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1.
Medicine (Baltimore) ; 100(2): e24031, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33466148

RESUMO

RATIONALE: Osteonecrosis (ON) is a devastating illness that leads to bone ischemia and potential joint destruction. Systemic lupus erythematosus (SLE) is a chronic, autoimmune disease, with multi-system involvement which is closely associated with occurrence of ON. Multifocal ON, with an estimated morbidity of 3% in SLE patients, is extremely rare in juvenile subjects. PATIENT CONCERNS: A 13.3-year-old female SLE patient was admitted to hospital 20 months following the SLE diagnosis because of a sudden aggravation of sore knees. She suffered from double knee joint pain and her left knee joint showed typical signs of inflammation including redness, swelling, heat, and pain. DIAGNOSES: The SLE patient was diagnosed with multifocal ON of her knee joint based on magnetic resonance imaging findings of bone destruction and osteoproliferation at the bilateral distal femur and proximal tibia. INTERVENTIONS: The patient received high-dose methylprednisolone and intravenous cyclophosphamide pulse therapies for controlling active lupus and nephritis. Oral calcitriol and dipyridamole were administered to alleviate knee pain and inhibit thrombi formation, thereby suppressing ON progress. OUTCOMES: Three weeks following the treatment, the swelling in patient's left knee subsided. Her self-reporting pain score decreased from 9 to 4 and walking time increased from 45minutes to 90minutes per day. Nearly 5 weeks later, the pain in bilateral knee joints disappeared and the patient could walk without difficulties. LESSONS: This patient is the youngest SLE patient who developed multifocal ON based on the reported literature. It suggests that ON can occur in young SLE patients. A combination of internal and external risk factors can promote the development of ON. The balanced approach to the application of corticosteroids and immunosuppressors in the treatment of SLE and prevention of ON is a challenging problem that deserves further exploration.


Assuntos
Lúpus Eritematoso Sistêmico/complicações , Osteonecrose/complicações , Adolescente , Conservadores da Densidade Óssea/uso terapêutico , Calcitriol/uso terapêutico , Ciclofosfamida/uso terapêutico , Dipiridamol/uso terapêutico , Feminino , Humanos , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/patologia , Metilprednisolona/uso terapêutico , Osteonecrose/tratamento farmacológico , Osteonecrose/patologia , Inibidores da Agregação de Plaquetas/uso terapêutico
2.
J Craniomaxillofac Surg ; 48(11): 1080-1086, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32998853

RESUMO

PURPOSE: Medication-related osteonecrosis of the jaw (MRONJ) is a previously described debilitating condition in which patients experience progressive bone destruction in the maxilla and/or mandible after exposure to certain drugs. Clinical management of MRONJ remains controversial, with no established guidelines. The aim of our study was to conduct a literature review on the effectiveness of pentoxifylline (PTX) and tocopherol (PENTO protocol) on MRONJ. STUDY DESIGN: A literature review was conducted, using two different scientific databases, to evaluate the effects of PTX and tocopherol on MRONJ. DISCUSSION: PENTO protocol prescription to treat MRONJ was reported to be well tolerated, with minimal side-effects, and non-expensive when compared with other non-surgical treatment modalities. It was shown to relieve painful symptoms in all patients, and significant new bone formation was observed at final follow-up. CONCLUSION: Observational and case-series studies have demonstrated that pentoxifylline and tocopherol are potentially useful in the non-surgical management of MRONJ.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Conservadores da Densidade Óssea , Osteonecrose , Pentoxifilina , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/tratamento farmacológico , Difosfonatos , Humanos , Mandíbula , Osteonecrose/induzido quimicamente , Osteonecrose/tratamento farmacológico , Pentoxifilina/uso terapêutico , Tocoferóis/uso terapêutico
3.
Int. j. morphol ; 38(3): 683-688, June 2020. graf
Artigo em Inglês | LILACS | ID: biblio-1098307

RESUMO

The aim was to evaluate bone repair and gingival tissue repair in osteopenic rats. Fifteen female wistar rats were included; in all of them ovariectomy was realized to induce osteopenia; after 45 days, the animals were submitted to 2 surgical techinques 1) dental extraction of the upper central incisor with no socket preservation and 2) 5 mm cranial defect in the calvarium; 5 rats were included in the control group (G1) withput alendronate application; in the group 2 (G2) was used subcutenous alendronate (0.5 mg/kg) once for three weeks and then was realizd the both surgical techniques. In group 3 (G3), after ovariectomy was realized the both dental extraction and the calvarium defect and after that was realized the alendronate protocol. In each group, after six week was realized euthanasia and descriptive histological analysis of the surgical areas involved. In bone formation of the 5 mm cranial defect was observed with good progression in the 3 experimental models and no modification in quality of bone repair was observed. For the gingival tissue in the extraction socket, no differences were observed between G1 and G3. On other hand, in G2 a thinner and reduced gingival epithelium was found. Our results showed that alendronate was not an obstacle for bone repair; deficiencies in re-epithelialization of oral mucosa show the impact of alendronate before dental extraction.


El objetivo fue evaluar la reparación ósea y gingival en ratas con osteopenia. Quince ratas wistar hembras fueron incluidas; en todas ellas se realizo ovarectomia y fue realizada la inducción de osteopenia; después de 45 días, los animales fueron sometidos a dos técnicas quirúrgicas 1) extracciones dentales del incisivo central superior sin preservación alveolar y 2) creación de un defecto craneano de 5 mm en la calota; 5 animales fueron incluidos como grupo control (G1) sin la aplicación de alendronato; en el grupo 2 (G2) se utilizó alendronato subcutáneo (0,5 mg/kg) una vez a la semana durante 3 semanas. En el grupo 3 (G3), después de la ovarectomia se realizó la exodoncia y el defecto en el cráneo y después de ello se inicio el protocolo con alendronato. En cada grupo, después de seis semanas se realizó la eutanasia con descripción histológica de los hallazgos. En el hueso formado en el defecto craneano de 5 mm se observó una adecuada progresión de reparación en los 3 modelos experimentales y no se observó cambios importantes en el modelo de reparación. Para el tejido gingival en el sitio de extracción, no se observaron diferencias entre el grupo G1 y G3. Por otra parte, el G2 presentó un tejido mas delgado con reducción del epitelio gingival; nuestros resultados demuestran que el alendronato no fue un obstáculo en la reparación ósea; deficiencias en la re epitelización de la mucosa oral muestran el impacto del alendronato después de la exodoncia.


Assuntos
Animais , Feminino , Ratos , Doenças Ósseas Metabólicas/tratamento farmacológico , Regeneração Óssea/efeitos dos fármacos , Alendronato/administração & dosagem , Gengiva/efeitos dos fármacos , Osteonecrose/tratamento farmacológico , Osteoporose/tratamento farmacológico , Doenças Ósseas Metabólicas/complicações , Ovariectomia , Ratos Wistar , Difosfonatos/administração & dosagem
4.
Medicine (Baltimore) ; 99(5): e18989, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32000434

RESUMO

RATIONALE: Although the treatment of femoral head necrosis has already been established with the adoption of daily teriparatide, a clear consensus on the treatment of spontaneous osteonecrosis of the knee (SONK) has yet to be reached. Therefore, we focused on the treatment of SONK with daily teriparatide administration (20 µg, subcutaneous) and confirmed its effects to determine whether it is a valid option. PATIENTS' CONCERNS: Three osteoporotic patients who were diagnosed with SONK complained of knee pain. DIAGNOSIS: SONK was diagnosed on magnetic resonance imaging in all cases. INTERVENTIONS: All patients took daily teriparatide as a treatment for SONK. OUTCOMES: There was a significant and dramatic reduction in the visual analog scale score 1 month after treatment. After 6 months of treatment, the sizes of the affected SONK lesions were smaller than in the initial phase, and plain X-rays showed no further signs of progression. LESSONS: Daily teriparatide might be an effective treatment for SONK.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Articulação do Joelho , Osteonecrose/tratamento farmacológico , Teriparatida/uso terapêutico , Idoso , Biomarcadores/sangue , Densidade Óssea , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Osteonecrose/diagnóstico por imagem , Medição da Dor , Teriparatida/administração & dosagem
5.
FASEB J ; 34(2): 2595-2608, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31919918

RESUMO

Dendritic cells are an important link between innate and adaptive immune response. The role of dendritic cells in bone homeostasis, however, is not understood. Osteoporosis medications that inhibit osteoclasts have been associated with osteonecrosis, a condition limited to the jawbone, thus called medication-related osteonecrosis of the jaw. We propose that disruption of the local immune response renders the oral microenvironment conducive to osteonecrosis. We tested whether zoledronate (Zol) treatment impaired dendritic cell (DC) functions and increased bacterial load in alveolar bone in vivo and whether DC inhibition alone predisposed the animals to osteonecrosis. We also analyzed the role of Zol in impairment of differentiation and function of migratory and tissue-resident DCs, promoting disruption of T-cell activation in vitro. Results demonstrated a Zol induced impairment in DC functions and an increased bacterial load in the oral cavity. DC-deficient mice were predisposed to osteonecrosis following dental extraction. Zol treatment of DCs in vitro caused an impairment in immune functions including differentiation, maturation, migration, antigen presentation, and T-cell activation. We conclude that the mechanism of Zol-induced osteonecrosis of the jaw involves disruption of DC immune functions required to clear bacterial infection and activate T cell effector response.


Assuntos
Conservadores da Densidade Óssea/farmacologia , Osso e Ossos/efeitos dos fármacos , Células Dendríticas/metabolismo , Homeostase/imunologia , Doenças Maxilomandibulares/imunologia , Osteonecrose/tratamento farmacológico , Ácido Zoledrônico/farmacologia , Animais , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/imunologia , Células Dendríticas/imunologia , Homeostase/efeitos dos fármacos , Imidazóis/farmacologia , Doenças Maxilomandibulares/tratamento farmacológico , Osteoclastos/efeitos dos fármacos , Osteoclastos/imunologia , Osteonecrose/imunologia , Extração Dentária/métodos , Cicatrização/efeitos dos fármacos
6.
Skeletal Radiol ; 49(1): 147-154, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31139921

RESUMO

Avascular necrosis (AVN) of the bone is thought to be a serious complication of treatment for acute lymphoblastic leukemia (ALL). The acetabulum is an unusual area to be affected by AVN, and there are currently no reports of successful joint salvage procedures found in the literature. We present a case of a 20-year-old man with ALL who was diagnosed with debilitating AVN of both acetabula 2 years following initial diagnosis of ALL and treatment with a multi-agent chemotherapy regimen including high-dose corticosteroids. After unsuccessful treatment with bisphosphonate therapy, the acetabular AVN underwent bilateral curettage and impaction bone grafting to prevent collapse of subchondral fractures with the hope of salvaging both hip joints. Computer tomography (CT) of the AVN affected areas, pre- and post-bone impaction grafting, demonstrated healing of the subchondral fractures and a doubling of bone density that was maintained at 2 years after surgery. The patient resumed full weight-bearing at 3 months after first surgery, continues to ambulate unrestricted, and remains pain free 3 years post-surgery.


Assuntos
Acetábulo/diagnóstico por imagem , Transplante Ósseo/métodos , Fraturas Ósseas/diagnóstico por imagem , Osteonecrose/diagnóstico por imagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Acetábulo/lesões , Acetábulo/patologia , Acetábulo/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Densidade Óssea , Curetagem , Difosfonatos/uso terapêutico , Consolidação da Fratura , Fraturas Ósseas/induzido quimicamente , Fraturas Ósseas/tratamento farmacológico , Fraturas Ósseas/cirurgia , Glucocorticoides/efeitos adversos , Glucocorticoides/uso terapêutico , Humanos , Imagem Cinética por Ressonância Magnética , Masculino , Osteonecrose/induzido quimicamente , Osteonecrose/tratamento farmacológico , Osteonecrose/cirurgia , Prednisolona/efeitos adversos , Prednisolona/uso terapêutico , Tomografia Computadorizada por Raios X , Adulto Jovem
7.
J Biol Regul Homeost Agents ; 34(6 Suppl. 2): 69-76, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33541066

RESUMO

Bisphosphonate Related Osteonecrosis of the Jaw (BRONJ) is a pathology initially described in the early 2000s that has become increasingly common in clinical dentistry and maxillofacial practice due to the frequent use of bisphosphonates medical drugs (BPs) to treat various diseases such as osteoporosis, Paget's syndrome, osteomyelitis and in bone metastases secondary to tumors. Supragingival irrigation applied as monotherapy and in combination with root planning or BFs related bone necrosectomy revealed that supragingival irrigation with a variety of agents reduced the gingival microbial load and gingival inflammation. In this 4-year follow-up study we analyze the use of hydrogen peroxide (H2O2) as an antimicrobial agent for maintenance periodontal health, improving the longevity of teeth and oral cavity healing process.


Assuntos
Perda do Osso Alveolar/tratamento farmacológico , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/complicações , Peróxido de Hidrogênio/administração & dosagem , Peróxido de Hidrogênio/farmacologia , Nervo Mandibular , Doenças Periodontais/complicações , Doenças Periodontais/tratamento farmacológico , Conservadores da Densidade Óssea/efeitos adversos , Difosfonatos/efeitos adversos , Seguimentos , Humanos , Osteonecrose/tratamento farmacológico
8.
Biomed Res Int ; 2019: 1271492, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31662968

RESUMO

Objectives: This study aimed to assess the effect of zoledronic acid on an immunocompromised mice model with periapical disease. Materials and Methods: Thirty C57BL/6N mice were randomly divided into three groups (N = 10). All animals were subjected to bilateral ovariectomy (OVX) and then treated with saline (Veh), zoledronic acid (ZA), or concomitant zoledronic acid and dexamethasone (ZA/Dx) for 12 weeks. Eight weeks after starting drug administration, pulpal exposure was conducted on the lower left first molar. Four weeks after pulpal exposure, all mice were sacrificed and the mandibles were collected for radiological and histological examinations. Results: Microcomputed tomography (µ-CT) examination showed significantly reduced periapical bone resorption in the ZA/Dx group and decreased periodontal bone resorption in both ZA and ZA/Dx groups. Higher bone mineral density (BMD) and strengthened microstructure were found in ZA and ZA/Dx groups. More empty lacunae were found in ZA and ZA/Dx groups. Conclusions: Apical periodontitis aggravates MRONJ under immunocompromised circumstances. Concurrent use of ZA and steroids inhibits alveolar bone resorption but increases the risk of developing MRONJ.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Doenças Periapicais/tratamento farmacológico , Ácido Zoledrônico/uso terapêutico , Perda do Osso Alveolar/diagnóstico por imagem , Perda do Osso Alveolar/tratamento farmacológico , Perda do Osso Alveolar/patologia , Animais , Densidade Óssea/efeitos dos fármacos , Dexametasona/farmacologia , Modelos Animais de Doenças , Feminino , Mandíbula/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Dente Molar/efeitos dos fármacos , Osteonecrose/tratamento farmacológico , Ovariectomia , Doenças Periapicais/diagnóstico por imagem , Doenças Periapicais/patologia , Microtomografia por Raio-X
9.
J Biosci ; 44(4)2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31502565

RESUMO

Bone marrow mesenchymal stem cells (BMSCs) play an important role in the process of bone repair. The present study investigated the effect of 5-azacytidine (AZA) and trichostatin A (TSA) on BMSC behaviors in vitro. The role of WNT family member 5A (WNT5A)/WNT family member 5A (WNT7A)/beta-catenin signaling was also investigated. BMSCs were isolated from a steroid-induced avascular necrosis of the femoral head (SANFH) rabbit model. The third-generation of BMSCs was used after identification. The results revealed obvious degeneration and necrosis in the SANFH rabbit model. AZA, TSA and TSA + AZA increased BMSC proliferation in a time-dependent fashion. AZA, TSA and TSA + AZA induced the cell cycle release from the G0/G1 phase and inhibited apoptosis in BMSCs. AZA, TSA and TSA + AZA treatment significantly decreased caspase-3 and caspase-9 activities. The treatment obviously increased the activity and relative mRNA expression of alkaline phosphatase. The treatment also significantly up-regulated the proteins associated with osteogenic differentiation, including osteocalcin and runt-related transcription factor 2 (RUNX2), and Wnt/beta-catenin signal transduction pathway-related proteins beta-catenin, WNT5A and WNT7A. The relative levels of Dickkopf-related protein 1 (an inhibitor of the canonical Wnt pathway) decreased remarkably. Notably, TSA + AZA treatment exhibited a stronger adjustment ability than either single treatment. Collectively, the present studies suggest that AZA, TSA and TSA + AZA promote cell proliferation and osteogenic differentiation in BMSCs, and these effects are potentially achieved via upregulation of WNT5A/WNT7A/b-catenin signaling.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Necrose da Cabeça do Fêmur/tratamento farmacológico , Osteogênese/efeitos dos fármacos , Osteonecrose/tratamento farmacológico , Fosfatase Alcalina/genética , Animais , Azacitidina/farmacologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/patologia , Humanos , Ácidos Hidroxâmicos/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteonecrose/induzido quimicamente , Osteonecrose/patologia , Coelhos , Esteroides/toxicidade , Via de Sinalização Wnt/efeitos dos fármacos , beta Catenina/genética
10.
Rev. osteoporos. metab. miner. (Internet) ; 11(2): 55-63, abr.-jun. 2019. tab
Artigo em Espanhol | IBECS | ID: ibc-188337

RESUMO

OBJETIVO: La osteonecrosis de maxilares (ONM) es una enfermedad recientemente descrita cuya etiopatogenia es desconocida, aunque se ha atribuido, entre otras causas, al tratamiento prolongado con bifosfonatos. Sin embargo, mientras que la ONM es una patología localizada, la acción de los bifosfonatos es generalizada, es decir, afecta a todos los huesos. No hay estudios que muestren el estado óseo general de los pacientes con ONM. Con este trabajo hemos querido estudiar en pacientes afectos de ONM dicho estado general mediante medidas cuantitativas y estimaciones cualitativas del hueso por medio de la densidad mineral ósea (DMO) y el trabecular bone score (TBS) y los parámetros ultrasonográficos en el calcáneo (QUS), además de la presencia de otras enfermedades y la toma de fármacos (especialmente los bifosfonatos) en los pacientes con ONM que pudieran participar en su etiopatogenia. MATERIAL Y MÉTODO: Estudio observacional y transversal de casos y controles, realizado en 304 pacientes de ambos sexos, en los que el grupo de casos (grupo I) estaba formado por 24 pacientes que habían sufrido una ONM, mientras que el grupo control (grupo II) estaba formado por 280 pacientes que no presentaban ONM y que recibían bifosfonatos desde un mínimo de 5 años por causas diversas. A todos ellos se les realizó una densitometría ósea (DXA, Hologic 4500 Discovery®) en la columna lumbar y en la extremidad proximal del fémur. Además, se les realizó mediciones del TBS en la columna lumbar, así como de los parámetros ultrasonográficos en el calcáneo (Hologic, Sahara®) en el pie dominante (QUS). RESULTADOS: Los pacientes afectos de ONM tenían una mayor comorbilidad que los controles, con una mayor prevalencia de las siguientes enfermedades: diabetes mellitus, cáncer, artritis reumatoide, hipertiroidismo, cardiopatía, arritmias, insuficiencia cardíaca e hipercolesterolemia. Por ello, el consumo de corticoides, (orales e inhalados), anticoagulantes, hipnóticos, bifosfonatos i.v. (zoledronato), y quimioterapia antineoplásica fue también mayor entre los pacientes afectos de ONM que los pacientes controles. Sin embargo, entre los pacientes con ONM el porcentaje que tomaba bifosfonatos orales fue menor. Los valores densitométricos (DMO medida en la columna lumbar L2-L4, cuello femoral y total de cadera) fueron más elevados en los pacientes con ONM en comparación con los de los controles. El TBS no mostró diferencias estadísticamente significativas entre ambos grupos, y los ultrasonidos presentaron valores más elevados de QUI y SOS en los pacientes con ONM que en los controles. La prevalencia de fracturas por fragilidad fue similar en ambos grupos. CONCLUSIONES: Nuestros pacientes afectos de ONM mostraron una mayor comorbilidad y un mayor consumo de fármacos que los pacientes del grupo control, a excepción de bifosfonatos orales. Por otro lado, tanto la DMO como los parámetros ultrasonográficos mostraron valores más elevados en los pacientes con ONM que los controles. Si consideramos la DXA como una técnica medidora de la cantidad de masa ósea, y el TBS y la ultrasonografía de calcáneo técnicas estimadoras de aspectos cualitativos del hueso, podemos suponer que ni la cantidad ni la calidad óseas en general parecen estar afectadas en la ONM, siendo probablemente otro su mecanismo etiopatogénico. Los bifosfonatos orales no parecen estar entre los fármacos que participen en la etiología de la ONM, aunque sí los bifosfonatos más potentes que se administran por vía intravenosa, si bien no pueden considerarse independientemente de la patología subyacente para la cual se administran


OBJECTIVE: Osteonecrosis of the jaw (ONJ) is a recently reported disease whose origin and development are unknown, although prolonged bisphosphonate treatment has been attributed, among other causes. While ONJ is a localized condition, the action of bisphosphonates is widespread and affects all bones. No studies show the general bone status of patients with ONJ. Our study examines the general condition in patients with ONJ using quantitative measurements and qualitative estimates of bone by means of bone mineral density (BMD) and trabecular bone score (TBS) and ultrasound parameters in the calcaneus (QUS), along with other diseases and the taking of drugs (especially bisphosphonates) in patients with ONJ who may be involved in the pathogenesis. MATERIAL AND METHOD: Observational and cross-sectional study of cases and controls, conducted in 304 patients of both sexes, in which the case group (group I) was formed by 24 patients who had suffered ONJ. The control group (group II) contained 280 patients who did not present ONJ and who received bisphosphonates over at least 5 years for various reasons. All of them underwent bone densitometry (DXA, Hologic 4500 Discovery®) in the lumbar spine and proximal femur. In addition, TBS measurements were made in the lumbar spine, as well as ultrasound parameters in the calcaneus (Hologic, Sahara®) in the dominant foot (QUS). RESULTS: Patients suffering ONJ presented greater comorbidity than controls, with a higher prevalence of diabetes mellitus, cancer, rheumatoid arthritis, hyperthyroidism, heart disease, arrhythmias, heart failure and hypercholesterolemia. Therefore, the consumption of corticosteroids, (oral and inhaled), anticoagulants, hypnotics, bisphosphonates i.v. (zoledronate), and antineoplastic chemotherapy was also higher among patients with ONJ than control patients. However, among the patients with ONJ the percentage taking oral bisphosphonates was lower. Densitometric values (BMD measured in lumbar spine L2-L4, femoral neck and total hip) were higher in patients with ONJ compared to those in controls. The TBS showed no statistically significant differences between the two groups, and the ultrasound showed higher values of QUI and SOS in patients with ONJ than in controls. The prevalence of fragility fractures was similar in both groups. CONCLUSIONS: Patients with ONJ in our study presented greater comorbidity and a higher consumption of drugs than the patients in the control group, except for oral bisphosphonates. On the other hand, both BMD and ultrasound showed higher values in patients with ONJ than in controls. If we consider DXA as a technique for measuring the amount of bone mass, and TBS and calcaneal ultrasound estimating qualitative aspects of bone, we could assume that neither bone quantity nor quality in general seems to be affected in ONJ, and that its etiopathogenic mechanism is probably another. Oral bisphosphonates do not appear to be among the drugs involved in ONJ's origin and development, but the most potent and intravenously administered bisphosphonates are, although they cannot be considered independently of the underlying disease for which they are administered


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Osteonecrose/tratamento farmacológico , Doenças Maxilares/tratamento farmacológico , Difosfonatos/uso terapêutico , Estudos de Casos e Controles , Osteonecrose/diagnóstico por imagem , Doenças Maxilares/diagnóstico por imagem , Estudos Transversais , Densitometria , Absorciometria de Fóton
11.
Mol Med Rep ; 20(1): 401-408, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31115574

RESUMO

Osteoblast apoptosis has been identified as an important event in the development of glucocorticoid (GC)­induced osteoporosis and osteonecrosis of the femoral head. Crocin, a bioactive ingredient of saffron, has been demonstrated to induce antiapoptotic effects on numerous types of cell in vitro; however, the effects of crocin on the dexamethasone (Dex)­induced apoptosis of osteoblasts remain unclear. In the present study, the protective effects of crocin during Dex­induced apoptosis of MC3T3­E1 osteoblasts, and the underlying mechanisms, were investigated. MTT and Annexin V­FITC/PI flow cytometry assays were performed to evaluate the viability and apoptosis of cells, respectively. The mitochondrial transmembrane potential, reactive oxygen species (ROS), intracellular Ca2+ levels and apoptosis­associated protein expression were assessed via flow cytometry, fluorescence microscopy and western blotting. It was demonstrated that crocin pretreatment inhibited Dex­induced apoptosis of osteoblasts in a dose­dependent manner. Crocin reversed Dex­induced decreases in the mitochondrial transmembrane potential, and increases in ROS and intracellular Ca2+ levels. Furthermore, crocin upregulated the expression levels of B­cell lymphoma-2 (Bcl­2) and mitochondrial cytochrome c (Cyt C), and downregulated those of cleaved caspase­9, cleaved caspase­3, Bcl­2­associated X protein and cytoplasmic Cyt C. N­acetylcysteine, a ROS inhibitor, and 1,2­bis(2­aminophenoxy)ethane­N,N,N',N'­tetraacetic acid, a calcium chelator, attenuated Dex­induced osteoblast apoptosis, whereas H2O2 and ionomycin, a calcium ionophore that increases intracellular calcium levels, reversed the antiapoptotic effects of crocin on Dex­treated osteoblasts. These results indicated that crocin may protect osteoblasts from Dex­induced apoptosis by inhibiting the ROS/Ca2+­mediated mitochondrial pathway, thus suggesting that crocin has potential value as a treatment for GC­induced bone diseases.


Assuntos
Apoptose/efeitos dos fármacos , Carotenoides/farmacologia , Glucocorticoides/metabolismo , Osteonecrose/tratamento farmacológico , Osteoporose/tratamento farmacológico , Acetilcisteína/farmacologia , Animais , Cálcio/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Dexametasona/toxicidade , Fraturas do Fêmur/tratamento farmacológico , Fraturas do Fêmur/genética , Fraturas do Fêmur/patologia , Humanos , Peróxido de Hidrogênio/farmacologia , Ionomicina/farmacologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Mitocôndrias/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Osteoblastos/patologia , Osteonecrose/induzido quimicamente , Osteonecrose/genética , Osteonecrose/patologia , Osteoporose/induzido quimicamente , Osteoporose/genética , Osteoporose/patologia , Espécies Reativas de Oxigênio/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos
12.
J Orthop Surg Res ; 14(1): 112, 2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31018848

RESUMO

BACKGROUND: Avascular necrosis at sites other than femoral head (AVNOFH)/Non-Femoral AVN is a rare entity. No standard of treatment still exists for treating early stages of AVNOFH with most of the cases eventually progressing to a late arthritic stage needing surgical intervention. Bisphosphonates have been shown to prevent disease progression, bone collapse, and the requirement for surgery in avascular necrosis of femoral head. The present study is conducted to evaluate the response of bisphosphonates in the non-surgical management of the early stages of AVNOFH. MATERIALS AND METHODS: Prospectively collected data of 20 patients diagnosed with an early stage of AVNOFH and treated with the combination of oral alendronate 70 mg weekly and intravenous zolendronic acid (ZA) for 1 year, between Jan 2009 to Dec 2015, was evaluated retrospectively. Clinical evaluation was done using the visual analogue scale (VAS), mean analgesic requirement, and range of motion. Radiographs and magnetic resonance imaging (MRI) were taken to classify the stage of AVN, monitor radiological collapse, and evaluate radiological progression and bone marrow edema changes. RESULTS: In our analysis of 18 patients (2 lost to follow-up), 5 patients had AVN of the humeral head, 4 patients of the talus, 3 of the lunate, and 2 each of the scaphoid, medial tibial plateau, and second metatarsal head. Pain relief with the drop in VAS score was seen at a mean duration of 4.3 weeks (range 3-13 weeks) after the start of therapy. A 50% reduction in mean analgesic requirement was achieved in the first 6 weeks (2-11 weeks). MRI showed complete resolution of BME in 13 patients at 6 months and in 17 patients (94.4%) at 1 year. Radiological collapse was seen in 6 out of 18 patients at a mean follow-up of 35.3 months (range 14-56 months). Only one out of 18 patients enrolled required surgery. CONCLUSION: A combination of oral alendronate and intravenous zolendronic acid provides a pragmatic solution to this rare entity of AVNOFH, where no standard treatment exists.


Assuntos
Alendronato/administração & dosagem , Conservadores da Densidade Óssea/administração & dosagem , Difosfonatos/administração & dosagem , Osteonecrose/diagnóstico por imagem , Osteonecrose/tratamento farmacológico , Ácido Zoledrônico/administração & dosagem , Administração Intravenosa , Administração Oral , Adolescente , Adulto , Idoso , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
13.
Eur Rev Med Pharmacol Sci ; 23(6): 2314-2317, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30964153

RESUMO

Denosumab is an antiresorptive drug that blocks osteoclast maturation, function and survival, improving bone mineral density and reducing the probability of fracture. It has adverse effects and can be the cause of hypocalcemia and osteonecrosis of the jaw. This report describes the case of a 59-year-old woman with hypothyroidism, antecedents of breast cancer, two strokes, and severe bone osteoporosis. Extraction of tooth 3.6 was performed, and within a month she was administered with a denosumab injection. One month later maxillary osteonecrosis appeared in the lingual distal area of the extraction site. Four months later the case was resolved by means of non-surgical treatment.


Assuntos
Denosumab/efeitos adversos , Osteonecrose/diagnóstico por imagem , Extração Dentária/efeitos adversos , Antibacterianos/uso terapêutico , Clorexidina/uso terapêutico , Humanos , Pessoa de Meia-Idade , Osteonecrose/induzido quimicamente , Osteonecrose/tratamento farmacológico
14.
BMJ Case Rep ; 12(2)2019 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-30814104

RESUMO

An 82-year-old man with a background of prostate carcinoma and bony metastases presented with bilateral discharging neck fistulae. Two years prior to presentation, the patient had been treated with intravenous zoledronic acid for 1 year as part of chemotherapy. Intraoral examination revealed extensive bilateral medication-related osteonecrosis, with orocutaneous fistulae within the neck. Treatment comprised removal of loose necrotic bone sequestrae, debridement of the fistulae and long-term administration of antibiotics, vitamin E and pentoxifylline. Four weeks later, the orocutaneous fistulae had healed.


Assuntos
Conservadores da Densidade Óssea/efeitos adversos , Mandíbula/patologia , Osteonecrose/induzido quimicamente , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Ácido Zoledrônico/efeitos adversos , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Depuradores de Radicais Livres/uso terapêutico , Humanos , Masculino , Osteonecrose/tratamento farmacológico , Pentoxifilina/uso terapêutico , Vitamina E/uso terapêutico
15.
Bone ; 123: 115-128, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30926440

RESUMO

Bisphosphonate (BP)-related osteonecrosis of the jaw, previously known as BRONJ, now referred to more broadly as medication-related osteonecrosis of the jaw (MRONJ), is a morbid condition that represents a significant risk for oncology patients who have received high dose intravenous (IV) infusion of a potent nitrogen containing BP (N-BP) drug. At present, no clinical procedure is available to prevent or effectively treat MRONJ. Although the pathophysiological basis is not yet fully understood, legacy adsorbed N-BP in jawbone has been proposed to be associated with BRONJ by one or more mechanisms. We hypothesized that removal of the pre-adsorbed N-BP drug common to these pathological mechanisms from alveolar bone could be an effective preventative/therapeutic strategy. This study demonstrates that fluorescently labeled BP pre-adsorbed on the surface of murine maxillo-cranial bone in vivo can be displaced by subsequent application of other BPs. We previously described rodent BRONJ models involving the combination of N-BP treatment such as zoledronate (ZOL) and dental initiating factors such as tooth extraction. We further refined our mouse model by using gel food during the first 7 days of the tooth extraction wound healing period, which decreased confounding food pellet impaction problems in the open boney socket. This refined mouse model does not manifest BRONJ-like severe jawbone exposure, but development of osteonecrosis around the extraction socket and chronic gingival inflammation are clearly exhibited. In this study, we examined the effect of benign BP displacement of legacy N-BP on tooth extraction wound healing in the in vivo model. Systemic IV administration of a low potency BP (lpBP: defined as inactive at 100 µM in a standard protein anti-prenylation assay) did not significantly attenuate jawbone osteonecrosis. We then developed an intra-oral formulation of lpBP, which when injected into the gingiva adjacent to the tooth prior to extraction, dramatically reduced the osteocyte necrosis area. Furthermore, the tooth extraction wound healing pattern was normalized, as evidenced by timely closure of oral soft tissue without epithelial hyperplasia, significantly reduced gingival inflammation and increased new bone filling in the extraction socket. Our results are consistent with the hypothesis that local application of a rescue BP prior to dental surgery can decrease the amount of a legacy N-BP drug in proximate jawbone surfaces below the threshold that promotes osteocyte necrosis. This observation should provide a conceptual basis for a novel strategy to improve socket healing in patients treated with BPs while preserving therapeutic benefit from anti-resorptive N-BP drug in vertebral and appendicular bones.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Osteonecrose/tratamento farmacológico , Ácido Zoledrônico/uso terapêutico , Administração Intravenosa , Animais , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Cicatrização/efeitos dos fármacos
16.
PLoS One ; 14(2): e0212931, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30794689

RESUMO

Avascular osteonecrosis (AVN) is a bone complication that indicates poor functional prognosis. Modern immunosuppressive and steroid-sparing drugs have significantly lowered the occurrence of AVN after kidney transplantation (KT). However, recent data on its incidence rates and risk factors are lacking. Using a large, recent cohort, we sought to investigate AVN incidence and risk factors, with a special focus on mineral and bone disorders. We conducted a cohort study in 805 patients who underwent KT between 2004 and 2014. AVN was identified in 32 patients (4%): before KT in 15 (1.8%) and after KT in 18 (2.2%) cases, including one patient with both. In the group with post-KT AVN, the median time intervals from KT to 1) first symptoms and 2) AVN diagnosis were 12 months [1-99] and 20 months [4-100], respectively. Being overweight/obese, having pre-transplant diabetes or hyperparathyroidism at transplantation, developing acute rejection, and receiving higher cumulative corticosteroid doses were associated with AVN occurrence. Multivariate analysis revealed that BMI ≥ 26 kg/m2 and higher cumulative corticosteroid doses were predictive of AVN. In conclusion, overweight/obesity is a strong risk factor for AVN. Despite a low maintenance dose, the use of corticosteroids-mostly for treatment of acute rejection-remains an independent risk factor.


Assuntos
Transplante de Rim/efeitos adversos , Osteonecrose/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Hiperparatireoidismo Secundário/tratamento farmacológico , Hiperparatireoidismo Secundário/epidemiologia , Hiperparatireoidismo Secundário/etiologia , Imunossupressores/uso terapêutico , Incidência , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Osteonecrose/tratamento farmacológico , Osteonecrose/etiologia , Fatores de Risco , Transplantados/estatística & dados numéricos , Adulto Jovem
17.
Biomed Mater ; 14(3): 035013, 2019 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-30802884

RESUMO

Glucocorticoids-induced osteonecrosis of femoral head (GIONFH) is difficult to treat due to the pathophysiology remains uncertain. Core decompression and bone grafting are regarded as effective measures for treating early GIONFH. Furthermore, commonly used bone graft materials at nowadays are still unsatisfactory. We generated a novel calcium polyphosphate (CPP) composite scaffold, which contains Li and VEGF-loaded gelatin microspheres (LiCPP/GMs/VEGF). The LiCPP/GMs/VEGF scaffold also demonstrated a porosity of 70.5% ± 2.3% with interconnected porous structures, and pore sizes of 100-200 µm and compressive strength of 3.7 MPa. Additionally, bone marrow mesenchymal stem cells (BMSCs) were seeded on scaffolds in vitro. Further characterization showed that the LiCPP/GMs/VEGF scaffolds were biocompatible and enhanced osteogenesis and angiogenesis in vitro. Using a rabbit model of GIONFH, LiCPP/GMs/VEGF scaffolds were implanted into the bone tunnels of core decompression in the femoral head for 12 weeks. Radiographic, histological analysis and western blot analysis demonstrated that the LiCPP/GMs/VEGF scaffolds exhibited good biocompatibility, and osteogenic and angiogenic activity in vivo. Besides, the osteogenic and angiogenic factors were increased along with VEGF release and the activation of factors in Wnt signal pathway. In conclusion, the LiCPP/GMs/VEGF scaffold has an effect on improving the osteogenesis and angiogenesis, which benefited to repair the GIONFH.


Assuntos
Cabeça do Fêmur/patologia , Glucocorticoides/efeitos adversos , Lítio/química , Osteonecrose/tratamento farmacológico , Tecidos Suporte/química , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Materiais Biocompatíveis , Células da Medula Óssea/citologia , Cálcio/química , Força Compressiva , Gelatina/química , Masculino , Células-Tronco Mesenquimais/citologia , Microesferas , Neovascularização Fisiológica , Osteogênese , Osteonecrose/induzido quimicamente , Polifosfatos/química , Porosidade , Pressão , Coelhos , Transdução de Sinais , Estresse Mecânico , Engenharia Tecidual , Proteínas Wnt/metabolismo , Microtomografia por Raio-X
18.
Thromb Haemost ; 119(1): 92-103, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30597504

RESUMO

Tranexamic acid (TXA) reduces surgical blood loss and alleviates inflammatory response in total hip arthroplasty. However, studies have not identified an optimal regimen. The objective of this study was to identify the most effective regimen of multiple-dose oral TXA in achieving maximum reduction of blood loss and inflammatory response based on pharmacokinetic recommendations. We prospectively studied four multiple-dose regimens (60 patients each) with control group (group A: matching placebo). The four multiple-dose regimens included: 2-g oral TXA 2 hours pre-operatively followed by 1-g oral TXA 3 hours post-operatively (group B), 2-g oral TXA followed by 1-g oral TXA 3 and 7 hours post-operatively (group C), 2-g oral TXA followed by 1-g oral TXA 3, 7 and 11 hours post-operatively (group D) and 2-g oral TXA followed by 1-g oral TXA 3, 7, 11 and 15 hours post-operatively (group E). The primary endpoint was estimated blood loss on post-operative day (POD) 3. Secondary endpoints were thromboelastographic parameters, inflammatory components, function recovery and adverse events. Groups D and E had significantly less blood loss on POD 3, with no significant difference between the two groups. Group E had the most prolonged haemostatic effect, and all thromboelastographic parameters remained within normal ranges. Group E had the lowest levels of inflammatory cytokines and the greatest range of motion. No thromboembolic complications were observed. The post-operative four-dose regimen brings about maximum efficacy in reducing blood loss, alleviating inflammatory response and improving analgaesia and immediate recovery.


Assuntos
Antifibrinolíticos/administração & dosagem , Artroplastia de Quadril/efeitos adversos , Perda Sanguínea Cirúrgica/prevenção & controle , Inflamação/sangue , Dor Pós-Operatória/tratamento farmacológico , Tromboembolia/tratamento farmacológico , Ácido Tranexâmico/administração & dosagem , Administração Oral , Adulto , Idoso , Método Duplo-Cego , Esquema de Medicação , Feminino , Hemostasia , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite/tratamento farmacológico , Osteonecrose/tratamento farmacológico , Período Pós-Operatório , Estudos Prospectivos , Amplitude de Movimento Articular , Resultado do Tratamento
19.
Emerg Med J ; 36(1): 17-32, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30635344

RESUMO

CLINICAL INTRODUCTION: A 77-year-old man presented to the ED with a history of fevers, purulent drainage and right mandibular pain. He had been diagnosed with multiple myeloma 2 years previously and was receiving treatment with pamidronate. On presentation, the lower right lip and chin were anaesthetic, tooth number 31 had grade 2 mobility and a 15 mm long ulceration was present on the lingual aspect of the mandible (figure 1). Antibiotics were administered, and a maxillofacial CT without contrast was performed (figure 2).emermed;36/1/17/F1F1F1Figure 1Clinical examination revealing a 15 mm long ulceration (arrow mark) associated with the lingual aspect of tooth number 31.emermed;36/1/17/F2F2F2Figure 2CT maxillofacial (coronal) demonstrating osseous destruction (arrow mark) of the right mandibular body. QUESTION: What is your diagnosis?Odontogenic abscessBenign fibro-osseous lesionMedication-related osteonecrosis of the jaw (MRONJ)Metastatic malignancy.


Assuntos
Osteonecrose/cirurgia , Pamidronato/efeitos adversos , Abscesso/tratamento farmacológico , Abscesso/cirurgia , Idoso , Antibacterianos/uso terapêutico , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Drenagem/métodos , Febre/etiologia , Humanos , Masculino , Mandíbula/microbiologia , Mandíbula/fisiopatologia , Osteonecrose/tratamento farmacológico , Dor/etiologia , Pamidronato/uso terapêutico , Tomografia Computadorizada por Raios X/métodos
20.
J Cell Physiol ; 234(4): 4314-4326, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30132874

RESUMO

PURPOSE: Suppressed osteogenic differentiation is considered a main cause of ethanol-induced osteonecrosis. Tumor necrosis factor α (TNF-α) and miR-31 have been reported to be involved in the osteogenic induction. This study aimed to explore a possible molecular mechanism regulating osteogenic differentiation in ethanol-induced osteonecrosis bone marrow stromal stem cells (BMSCs). METHODS: Alizarin red staining was used to examine the level of mineralization in osteogenic differentiation process. Alkaline phosphatase assay was applied to the validation of ALP level which was essential to bone mineralization. The level of osteogenesis markers was determined by western blot assay, whereas the fluctuations of messenger RNA levels were tested by quantitative real-time polymerase chain reaction. Microarray analysis was conducted to identify differentially expressed genes, because the possible target relationship was predicted and validated by miRBase and luciferase reporter assay, respectively. Colony forming unit of fibroblast assay was used to observe the proliferation of BMSCs. RESULTS: BMSCs from patients with ethanol-induced osteonecrosis exhibited weaker osteogenic differentiation and proliferation abilities. TNF-α inhibitor added in the osteogenic medium significantly enhanced the osteogenic differentiation ability and BMSCs proliferation ability. TNF-α by regulating miR-31 downregulated the expressions of RUNX2 and SATB2, two contributors of osteoblast differentiation, further suppressed osteogenic differentiation. On the contrary, TNF-α inhibitor could promote osteogenic differentiation in BMSCs from patients with ethanol-induced osteonecrosis. CONCLUSION: TNF-α inhibitor could downregulate miR-31 expressions, which directly promoted SATB2 and RUNX2 expressions and enhanced osteogenic differentiation of BMSCs from patients with ethanol-induced osteonecrosis.


Assuntos
Adalimumab/farmacologia , Diferenciação Celular/efeitos dos fármacos , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Proteínas de Ligação à Região de Interação com a Matriz/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , MicroRNAs/metabolismo , Osteoblastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Osteonecrose/tratamento farmacológico , Fatores de Transcrição/metabolismo , Inibidores do Fator de Necrose Tumoral/farmacologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Idoso , Estudos de Casos e Controles , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Regulação para Baixo , Etanol/efeitos adversos , Feminino , Humanos , Masculino , Proteínas de Ligação à Região de Interação com a Matriz/genética , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/patologia , MicroRNAs/genética , Pessoa de Meia-Idade , Osteoblastos/metabolismo , Osteoblastos/patologia , Osteonecrose/induzido quimicamente , Osteonecrose/genética , Osteonecrose/metabolismo , Transdução de Sinais , Fatores de Transcrição/genética , Fator de Necrose Tumoral alfa/metabolismo
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