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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 -
Journal of Dentistry May 2024To map the current scientific landscape regarding the association/causality of medication-related osteonecrosis of the jaw (MRONJ) after tooth extraction under... (Review)
Review
OBJECTIVE
To map the current scientific landscape regarding the association/causality of medication-related osteonecrosis of the jaw (MRONJ) after tooth extraction under bisphosphonate (BF) therapy to identify knowledge gaps and guide future research.
DATA
This review used the PCC strategy (P = Patient; C = Concept; C = Context).
SOURCES
The MEDLINE/PubMed, Scopus, Web of Science/Clarivate Analytics, and gray literature databases were used.
STUDY SELECTION
Searches were conducted by two independent reviewers until April 2024. Studies involving prior BF use and tooth extraction in humans or animals were included. Among the 176 studies, 73 (41.4%) were in animals, and 103 (58.5%) were in humans. Brazil led in animal studies (n=14; 19.1%), while Italy led in human studies (n=14; 13.6%). Zoledronic acid was the most cited BF (79.4% in animals; 34.9% in humans), with intravenous administration being most frequent (38.3% in animals; 35.9% in humans). The mandible was the main extraction site (n=36 in animals; n=41 in humans). In 91.7% of the animal studies, sequelae compatible with osteonecrosis signs and symptoms were observed, with bone necrosis being most common (n=39; 53.4%). In humans, 93.2% of studies presented 239 sequelae, with bone necrosis (n=53; 22.1%) being the most cited. The main location of sequelae was the mandible (n=36 in animals; n=41 in humans).
CONCLUSIONS
Animal studies highlighted bone exposure, notably using murine models, with a significant Brazilian contribution. In human studies, bone necrosis was the main sequela of MRONJ, which has been reported by researchers in the Italy.
CLINICAL SIGNIFICANCE
These findings underscore the importance of careful consideration and monitoring of patients who have a history of bisphosphonate use and who are undergoing tooth extraction, highlighting the potential risk of MRONJ.
PubMed: 38763386
DOI: 10.1016/j.jdent.2024.105051 -
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 -
Journal of Bone and Mineral Research :... May 2024Although clinical trials have shown that denosumab significantly increases bone mineral density at key skeletal sites more than oral bisphosphonates, evidence is lacking...
Although clinical trials have shown that denosumab significantly increases bone mineral density at key skeletal sites more than oral bisphosphonates, evidence is lacking from head-to-head randomized trials evaluating fracture outcomes. This retrospective cohort study uses administrative claims data from Medicare fee-for service beneficiaries to evaluate the comparative effectiveness of denosumab versus alendronate in reducing fracture risk among women with postmenopausal osteoporosis (PMO) in the US. Women with PMO ≥ 66 years of age with no prior history of osteoporosis treatment, who initiated denosumab (n = 89 115) or alendronate (n = 389 536) from 2012 to 2018, were followed from treatment initiation until the first of a specific fracture outcome, treatment discontinuation or switch, end of study (December 31, 2019), or other censoring criteria. A doubly robust inverse-probability of treatment and censoring weighted function was used to estimate the risk ratio associated with the use of denosumab compared with alendronate for hip, nonvertebral (NV; includes hip, humerus, pelvis, radius/ulna, other femur), non-hip nonvertebral (NHNV), hospitalized vertebral (HV), and major osteoporotic (MOP; consisting of NV and HV) fractures. Overall, denosumab reduced the risk of MOP by 39%, hip by 36%, NV by 43%, NHNV by 50%, and HV fractures by 30% compared with alendronate. Denosumab reduced the risk of MOP fractures by 9% at year 1, 12% at year 2, 18% at year 3, and 31% at year 5. An increase in the magnitude of fracture risk reduction with increasing duration of exposure was also observed for other NV fracture outcomes. In this cohort of almost half-a-million treatment-naive women with PMO, we observed clinically significant reductions in the risk of MOP, hip, NV, NHNV, and HV fractures for patients on denosumab compared with alendronate. Patients who remained on denosumab for longer periods of time experienced greater reductions in fracture risk.
PubMed: 38753892
DOI: 10.1093/jbmr/zjae079 -
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 -
Modern Rheumatology Case Reports May 2024Synovitis-acne-pustulosis-hyperostosis-osteomyelitis (SAPHO) syndrome is characterised by aseptic osteitis and is often complicated by pustular dermatitis, such as...
Synovitis-acne-pustulosis-hyperostosis-osteomyelitis (SAPHO) syndrome is characterised by aseptic osteitis and is often complicated by pustular dermatitis, such as palmoplantar pustulosis or acne. Although bone lesions are most found in the anterior thoracic region or spine, femoral lesions are not well documented in the literature. There is no established treatment for this condition, and few reports have described its long-term course. Here, we describe two cases of SAPHO syndrome involving the femur and discuss their long-term follow-up. A 40-year-old man (Case 1) presented with right thigh pain. Fifteen years after the initial diagnosis, the pain could be controlled with minomycin, salazosulfapyridine, and methotrexate. X-rays of the femur showed gradual cortical thickening. Although there were waves of pain, it gradually improved with the adjustment of drugs 25 years following the initial diagnosis. A 35-year-old man (Case 2) with right thigh pain was prescribed salazosulfapyridine and methotrexate; however, these were ineffective. Alendronate and guselkumab also proved ineffective. Ultimately, infliximab was started 9 years following disease onset, and pain became manageable. X-rays of the femur showed cortical thickening. SAPHO syndrome can be managed with drug therapies, such as nonsteroidal anti-inflammatory drugs, methotrexate, and conventional synthetic disease-modifying antirheumatic drugs; however, there are occasional treatment-resistant cases.
PubMed: 38748401
DOI: 10.1093/mrcr/rxae024 -
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 Pediatric Endocrinology &... Apr 2006
Topics: Humans; Alendronate; Child; Adolescent; Osteoporosis; Bone Density Conservation Agents; Female; Administration, Oral; Male; Bone Density; Treatment Outcome
PubMed: 38742779
DOI: 10.1515/jpem-2006-190410 -
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