Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.794
Filtrar
1.
Rev. Flum. Odontol. (Online) ; 1(66): 180-190, jan-abr.2025. ilus
Artículo en Portugués | LILACS, BBO | ID: biblio-1570764

RESUMEN

A osteonecrose dos maxilares induzida por medicamentos (MRONJ) caracteriza-se por exposição óssea ou osso que pode ser sondado através de fístula intra ou extraoral, em região maxilofacial, e que não cicatriza dentro de oito semanas. A MRONJ é uma condição rara e debilitante que pode causar dor, disfagia e odor desagradável na cavidade oral, afetando pacientes com histórico ou sob uso contínuo de terapia antirreabsortiva, isolada ou associada a imunomoduladores ou drogas antiangiogênicas, mas sem histórico de radioterapia nos maxilares. O objetivo desta revisão narrativa de literatura é compilar os principais aspectos sobre a etiopatogenia da MRONJ e as opções terapêuticas disponíveis. A etiologia da MRONJ é multifatorial, complexa, e não está totalmente compreendida, não havendo um tratamento definitivo, mas diversas modalidades terapêuticas que visam o controle da dor e da progressão da osteonecrose. Conclui-se com essa revisão que o entendimento da etiopatogenia da MRONJ pelo cirurgião-dentista lhe permite adotar medidas preventivas, bem como o conhecimento das modalidades terapêuticas disponíveis lhe possibilita oferecer o manejo adequado para seu paciente, conforme o estágio da doença.


Medication-related osteonecrosis of the jaw (MRONJ) is characterized by exposed bone or bone that can be probed through an intra or extraoral fistula, in the maxillofacial region, which does not heal within eight weeks. MRONJ is a rare and debilitating condition that can cause pain, dysphagia and unpleasant odor in the oral cavity, affecting patients with a history or continuous use of antiresorptive therapy, alone or associated with immunomodulators or antiangiogenic drugs, but without a history of radiotherapy to the jaws. The aim of this narrative literature review is to compile the main aspects about the etiopathogenesis of MRONJ and the available therapeutic options. The etiology of MRONJ is multifactorial, complex, and is not fully understood, with no definitive treatment, but several therapeutic modalities that aim to control pain and the progression of osteonecrosis. It is concluded from this review that the understanding of the etiopathogenesis of MRONJ by the dental surgeon allows him to adopt preventive measures, as well as the knowledge of the therapeutic modalities available allows him to offer the appropriate management for his patient, depending on the stage of the disease.


Asunto(s)
Osteonecrosis , Patología Bucal , Terapéutica , Osteonecrosis de los Maxilares Asociada a Difosfonatos , Ácido Zoledrónico , Maxilares
2.
BMC Med Inform Decis Mak ; 24(1): 320, 2024 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-39482688

RESUMEN

BACKGROUND: Femoral head collapse is a critical pathological change and is regarded as turning point in disease progression in osteonecrosis of the femoral head (ONFH). In this study, we aim to build an automatic femoral head collapse prediction pipeline for ONFH based on magnetic resonance imaging (MRI) radiomics. METHODS: In the segmentation model development dataset, T1-weighted MRI of 222 hips from two hospitals were retrospectively collected and randomly split into training (n = 190) and test (n = 32) sets. In the prognosis prediction model development dataset, 206 hips were also retrospectively collected from two hospitals and divided into training set (n = 155) and external test set (n = 51) according to data source. A deep learning model for automatic lesion segmentation was trained with nnU-Net, from which three-dimensional regions of interest were segmented and a total of 107 radiomics features were extracted. After intra-class correlation coefficients screening, feature correlation coefficient screening and Least Absolute Shrinkage and Selection Operator regression feature selection, a machine learning model for ONFH prognosis prediction was trained with Logistic Regression (LR) and Light Gradient Boosting Machine (LightGBM) algorithm. RESULTS: The segmentation model achieved an average dice similarity coefficient of 0.848 and an average 95% Hausdorff distance of 3.794 in the test set, compared to the manual segmentation results. After feature selection, nine radiomics features were included in the prognosis prediction model. External test showed that the LightGBM model exhibited acceptable predictive performance. The area under the curve (AUC) of the prediction model was 0.851 (95% CI: 0.7268-0.9752), with an accuracy of 0.765, sensitivity of 0.833, and specificity of 0.727. Decision curve analysis showed that the LightGBM model exhibited favorable clinical utility. CONCLUSION: This study presents an automated pipeline for predicting femoral head collapse in ONFH with acceptable performance. Further research is necessary to determine the clinical applicability of this radiomics-based approach and to assess its potential to assist in treatment decision-making for ONFH.


Asunto(s)
Aprendizaje Profundo , Necrosis de la Cabeza Femoral , Imagen por Resonancia Magnética , Humanos , Necrosis de la Cabeza Femoral/diagnóstico por imagen , Masculino , Femenino , Adulto , Persona de Mediana Edad , Estudios Retrospectivos , Pronóstico , Cabeza Femoral/diagnóstico por imagen , Radiómica
3.
Front Pharmacol ; 15: 1456900, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39380906

RESUMEN

Background: Osteonecrosis of the jaw (ONJ) stands as a severe complication linked to the use of bisphosphonates, particularly zoledronic acid, which is widely prescribed for managing conditions like osteoporosis and bone metastasis. This study is geared towards the development and validation of a clinical prediction model for ONJ in patients undergoing zoledronic acid treatment. Methods: We harnessed data from the FDA Adverse Event Reporting System (FAERS) as our training dataset, while the Canada Vigilance Adverse Reaction (CVAR) database served as the testing dataset. The study encompassed patients treated with zoledronic acid and subsequently diagnosed with ONJ. We analysed a range of predictive factors, including breast cancer, bone metastasis, osteoporosis, vitamin D and calcium levels, comorbidities, the number of concomitant medications, dosage, age, weight, and gender. Logistic regression and nomogram analysis were the chosen methodologies for constructing the predictive model. To evaluate the model's performance, we utilized receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Results: The study encompassed a total of 2,126 patients in the training cohort, 911 patients in the internal test cohort from the FAERS database, and 121 patients in the external test cohort from the CVAR database. Notable predictors for ONJ included bone metastasis (OR: 1.65, 95% CI: 1.22-2.24), osteoporosis (OR: 0.33, 95% CI: 0.21-0.52), the number of concomitant medications (OR: 1.07, 95% CI: 1.05-1.09), and the dosage of zoledronic acid (OR: 1.24, 95% CI: 1.10-1.39). The nomogram exhibited robust discriminatory power, evidenced by an area under the curve (AUC) of 0.77 in the training cohort, 0.76 in the internal test cohort, and 0.90 in the external test cohort. Calibration plots demonstrated a strong alignment between observed and predicted probabilities. Furthermore, DCA highlighted the prediction model's significant net benefit across various threshold probabilities. Conclusion: By leveraging data from both the FAERS and Canadian databases, this study has successfully developed and validated a clinical prediction model for ONJ in patients receiving zoledronic acid. This model stands as a valuable tool for clinicians, enabling them to pinpoint high-risk patients and make evidence-based treatment decisions to minimize the risk of ONJ.

4.
Adv Mater ; : e2312920, 2024 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-39385647

RESUMEN

The healing of bone defects after debridement in medication-related osteonecrosis of the jaw (MRONJ) is a challenging medical condition with impaired angiogenesis, susceptible infection, and pro-inflammatory responses. Magnesium (Mg) nanocomposite hydrogel is developed to specifically tackle multiple factors involved in MRONJ. Mg-oxide nanoparticles tune the gelation kinetics in the reaction between N-hydroxysuccinimide-functionalized hyperbranched poly (ethylene glycol) and proteins. This reaction allows an enhanced mechanical property after instant solidification and, more importantly, also stable gelation in challenging environments such as wet and hemorrhagic conditions. The synthesized hydrogel guides mandible regeneration in MRONJ rats by triggering the formation of type H vessels, activating Osterix+ osteoprogenitor cells, and generating anti-inflammatory microenvironments. Additionally, this approach demonstrates its ability to suppress infection by inhibiting specific pathogens while strengthening stress tolerance in the affected alveolar bone. Furthermore, the enhanced osteogenic properties and feasibility of implantation of the hydrogel are validated in mandible defect and iliac crest defect created in minipigs, respectively. Collectively, this study offers an injectable and innovative bone substitute to enhance mandible defect healing by tackling multiple detrimental pathologies.

5.
Artículo en Inglés | MEDLINE | ID: mdl-39363854

RESUMEN

Multifocal osteonecrosis is a rare entity which can lead to bone fragility, fractures and considerable morbidity. The objective of this report is to describe the presentation, evaluation and management of a case of multifocal osteonecrosis. A 34-year-old lady presented with multiple fractures and bone pain which was exacerbated during pregnancy. She was found to have osteonecrosis involving multiple sites. Investigation revealed that she had an undefined autoimmune condition with antinuclear antibody and anti-Ro (SS-A) positivity, not fulfilling criteria for diagnosis of Sjogren syndrome. She had low Protein S levels for age and gender (confirmed on 2 occasions 12 weeks apart outside pregnancy). She had a novel variant in the PROS1 gene (NM_000313.4:c.1513G>A; p.Gly505Ser) which is associated with heterozygous Protein S (PS) deficiency. She had a good response to treatment with anticoagulation. The combination of inherited thrombophilia, autoimmunity and the thrombophilic state induced by pregnancy probably contributed to the severe phenotype in this patient. The variant was identified in the Lamin G1 domain, which is instrumental in PS binding to tissue factor pathway inhibitor and C4 binding protein, thus playing a role in both the coagulation and complement pathway, and could explain the coexistence of autoimmunity with thrombophilia. This variant is present in 0.034% of South Asians in the gnomAD population database, and may represent an important cause of inherited thrombophilia in this group.

6.
Chem Biol Interact ; 404: 111263, 2024 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-39393751

RESUMEN

Osteonecrosis of the femoral head (ONFH) is a devastating and irreversible hip disease usually associated with increased oxidative stress due to the clinical application of high-dose or long-term glucocorticoids (GCs). Previous publications have demonstrated protein disulfide isomerase (PDI) plays a critical role in regulating cellular production of reactive oxygen species (ROS). We therefore ask whether interfering PDI could affect GCs-stimulated osteoclastogenesis. To test the hypothesis, we conducted bioinformatics and network analysis based on potential gene targets of steroid-induced osteonecrosis of the femoral head (SIONFH) in light of multiple databases and concomitantly verified the associated biological effect via the in vitro model of dexamethasone (DEX)-stimulated osteoclastogenesis. The results revealed 70 potential gene targets for SIONFH intervention, including the P4HB gene that encodes PDI. Further analysis based on network topology-based analysis techniques (NTA), protein-protein interaction (PPI) networks, and mouse cell atlas database identified the importance of PDI in regulating the cellular redox state of osteoclast during ONFH. Western blotting (WB) validations also indicated that PDI may be a positive regulator in the process of DEX-stimulated osteoclastogenesis. Hence, various PDI inhibitors were subjected to molecular docking with PDI and their performances were analyzed, including 3-Methyltoxoflavin (3 M) which inhibits PDI expression, and ribostamycin sulfate (RS) which represses PDI chaperone activity. The binding energies of DEX, 3 M, and RS to PDI were -5.3547, -4.2324, and -5.9917 kcal/mol, respectively. The Protein-Ligand Interaction Profiler (PLIP) analysis demonstrated that both hydrogen bonds and hydrophobic interactions were the key contributions to the DEX-PDI and 3M-PDI complexes, while only hydrogen bonds were identified as the predominant driving forces in the RS-PDI complex. Subsequent experiments showed that both 3 M and RS reduced osteoclast differentiation and bone resorption activity by stifling the expression of osteoclastic markers. This reduction was primarily due to the PDI inhibitors boosting the antioxidant system, thereby reducing the production of intracellular ROS. In conclusion, our results supported PDI's involvement in SIONFH progression by regulating ROS in osteoclasts and highlighted PDI inhibitors may serve as potential options for SIONFH treatment.

7.
Am J Transl Res ; 16(9): 4876-4884, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39398544

RESUMEN

AIMS: To explore the efficacy and safety of lumbar sympathetic ganglion radiofrequency combined with anhydrous ethanol in treating pain associated with osteonecrosis of the femoral head, providing clinical reference. METHODS: This retrospective study involved 101 patients with osteonecrosis of the femoral head. According to the different treatment methods, the patients were classified into an observation group where lumbar sympathetic ganglion radiofrequency combined with anhydrous ethanol therapy was applied (n=51) and a control group where lumbar sympathetic ganglion radiofrequency alone was applied (n=50). The Visual Analogue Scale (VAS) was used to assess the joint pain. Harris hip joint scores, incidence of complications, levels of inflammatory factors (hs-CRP and IL-6), and overall therapeutic effects were also compared between the two groups. RESULTS: The total effective rate of the observation group was significantly higher than that of the control group (P<0.05). The VAS score of joint pain was significantly lower in the observation group as compared with the control group (P<0.05). Harris scores were higher in the observation group than in the control group (P<0.05). The observation group had significantly lower levels of hs-CRP and IL-6 than the control group (P<0.001). In addition, there was no difference between the two groups in the incidence of complications (P=0.11). CONCLUSION: Lumbar sympathetic ganglion radiofrequency combined with anhydrous ethanol provides an effective method for treating avascular necrosis of the femoral head, with good therapeutic effects on improving blood supply to the femoral head and relieving pain, and with good safety profile.

8.
Cureus ; 16(9): e69271, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39398835

RESUMEN

BACKGROUND: Osteonecrosis is characterized by the necrosis of trabecular bone and cells within the femoral head, which often results in the subchondral collapse and deformation of the articulating surface of the head. For the treatment of early stages of this condition, specifically Stage I and Stage II, bone marrow-derived stem cells have been employed effectively for several years. In our approach, we have utilized a modified technique to collect bone marrow aspirate, which has yielded favorable outcomes. METHODS: In our study, we performed surgeries on 32 hips afflicted with early-stage osteonecrosis of the femoral head. Each patient underwent core decompression and the injection of bone marrow concentrate, guided by C-arm imaging in the operating theater. Evaluations were conducted using the Harris Hip Score and the Visual Analogue Scale (VAS), along with radiological assessments to track the progression of osteonecrosis stages before and after the surgical procedure. RESULTS: The comparison of pre- and post-surgery data, including the Harris Hip Score, VAS, progression of osteonecrosis stages, and radiological findings, revealed significantly positive outcomes. Since May 2013, 32 hips, regardless of the etiology of avascular necrosis (AVN), have been treated with this procedure. Notably, only four patients with bilateral AVN progressed to Stage III in one hip, while the other hip remained stable. In the remaining patients, pain was alleviated, and none progressed to later stages. No complications were observed in this study. CONCLUSION: This minimally invasive technique, characterized by its simplicity and lack of associated complications or donor site morbidity, has proven to be an effective joint-preserving surgical intervention for early stages of femoral head osteonecrosis (Stages 1 and 2).

9.
Cureus ; 16(9): e69226, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39398845

RESUMEN

Medication-related osteonecrosis of the jaws (MRONJ) has emerged as one of the major adverse effects of antiresorptive agents in the treatment of patients with cancer and osteoporosis. MRONJ presents as a chronic inflammation of the maxillary and/or mandibular bones accompanied by necrotic bone exposure and intra-/extraoral fistula. Given the increasing number of patients with MRONJ, surgical treatment is highlighted to be significantly beneficial for those patients. However, extensive surgical treatment generally induces physiological and psychological burden on patients with MRONJ. Specifically, older patients with advanced MRONJ require further concerns about their systemic conditions. Thus, oral surgeons are obliged to consider their conditions when determining the indications for extensive surgical treatment. Recently, our department has established a novel therapeutic strategy based on hyperbaric oxygen (HBO) therapy for patients with advanced MRONJ. In this study, we report cases of three older patients with MRONJ who received the combination of conventional treatment and HBO therapy, which resulted in successful management and the avoidance of extensive surgical treatment.

10.
Stem Cells ; 2024 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-39460600

RESUMEN

Methylprednisolone (MPS) use is linked to increased cases of osteonecrosis of the femoral head (ONFH). Bone marrow mesenchymal stem cells (BMSCs) have shown potential for treating MPS-induced ONFH, but their effectiveness is limited by high apoptosis rates post-transplantation. We developed a pre-treatment strategy for BMSCs to improve their viability. In a rat model of MPS-induced ONFH, we evaluated the effects of USP13 overexpression in BMSCs through micro-CT, HE staining, and TUNEL staining. USP13-overexpressing BMSCs significantly reduced ONFH severity compared to plain BMSCs and direct lentivirus injection. USP13 also protected BMSCs from MPS-induced apoptosis by modulating PTEN and reducing AKT phosphorylation. This led to decreased expression of apoptotic genes and proteins in USP13-overexpressing BMSCs. Our findings highlight USP13 as a promising target for enhancing BMSC survival and efficacy in treating MPS-induced ONFH.

11.
Head Neck ; 2024 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-39463136

RESUMEN

INTRODUCTION: Bisphosphonates (BPs) are widely used for osteoporosis and cancer-induced bone diseases due to their antiresorptive properties, yet they pose risks such as medication-related osteonecrosis of the jaw (MRONJ). METHODS: We present a unique case of concurrent oral squamous cell carcinoma (SCC) and MRONJ in a 72-year-old female chronically treated with oral ibandronate for osteoporosis. Following a dental extraction, she developed a nonhealing wound in the maxilla. Following conservative treatment, the patient underwent a maxillectomy and extensive tissue reconstructions to control her infection and address suspicions of an underlying malignancy. RESULTS: Histopathological examinations confirmed simultaneous osteonecrosis and well-differentiated SCC in the maxillary sinus and surrounding tissues. Despite multiple surgeries, the patient's disease progressed rapidly. Upon examining the literature for patients with a history of BP use diagnosed with MRONJ and/or SCC, a total of 16 cases report a diagnostic dilemma between MRONJ and locoregional SCC. Three of the 16 cases report a final diagnosis of concurrent MRONJ and SCC. This report is the fourth reported case of concurrency to date. CONCLUSIONS: The patient's complex clinical course underscores the diagnostic challenges and therapeutic dilemmas in managing concurrent MRONJ and SCC, highlighting the need for vigilant monitoring and interdisciplinary collaboration in similar cases.

12.
Pharmaceuticals (Basel) ; 17(10)2024 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-39459006

RESUMEN

Although mesenchymal stem cells (MSCs) insertion has gained recent attention as a joint-preserving procedure, no study has conducted direct intralesional implantation of human umbilical cord-derived MSCs (hUCMSCs) in patients with ONFH. This is a protocol for a phase 1 clinical trial designed to assess the safety and exploratory efficacy of human umbilical cord-derived osteoblasts (hUC-Os), osteogenic differentiation-induced cells from hUCMSCs, in patients with early-stage ONFH. Nine patients with Association Research Circulation Osseous (ARCO) stage 1 or 2 will be assigned to a low-dose (1 × 107 hUC-O cells, n = 3), medium-dose (2 × 107 cells, n = 3), and high-dose group (4 × 107 cells, n = 3) in the order of their arrival at the facility, and, depending on the occurrence of dose-limiting toxicity, up to 18 patients can be enrolled by applying the 3 + 3 escalation method. We will perform hUC-O (CF-M801) transplantation combined with core decompression and follow-up for 12 weeks according to the study protocol. Safety will be determined through adverse event assessment, laboratory tests including a panel reactive antibody test, vital sign assessment, physical examination, and electrocardiogram. Efficacy will be explored through the change in pain visual analog scale, Harris hip score, Western Ontario and McMaster Universities Osteoarthritis Index, ARCO stage, and also size and location of necrotic lesion according to Japanese Investigation Committee classification before and after the procedure. Joint preservation is important, particularly in younger, active patients with ONFH. Confirmation of the safety and efficacy of hUC-Os will lead to a further strategy to preserve joints for those suffering from ONFH and improve our current knowledge of cell therapy.

13.
Cell Mol Life Sci ; 81(1): 418, 2024 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-39368012

RESUMEN

The leading cause of steroid-induced femoral head osteonecrosis (ONFH) is the imbalance of bone homeostasis. Bone marrow-derived mesenchymal stem cell (BMSC) differentiation and fate are closely associated with bone homeostasis imbalance. Blocking monoacylglycerol lipase (MAGL) could effectively ameliorate ONFH by mitigating oxidative stress and apoptosis in BMSCs induced by glucocorticoids (GC). Nevertheless, whether MAGL inhibition can modulate the balance during BMSC differentiation, and therefore improve ONFH, remains elusive. Our study indicates that MAGL inhibition can effectively rescue the enhanced BMSC adipogenic differentiation caused by GC and promote their differentiation toward osteogenic lineages. Cannabinoid receptor 2 (CB2) is the direct downstream target of MAGL in BMSCs, rather than cannabinoid receptor 1(CB1). Using RNA sequencing analyses and a series of in vitro experiments, we confirm that the MAGL blockade-induced enhancement of BMSC osteogenic differentiation is primarily mediated by the phosphoinositide 3-kinases (PI3K)/ the serine/threonine kinase (AKT)/ (glycogen synthase kinase-3 beta) GSK3ß pathway. Additionally, MAGL blockade can also reduce GC-induced bone resorption by directly suppressing osteoclastogenesis and indirectly reducing the expression of receptor activator of nuclear factor kappa-Β ligand (RANKL) in BMSCs. Thus, our study proposes that the therapeutic effect of MAGL blockade on ONFH is partly mediated by restoring the balance of bone homeostasis and MAGL may be an effective therapeutic target for ONFH.


Asunto(s)
Diferenciación Celular , Necrosis de la Cabeza Femoral , Células Madre Mesenquimatosas , Monoacilglicerol Lipasas , Osteogénesis , Animales , Masculino , Ratas , Adipogénesis/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Necrosis de la Cabeza Femoral/patología , Necrosis de la Cabeza Femoral/metabolismo , Necrosis de la Cabeza Femoral/inducido químicamente , Glucocorticoides/farmacología , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/efectos de los fármacos , Monoacilglicerol Lipasas/metabolismo , Monoacilglicerol Lipasas/antagonistas & inhibidores , Monoacilglicerol Lipasas/genética , Osteogénesis/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Ratas Sprague-Dawley , Receptor Cannabinoide CB2/metabolismo , Receptor Cannabinoide CB2/genética , Transducción de Señal/efectos de los fármacos
14.
Imaging Sci Dent ; 54(3): 221-231, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39371309

RESUMEN

Purpose: Multiple myeloma (MM) is a rare cancer that is typically managed with bisphosphonates to slow bone resorption and prevent skeletal complications. This study aimed to identify imaging patterns in MM patients receiving bisphosphonate therapy. Materials and Methods: This systematic review included studies investigating maxillomandibular bone alterations based on imaging examinations in MM patients treated with bisphosphonates. The selected studies were qualitatively assessed using the Critical Appraisal Tools from SUMARI. Results: Six studies, involving 669 MM patients, were included, with 447 receiving bisphosphonate treatment. The majority were treated with pamidronate, zoledronate, or a combination of both. Seventy patients developed medication-related osteonecrosis of the jaw (MRONJ), predominantly in the mandible, characterized by the presence of bony sequestrum, bone sclerosis, increased periodontal ligament space, osteolytic lesions, and osteomyelitis as observed in imaging analyses. For non-MRONJ lesions, the mandible also exhibited the highest frequency of asymptomatic bone alterations. These ranged from "punched-out" osteolytic lesions or "soap bubble" lesions to solitary bone lesions, areas of bone sclerosis, abnormalities of the hard palate, osteoporosis, non-healed alveoli, and cortical bone rupture. Conclusion: MM patients treated with bisphosphonates display radiographic patterns of maxillomandibular bone lesions. These patterns aid in diagnosis and facilitate early and targeted treatment, thereby contributing to improved morbidity outcomes for these patients.

15.
Clin Orthop Surg ; 16(5): 702-710, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39364109

RESUMEN

Background: Stem cell therapy for the treatment of osteonecrosis of the femoral head (ONFH) showed promising outcomes. However, ONFH with a large lesion in the weight-bearing portion is a poor prognostic factor and still challenging issue to be solved. We aimed to evaluate the effect of tissue-engineered bone regeneration for this challenging condition to preserve the femoral head. Methods: A total of 7 patients (9 hips) with ONFH who received osteoblasts expanded ex vivo from bone marrow-derived mesenchymal stem cells (BMdMSCs) and calcium metaphosphate (CMP) as scaffolds from March 2002 to March 2004 were retrospectively reviewed. The median age was 27.0 years (interquartile range [IQR], 23.0-34.0 years), and the median follow-up period was 20.0 years (IQR, 11.0-20.0 years). After culture and expansion of stem cells, we performed core decompression with BMdMSC implantation at a median number of 10.1 ×107 (IQR, 9.9-10.9 ×107). To evaluate radiographic outcomes, the Association Research Circulation Osseous (ARCO) classifications, the Japanese Investigation Committee (JIC) classification, and modified Kerboul combined necrotic angle (mKCNA) were evaluated preoperatively and during follow-up. Clinical outcomes were evaluated by a visual analog scale (VAS) and Harris Hip Score (HHS). Results: The preoperative stage of ONFH was ARCO 2 in 5 hips and ARCO 3a in 4 hips. The ARCO staging was maintained in 3 hips of ARCO 2 and 4 hips of ARCO 3a. Two hips of ARCO 2 with radiographic progression underwent total hip arthroplasty. According to mKCNA, 2 hips showed medium lesions, and 7 hips showed large lesions. The size of necrotic lesion was decreased in 4 hips (2 were ARCO 2 and 2 were ARCO 3a). There were no significant changes in JIC classification in all hips (type C1: 3 hips and type C2: 6 hips) (p = 0.655). Clinically, there were no significant changes in the VAS and HHS between preoperative and last follow-up (p = 0.072 and p = 0.635, respectively). Conclusions: Tissue engineering technique using osteoblasts expanded ex vivo from BMdMSC and CMP showed promising outcomes for the treatment of pre-collapsed and early-collapsed stage ONFH with medium-to-large size, mainly located in weight-bearing areas.


Asunto(s)
Regeneración Ósea , Necrosis de la Cabeza Femoral , Ingeniería de Tejidos , Soporte de Peso , Humanos , Necrosis de la Cabeza Femoral/cirugía , Adulto , Masculino , Femenino , Ingeniería de Tejidos/métodos , Estudios Retrospectivos , Adulto Joven , Soporte de Peso/fisiología , Trasplante de Células Madre Mesenquimatosas/métodos , Andamios del Tejido , Osteoblastos
16.
Int J Biol Macromol ; 280(Pt 4): 136177, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39357704

RESUMEN

Recently, exosomes that are derived from bone marrow mesenchymal stem cells (BMSCs) have garnered considerable interest due to their significant roles in the processes of bone regeneration and repair. Among the various molecular components present within these exosomes, miR-668-3p has emerged as a pivotal microRNA that may be instrumental in modulating the function and proliferation of osteoblasts, the cells responsible for bone formation. The primary objective of this research was to examine the enhancing effects of BMSC-derived exosomes that are enriched with miR-668-3p on the advancement of osteoblasts in the context of osteonecrosis of the femoral head. Furthermore, the study aimed to analyze how the expression of specific exosomal proteins, namely CD63 and CD9, influences this biological process. To conduct the investigation, BMSCs were isolated from healthy rat models, followed by the extraction of their secreted exosomes. The subsequent phase of the study involved assessing the proliferation and differentiation of osteoblasts by introducing the exosomes enriched with miR-668-3p into an experimental setup representing osteonecrosis of the femoral head. The findings revealed that exosomes derived from BMSCs, which contained miR-668-3p, significantly enhanced the proliferation of osteoblasts as well as the expression of key osteogenic marker genes. Notably, the levels of CD63 and CD9 proteins were markedly increased in the treated groups, indicating that the mechanisms underlying this promotion might involve cell adhesion and the endocytic uptake of exosomes.

17.
Osteoporos Int ; 2024 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-39400702

RESUMEN

Osteonecrosis of the jaw (ONJ) is an adverse effect of antiresorptives. Among female patients treated for osteoporosis, ONJ risk was threefold higher after 2-3 years of treatment and eightfold after 10 years compared with past use. Absolute risks remained low (~ 0.05% after 5 years) and diminished after discontinuation. PURPOSE: Osteonecrosis of the jaw (ONJ) is a rare adverse effect of antiresorptive drug use; however, the magnitude of risk in osteoporosis patients has not been clearly described. METHODS: We conducted a cohort study among cancer-free female patients aged 40-89 with, or at risk for, osteoporosis in United Kingdom Clinical Practice Research Datalink (CPRD) Aurum. We followed patients from first osteoporosis treatment until first of osteonecrosis diagnosis, age 90, record end, or other prespecified censoring event, and accumulated person-time by osteoporosis treatment. ONJ cases were selected from CPRD Aurum and linked Hospital Episode Statistics data using an algorithm and manual review. We estimated incidence rates (IR) of ONJ by current treatment type and post discontinuation. We conducted a nested case-control analysis to further describe risk by cumulative dose and duration of antiresorptive therapies. RESULTS: Among 467,654 eligible patients, there were 208 ONJ cases. IR among patients currently treated with antiresorptives (primarily alendronate) was 1.2 (95% confidence interval [CI] 1.0-1.4) per 10,000 person-years. Compared with past use of antiresorptives, odds ratios of ONJ were 3.0 (95% CI 1.5-5.7) after 2-3 years of treatment and 8.1 (95% CI 4.4-15) after 10 years. However, absolute risks remained low (~ 0.05% after 5 years and ~ 0.18% after 10 years) and elevated risks diminished to near zero within 6 to 9 months of discontinuation. CONCLUSION: Risk of ONJ increased after 2-3 years of treatment with antiresorptives; however, the absolute risk was low and returned to baseline shortly after treatment discontinuation.

18.
Aust Endod J ; 2024 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-39394868

RESUMEN

Medication-related osteonecrosis of the jaw (MRONJ) is a progressive condition that can cause significant bone loss and its diagnosis can be challenging. A 68-year-old man with a diagnosis of hepatocellular carcinoma, undergoing treatment with atezolizumab, bevacizumab and zoledronic acid, complained of spontaneous pain in the right lower second premolar. Oral examination revealed no dental changes and implants in the right jaw. A patient history and thorough clinical and radiographic examinations mimic endodontic disease. The implant crowns were removed, bleeding on probing, and peri-implant pockets were observed. The main hypothesis was MRONJ Stage 2, and the surgical treatment was performed. The pain ceased and signs of MRONJ were not observed within 3 months. MRONJ should be considered as a hypothesis in the case of odontalgia and a patient's history of antiresorptive and antiangiogenic therapies. Furthermore, monitoring patients with dental implants in the mandible through detailed clinical and imaging evaluation is required.

19.
Clin Exp Pharmacol Physiol ; 51(11): e13923, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39358837

RESUMEN

Adipocyte enhancer-binding protein 1 (AEBP1) is closely implicated in osteoblastic differentiation and bone fracture; this research aimed to investigate the effect of AEBP1 on restoring osteoblastic differentiation under dexamethasone (Dex) treatment, and its interaction with the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway. Pre-osteoblastic MC3T3-E1 cells were cultured in osteogenic medium and treated by Dex to mimic steroid-induced osteonecrosis cellular model. They were then further transfected with control or AEBP1-overexpressed lentiviral vectors. Finally, cells were treated with the PI3K inhibitor LY294002, with or without AEBP1-overexpressed lentiviral vectors. AEBP1 expression showed a downward trend in MC3T3-E1 cells under Dex treatment in a dose-dependent manner. AEBP1-overexpressed lentiviral vectors increased relative cell viability, alkaline phosphatase (ALP) staining, Alizarin red staining and osteoblastic differentiation markers including osteocalcin (OCN), osteopontin (OPN), collagen type I alpha 1 (COL1A1), runt-related transcription factor 2 (RUNX2) and bone morphogenetic protein 2 (BMP2), but decreased cell apoptosis rate in MC3T3-E1 cells under Dex treatment; besides, AEBP1-overexpressed lentiviral vectors positively regulated p-PI3K and p-AKT expressions. Furthermore, LY294002 treatment decreased relative cell viability, Alizarin red staining, osteoblastic differentiation markers including OCN, OPN, RUNX2 and BMP, increased cell apoptosis rate and did not affect ALP staining in MC3T3-E1 cells under Dex treatment; meanwhile, LY294002 treatment weakened the effect of AEBP1 overexpression vectors on the above cell functions. AEBP1 restores osteoblastic differentiation under Dex treatment by activating the PI3K/AKT pathway.


Asunto(s)
Carboxipeptidasas , Dexametasona , Osteoblastos , Proteínas Proto-Oncogénicas c-akt , Proteínas Represoras , Transducción de Señal , Animales , Ratones , Apoptosis/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Línea Celular , Dexametasona/farmacología , Osteoblastos/efectos de los fármacos , Osteoblastos/citología , Osteoblastos/metabolismo , Osteogénesis/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Carboxipeptidasas/genética , Carboxipeptidasas/metabolismo
20.
Rev Cient Odontol (Lima) ; 12(3): e213, 2024.
Artículo en Español | MEDLINE | ID: mdl-39444725

RESUMEN

This report presents the case of a 61-year-old male patient with diabetes, hypertension, and a history of severe COVID-19 with osteomyelitis of the frontal sinus and upper jaw. The patient reported intense pain in the facial and maxillary area for two months. The computed tomography images showed mucoperiosteal thickening of the maxillary sinus and the magnetic resonance imaging showed multiple lytic lesions at the frontal sinus level, as well as brain abscesses in the left frontal region that were correlated with the microbiological cultures. In the intraoral clinical examination, segments with a necrotic appearance of the upper jaw, orosinusal fistula and multiple dental infectious foci were observed. The patient was treated with antibiotics, analgesics, anti-inflammatories, insulin, and proton pump inhibitor. Trephination of the frontal sinus, drainage of the abscess and sequestrectomy in the maxilla were performed and sessions with a hyperbaric chamber were ordered.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...