendronate was found to be dominant, with higher QALYs and lower costs. The base-case results were robust to uncertainty in the input parameters when conducting the sensitivity analysis.
CONCLUSION
Sequential treatment with romosozumab followed by alendronate was found to be cost-effective compared to alendronate monotherapy and dominant compared to teriparatide followed by alendronate for postmenopausal women with osteoporosis at high risk of fracture in Belgium.
Topics: Humans; Female; Cost-Benefit Analysis; Osteoporotic Fractures; Bone Density Conservation Agents; Belgium; Osteoporosis, Postmenopausal; Quality-Adjusted Life Years; Markov Chains; Alendronate; Teriparatide; Aged; Drug Costs; Antibodies, Monoclonal; Drug Therapy, Combination; Middle Aged; Drug Administration Schedule; Drug Substitution
PubMed: 38565690
DOI: 10.1007/s00198-024-07043-2 -
Drug utilization analysis of osteoporosis medications in seven European electronic health databases.Osteoporosis International : a Journal... Oct 2023We studied the characteristics of patients prescribed osteoporosis medication and patterns of use in European databases. Patients were mostly female, older, had...
UNLABELLED
We studied the characteristics of patients prescribed osteoporosis medication and patterns of use in European databases. Patients were mostly female, older, had hypertension. There was suboptimal persistence particularly for oral medications. Our findings would be useful to healthcare providers to focus their resources on improving persistence to specific osteoporosis treatments.
PURPOSE
To characterise the patients prescribed osteoporosis therapy and describe the drug utilization patterns.
METHODS
We investigated the treatment patterns of bisphosphonates, denosumab, teriparatide, and selective estrogen receptor modulators (SERMs) in seven European databases in the United Kingdom, Italy, the Netherlands, Denmark, Spain, and Germany. In this cohort study, we included adults aged ≥ 18 years, with ≥ 1 year of registration in the respective databases, who were new users of the osteoporosis medications. The study period was between 01 January 2018 to 31 January 2022.
RESULTS
Overall, patients were most commonly initiated on alendronate. Persistence decreased over time across all medications and databases, ranging from 52-73% at 6 months to 29-53% at 12 months for alendronate. For other oral bisphosphonates, the proportion of persistent users was 50-66% at 6 months and decreased to 30-44% at 12 months. For SERMs, the proportion of persistent users at 6 months was 40-73% and decreased to 25-59% at 12 months. For parenteral treatment groups, the proportions of persistence with denosumab were 50-85% (6 month), 30-63% (12 month) and with teriparatide 40-75% (6 month) decreasing to 21-54% (12 month). Switching occurred most frequently in the alendronate group (2.8-5.8%) and in the teriparatide group (7.1-14%). Switching typically occurred in the first 6 months and decreased over time. Patients in the alendronate group most often switched to other oral or intravenous bisphosphonates and denosumab.
CONCLUSION
Our results show suboptimal persistence to medications that varied across different databases and treatment switching was relatively rare.
Topics: Adult; Humans; Female; Male; Alendronate; Bone Density Conservation Agents; Teriparatide; Denosumab; Cohort Studies; Selective Estrogen Receptor Modulators; Osteoporosis; Diphosphonates; Drug Utilization; Electronics; Osteoporosis, Postmenopausal
PubMed: 37436441
DOI: 10.1007/s00198-023-06837-0 -
Journal of Oral Biology and... 2022Alendronate is a drug for the treatment of excessive bone resorption. Alendronate reduces osteoblast viability and mineralization in a dose-dependent manner. Other views...
BACKGROUND
Alendronate is a drug for the treatment of excessive bone resorption. Alendronate reduces osteoblast viability and mineralization in a dose-dependent manner. Other views of alendronate could affect mineralization. Therefore, the effects of timing and duration of alendronate treatment on mineralization were investigated.
MATERIALS AND METHODS
MC3T3 cells were treated with alendronate at different time periods ranging from 1 to 3 weeks. Mineralization was quantified using image analysis. Cell viability was measured by Thiazolyl Blue Tetrazolium Bromide assay.
RESULTS
At low concentration (1 μM), 2-3 weeks of alendronate addition decreased mineralized area and staining intensity. Longer exposure to alendronate had more effect than short exposure. At moderate to high concentrations (5-10 μM), every alendronate treatment timing inhibited mineralization. Week 3 treatment of alendronate showed less reduction of mineralization than other time treatments. Furthermore, 10 μM alendronate reduced osteoblast viability at week 1, week 1-2, and week 1-3.
CONCLUSION
Timing and duration of alendronate addition inhibited total mineralization. Longer period of treatment reduced mineralization more than short period of treatment. In addition, reduction of total mineralization depended upon both osteoblast viability and function.
PubMed: 35957942
DOI: 10.1016/j.jobcr.2022.07.011 -
Osteoporosis International : a Journal... Feb 2024Denosumab discontinuation results in accelerated bone remodeling, decreased bone mineral density (BMD), and an increased risk of multiple vertebral fractures.... (Randomized Controlled Trial)
Randomized Controlled Trial
UNLABELLED
Denosumab discontinuation results in accelerated bone remodeling, decreased bone mineral density (BMD), and an increased risk of multiple vertebral fractures. Bisphosphonates are at least partially effective at inhibiting these consequences but there have been no randomized clinical trials assessing the efficacy of alternative antiresorptives.
PURPOSE
The aim of this study was to evaluate the comparative efficacy of alendronate and the SERM, raloxifene, in preventing the post-denosumab high-turnover bone loss.
METHODS
We conducted an open-label randomized controlled trial in which 51 postmenopausal women at increased risk of fracture were randomized with equal probability to receive 12-months of denosumab 60-mg 6-monthly followed by 12-months of either alendronate 70-mg weekly or raloxifene 60-mg daily. Serum bone remodeling markers were measured at 0,6,12,15,18, and 24 and areal BMD of the distal radius, spine, and hip were measured at 0,12,18 and 24 months.
RESULTS
After denosumab discontinuation, serum markers of bone remodeling remained suppressed when followed by alendronate, but gradually increased to baseline when followed by raloxifene. In the denosumab-to-alendronate group, denosumab-induced BMD gains were maintained at all sites whereas in the denosumab-to-raloxifene group, BMD decreased at the spine by 2.0% (95% CI -3.2 to -0.8, P = 0.003) and at the total hip by 1.2% (-2.1 to -0.4%, P = 0.008), but remained stable at the femoral neck and distal radius and above the original baseline at all sites. The decreases in spine and total hip BMD in the denosumab-to-raloxifene group (but not the femoral neck or distal radius) were significant when compared to the denosumab-to-alendronate group.
CONCLUSIONS
These results suggest that after one year of denosumab, one year of alendronate is better able to maintain the inhibition of bone remodeling and BMD gains than raloxifene.
Topics: Female; Humans; Alendronate; Raloxifene Hydrochloride; Denosumab; Bone Density Conservation Agents; Bone Density; Biomarkers; Osteoporosis, Postmenopausal
PubMed: 37798320
DOI: 10.1007/s00198-023-06932-2 -
Aging Jan 2022To explore the anti-osteoporosis and anti-diabetes effects and potential underlying mechanisms of treatment with metformin and alendronate in diabetes mellitus mice.
BACKGROUND
To explore the anti-osteoporosis and anti-diabetes effects and potential underlying mechanisms of treatment with metformin and alendronate in diabetes mellitus mice.
METHODS
Eight-week-old C57 BL/KS db/db and db/+ female mice were evaluated according to the following treatment group for 12 weeks: control group, diabetes mellitus group, diabetes mellitus with metformin group, diabetes mellitus with Alendronate group, diabetes mellitus with metformin plus alendronate group. Glucose level, glucose tolerance test, bone mineral density, bone microarchitecture, bone histomorphometry, serum biomarkers, and qPCR analysis.
RESULTS
Combined metformin and alendronate can improve progression in glucose metabolism and bone metabolism, including blood glucose levels, blood glucose levels after 4 and 16 hours fasting, glucose tolerance test results, insulin sensitivity and reduces bone loss than the diabetes group. The use of alendronate alone can increase significantly serum glucagon-like peptide-1 levels than the diabetes group. The use of metformin alone can improve bone microstructure such as Tb.Sp and Tb.N of spine in diabetic mice.
CONCLUSION
The combined use of alendronate and metformin has an anti-diabetes and anti-osteoporotic effect compared with diabetic mice, but they appear to act no obvious synergistically between alendronate and metformin.
Topics: Alendronate; Animals; Blood Glucose; Bone Demineralization, Pathologic; Bone Density; Bone Density Conservation Agents; Diabetes Mellitus; Drug Therapy, Combination; Female; Glucose; Hypoglycemic Agents; Metformin; Mice; Mice, Inbred NOD
PubMed: 35027504
DOI: 10.18632/aging.203729 -
Iranian Journal of Kidney Diseases Dec 2021Both teriparatide and alendronate were used in the treatment of osteoporosis after renal transplantation. However, there are few studies comparing their application...
INTRODUCTION
Both teriparatide and alendronate were used in the treatment of osteoporosis after renal transplantation. However, there are few studies comparing their application after renal transplant surgeries. This study was carried out to compare the effect of alendronate and teriparatide on bone mineral density in the treatment of osteoporosis after renal transplantation.
METHODS
This is a retrospective cohort study of 153 patients who were diagnosed with osteoporosis after receiving renal transplantation, and received either alendronate or teriparatide treatment. The demographic patient information, changes in patients' quality of life, mobility and pain scores, serum biochemical markers and bone density of lumbar spine, hip and femoral neck were measured and compared between groups a year after treatment.
RESULTS
there were no significant differences between the two groups concerning patient demographics such as age, gender and BMI. After a year of treatment, there were no significant differences between the two groups in biochemical markers such as serum calcium, phosphorus, creatinine and 25-OH Vitamin D (P > .05). BMD of lumbar spine, hip and femoral neck after the treatment was significantly higher in the teriparatide group than alendronate group (P < .05), while the incidence of adverse effects was higher in the teriparatide group than alendronate group (P < .05).
CONCLUSION
teriparatide can be more effective than the alendronate in the treatment of osteoporosis in renal transplant patients, while having more adverse effects. DOI: 10.52547/ijkd.6475.
Topics: Alendronate; Bone Density; Bone Density Conservation Agents; Female; Humans; Kidney Transplantation; Osteoporosis; Osteoporosis, Postmenopausal; Quality of Life; Retrospective Studies; Teriparatide
PubMed: 34930857
DOI: No ID Found -
Aerospace Medicine and Human Performance May 2023Prolonged exposure to microgravity is associated with a significant reduction in bone density, exposing astronauts to renal calculi in flight and osteoporotic fractures... (Review)
Review
Prolonged exposure to microgravity is associated with a significant reduction in bone density, exposing astronauts to renal calculi in flight and osteoporotic fractures on return to Earth. While physical countermeasures and bisphosphonates may reduce demineralization, additional therapies are needed for future interplanetary missions. This literature review aims to understand the current background pertaining to denosumab (a monoclonal antibody therapy used in osteoporosis) and its potential use for long duration spaceflight. A literature review was conducted using the following keywords: "osteoporosis"; "osteopaenia"; "microgravity"; "space flight"; "bed rest"; "denosumab"; "alendronate"; "bisphosphonates"; and "countermeasures". Additional articles were identified through references. Included for discussion were 48 articles, including systemic reviews, clinical trials, practice guidelines, and textbooks. No previous bed rest or in-flight studies regarding denosumab were identified. In osteoporosis, denosumab is superior to alendronate in maintaining bone density with a lower rate of side-effects. Emerging evidence in reduced biomechanical loading state suggests denosumab improves bone density and decreases fracture risk. Concerns exists over vertebral fracture risk following discontinuation. The dosing regimen of denosumab offers practical advantages over bisphosphonates. Existing spaceflight studies with alendronate serve as a template for a study with denosumab and allow for a direct comparison of efficacy and safety. Denosumab has numerous potential advantages as a countermeasure to microgravity-induced osteopenia when compared to alendronate, including: improved efficacy; fewer side-effects: better tolerability; and a convenient dosing regimen. Two further studies are proposed to determine in-flight efficacy and the suitability of monoclonal antibody therapy in the spaceflight environment.
Topics: Humans; Bone Density Conservation Agents; Diphosphonates; Alendronate; Osteoporotic Fractures; Space Flight; Antibodies, Monoclonal; Bone Diseases, Metabolic
PubMed: 37069761
DOI: 10.3357/AMHP.6053.2023 -
Journal of Bone and Mineral Research :... Nov 2022Both medical and surgical therapy represent potential management options for patients with asymptomatic primary hyperparathyroidism (PHPT). Because uncertainty remains... (Meta-Analysis)
Meta-Analysis
The Efficacy and Safety of Medical and Surgical Therapy in Patients With Primary Hyperparathyroidism: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Both medical and surgical therapy represent potential management options for patients with asymptomatic primary hyperparathyroidism (PHPT). Because uncertainty remains regarding both medical and surgical therapy, this systematic review addresses the efficacy and safety of medical therapy in asymptomatic patients or symptomatic patients who decline surgery and surgery in asymptomatic patients. We searched Medline, Embase, Cochrane Central Register of Controlled Trials, and PubMed from inception to December 2020, and included randomized controlled trials in patients with PHPT that compared nonsurgical management with medical therapy versus without medical therapy and surgery versus no surgery in patients with asymptomatic PHPT. For surgical complications we included observational studies. Paired reviewers addressed eligibility, assessed risk of bias, and abstracted data for patient-important outcomes. We conducted random-effects meta-analyses to pool relative risks and mean differences with 95% confidence intervals and used Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) to assess quality of evidence for each outcome. For medical therapy, 11 trials reported in 12 publications including 438 patients proved eligible: three addressed alendronate, one denosumab, three cinacalcet, two vitamin D, and two estrogen therapy. Alendronate, denosumab, vitamin D, and estrogen therapy all increased bone density. Cinacalcet probably reduced serum calcium and parathyroid hormone (PTH) levels. Cinacalcet and vitamin D may have a small or no increase in overall adverse events. Very-low-quality evidence raised the possibility of an increase in serious adverse events with alendronate and denosumab. The trials also provided low-quality evidence for increased bleeding and mastalgia with estrogen therapy. For surgery, six trials presented in 12 reports including 441 patients proved eligible. Surgery achieved biochemical cure in 96.1% (high quality). We found no convincing evidence supporting an impact of surgery on fracture, quality of life, occurrence of kidney stones, and renal function, but the evidence proved low or very low quality. Surgery was associated with an increase in bone mineral density. For patients with symptomatic and asymptomatic PHPT, who are not candidates for parathyroid surgery, cinacalcet probably reduced serum calcium and PTH levels; anti-resorptives increased bone density. For patients with asymptomatic PHPT, surgery usually achieves biochemical cure. These results can help to inform patients and clinicians regarding use of medical therapy and surgery in PHPT. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Topics: Humans; Cinacalcet; Hyperparathyroidism, Primary; Alendronate; Calcium; Quality of Life; Denosumab; Randomized Controlled Trials as Topic; Parathyroid Hormone; Vitamin D; Estrogens
PubMed: 36053960
DOI: 10.1002/jbmr.4685