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Drug Delivery Dec 2023Low bone mass, degeneration of bone tissue, and disruption of bone microarchitecture are all symptoms of the disease osteoporosis, which can decrease bone strength and...
Low bone mass, degeneration of bone tissue, and disruption of bone microarchitecture are all symptoms of the disease osteoporosis, which can decrease bone strength and increase the risk of fractures. The main objective of the current study was to use a phospholipid-based phase separation gel (PPSG) in combination with an alendronate sodium nanoemulsion (ALS-NE) to help prevent bone resorption in rats. The effect of factors such as concentrations of the ALS aqueous solution, surfactant Plurol Oleique CC 497, and Maisine CC oil on nanoemulsion characteristics such as stability index and globular size was investigated using an l-optimal coordinate exchange statistical design. Injectable PPSG with the best nanoemulsion formulation was tested for viscosity, gel strength, water absorption, and ALS release. ALS retention in the rats' muscles was measured after 30 days. The droplet size and stability index of the optimal nanoemulsion were 90 ± 2.0 nm and 85 ± 1.9%, respectively. When mixed with water, the optimal ALS-NE-loaded PPSG became viscous and achieved 36 seconds of gel strength, which was adequate for an injectable formulation. In comparison with the ALS solution-loaded gel, the newly created optimal ALS-NE-loaded PPSG produced the sustained and regulated release of ALS; hence, a higher percentage of ALS remained in rats' muscles after 30 days. PPSG that has been loaded with an ALS-NE may therefore be a more auspicious, productive, and effective platform for osteoporosis treatment than conventional oral forms.
Topics: Animals; Rats; Alendronate; Emulsions; Osteoporosis; Water
PubMed: 36588399
DOI: 10.1080/10717544.2022.2164094 -
Heliyon Sep 2023Bisphosphonates are known to induce a severe adverse effect known as medication-related osteonecrosis of the jaw (MRONJ). Previous studies have proven the impact of...
OBJECTIVES
Bisphosphonates are known to induce a severe adverse effect known as medication-related osteonecrosis of the jaw (MRONJ). Previous studies have proven the impact of bisphosphonates on microperfusion; therefore, this study aimed to investigate alendronate-induced microcirculatory reactions in the calvarial periosteum of rats.
STUDY DESIGN
Bone chambers were implanted into 48 Lewis rats. Microhemodynamics, inflammatory parameters, functional capillary density and defect healing were examined after alendronate treatment for two and six weeks using repetitive intravital fluorescence microscopy for two weeks.
RESULTS
Microhemodynamics remained unchanged. In alendronate-treated rats, inflammation was slightly increased, functional capillary density was significantly reduced (day 10: controls 100.45 ± 5.38 cm/cm, two weeks alendronate treatment 44.77 ± 3.55 cm/cm, six weeks alendronate treatment 27.54 ± 2.23 cm/cm) and defect healing was decelerated. The changes in functional capillary density and defect healing were dose-dependent.
CONCLUSION
The bisphosphonate alendronate has a significant negative impact on periosteal microperfusion in vivo. This could be a promising target for the treatment of MRONJ.
PubMed: 37681156
DOI: 10.1016/j.heliyon.2023.e19468 -
Frontiers in Pharmacology 2024Several medications have been used for glucocorticoids-induced osteoporosis (GIO). However, the best therapeutic option for GIO is still controversial. A Bayesian...
Several medications have been used for glucocorticoids-induced osteoporosis (GIO). However, the best therapeutic option for GIO is still controversial. A Bayesian network meta-analysis was conducted to compare the efficacy and safety of denosumab, teriparatide and bisphosphonates for patients with GIO. Relevant randomized controlled trials published in PubMed, Embase, Cochrane Library and ClinicalTrials.gov up to August 2023 were searched. The following efficiency and safety outcomes were extracted for comparison: bone mineral density (BMD) percentage changes in lumbar spine, femur neck and total hip, and incidences of adverse events (AEs), serious adverse events (SAEs), vertebrae and non-vertebrae fracture. Bayesian random effects models were used for multiple treatment comparisons. 11 eligible RCTs involving 2,877 patients were identified. All the six medications including alendronate, risedronate, etidronate, zoledronate, teriparatide, and denosumab and were effective in increasing BMD. Teriparatide and denosumab were more effective in improving lumbar spine and femur neck BMD, and reducing vertebrae fracture. Alendronate and denosumab were more effective in improving total hip BMD. Alendronate and teriparatide had the lowest incidences of AEs and SAEs. Teriparatide denosumab and the bisphosphonates are all effective in improving BMD for GIO patients. Based on this network meta-analysis, teriparatide and denosumab have higher efficiency in improving lumbar spine and femur neck BMD, and reducing vertebrae fracture. 10.17605/OSF.IO/2G8YA, identifier CRD42023456305.
PubMed: 38313307
DOI: 10.3389/fphar.2024.1336075 -
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 -
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 -
The Journal of Pharmacy Technology :... Jun 2024The objective of the study is to highlight the role and safety of romosozumab in patients at high risk of fractures in primary care. A systemic database search of... (Review)
Review
The objective of the study is to highlight the role and safety of romosozumab in patients at high risk of fractures in primary care. A systemic database search of PubMed/MEDLINE, ClinicalTrials.gov, and Cochrane Library was conducted for articles with keywords romosozumab, osteoporosis, and safety between inception and July 2022. Phase 3 trials in patients with osteoporosis were included. Data results from these trials were utilized for assessment. Romosozumab decreased vertebral fracture incidence by 73% at 12 months ( < 0.001) in osteoporotic postmenopausal women compared with placebo. In an active-controlled fracture study in postmenopausal women with osteoporosis at high risk of fracture, a 48% lower risk of new vertebral fracture was observed at 24 months in the romosozumab-alendronate group ( < 0.001) compared with alendronate group. In a study comparing romosozumab with teriparatide in postmenopausal women with osteoporosis at high risk of fracture, 2.6% of the mean percentage change from baseline in the total hip (TH) areal bone mineral density (BMD) was observed with romosozumab, while teriparatide led -0.6% of change ( < 0.0001). Romosozumab significantly increased the mean percentage change from baseline in the lumbar spine (LS) and total hip (TH) BMD than placebo in men with osteoporosis (LS, 12.1% vs 1.2%; TH, 2.5% vs -0.5%; < 0.001). Serious cardiovascular events were observed in the romosozumab compared with alendronate (2.5% vs 1.9%; odds ratio [OR] = 1.31; 95% confidence interval [CI] = 0.85-2.00) in postmenopausal women, and placebo (4.9% vs 2.5%) in men with osteoporosis. This review discusses the role of romosozumab in patients with high fracture risk and its safety in primary care. Primary care physicians should consider romosozumab for patients at high fracture risk who are intolerant or have not responded to other pharmacological treatment. Further studies are needed to clarify the safety of cardiovascular events.
PubMed: 38784024
DOI: 10.1177/87551225231220221 -
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 -
ACS Biomaterials Science & Engineering Dec 2023The development of magnesium-derived biomaterials is one of the most promising research in bone tissue engineering, and related strategies have been extensively used for...
The development of magnesium-derived biomaterials is one of the most promising research in bone tissue engineering, and related strategies have been extensively used for tendon, skull, cartilage, and bone regeneration. Also, alendronate, a well-recognized drug for osteoporosis treatment, has recently attracted a great deal of attention for bone repair. However, rapid corrosion of Mg and low systemic bioavailability of alendronate are the main limitations hampering their full exploitation. In this work, by means of physical and chemical cross-linking conjugating magnesium-metal-organic frameworks (Mg-MOFs) and bone-targeting alendronate to biocompatible gelatin scaffolds, a facile method is developed for the preparation of organic/inorganic nanocomposite gel scaffolds. The results affirmed that the nanocomposite gel scaffolds possessed excellent biocompatibility, continuous slow release of Mg and alendronate, strong bone affinity, and bone regeneration. It is noteworthy that the continuous slow release of Mg and alendronate could induce the macrophage switch to the M2 phenotype and promote osteogenic differentiation in the early stage, resulting in improved bone regeneration during implanting the scaffolds into the distal femoral. In summary, Mg-MOFs-loaded alendronate-modified gelatin gel scaffolds have been developed, exhibiting great potential for bone regenerative.
Topics: Diphosphonates; Osteogenesis; Alendronate; Magnesium; Gelatin; Nanogels; Tissue Scaffolds; Bone Regeneration
PubMed: 37942941
DOI: 10.1021/acsbiomaterials.3c01080 -
Pharmacotherapy Sep 2023To compare the effect of denosumab and alendronate on bone mineral density (BMD) in renal transplant recipients (RTRs) with low bone mass. (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
To compare the effect of denosumab and alendronate on bone mineral density (BMD) in renal transplant recipients (RTRs) with low bone mass.
METHODS
Patients were randomized to receive either denosumab subcutaneously (60 mg/6 months), oral alendronate (70 mg/week), or no treatment for 1 year. The three groups were prescribed daily calcium and vitamin D. Primary outcome was BMD assessed at lumbar spine, hip, and radius and measured by dual-energy X-ray absorptiometry (DEXA) at baseline and after 6 and 12 months. Adverse events and laboratory assessments (calcium, phosphate, vitamin D, renal functions, and intact parathyroid hormone) were monitored for all patients. Quality of life was assessed at baseline and after 6 and 12 months for all patients.
RESULTS
Ninety RTRs were included in the study (30 in each group). Baseline clinical characteristics and BMD values were comparable in the three groups. After 12 months, lumbar spine T-score of patients treated with denosumab and alendronate showed a median increase of 0.5 [95% confidence interval (CI): 0.4-0.6] and 0.5 (95% CI: 0.4-0.8), respectively, and patients in the control group showed a decrease of -0.2 (95% CI: -0.3 to -0.1), p < 0.001. Denosumab and alendronate showed a significant comparable gain in T-scores at hip and radius versus a significant decrease in the control group. Adverse events and laboratory values were similar in the three groups. Both treatments resulted in comparable significant improvement in physical functioning, physical role limitations, vitality, and pain scores.
CONCLUSION
Denosumab and alendronate showed comparable efficacy in improving BMD at all measured skeletal sites and were safe and well-tolerated, with no serious adverse effects reported in RTRs with low bone mass. The study was registered on ClinicalTrials.gov, number NCT04169698.
Topics: Humans; Alendronate; Denosumab; Bone Density Conservation Agents; Bone Density; Kidney Transplantation; Calcium; Quality of Life; Vitamin D
PubMed: 37323099
DOI: 10.1002/phar.2838 -
Journal of Bone and Mineral Metabolism Nov 2023To investigate the differences in the incidence rates of suspected stage 0/1 osteonecrosis of the jaw (ONJ) and incidence risk of relevant clinical findings of suspected... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
To investigate the differences in the incidence rates of suspected stage 0/1 osteonecrosis of the jaw (ONJ) and incidence risk of relevant clinical findings of suspected stage 0 ONJ between patients treated with sequential therapy comprising weekly teriparatide for 72 weeks followed by alendronate for 48 weeks vs. those who received monotherapy with alendronate for 120 weeks.
MATERIALS AND METHODS
Suspected stage 0/1 ONJ was defined by non-specific symptoms. Tooth mobility and periodontal symptoms (gingival bleeding, swelling, and/or pain) were selected as clinical findings of suspected stage 0 ONJ. Poisson regression models were applied to calculate the incidence rate ratios of suspected stage 0/1 between the teriparatide group (TG) and alendronate group (AG). Generalized linear models were used to calculate the risk ratios of clinical findings between groups.
RESULTS
Two hundred and sixty-one participants in the TG and 344 in the AG answered a structured questionnaire on oral health and were included in this study. There were no significant differences between the groups in the incidence rate of suspected stage 0/1 ONJ at both 72 and 120 weeks. The risk ratio of the TG to AG for tooth mobility was 0.34 (95% confidence interval [CI] 0.13-0.88, p = 0.02) at 72 weeks and 0.90 (95% CI 0.40-2.03, p = 0.83) at 120 weeks. The incidence rate of tooth mobility related to periodontal symptoms decreased in the TG and increased in the AG during the study.
CONCLUSION
Tooth mobility accompanied by clinical periodontal symptoms may be a useful early sign of stage 0 ONJ.
Topics: Humans; Alendronate; Bisphosphonate-Associated Osteonecrosis of the Jaw; Bone Density Conservation Agents; Diphosphonates; East Asian People; Osteoporosis; Reproducibility of Results; Teriparatide; Tooth Mobility
PubMed: 37897672
DOI: 10.1007/s00774-023-01466-3