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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 -
Beilstein Journal of Nanotechnology 2024Sodium alendronate (ALN) is a very hydrosoluble and poorly permeable molecule used as an antiresorptive agent and with vascular anticalcifying capacity. Loaded into...
Sodium alendronate (ALN) is a very hydrosoluble and poorly permeable molecule used as an antiresorptive agent and with vascular anticalcifying capacity. Loaded into targeted nanovesicles, its anti-inflammatory activity may be amplified towards extra-osseous and noncalcified target cells, such as severely irritated vascular endothelium. Here cytotoxicity, mitochondrial membrane potential, ATP content, and membrane fluidity of human endothelial venous cells (HUVECs) were determined after endocytosis of ALN-loaded nanoarchaeosomes (nanoARC-Chol(ALN), made of polar lipids from : cholesterol 7:3 w/w, 166 ± 5 nm, 0.16 ± 0.02 PDI, -40.8 ± 5.4 mV potential, 84.7 ± 21 µg/mg ALN/total lipids, TL). The effect of nanoARC-Chol(ALN) was further assessed on severely inflamed HUVECs. To that aim, HUVECs were grown on a porous barrier on top of a basal compartment seeded either with macrophages or human foam cells. One lighter and one more pronounced inflammatory context was modelled by adding lipopolysaccharide (LPS) to the apical or the apical and basal compartments. The endocytosis of nanoARC-Chol(ALN), was observed to partly reduce the endothelial-mesenchymal transition of HUVECs. Besides, while 10 mg/mL dexamethasone, 7.6 mM free ALN and ALN-loaded liposomes failed, 50 μg/mL TL + 2.5 μg/mL ALN (i.e., nanoARC-Chol(ALN)) reduced the IL-6 and IL-8 levels by, respectively, 75% and 65% in the mild and by, respectively, 60% and 40% in the pronounced inflammation model. This is the first report showing that the endocytosis of nanoARC-Chol(ALN) by HUVECs magnifies the anti-inflammatory activity of ALN even under conditions of intense irritation, not only surpassing that of free ALN but also that of dexamethasone.
PubMed: 38774586
DOI: 10.3762/bjnano.15.46 -
European Journal of Dentistry May 2024Osteoporosis is a disease characterized by disruption of the bone microarchitecture. It is observed in both sexes, but to a greater extent in women. It affects the whole...
Osteoporosis is a disease characterized by disruption of the bone microarchitecture. It is observed in both sexes, but to a greater extent in women. It affects the whole body, including the jaws. The main indicator of the presence of osteoporosis accepted by the World Health Organization is bone mineral density. The aim of this article is to find data on the influence of osteoporosis on apical periodontitis, to investigate how the intake of osteoporosis drugs affects apical periodontitis, and to establish various data that may be of benefit to the dental practitioner when treating patients with osteoporosis and apical periodontitis. Open-access publications are included. The presence of osteoporosis is important to the dentist. Apical periodontitis in these patients has a faster progression. They are characterized by inflammation and destruction of the tissues located around the tooth root. Osteoporosis has a destructive effect on bone tissue through different mechanisms: nuclear factor-κβ ligand and NLRP3/Caspase-1/IL-1β cascade. It is also associated with low estrogen levels. Various medications such as corticosteroids, bisphosphonates (alendronate, zoledronate (Zoledronic acid), calcitonin, raloxifene, and strontium used to treat osteoporosis can affect the course of apical periodontitis. When treating patients with periapical lesions, the dentist must take a proper medical history and general medical history. In cases of osteoporosis or taking bisphosphonates and other medications, consideration should be given to whether consultation with a specialist is necessary, what treatment approach would be most appropriate, and what the prognosis will be. Chronic diseases affect both the general state of the body and dental health. It has been found that in patients with osteoporosis, inflammation of the apical periodontium develops with faster bone resorption. Before starting dental treatment, it is important to specify the etiology of osteoporosis, the bone density of each patient, as well as the medications they are taking.
PubMed: 38759999
DOI: 10.1055/s-0044-1785533 -
Journal of Bone and Mineral Metabolism May 2024The purpose of this study was to evaluate whether bone mineral density (BMD) ≥ -2.5 SD could be used as the treat-to-target (T2T) goal when treating osteoporosis... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
The purpose of this study was to evaluate whether bone mineral density (BMD) ≥ -2.5 SD could be used as the treat-to-target (T2T) goal when treating osteoporosis with teriparatide (TPTD) and alendronate (ALN), and to investigate the relationship with incident vertebral fracture by re-analyzing data from a randomized, controlled trial (JOINT-05) involving postmenopausal Japanese women at high fracture risk.
MATERIALS AND METHODS
Participants received sequential therapy with once-weekly TPTD for 72 weeks, followed by ALN for 48 weeks (TPTD-ALN group) or ALN monotherapy for 120 weeks (ALN group). BMDs were measured at the lumbar spine (L2-4), total hip, and femoral neck at 0, 24, 48, 72, and 120 weeks by dual-energy X-ray absorptiometry. The T2T goal was BMD ≥ -2.5 SD, and the endpoint was the proportion of participants with baseline BMD < -2.5 SD in three measurement sites achieving BMD ≥ -2.5 SD.
RESULTS
A total of 559 participants were selected. BMD ≥ -2.5 SD at 120 weeks in the L2-4, total hip, and femoral neck sites was achieved in 20.5%, 23.1%, and 5.9%, respectively, in the TPTD-ALN group and 22.2%, 11.7%, and 7.3%, respectively, in the ALN group. Incident vertebral fractures occurred in areas of both lower and high BMD.
CONCLUSION
During the 1.5-year treatment period, more than 20% of participants achieved BMD ≥ -2.5 SD as a T2T goal at L2-4. Since the achievement level differed depending on the BMD measurement site, the appropriate site should be selected according to the baseline BMD level.
Topics: Humans; Alendronate; Female; Teriparatide; Bone Density; Aged; Middle Aged; Bone Density Conservation Agents; Japan; Osteoporosis; Osteoporosis, Postmenopausal; Spinal Fractures; Lumbar Vertebrae; East Asian People
PubMed: 38755328
DOI: 10.1007/s00774-024-01515-5 -
Brazilian Oral Research 2024The aim of this systematic review was to answer the following question: "Does alendronate, a nitrogen-containing bisphosphonate, improve or impair alveolar socket...
The aim of this systematic review was to answer the following question: "Does alendronate, a nitrogen-containing bisphosphonate, improve or impair alveolar socket healing after tooth extraction in animal models"? To this end, a systematic review of the literature was carried out in PubMed, Scopus, LILACS, Web of Science, as well as in the gray literature up to May 2023. Preclinical studies that evaluated alveolar healing after tooth extraction and the intake of sodium alendronate compared with placebo were included. Two investigators were responsible for screening the articles independently, extracting the data, and assessing their quality through the SYRCLE's RoB tool for randomized trials in animal studies. The study selection process, study characteristics, risk of bias in studies, impact of alendronate on bone healing, and certainty of evidence were described in text and table formats. Methodological differences among the studies were restricted to the synthesis methods. The synthesis of qualitative results followed the Synthesis Without Meta-analysis (SWiM) reporting guideline. From the 19 included studies, five were considered to have low risk, three were of unclear risk, and eleven presented a high risk of bias. The studies were considered heterogeneous regarding alendronate posology, including its dosage and route of administration. Furthermore, a variety of animal species, different age ranges, diverse teeth extracted, and exposure or not to ovariectomy contributed to the lack of parity of the selected studies. Our results indicated that alendronate monotherapy negatively affects the early phase of wound healing after tooth extraction in preclinical studies, suggesting that the bone resorption process after tooth extraction in animals treated with alendronate might impair the bone healing process of the extraction socket. In conclusion, alendronate administration restrains bone resorption, thereby delaying alveolar socket healing . Future studies should be conducted to validate these findings and to better understand the effects of alendronate therapy on oral tissues.
Topics: Alendronate; Tooth Extraction; Animals; Wound Healing; Tooth Socket; Bone Density Conservation Agents
PubMed: 38747825
DOI: 10.1590/1807-3107bor-2024.vol38.0038 -
Journal of Orthopaedic Surgery and... May 2024Low back pain (LBP) affects a significant proportion of the adult population. Potent anti-resorptive drugs such as intravenous zoledronic acid have been demonstrated to...
BACKGROUND
Low back pain (LBP) affects a significant proportion of the adult population. Potent anti-resorptive drugs such as intravenous zoledronic acid have been demonstrated to reduce Modic changes (MCs) upon magnetic resonance imaging (MRI) of the spine and concomitantly decrease associated LBP. It is uncertain whether oral alendronic acid has a similar effect.
METHODS
82 subjects were recruited in this case-control study. Treatment subjects (n = 41) received oral alendronic acid treatment for at least 1-year and were matched by gender and age (± 2) to control subjects (n = 41) not receiving any anti-osteoporotic medication. The prevalence, type, and extent of MCs were quantified upon T1 and T2-weighted MRIs of the lumbosacral spine.
RESULTS
Treatment subjects received oral alendronic acid for 124.0 ± 62.1 weeks at the time of MRI assessment and exhibited a lower prevalence of MCs over the lumbosacral spine (18/41 vs. 30/41, p < 0.001) as compared to control subjects. Amongst both groups, type 2 MCs were predominant. Quantification of type 2 MCs in treatment subjects revealed a significant reduction in area (113 ± 106 mm vs. 231 ± 144 mm, p < 0.01) and volume (453 ± 427 mm vs. 925 ± 575 mm, p < 0.01) affected by type 2 MCs in comparison to matched controls.
CONCLUSION
Oral alendronic acid may be useful in the treatment of MC-associated LBP in patients with concomitant osteoporosis.
Topics: Humans; Male; Female; Lumbar Vertebrae; Case-Control Studies; Middle Aged; Bone Density Conservation Agents; Aged; Low Back Pain; Magnetic Resonance Imaging; Alendronate; Time Factors; Adult; Administration, Oral; Age Factors; Treatment Outcome; Sex Factors
PubMed: 38735917
DOI: 10.1186/s13018-024-04780-2 -
BMC Oral Health May 2024Antiresorptive therapy (AR) disrupts osseous homeostasis and can induce direct irritation over the gastrointestinal mucosa; however, its possible erosive effects on the...
BACKGROUND
Antiresorptive therapy (AR) disrupts osseous homeostasis and can induce direct irritation over the gastrointestinal mucosa; however, its possible erosive effects on the oral epithelium have not been totally described. Among the most frequent oral erosive lesions, oral lichen planus (OLP) frequently presents as painful mucosal ulcerations, arising from basal membrane inflammatory damage. Thus, the aim of this retrospective study was to describe the association between AR and the incidence of OLP.
METHODS
This case-control study included data from 148 patients (17 patients undergoing AR therapy (AR group) / 131 without AR therapy (Control group)). Each patient record was systematically processed and the association between AR drugs and OLP clinical characteristics within both groups was assessed.
RESULTS
The erosive form of OLP was significantly more frequent in the AR group than in the Control group (p = 0.029). Indeed, the AR treatment using alendronic acid (41.2%) was the most frequently reported. Additionally, the erosive form of OLP showed the strongest association with pain and burning sensation among the OLP types (p < 0.050). However, disease worsening and AR consumption were not significantly associated (p = 0.150).
CONCLUSIONS
Patients under AR therapy show more clinical symptoms associated to the erosive type of OLP. Regardless of the AR therapy, the erosive type of OLP is associated with more severe symptoms.
Topics: Humans; Lichen Planus, Oral; Retrospective Studies; Female; Male; Case-Control Studies; Aged; Middle Aged; Bone Density Conservation Agents; Prevalence; Severity of Illness Index; Adult; Aged, 80 and over; Alendronate
PubMed: 38730315
DOI: 10.1186/s12903-024-04331-5 -
Archives of Osteoporosis May 2024This study demonstrated a large treatment gap in elderly subjects experiencing fragility fracture in Spanish primary care, a low treatment persistence among subjects who... (Observational Study)
Observational Study
UNLABELLED
This study demonstrated a large treatment gap in elderly subjects experiencing fragility fracture in Spanish primary care, a low treatment persistence among subjects who do receive treatment, and more than one-quarter having no follow-up visits post-fracture. These data highlight the need to improve secondary fracture prevention in primary care.
PURPOSE
To describe osteoporosis (OP) treatment patterns and follow-up in subjects with fragility fracture seen in Spanish primary care (PC).
METHODS
This observational, retrospective chart review included subjects aged ≥ 70 years listed in the centers' records (November 2018 to March 2020), with ≥ 1 fragility fracture and prior consultation for any reason; subjects who had participated in another study were excluded. Outcomes included OP treatments and follow-up visits post-fragility fracture.
RESULTS
Of 665 subjects included, most (87%) were women; overall mean (SD) age, 82 years. Fewer than two thirds (61%) had received any prior OP treatment (women, 65%; men, 38%); of these, 38% had received > 1 treatment (women, 25%; men, 13%). Among treated subjects, the most frequent first-line treatments were alendronate (43%) and RANKL inhibitor denosumab (22%), with a higher discontinuation rate and shorter treatment duration observed for alendronate (discontinuation, 42% vs 16%; median treatment duration, 2.5 vs 2.1 years). Over one-quarter (26%) of subjects had no follow-up visits post-fragility fracture, with this gap higher in women than men (35% versus 25%). The most common schedule of follow-up visits was yearly (43% of subjects with a fragility fracture), followed by half-yearly (17%) and biennial (10%), with a similar trend in men and women. Most OP treatments were prescribed by PC physicians, other than teriparatide and zoledronate.
CONCLUSIONS
Across Spanish PC, we observed a large gap in the treatment and follow-up of elderly subjects experiencing a fragility fracture. Our data highlights the urgent need to improve secondary fracture prevention in PC.
Topics: Humans; Female; Male; Aged; Spain; Aged, 80 and over; Secondary Prevention; Retrospective Studies; Primary Health Care; Bone Density Conservation Agents; Osteoporotic Fractures; Osteoporosis; Alendronate; Denosumab
PubMed: 38722400
DOI: 10.1007/s11657-024-01394-3 -
Neurospine May 2024We investigated the clinical efficacy of anabolic agents compared with bisphosphonates (BPs) for the incidence of new osteoporotic vertebral fracture (OVF) and fracture...
Comparison of the Clinical Efficacy of Anabolic Agents and Bisphosphonates in the Patients With Osteoporotic Vertebral Fracture: Systematic Review and Meta-analysis of Randomized Controlled Trials.
OBJECTIVE
We investigated the clinical efficacy of anabolic agents compared with bisphosphonates (BPs) for the incidence of new osteoporotic vertebral fracture (OVF) and fracture healing of OVF in the patients with OVF via meta-analyses of randomized controlled trials (RCTs).
METHODS
Electronic databases, including PubMed, Embase, and Cochrane Library were searched for published RCTs till December 2022. The RCTs that recruited participants with osteoporosis at high-/very high-risk of fracture (a history of osteoporotic vertebral or hip fracture) or fresh OVF were included in this study. We assessed the risk of bias on every included RCTs, estimated relative risk (RR) for the incidence of new OVF and fracture healing of OVF, and overall certainty of evidence. Meta-analyses were performed by Cochrane review manager (RevMan) version 5.3. Cochrane risk of bias 2.0 and GRADEpro/GDT were applied for evaluating methodological quality and overall certainty of evidence, respectively.
RESULTS
Five hundred eighteen studies were screened, and finally 6 eligible RCTs were included in the analysis. In the patients with prevalent OVF, anabolic agents significantly reduced the incidence of new OVF (teriparatide and romosozumab vs alendronate and risedronate [RR = 0.57, 95% CI 0.45 - 0.71; p < 0.00001; high-certainty of evidence]; teriparatide vs risedronate [RR = 0.50, 95% CI 0.37 - 0.68; p < 0.0001; high-certainty of evidence]. However, there was no evidence of teriparatide compared to alendronate in fracture healing of OVF (RR = 1.23, 95% CI 0.95 - 1.60; p = 0.12; low-certainty of evidence).
CONCLUSION
In the patients with prevalent OVF, anabolic agents showed a significant superiority for preventing new OVF than BPs, with no significant evidence for promoting fracture healing of OVF. However, considering small number of RCTs in this study, additional studies with large-scale data are required to obtain more robust evidences.
PubMed: 38697911
DOI: 10.14245/ns.2347256.628 -
Microbiology Spectrum Jun 2024Candidiasis places a significant burden on human health and can range from common superficial vulvovaginal and oral infections to invasive diseases with high mortality....
UNLABELLED
Candidiasis places a significant burden on human health and can range from common superficial vulvovaginal and oral infections to invasive diseases with high mortality. The most common species implicated in human disease is , but other species like are emerging. The use of azole antifungals for treatment is limited by increasing rates of resistance. This study explores repositioning bisphosphonates, which are traditionally used for osteoporosis, as antifungal synergists that can improve and revitalize the use of azoles. Risedronate, alendronate, and zoledronate (ZOL) were tested against isolates from six different species of , and ZOL produced moderate antifungal activity and strong synergy with azoles like fluconazole (FLC), particularly in . FLC:ZOL combinations had increased fungicidal and antibiofilm activity compared to either drug alone, and the combination prevented the development of antifungal resistance. Mechanistic investigations demonstrated that the synergy was mediated by the depletion of squalene, resulting in the inhibition of ergosterol biosynthesis and a compromised membrane structure. In , synergy compromised the function of membrane-bound multidrug transporters and caused an accumulation of reactive oxygen species, which may account for its acute sensitivity to FLC:ZOL. The efficacy of FLC:ZOL was confirmed in a infection model, where combinations improved the survival of larvae infected with and to a greater extent than monotherapy with FLC or ZOL, and at reduced dosages. These findings demonstrate that bisphosphonates and azoles are a promising new combination therapy for the treatment of topical candidiasis.
IMPORTANCE
is a common and often very serious opportunistic fungal pathogen. Invasive candidiasis is a prevalent cause of nosocomial infections with a high mortality rate, and mucocutaneous infections significantly impact the quality of life of millions of patients a year. These infections pose substantial clinical challenges, particularly as the currently available antifungal treatment options are limited in efficacy and often toxic. Azoles are a mainstay of antifungal therapy and work by targeting the biosynthesis of ergosterol. However, there are rising rates of acquired azole resistance in various species, and some species are considered intrinsically resistant to most azoles. Our research demonstrates the promising therapeutic potential of synergistically enhancing azoles with non-toxic, FDA-approved bisphosphonates. Repurposing bisphosphonates as antifungal synergists can bypass much of the drug development pipeline and accelerate the translation of azole-bisphosphonate combination therapy.
Topics: Antifungal Agents; Drug Synergism; Microbial Sensitivity Tests; Azoles; Humans; Diphosphonates; Candida; Animals; Drug Resistance, Fungal; Candidiasis; Fluconazole; Biofilms; Candida glabrata; Candida albicans
PubMed: 38695556
DOI: 10.1128/spectrum.00121-24