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1.
Hip Int ; 33(6): 992-1016, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36348521

RESUMO

INTRODUCTION: Reported cases of inferior dislocation in the literature are found under several names (inferior, anteroinferior, obturator, or erecta), which may be source of confusion. The purpose of this comprehensive review of the literature is to collect as many cases of inferior dislocation as possible to determine better therapeutic strategies, outcome after reduction, complications, and prognostic factors. METHODS: In April 2020, a literature search was performed in Pubmed, Medline, Scopus, Cochrane, and Embase databases. The MeSH keywords were "OBTURATOR DISLOCATION HIP" or "ANTERIOR DISLOCATION HIP" or "INFERIOR DISLOCATION HIP." Authors independently selected articles that met the selection criteria, with no time limit. RESULTS: Out of the 97 articles selected, there were 119 cases of primary inferior hip dislocations. This review of the literature has allowed us to differentiate 3 radiographic subtypes of inferior dislocations, which correspond to 3 different anatomical positions of the femoral head: "obturator" dislocation, "proximal anterior-inferior" dislocation, and "distal anterior-inferior" dislocation. Our subtype classification yielded 39 obturator subtype inferior dislocations (32.8%), 66 proximal anteroinferior subtypes (55.4%), and 14 distal anteroinferior (11.8%). The obturator subtype is at risk of reduction failure and femoral neck fracture during the reduction manoeuver. CONCLUSIONS: Our study identified 3 subtypes with different prognosis, with obturator and distal anteroinferior dislocations having a poorer prognosis because of their pre- and post-reduction complications. We were unable to determine the correct manoeuver to reduce inferior dislocations without taking the risk of femoral neck fracture, but each of these subtypes may require a different manoeuver.


Assuntos
Artroplastia de Quadril , Fraturas do Colo Femoral , Luxação do Quadril , Humanos , Prognóstico , Artroplastia de Quadril/efeitos adversos , Fraturas do Colo Femoral/cirurgia , Luxação do Quadril/diagnóstico por imagem , Luxação do Quadril/terapia
2.
Arthrosc Tech ; 8(5): e489-e493, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31194136

RESUMO

To date, there is no consensus concerning the treatment of acute Achilles tendon ruptures. Although surgical treatment decreases the risk of a recurrent rupture, it is not without complications. In particular, percutaneous sutures may cause a lesion of the sural nerve. The purpose of this Technical Note is to describe a reliable and reproducible surgical procedure for treating these lesions. The first operative phase consists of an ultrasound detection that makes it possible to identify the tendon extremities and the sural nerve, which is necessary to secure the posterolateral arthroscopic tract as well as to perform the percutaneous suture. The entry point is thus centered on the lesion and placed at a distance from any surrounding nerve risk. The second arthroscopic phase makes it possible to release the tendon lesion, control the transtendon passage of the surgical threads, and evaluate the dynamic contact of the tendon edges. At the end of the intervention, the complete disappearance from the transillumination via the rupture also makes it possible to ensure the disappearance of the tendon gap. Achilles tendon percutaneous sutures after the ultrasound detection and under arthroscopic control thus makes it possible to control the contact of the tendon edges, while at the same time decreasing the risk of a lesion of the sural nerve, with minimal scarring.

3.
Adv Clin Exp Med ; 27(7): 1001-1008, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29999253

RESUMO

BACKGROUND: Validation of three-dimensional (3D) reconstructions of full dental arches with crowns and roots based on cone beam computed tomography (CBCT) imaging represents a key issue in 3D digital dentistry. OBJECTIVES: The aim of the study was to search for the most accurate in vivo windowing-based manual tooth segmentation using CBCT. The null hypothesis was that all applied windowing protocols were equivalent in terms of in vivo tooth volume measurement using CBCT. MATERIAL AND METHODS: This retrospective study was based on preoperative CBCT images from patients who underwent further tooth extractions for reasons independent of this study. Written informed consent was obtained from all the participants, and the study was approved by the Ethics Committee of Cliniques Universitaires Saint Luc (Brussels, Belgium). The radiological protocol was I-CAT CBCT, 0.3 mm slice thickness, 8 cm × 16 cm field of view, 120 kVp, and 18 mAs. A total of 36 teeth were extracted from 14 patients between the ages of 18 and 68 years. Using 3D Slicer software, segmentations were performed twice by 2 independent observers, with a 1-month time period between the 2 segmentations to study intraand inter-observer repeatability and reproducibility. Four windowing protocols (level/window) were applied: 1. 1131/1858, 2. 2224/4095, 3. 1131/4095, and 4. AUTO, an automatic protocol provided by default by the software. A total of 576 segmentations were performed. Tooth volumes were automatically calculated using the software. To compare the volumes obtained from CBCT segmentations with a gold-standard method, we laser-scanned the extracted teeth. RESULTS: Excellent intraand inter-observer intraclass correlations were found for all of the protocols used. The best windowing protocol was 1131/1858 for both observers. Tooth volumes were obtained by manual segmentation of the CBCT images and using windowing protocol 1131/1858. No significantly different tooth volumes were found by laser scanning. CONCLUSIONS: Our null hypothesis was rejected. Only windowing protocol 1131/1858 allowed for significantly closer 3D in vivo segmentation of a tooth compared to I-CAT CBCT, with excellent intra-observer repeatability and inter-observer reproducibility.


Assuntos
Tomografia Computadorizada de Feixe Cônico/métodos , Interpretação de Imagem Assistida por Computador/métodos , Dente/diagnóstico por imagem , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Estudos Retrospectivos , Adulto Jovem
4.
J Craniomaxillofac Surg ; 46(2): 305-311, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29275073

RESUMO

Orbito-palpebral reconstruction is a challenge in Treacher Collins syndrome (TCS). This study investigates orbital phenotypes in TCS using cephalometry and orbital shape analysis. Eighteen TCS and 52 control patients were included in this study, using the Dr Warehouse database. Orbital cephalometry was based on 20 landmarks, 10 planes, 16 angles, and 22 distances. Orbits were segmented. Registration-based, age-specific mean models were generated using semi-automatic segmentation, and aligned and compared using color-coded distance maps - mean absolute distance (MAD), Hausdorff distance (HD), and Dice similarity coefficient (DSC). Symmetry was assessed by mirroring and DSC computing. Central orbital depth (COD) and medial orbital depth (MOD) allowed 100% of orbits to be classified. COD and lateral orbital depth (LOD) were different from the controls. Average MAD between TCS and controls was ≤1.5 mm, while for HD it was >1.5 mm, and for DSC <1. TCS orbits were more asymmetrical than controls, and orbital volumes were smaller when age was considered as a confounding factor, and had a trend for normalization with age. This report emphasizes the importance of combining different morphometric approaches in the phenotype characterization of non-trivial structures such as the orbit, and supports composite skeletal and soft-tissue strategies for the management of the peri-orbital region.


Assuntos
Disostose Mandibulofacial/patologia , Órbita/patologia , Adolescente , Estudos de Casos e Controles , Cefalometria , Criança , Pré-Escolar , Humanos , Imageamento Tridimensional , Lactente , Recém-Nascido , Disostose Mandibulofacial/diagnóstico por imagem , Órbita/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Adulto Jovem
5.
Eur J Orthod ; 40(3): 239-248, 2018 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-29016738

RESUMO

Background: To assess the reproducibility of landmarks in three dimensions that determine the Frankfort horizontal plane (FH) as well as two new landmarks, and to evaluate the angular differences of newly introduced planes to the FH. Methods: Three-dimensional (3D) surface models were created from CBCT scans of 26 dry human skulls. Porion (Po), orbitale (Or), internal acoustic foramen (IAF), and zygomatico-maxillary suture (ZyMS) were indicated in the software by three observers twice with a 4-week interval. Angles between two FHs (FH 1: Or-R, Or-L, mid-Po; FH 2: Po-R, Po-L, mid-Or) and between FHs and new planes (Plane 1-6) were measured. Coordinates were exported to a spreadsheet. A statistical analysis was performed to define the landmark reproducibility and 3D angles. Results: Intra- and inter-observer landmark reproducibility showed mean difference more than 1 mm for x-coordinates of all landmarks except IAF. IAF showed significantly better reproducibility than other landmarks (P < 0.0018). The mean angular difference between FH 1 and FH 2 was 0.7 degrees. Plane 3, connecting Or-R, Or-L and mid-IAF, and Plane 4, connecting Po-R, Po-L and mid-ZyMS, both showed an angular difference of less than 1 degree when compared to FHs. Conclusions: This study revealed poor reproducibility of the traditional FH landmarks on the x-axis and good reproducibility of a new landmark tested to replace Po, the IAF. Yet, Or showed superior results compared to ZyMS. The potential of using new horizontal planes was demonstrated. Future studies should focus on identification of a valid alternative for Or and ZyMS and on clinical implementation of the findings.


Assuntos
Pontos de Referência Anatômicos/diagnóstico por imagem , Cefalometria/métodos , Crânio/diagnóstico por imagem , Tomografia Computadorizada de Feixe Cônico/métodos , Humanos , Imageamento Tridimensional/métodos , Maxila/diagnóstico por imagem , Variações Dependentes do Observador , Reprodutibilidade dos Testes
6.
Med Sci Monit ; 23: 1394-1400, 2017 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-28323814

RESUMO

BACKGROUND: The aim of our study was to investigate, in 3 dimensions, the maxillary sinus septa as an alternative site for dental implant placement to avoid sinus lift procedures. MATERIAL AND METHODS: We selected 100 dentate and 100 edentate patients with the presence of a maxillary sinus septum by reviewing a larger cone beam computer tomography (CBCT) database from the Department of Oral and Maxillofacial Surgery at Cliniques Universitaires Saint Luc in Bruxelles, Belgium. Three-dimensional reconstructions of 200 maxillary sinus septa were performed using Maxilim software. Ten measurements (length, lateral height, and thickness of the middle and medial region of the septum) were performed by 1 observer, 2 times, with an interval of 1 week between measurements. The angle between the septum and the maxillary plane was also measured. Finally, localization and orientation were assessed for each septum. RESULTS: There was no statistically significant difference between the 2 intraobserver measurements (p>0.05). Student's t-test was used to compare means. Middle height was the only measurement for which there was a difference between edentate and dentate patients (p=0.0095, edentate mean < dentate mean). The location of the septa observed in our study groups demonstrated greater prevalence in the posterior region than in the anterior and middle regions. For the spatial orientation of the septum, we found that most septa (81.2% in dentate patients, 53% in edentate patients) were oblique. CONCLUSIONS: Three-dimensional evaluation of maxillary sinus septa using 3D CBCT imaging showed that the sinus septum could offer an alternative site for implant placement in the maxillary sinus.


Assuntos
Tomografia Computadorizada de Feixe Cônico/métodos , Seio Maxilar/cirurgia , Levantamento do Assoalho do Seio Maxilar/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Implantes Dentários , Feminino , Humanos , Masculino , Maxila , Pessoa de Meia-Idade , Prevalência , Tomografia Computadorizada por Raios X/métodos
7.
J Craniomaxillofac Surg ; 44(10): 1567-1575, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27639780

RESUMO

A major concern in FGFR2 craniofaciosynostosis is oculo-orbital disproportion, such that orbital malformation provides poor accommodation and support for the orbital contents and peri-orbita, leading to insufficient eyelid closure, corneal exposure and eventually to functional visual impairment. Fronto-facial monobloc osteotomy followed by distraction osteogenesis aims to correct midfacial growth deficiencies in Crouzon-Pfeiffer syndrome patients. Fronto-facial bipartition osteotomy followed by distraction is a procedure of choice in Apert syndrome patients. These procedures modify the shape and volume of the orbit and tend to correct oculo-orbital disproportion. Little is known about the detailed 3D shape of the orbital phenotype in CPS and AS, and about how this is modified by fronto-facial surgery. Twenty-eight patients with CMS, 13 patients with AS and 40 control patients were included. CT scans were performed before and after fronto-facial surgery. Late post-operative scans were available for the Crouzon-Pfeiffer syndrome group. Orbital morphology was investigated using conventional three-dimensional cephalometry and shape analysis after mesh-based segmentation of the orbital contents. We characterized the 3D morphology of CPS and AS orbits and showed how orbital shape is modified by surgery. We showed that monobloc-distraction in CPS and bipartition-distraction in AS specifically address the morphological characteristics of the two syndromes.


Assuntos
Acrocefalossindactilia/cirurgia , Disostose Craniofacial/cirurgia , Ossos Faciais/cirurgia , Órbita/cirurgia , Acrocefalossindactilia/diagnóstico por imagem , Adolescente , Estudos de Casos e Controles , Cefalometria , Criança , Pré-Escolar , Disostose Craniofacial/diagnóstico por imagem , Ossos Faciais/diagnóstico por imagem , Humanos , Imageamento Tridimensional , Lactente , Órbita/diagnóstico por imagem , Órbita/patologia , Osteogênese por Distração/métodos , Osteotomia/métodos , Sistema Respiratório/patologia , Tomografia Computadorizada por Raios X
8.
Eur J Orthod ; 38(6): 563-568, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26683131

RESUMO

OBJECTIVES: To develop a novel 3D landmark reference system that is specific for mandibular midline cephalometric landmarks and to assess its repeatability and reproducibility. METHODS: Cone-beam computed tomography (CBCT) scans (3D Accuitomo® 170) were performed on 26 dry human skulls. The CBCT data were exported into DICOM files and imported to Maxilim® software to create 3D surface models. Two observers identified five landmarks to create a specific mid-sagittal mandibular plane: two mandibular foramina, two molar landmarks and one interincisive landmark. On this mid-sagittal mandibular plane, four mandibular cephalometric landmarks were marked: Point B, Pogonion, Gnathion and Menton. All observations were repeated by the two observers after an interval of 4 weeks. The coordinates (x, y, z) of each landmark were exported, and statistical analyses were performed to evaluate inter- and intra-rater precision. RESULTS: The intra-observer median precision in locating all landmarks ranged between 0.17 and 0.61mm. The intra-observer repeatability was generally good with a precision under 1mm in more than 50 per cent. The overall median inter-observer precision was 0.26-2.30mm. The mandibular foramina showed the best inter-observer reproducibility. The general inter-observer reproducibility was moderate to good, except for Pogonion and Point B. LIMITATIONS: Dry human skulls may not represent anatomical conditions found in living patients, thus the system should be validated using patients' data. CONCLUSION: The novel reference system offered good precision and generally good to moderate repeatability and reproducibility for mandibular midline cephalometric landmark identification in three dimensions. These findings will be useful for further improvement of 3D cephalometric systems.


Assuntos
Pontos de Referência Anatômicos , Cefalometria/métodos , Tomografia Computadorizada de Feixe Cônico/métodos , Mandíbula/anatomia & histologia , Humanos , Imageamento Tridimensional/métodos , Mandíbula/diagnóstico por imagem , Dente Molar/anatomia & histologia , Dente Molar/diagnóstico por imagem , Variações Dependentes do Observador , Reprodutibilidade dos Testes
9.
Imaging Sci Dent ; 45(1): 15-22, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25793179

RESUMO

PURPOSE: This study was performed to assess the reproducibility of identifying the sella turcica landmark in a three-dimensional (3D) model by using a new sella-specific landmark reference system. MATERIALS AND METHODS: Thirty-two cone-beam computed tomographic scans (3D Accuitomo® 170, J. Morita, Kyoto, Japan) were retrospectively collected. The 3D data were exported into the Digital Imaging and Communications in Medicine standard and then imported into the Maxilim® software (Medicim NV, Sint-Niklaas, Belgium) to create 3D surface models. Five observers identified four osseous landmarks in order to create the reference frame and then identified two sella landmarks. The x, y, and z coordinates of each landmark were exported. The observations were repeated after four weeks. Statistical analysis was performed using the multiple paired t-test with Bonferroni correction (intraobserver precision: p<0.005, interobserver precision: p<0.0011). RESULTS: The intraobserver mean precision of all landmarks was <1 mm. Significant differences were found when comparing the intraobserver precision of each observer (p<0.005). For the sella landmarks, the intraobserver mean precision ranged from 0.43±0.34 mm to 0.51±0.46 mm. The intraobserver reproducibility was generally good. The overall interobserver mean precision was <1 mm. Significant differences between each pair of observers for all anatomical landmarks were found (p<0.0011). The interobserver reproducibility of sella landmarks was good, with >50% precision in locating the landmark within 1 mm. CONCLUSION: A newly developed reference system offers high precision and reproducibility for sella turcica identification in a 3D model without being based on two-dimensional images derived from 3D data.

10.
J Arthroplasty ; 29(4): 753-6, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23927907

RESUMO

After total hip arthroplasty (THA) some patients have persistent postoperative pain (POP). Some of these POP are anterior and are caused by an anterior iliopsoas impingement (AIPI). We have hypothesized that oversized implanted cups could be responsible for POP and especially AIPI. We screened 237 patients who had a primary THA and compared the size difference (ΔS) between the native femoral head and the implanted cup, in patients with and without POP. Median ΔS was 2 mm [-6; 11 mm] and patients with POP had a significantly increased ΔS (P < 0.0001). The threshold above which pain was significantly more frequent was ΔS ≥ 6 mm. Odds ratio was 14.4 for POP and 26 for AIPI pain when ΔS ≥ 6 mm.


Assuntos
Acetábulo/cirurgia , Prótese de Quadril/efeitos adversos , Osteoartrite do Quadril/cirurgia , Dor Pós-Operatória/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Artroplastia de Quadril/efeitos adversos , Mau Alinhamento Ósseo/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Falha de Prótese , Fatores de Risco
11.
Expert Opin Emerg Drugs ; 18(3): 339-52, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23957761

RESUMO

INTRODUCTION: Ewing's sarcoma (ES) is the second most frequent malignant primary bone tumour in children, adolescents and young adults. The overall survival is 60 - 70% at 5 years but still very poor for patients with metastases, disease relapse or for those not responding to chemotherapy. For these high risk patients, new therapeutic approaches are needed beyond conventional therapies (chemotherapy, surgery and radiation) such as targeted therapies. AREAS COVERED: Transcriptomic and genomic analyses in ES have revealed alterations in genes that control signalling pathways involved in many other cancer types. To set up more specific approaches, it is reasonable to think that the particular microenvironment of these bone tumours is essential for their initiation and progression, including in ES. To support this hypothesis, preclinical studies using drugs targeting bone cells (bisphosphonate zoledronate, anti-receptor activator of NF-κB ligand strategies) showed promising results in animal models. This review will discuss the new targeted therapeutic options in ES, focusing more particularly on the ones modulating the bone microenvironment. EXPERT OPINION: Targeting the microenvironment represents a new option for patients with ES. The proof-of-concept has been demonstrated in preclinical studies using relevant animal models, especially for zoledronate, which induced a strong inhibition of tumour progression in an orthotopic bone model.


Assuntos
Neoplasias Ósseas/terapia , Sarcoma de Ewing/terapia , Animais , Antineoplásicos/uso terapêutico , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Sistemas de Liberação de Medicamentos , Humanos , Radiografia , Sarcoma de Ewing/metabolismo , Sarcoma de Ewing/patologia , Microambiente Tumoral
12.
Hum Mol Genet ; 22(9): 1873-85, 2013 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-23390131

RESUMO

Polycystin 2 (Pkd2), which belongs to the transient receptor potential family, plays a critical role in development. Pkd2 is mainly localized in the primary cilia, which also function as mechanoreceptors in many cells that influence multiple biological processes including Ca(2+) influx, chemical activity and signalling pathways. Mutations in many cilia proteins result in craniofacial abnormalities. Orofacial tissues constantly receive mechanical forces and are known to develop and grow through intricate signalling pathways. Here we investigate the role of Pkd2, whose role remains unclear in craniofacial development and growth. In order to determine the role of Pkd2 in craniofacial development, we located expression in craniofacial tissues and analysed mice with conditional deletion of Pkd2 in neural crest-derived cells, using Wnt1Cre mice. Pkd2 mutants showed many signs of mechanical trauma such as fractured molar roots, distorted incisors, alveolar bone loss and compressed temporomandibular joints, in addition to abnormal skull shapes. Significantly, mutants showed no indication of any of these phenotypes at embryonic stages when heads perceive no significant mechanical stress in utero. The results suggest that Pkd2 is likely to play a critical role in craniofacial growth as a mechanoreceptor. Pkd2 is also identified as one of the genes responsible for autosomal dominant polycystic kidney disease (ADPKD). Since facial anomalies have never been identified in ADPKD patients, we carried out three-dimensional photography of patient faces and analysed these using dense surface modelling. This analysis revealed specific characteristics of ADPKD patient faces, some of which correlated with those of the mutant mice.


Assuntos
Anormalidades Craniofaciais/genética , Rim Policístico Autossômico Dominante/genética , Canais de Cátion TRPP/genética , Adulto , Animais , Cílios/genética , Cílios/metabolismo , Anormalidades Craniofaciais/patologia , Face , Feminino , Deleção de Genes , Regulação da Expressão Gênica , Humanos , Masculino , Mecanorreceptores/metabolismo , Camundongos , Camundongos Transgênicos , Pessoa de Meia-Idade , Fenótipo , Rim Policístico Autossômico Dominante/patologia , Transdução de Sinais , Canais de Cátion TRPP/metabolismo
13.
J Orthop Sci ; 18(2): 321-30, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23203844

RESUMO

INTRODUCTION: Combining bone marrow (BM) with graft materials can stimulate bone healing. However, bone growth is not quantified in most studies, and the influence of the rate of interconnectivity of ceramics loaded with bone marrow has not yet been quantified. Here, a rabbit model of posterolateral intertransverse arthrodesis was used to quantify the effect of adding BM to partially (PIC) or totally (TIC) interconnected ceramics. MATERIALS AND METHODS: A single lumbar level was grafted on two sides with TIC (n = 12) or PIC (n = 18). The ceramic was loaded with 1.5 ml of BM on one side (chosen at random). The fusion rate was assessed by manual palpation test. Bone formation was quantified on scanning electron microscopy images and by dual-energy X-ray absorptiometry. RESULTS: At week 6, bone formation with TIC was twice as high as that with PIC. When BM was added, 35.1 and 87.8 % more bone formation was observed in the TIC and PIC, respectively. In ceramics loaded with BM, the bone mineral density was significantly higher than that in ceramics alone. CONCLUSIONS: Differences in interconnectivity within the family of biphasic ceramics should be taken into account when applying them clinically. BM increased bone formation regardless of the type of ceramic employed.


Assuntos
Artrodese/métodos , Transplante de Medula Óssea , Fosfatos de Cálcio , Vértebras Lombares/cirurgia , Fusão Vertebral/métodos , Absorciometria de Fóton , Análise de Variância , Animais , Vértebras Lombares/diagnóstico por imagem , Microscopia Eletrônica de Varredura , Coelhos , Transplante Autólogo , Cicatrização
14.
Cancer Res ; 70(19): 7610-9, 2010 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-20841471

RESUMO

Ewing's sarcoma (ES) is the second most frequent pediatric bone tumor also arising in soft tissues (15% of cases). The prognosis of patients with clinically detectable metastases at diagnosis, not responding to therapy or with disease relapse, is still very poor. Among new therapeutic approaches, bisphosphonates represent promising adjuvant molecules to chemotherapy to limit the osteolytic component of bone tumors and to protect from bone metastases. The combined effects of zoledronic acid and mafosfamide were investigated on cell proliferation, viability, apoptosis, and cell cycle distribution of human ES cell lines differing in their p53 and p16/ink4 status. ES models were developed to reproduce both soft tissue and intraosseous tumor development. Mice were treated with 100 µg/kg zoledronic acid (two or four times per week) and/or ifosfamide (30 mg/kg, one to three cycles of three injections). ES cell lines showed different sensitivities to zoledronic acid and mafosfamide at the cell proliferation level, with no correlation with their molecular status. Both drugs induced cell cycle arrest, but in the S or G(2)M phase, respectively. In vivo, zoledronic acid had no effect on soft tissue tumor progression, although it dramatically inhibited ES development in bone. When combined with ifosfamide, zoledronic acid exerted synergistic effects in the soft tissue model: Its combination with one cycle of ifosfamide resulted in an inhibitory effect similar to three cycles of ifosfamide alone. This very promising result could allow clinicians to diminish the doses of chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias Ósseas/tratamento farmacológico , Difosfonatos/farmacologia , Imidazóis/farmacologia , Sarcoma de Ewing/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Ciclofosfamida/administração & dosagem , Ciclofosfamida/análogos & derivados , Difosfonatos/administração & dosagem , Sinergismo Farmacológico , Humanos , Ifosfamida/administração & dosagem , Imidazóis/administração & dosagem , Masculino , Camundongos , Camundongos Nus , Sarcoma de Ewing/patologia , Ácido Zoledrônico
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