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JAMA Jun 2024
Topics: Humans; Fractures, Bone; United States; United States Food and Drug Administration; Alendronate; Bone Density Conservation Agents; Hip Fractures; Bone Remodeling; Fractures, Spontaneous; Drug Approval; Drug Labeling
PubMed: 38748439
DOI: 10.1001/jama.2024.6077 -
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 -
Journal of Investigative Medicine : the... Oct 2023This study conducted a meta-analysis to analyze the efficacy and safety of osteoporosis medications in kidney transplant recipients and patients with chronic kidney... (Meta-Analysis)
Meta-Analysis Review
This study conducted a meta-analysis to analyze the efficacy and safety of osteoporosis medications in kidney transplant recipients and patients with chronic kidney disease (CKD). PubMed, Embase, the Cochrane Central Register of Controlled Trials were searched from the date of their inception through October 21, 2022. We performed a meta-analysis of the efficacy and safety of osteoporosis medications in adult patients with stage 3-5 CKD or kidney transplant recipients enrolled in randomized clinical trials (RCTs). We calculated the standard mean deviations with 95% confidence intervals (CI) for bone mineral density (BMD) and T scores after 6 and 12 months treatment, pooled odds ratio and 95% CI for fracture risk, and summarized adverse events. The inclusion criteria were met by 27 studies. Out of this, 19 studies were included for the meta-analysis. In stage 3-4 CKD patients, alendronate increased lumbar spine BMD. In patients at stage 5 CKD and undergoing hemodialysis, alendronate and raloxifene increased lumbar spine BMD. After 6 months, the BMD of kidney transplant recipients was seen to be significantly increased; however, there was no difference after 12 months, and the risk of fracture did not reduce. Thus, there is no evidence that these medications reduce the risk of fracture, and their effect on BMD and fracture remains unproven. These medications may increase the incidence of adverse events and their safety needs to be further evaluated. Therefore, we cannot draw a definitive conclusion about the efficacy and safety of osteoporosis medications in the above group of patients.
Topics: Adult; Humans; Alendronate; Bone Density Conservation Agents; Diphosphonates; Kidney Transplantation; Osteoporosis; Bone Density; Fractures, Bone; Renal Insufficiency, Chronic; Kidney Failure, Chronic
PubMed: 37387531
DOI: 10.1177/10815589231184215 -
Osteoporosis International : a Journal... Nov 2023This registry-based study of 3068 patients with osteoporosis compared the anti-fracture effectiveness of denosumab versus bisphosphonates. Denosumab was associated with...
UNLABELLED
This registry-based study of 3068 patients with osteoporosis compared the anti-fracture effectiveness of denosumab versus bisphosphonates. Denosumab was associated with significantly greater risk reduction than alendronate or ibandronate for vertebral and any fractures. No difference in fracture risk reduction was found between zoledronate and denosumab.
PURPOSE
To analyse the fracture risk of patients with osteoporosis receiving bisphosphonates or denosumab in a real-world setting.
METHODS
This registry-based cohort study evaluated patients taking denosumab, bisphosphonates or both sequentially. Fractures were analysed using rates, rate ratios and hazard ratios (HR), including both therapies as time-varying co-variates. Fracture risk hazards were adjusted (aHR) for baseline T-Scores and trabecular bone score (TBS) and were additionally analysed with inverse probability treatment weighting.
RESULTS
A total of 3068 patients (89% female; median age at treatment onset, 69 years [63 to 76]) received denosumab (median duration 2.8 years, [2.2 to 4.7]), bisphosphonates (3.4 years, [2.1 to 5.7]) or both sequentially. Thus, 11,078 subject-years were assessed for bisphosphonates (41% alendronate, 36% ibandronate, 23% zoledronate) and 4216 for denosumab. Moreover, 48,375 subject-years were observed before treatment onset, in addition to 2593 years of drug holidays. A total of 1481 vertebral fractures (435 under therapy), 1508 non-vertebral fractures (499 under therapy) and 202 hip fractures (67 under therapy) occurred after age 50. The risks of vertebral, non-vertebral and hip fractures were significantly lower under all bisphosphonates, denosumab and drug holidays than before treatment onset (all p < 0.001). After adjusting for age, baseline T-scores and TBS, denosumab was associated with lower risk than alendronate or ibandronate for vertebral fractures (aHR 0.47 (0.35 to 0.64) and 0.70 [0.53 to 0.91], p < 0.001 and p = 0.009, respectively) and any fractures (aHR 0.62 [0.51 to 0.76] and 0.77 [0.64 to 0.92], p < 0.001 and p = 0.004). With propensity weighting, denosumab was associated with a lower hip fracture risk compared to alendronate (HR 0.54 [0.29 to 0.98], p = 0.044). No difference in fracture risk reduction (vertebral, non-vertebral or hip) was found between zoledronate and denosumab.
CONCLUSIONS
When adjusting for disease severity, denosumab was associated with significantly greater risk reduction than alendronate and ibandronate for vertebral fractures. No difference in fracture risk reduction was found between zoledronate and denosumab.
Topics: Humans; Female; Aged; Middle Aged; Male; Alendronate; Ibandronic Acid; Zoledronic Acid; Denosumab; Cohort Studies; Bone Density Conservation Agents; Diphosphonates; Osteoporosis; Hip Fractures; Spinal Fractures; Registries; Osteoporosis, Postmenopausal
PubMed: 37493978
DOI: 10.1007/s00198-023-06863-y -
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 -
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 -
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 -
Biomaterials Advances Jun 2024Chronic myeloid leukemia is a hematological cancer, where disease relapse and drug resistance are caused by bone-hosted-residual leukemia cells. An innovative resolution...
Chronic myeloid leukemia is a hematological cancer, where disease relapse and drug resistance are caused by bone-hosted-residual leukemia cells. An innovative resolution is bone-homing and selective-active targeting of anticancer loaded-nanovectors. Herein, ivermectin (IVM) and methyl dihydrojasmonate (MDJ)-loaded nanostructured lipid carriers (IVM-NLC) were formulated then dually decorated by lactoferrin (Lf) and alendronate (Aln) to optimize (Aln/Lf/IVM-NLC) for active-targeting and bone-homing potential, respectively. Aln/Lf/IVM-NLC (1 mg) revealed nano-size (73.67 ± 0.06 nm), low-PDI (0.43 ± 0.06), sustained-release of IVM (62.75 % at 140-h) and MDJ (78.7 % at 48-h). Aln/Lf/IVM-NLC afforded substantial antileukemic-cytotoxicity on K562-cells (4.29-fold lower IC), higher cellular uptake and nuclear fragmentation than IVM-NLC with acceptable cytocompatibility on oral-epithelial-cells (as normal cells). Aln/Lf/IVM-NLC effectively upregulated caspase-3 and BAX (4.53 and 15.9-fold higher than IVM-NLC, respectively). Bone homing studies verified higher hydroxyapatite affinity of Aln/Lf/IVM-NLC (1 mg; 22.88 ± 0.01 % at 3-h) and higher metaphyseal-binding (1.5-fold increase) than untargeted-NLC. Moreover, Aln/Lf/IVM-NLC-1 mg secured 1.35-fold higher in vivo bone localization than untargeted-NLC, with lower off-target distribution. Ex-vivo hemocompatibility and in-vivo biocompatibility of Aln/Lf/IVM-NLC (1 mg/mL) were established, with pronounced amelioration of hepatic and renal toxicity compared to higher Aln doses. The innovative Aln/Lf/IVM-NLC could serve as a promising nanovector for bone-homing, active-targeted leukemia therapy.
PubMed: 38875802
DOI: 10.1016/j.bioadv.2024.213924