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Biointerphases May 2024Titanium (Ti) is widely utilized as an implant material; nonetheless, its integration with bone tissue faces limitations due to a patient's comorbidities. To address...
Titanium (Ti) is widely utilized as an implant material; nonetheless, its integration with bone tissue faces limitations due to a patient's comorbidities. To address this challenge, we employed a strategic approach involving the growth of thin films by spin-coating and surface functionalization with etidronate (ETI), alendronate (ALE), and risedronate (RIS). Our methodology involved coating of Ti cp IV disks with thin films of TiO2, hydroxyapatite (HA), and their combinations (1:1 and 1:2 v/v), followed by surface functionalization with ETI, ALE, and RIS. Bisphosphonate-doped films were evaluated in terms of surface morphology and physical-chemical properties by techniques such as electron microscopy, confocal microscopy, and x-ray photoelectron spectroscopy. The antibacterial potential of bisphosphonates alone or functionalized onto the Ti surface was tested against Staphylococcus aureus biofilms. Primary human bone mesenchymal stem cells were used to determine in vitro cell metabolism and mineralization. Although RIS alone did not demonstrate any antibacterial effect as verified by minimum inhibitory concentration assay, when Ti surfaces were functionalized with RIS, partial inhibition of Staphylococcus aureus growth was noted, probably because of the physical-chemical surface properties. Furthermore, samples comprising TiO2/HA (1:1 and 1:2 v/v) showcased an enhancement in the metabolism of nondifferentiated cells and can potentially enhance the differentiation of osteoblastic precursors. All samples demonstrated cell viability higher than 80%. Addition of hydroxyapatite and presence of bisphosphonates increase the metabolic activity and the mineralization of human bone mesenchymal cells. While these findings hold promise, it is necessary to conduct further studies to evaluate the system's performance in vivo and ensure its long-term safety. This research marks a significant stride toward optimizing the efficacy of titanium implants through tailored surface modifications.
Topics: Titanium; Humans; Anti-Bacterial Agents; Staphylococcus aureus; Diphosphonates; Microbial Sensitivity Tests; Mesenchymal Stem Cells; Surface Properties; Biofilms; Coated Materials, Biocompatible; Cells, Cultured; Durapatite
PubMed: 38836787
DOI: 10.1116/6.0003611 -
JGH Open : An Open Access Journal of... Jun 2024Alendronate is used to treat Paget's bone disease, glucocorticoid-induced osteoporosis, and postmenopausal osteoporosis because it suppresses osteoclast activity to stop...
BACKGROUND
Alendronate is used to treat Paget's bone disease, glucocorticoid-induced osteoporosis, and postmenopausal osteoporosis because it suppresses osteoclast activity to stop bone resorption.
CASE REPORT
We present an exceptional case of esophagitis caused by alendronate. Blood tests and other data were normal when the patient was taken to the hospital, but an endoscopic examination revealed significant esophageal redness, erosion, and ulceration, along with pseudomembrane. The patient was given medicine after receiving a diagnosis of alendronate pill-induced esophagitis based on the pathological findings.
CONCLUSION
This case report is a timely reminder of the importance of thorough pharmacovigilance, patient education, and smart therapeutic decision-making in the context of alendronate use. To properly treat and prevent problems with the esophagus caused by alendronate, additional research is required.
PubMed: 38832136
DOI: 10.1002/jgh3.13080 -
Experimental Biology and Medicine... 2024[This corrects the article DOI: 10.1177/15353702231211977.].
[This corrects the article DOI: 10.1177/15353702231211977.].
PubMed: 38826627
DOI: 10.3389/ebm.2024.10149 -
Advanced Healthcare Materials May 2024Synthetic hydrogels provide controllable 3D environments, which can be used to study fundamental biological phenomena. The growing body of evidence that cell behavior...
Synthetic hydrogels provide controllable 3D environments, which can be used to study fundamental biological phenomena. The growing body of evidence that cell behavior depends upon hydrogel stress relaxation creates a high demand for hydrogels with tissue-like viscoelastic properties. Here, a unique platform of synthetic polyethylene glycol (PEG) hydrogels in which star-shaped PEG molecules are conjugated with alendronate and/or RGD peptides, attaining modifiable degradability as well as flexible cell adhesion, is created. Novel reversible ionic interactions between alendronate and calcium phosphate nanoparticles, leading to versatile viscoelastic properties with varying initial elastic modulus and stress relaxation time, are identified. This new crosslinking mechanism provides shear-thinning properties resulting in differential cellular responses between cancer cells and stem cells. The novel hydrogel system is an improved design to the other ionic crosslink platforms and opens new avenues for the development of pathologically relevant cancer models, as well as minimally invasive approaches for cell delivery for potential regenerative therapies.
PubMed: 38809180
DOI: 10.1002/adhm.202400472 -
Clinical Therapeutics May 2024The generic drug industry currently faces multiple, serious issues that threaten the US drug supply. So-called "skinny labels" are one of the few tools authorized by... (Review)
Review
PURPOSE
The generic drug industry currently faces multiple, serious issues that threaten the US drug supply. So-called "skinny labels" are one of the few tools authorized by Congress to expedite entry into the market by generic competitors when the first patent for a brand's drug compound (only) expires. This article reviews the law on this expedited marketing pathway for generic competitors, as well as limitations on its use.
METHODS
We examined the literature on patent protection of brand drugs, including the timelines for production of generic competitors. We also examined the law concerning skinny labels, including a recent decision of the US Federal Circuit Court that clearly articulates the guidelines concerning entry into the generic market, including labeling, marketing, and promotion.
FINDINGS
Skinny labels that follow the regulations set forth in the Hatch-Waxman Act, including the necessary carve-out procedure for "methods of use" still protected by 1 or more active patents, do not infringe a brand drug's label. Furthermore, the skinny label does not induce or contribute to infringement merely because its label contains US Food and Drug Administration-required safety profile data-even when the data cross-reference superiority studies on still-patent protected methods of use elsewhere in the label.
IMPLICATIONS
Generic drugs have become essential to the broad, general availability of clinical therapeutic agents. The Hatch-Waxman Act was intended to facilitate entry of generic competitors into the marketplace, and the skinny label is an important tool to accomplish that end. As long as the generic manufacturer follows the essential skinny-label rules, specifically including marketing the compound without promoting or advertising those methods of use still protected by ongoing patents, the law will not find induced or contributory infringement.
Topics: Drugs, Generic; Humans; United States; Patents as Topic; Drug Labeling; Economic Competition; United States Food and Drug Administration; Drug Industry
PubMed: 38796336
DOI: 10.1016/j.clinthera.2024.04.007 -
Osteoporosis International : a Journal... May 2024This study uses NHS waiting times and osteoporosis medication community prescription datasets to assess the impact of COVID-19 on DXA waits and osteoporosis medication...
UNLABELLED
This study uses NHS waiting times and osteoporosis medication community prescription datasets to assess the impact of COVID-19 on DXA waits and osteoporosis medication patterns in England. Results show significant increases in DXA waiting list times and variation in prescription rates. Investment is needed to improve waiting list times.
PURPOSE
This study investigates the impact of COVID-19 on DXA scan waiting lists, service recovery and osteoporosis medication prescriptions in the NHS following the March 2020 national lockdowns and staff redeployment.
METHODS
Data from March 2019 to June 2023, including NHS digital diagnostics waiting times (DM01) and osteoporosis medication prescriptions from the English Prescribing Dataset (EPD), were analysed. This encompassed total waiting list data across England's seven regions and prescribing patterns for various osteoporosis medications. Analyses included total activity figures and regression analysis to estimate expected activity without COVID-19, using R for all data analysis.
RESULTS
In England, DXA waiting lists have grown significantly, with the yearly mean waiting list length increasing from 31,851 in 2019 to 65,757 in 2023. The percentage of patients waiting over 6 weeks for DXA scans rose from 0.9% in 2019 to 40% in 2020, and those waiting over 13 weeks increased from 0.1% in 2019 to 16.7% in 2020. Prescription trends varied, with increases in denosumab, ibandronic acid and risedronate sodium and decreases in alendronic acid, raloxifene hydrochloride and teriparatide. A notable overall prescription decrease occurred in the second quarter of 2020.
CONCLUSION
COVID-19 has significantly increased DXA scan waiting lists with ongoing recovery challenges. There is a noticeable disparity in DXA service access across England. Osteoporosis care, indicated by medication prescriptions, also declined during the pandemic. Addressing these issues requires focused investment and effort to improve DXA scan waiting times and overall access to osteoporosis care in England.
PubMed: 38795142
DOI: 10.1007/s00198-024-07120-6 -
Molecules (Basel, Switzerland) May 2024Vitamin D, an essential micronutrient crucial for skeletal integrity and various non-skeletal physiological functions, exhibits limited bioavailability and stability in...
Vitamin D, an essential micronutrient crucial for skeletal integrity and various non-skeletal physiological functions, exhibits limited bioavailability and stability in vivo. This study is focused on the development of polyethylene glycol (PEG)-grafted phospholipid micellar nanostructures co-encapsulating vitamin D3 and conjugated with alendronic acid, aimed at active bone targeting. Furthermore, these nanostructures are rendered optically traceable in the UV-visible region of the electromagnetic spectrum via the simultaneous encapsulation of vitamin D3 with carbon dots, a newly emerging class of fluorescents, biocompatible nanoparticles characterized by their resistance to photobleaching and environmental friendliness, which hold promise for future in vitro bioimaging studies. A systematic investigation is conducted to optimize experimental parameters for the preparation of micellar nanostructures with an average hydrodynamic diameter below 200 nm, ensuring colloidal stability in physiological media while preserving the optical luminescent properties of the encapsulated carbon dots. Comprehensive chemical-physical characterization of these micellar nanostructures is performed employing optical and morphological techniques. Furthermore, their binding affinity for the principal inorganic constituent of bone tissue is assessed through a binding assay with hydroxyapatite nanoparticles, indicating significant potential for active bone-targeting. These formulated nanostructures hold promise for novel therapeutic interventions to address skeletal-related complications in cancer affected patients in the future.
Topics: Micelles; Cholecalciferol; Nanostructures; Bone and Bones; Alendronate; Polyethylene Glycols; Humans; Drug Delivery Systems; Luminescence; Nanoparticles; Drug Carriers; Quantum Dots
PubMed: 38792228
DOI: 10.3390/molecules29102367 -
International Journal of Molecular... May 2024In this study, spherical or hexagonal NaYF:Yb,Er nanoparticles (UCNPs) with sizes of 25 nm (S-UCNPs) and 120 nm (L-UCNPs) were synthesized by high-temperature...
In this study, spherical or hexagonal NaYF:Yb,Er nanoparticles (UCNPs) with sizes of 25 nm (S-UCNPs) and 120 nm (L-UCNPs) were synthesized by high-temperature coprecipitation and subsequently modified with three kinds of polymers. These included poly(ethylene glycol) (PEG) and poly(N,N-dimethylacrylamide-co-2-aminoethylacrylamide) [P(DMA-AEA)] terminated with an alendronate anchoring group, and poly(methyl vinyl ether-co-maleic acid) (PMVEMA). The internalization of nanoparticles by rat mesenchymal stem cells (rMSCs) and C6 cancer cells (rat glial tumor cell line) was visualized by electron microscopy and the cytotoxicity of the UCNPs and their leaches was measured by the real-time proliferation assay. The comet assay was used to determine the oxidative damage of the UCNPs. An in vivo study on mice determined the elimination route and potential accumulation of UCNPs in the body. The results showed that the L- and S-UCNPs were internalized into cells in the lumen of endosomes. The proliferation assay revealed that the L-UCNPs were less toxic than S-UCNPs. The viability of rMSCs incubated with particles decreased in the order S-UCNP@Ale-(PDMA-AEA) > S-UCNP@Ale-PEG > S-UCNPs > S-UCNP@PMVEMA. Similar results were obtained in C6 cells. The oxidative damage measured by the comet assay showed that neat L-UCNPs caused more oxidative damage to rMSCs than all coated UCNPs while no difference was observed in C6 cells. An in vivo study indicated that L-UCNPs were eliminated from the body via the hepatobiliary route; L-UCNP@Ale-PEG particles were almost eliminated from the liver 96 h after intravenous application. Pilot fluorescence imaging confirmed the limited in vivo detection capabilities of the nanoparticles.
Topics: Animals; Mice; Rats; Mesenchymal Stem Cells; Nanoparticles; Cell Line, Tumor; Polyethylene Glycols; Cell Survival; Particle Size; Male; Oxidative Stress
PubMed: 38791332
DOI: 10.3390/ijms25105294 -
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 -
Materials Today. Bio Jun 2024Osteogenic-osteoclast coupling processes play a crucial role in bone regeneration. Recently, strategies that focus on multi-functionalized implant surfaces to enhance...
Osteogenic-osteoclast coupling processes play a crucial role in bone regeneration. Recently, strategies that focus on multi-functionalized implant surfaces to enhance the healing of bone defects through the synergistic regulation of osteogenesis and osteoclastogenesis is still a challenging task in the field of bone tissue engineering. The aim of this study was to create a dual-drug release-based core-shell nanofibers with the intent of achieving a time-controlled release to facilitate bone regeneration. We fabricated core-shell P/PCL nanofibers using coaxial electrospinning, where alendronate (ALN) was incorporated into the core layer and hydroxyapatite (HA) into shell. The surface of the nanofiber construct was further modified with mussel-derived polydopamine (PDA) to induce hydrophilicity and enhance cell interactions. Surface characterizations confirmed the successful synthesis of PDA@PHA/PCL-ALN nanofibers endowed with excellent mechanical strength (20.02 ± 0.13 MPa) and hydrophilicity (22.56°), as well as the sustained sequential release of ALN and Ca ions. experiments demonstrated that PDA-functionalized core-shell PHA/PCL-ALN scaffolds possessed excellent cytocompatibility, enhanced cell adhesion and proliferation, alkaline phosphatase activity and osteogenesis-related genes. In addition to osteogenesis, the engineered scaffolds also significantly reduced osteoclastogenesis, such as tartrate-resistant acid phosphatase activity and osteoclastogenesis-related gene expression. After 12-week of implantation, it was observed that PDA@PHA/PCL-ALN nanofiber scaffolds, in a rat cranial defect model, significantly promoted bone repair and regeneration. Microcomputed tomography, histological examination, and immunohistochemical analysis collectively demonstrated that the PDA-functionalized core-shell PHA/PCL-ALN scaffolds exhibited exceptional osteogenesis-inducing and osteoclastogenesis-inhibiting effects. Finally, it may be concluded from our results that the bio-inspired surface-functionalized multifunctional, biomimetic and controlled release core-shell nanofiber provides a promising strategy to facilitate bone healing.
PubMed: 38779556
DOI: 10.1016/j.mtbio.2024.101088