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1.
Clin Nucl Med ; 45(10): 781-783, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32796238

RESUMO

A 7-year-old boy presented with diffuse bone pain. FDG PET/CT was performed to find the possible underlying malignant cause of hypercalcemia. The images demonstrated multiple foci of abnormal FDG activity at the sites of periosteal reaction. In addition, calcium deposit was noted in the basal ganglia, stomach, and the colon. History taking revealed that the patient had routinely taken an over-the-counter "supplement" that contains a high dose of vitamin D. One week after calcitonin therapy and stopping the supplement, the patient became symptom free. This case suggests that hypervitaminosis D might cause hypermetabolic periosteal reaction on FDG PET/CT imaging.


Assuntos
Fluordesoxiglucose F18/metabolismo , Distúrbios Nutricionais/diagnóstico por imagem , Distúrbios Nutricionais/fisiopatologia , Osteogênese , Periósteo/fisiopatologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Artefatos , Transporte Biológico , Criança , Humanos , Masculino , Distúrbios Nutricionais/metabolismo , Osteogênese/efeitos dos fármacos , Periósteo/efeitos dos fármacos , Vitamina D/farmacologia
2.
ACS Appl Mater Interfaces ; 12(6): 6840-6851, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-31999085

RESUMO

Recombinant human bone morphogenetic protein-2 (rhBMP-2) and bioceramic are the widely used bioactive factors in treatment of bone defects, but these easily cause side effects because of uncontrollable local concentration. In this study, rhBMP-2 was grafted on the surface of mesoporous bioglass nanoparticles (MBGNs) with an amide bond and then photo-cross-linked together with methacrylate gelatin (GelMA); in this way, a GelMA/MBGNs-rhBMP-2 hydrogel membrane was fabricated to release rhBMP-2 in a controllable program during the early bone regeneration period and then release calcium and silicon ions to keep promoting osteogenesis instead of rhBMP-2 in a long term. In this way, rhBMP-2 can keep releasing for 4 weeks and then the ions keep releasing after 4 weeks; this process is matched to early and late osteogenesis procedures. In vitro study demonstrated that the early release of rhBMP-2 can effectively promote local cell osteogenic differentiation in a short period, and then, the inorganic ions can promote cell adhesion not only in the early stage but also keep promoting osteogenic differentiation for a long period. Finally, the GelMA/MBGNs-rhBMP-2 hydrogel shows a superior capacity in long-term osteogenesis and promoting bone tissue regeneration in rat calvarial critical size defect. This GelMA/MBGNs-rhBMP-2 hydrogel demonstrated a promising strategy for the controllable and safer use of bioactive factors such as rhBMP-2 in artificial periosteum to accelerate bone repairing.


Assuntos
Proteína Morfogenética Óssea 2/administração & dosagem , Cálcio/administração & dosagem , Anormalidades Craniofaciais/tratamento farmacológico , Preparações de Ação Retardada/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Periósteo/efeitos dos fármacos , Silício/administração & dosagem , Fator de Crescimento Transformador beta/administração & dosagem , Animais , Proteína Morfogenética Óssea 2/química , Proteína Morfogenética Óssea 2/genética , Proteína Morfogenética Óssea 2/metabolismo , Regeneração Óssea/efeitos dos fármacos , Cálcio/química , Adesão Celular/efeitos dos fármacos , Anormalidades Craniofaciais/fisiopatologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/metabolismo , Gelatina/química , Humanos , Hidrogéis/química , Nanopartículas/química , Osteogênese/efeitos dos fármacos , Periósteo/fisiopatologia , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Silício/química , Fator de Crescimento Transformador beta/química , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo
3.
J Bone Miner Metab ; 37(6): 1048-1057, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31292723

RESUMO

In this study, we evaluated the effect of functional disuse-induced bone remodeling on its mechanical properties, individually at periosteum and medullary endosteum regions of the cortical bone. Left middle tibiae were obtained from 5-month-old female Sprague-Dawley rats for the baseline control as well as hindlimb suspended (disuse) groups. Micro-nano-mechanical elastic moduli (at lateral region) was evaluated along axial (Z), circumferential (C) and radial (R) orientations using nanoindentation. Results indicated an anisotropic microstructure with axial orientation having the highest and radial orientation with the lowest moduli at periosteum and medullary endosteum for both baseline control as well as disuse groups. Between the groups: at periosteum, an insignificant difference was evaluated for each of the orientations (p > 0.05) and at endosteum, a significant decrease of elastic moduli in the radial (p < 0.0001), circumferential (p < 0.001) and statistically insignificant difference in axial (p > 0.05) orientation. For the moduli ratios between groups: at periosteum, only significant difference in the Z/R (p < 0.05) anisotropy ratio, whereas at endosteum, a statistically significant difference in Z/C (p < 0.001), and Z/R (p < 0.001), as well as C/R (p < 0.05) anisotropy ratios, was evaluated. The results suggested initial bone remodeling impaired bone micro-architecture predominantly at the medullary endosteum with possible alterations in the geometric orientations of collagen and mineral phases inside the bone. The findings could be significant for studying the mechanotransduction pathways involved in maintaining the bone micro-architecture and possibly have high clinical significance for drug use against impairment from functional disuse.


Assuntos
Osso Cortical/patologia , Transtornos Musculares Atróficos/patologia , Animais , Anisotropia , Fenômenos Biomecânicos , Peso Corporal , Osso Cortical/fisiopatologia , Módulo de Elasticidade , Feminino , Periósteo/patologia , Periósteo/fisiopatologia , Ratos Sprague-Dawley , Tíbia/patologia , Tíbia/fisiopatologia
4.
Reumatol. clin., Supl. (Barc.) ; 15(supl.1): 2-6, abr. 2019. ilus
Artigo em Espanhol | IBECS | ID: ibc-184207

RESUMO

Una de las características patogénicas de las espondiloartritis (EspA) es la neoformación ósea. Distintos estudios han puesto de manifiesto que el origen de este proceso está en las entesis, donde algunos factores desen cadenantes, como el estrés biomecánico, en un individuo genéticamente predispuesto producirían una compleja cascada de señales que favorecería la vasodilatación local y la activación de células inmunocompetentes residentes. Estas, a su vez, provocarían una respuesta inflamatoria caracterizada por la secreción de factor de necrosis tumoral alfa e interleucina 17 (IL-17), entre otros, y reclutamiento de otras células inmunocompetentes. Además, se ha demostrado que la IL-17 y la IL-22 favorecen la proliferación de células madre mesenquimatosas del periostio perientesítico, lo que lleva a la formación de hueso nuevo en la entesis. En las EspA, la formación de hueso nuevo es principalmente ortotópica (en continuidad con el hueso existente) y se origina a partir de la entesis y del periostio. Al parecer, la mayoría de la neoformación ósea se produce mediante osificación endocondral. En la osificación endocondral, las células progenitoras mesenquimatosas se diferencian en condrocitos, que construyen un «molde» de cartílago, en el cual las células progresivamente maduran y evolucionan hacia condrocitos hipertróficos. Esta matriz es invadida por vasos y precursores osteoblásticos que reemplazan progresivamente el modelo por hueso maduro


One of the pathogenic characteristics of spondyloarthritis (SpA) is bone neoformation. Several studies have revealed that this process originates in the enthesis, in which triggering factors such as biomechanical stress in genetically predisposed individuals may produce a complex cascade of signals favouring local vasodilation and activation of resident immune cells. These in turn induce an inflammatory response characterised by secretion of TNF-alfa and IL-17 (among other substances) and recruitment of other immune cells. In addition, it has been demonstrated that IL-17 and IL-22 favour the proliferation of mesenchymal stem cells of the peri-enthesic periosteum, leading to the formation of new bone in the enthesis. In SpA, new bone formation is mainly orthotopic (in continuity with existing bone) and arises from the enthesis and periosteum. Most bone neoformation seems to occur through endochondral ossification. In this process, mesenchymal progenitor cells differentiate towards chondrocytes, which construct a cartilaginous "mould" in which the cells progressively mature and develop towards hypertrophic chondrocytes. This matrix is invaded by vessels and osteoblastic precursors that progressively replace the model with mature bone


Assuntos
Humanos , Espondilartrite/fisiopatologia , Osteocondrodisplasias/fisiopatologia , Ossificação Heterotópica/fisiopatologia , Periósteo/fisiopatologia , Osteogênese/fisiologia
5.
J Bone Miner Res ; 34(5): 883-895, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30667555

RESUMO

Melorheostosis is a rare non-hereditary condition characterized by dense hyperostotic lesions with radiographic "dripping candle wax" appearance. Somatic activating mutations in MAP2K1 have recently been identified as a cause of melorheostosis. However, little is known about the development, composition, structure, and mechanical properties of the bone lesions. We performed a multi-method phenotype characterization of material properties in affected and unaffected bone biopsy samples from six melorheostosis patients with MAP2K1 mutations. On standard histology, lesions show a zone with intensively remodeled osteonal-like structure and prominent osteoid accumulation, covered by a shell formed through bone apposition, consisting of compact multi-layered lamellae oriented parallel to the periosteal surface and devoid of osteoid. Compared with unaffected bone, melorheostotic bone has lower average mineralization density measured by quantitative backscattered electron imaging (CaMean: -4.5%, p = 0.04). The lamellar portion of the lesion is even less mineralized, possibly because the newly deposited material has younger tissue age. Affected bone has higher porosity by micro-CT, due to increased tissue vascularity and elevated 2D-microporosity (osteocyte lacunar porosity: +39%, p = 0.01) determined on quantitative backscattered electron images. Furthermore, nano-indentation modulus characterizing material hardness and stiffness was strictly dependent on tissue mineralization (correlation with typical calcium concentration, CaPeak: r = 0.8984, p = 0.0150, and r = 0.9788, p = 0.0007, respectively) in both affected and unaffected bone, indicating that the surgical hardness of melorheostotic lesions results from their lamellar structure. The results suggest a model for pathophysiology of melorheostosis caused by somatic activating mutations in MAP2K1, in which the genetically induced gradual deterioration of bone microarchitecture triggers a periosteal reaction, similar to the process found to occur after bone infection or local trauma, and leads to an overall cortical outgrowth. The micromechanical properties of the lesions reflect their structural heterogeneity and correlate with local variations in mineral content, tissue age, and remodeling rates, in the same way as normal bone. © 2018 American Society for Bone and Mineral Research.


Assuntos
Densidade Óssea , MAP Quinase Quinase 1 , Melorreostose , Modelos Biológicos , Mutação , Periósteo , Microtomografia por Raio-X , Adulto , Feminino , Humanos , MAP Quinase Quinase 1/genética , MAP Quinase Quinase 1/metabolismo , Masculino , Melorreostose/diagnóstico por imagem , Melorreostose/genética , Melorreostose/metabolismo , Melorreostose/fisiopatologia , Pessoa de Meia-Idade , Periósteo/diagnóstico por imagem , Periósteo/metabolismo , Periósteo/fisiopatologia
6.
J Pediatr Hematol Oncol ; 41(2): 148-151, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-29621061

RESUMO

Melanotic neuroectodermal tumor of infancy (MNTI) is a rare entity primarily affecting the craniofacial bones during the first year of life, with only 5 reported cases involving peripheral long bones. We herein present a case of MNTI in the tibia of an infant, with a somewhat atypical presentation, and a noteworthy clinical course characterized by progressive spontaneous resolution without therapy, thus sparing the child the trauma of amputation. There is no evidence of active residual or recurrent disease with 13-year follow-up. To the best of our knowledge, essentially all reported cases of MNTI have received empirical treatment, some at the price of mutilating surgery or fatal chemotherapy. We propose that the necessity of aggressive treatment be evaluated on a case-by-case basis, especially in patients with diffuse periosteal involvement, as in this patient. A trial of watchful waiting can be considered when treatment would involve substantial morbidity or risk of complications.


Assuntos
Neoplasias Ósseas , Regressão Neoplásica Espontânea , Tumor Neuroectodérmico Melanótico , Periósteo/fisiopatologia , Tíbia/fisiopatologia , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/fisiopatologia , Feminino , Humanos , Lactente , Tumor Neuroectodérmico Melanótico/diagnóstico , Tumor Neuroectodérmico Melanótico/fisiopatologia
7.
Bone ; 120: 465-475, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30550849

RESUMO

Profound bone loss occurs following spinal cord injury (SCI) resulting in a high incidence of fractures. While likely caused in part by loss of weight-bearing, there is greater bone loss following SCI when compared to that observed in other disuse animal models. Patients with SCI have a protracted inflammatory response, with elevated circulating levels of pro-inflammatory markers. This chronic inflammation could compound the bone loss attributed to disuse and the loss of neural signaling. To assess this, we examined inflammatory markers and bone turnover regulators in osteocytes from rats with a moderate spinal contusion injury (SCI) and intact controls (CON). We counted osteocytes positive for cytokines [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-17 (IL-17), and interleukin-10 (IL-10)], osteoclastogenesis regulators RANKL and OPG, and the bone formation inhibitor sclerostin, 32 days after the spinal contusion. By day 9 post-injury, the majority of SCI rats had recovered significant locomotor function and were bearing weight on their hindlimbs. However, despite weight-bearing, peripheral QCT scans demonstrated lower bone mass due to SCI in the proximal tibia metaphysis compared to CON. SCI animals also had lower cancellous bone volume, lower bone formation rate (BFR), lower osteoid surface (OS), and higher osteoclast surface (Oc.S). Tibial mid-shaft periosteal BFR was also lower after SCI. Immunohistochemical staining of the distal femur bone revealed cancellous osteocytes positive for TNF-α, IL-6, IL-17, and IL-10 were elevated in SCI animals relative to intact controls. Protein expression of RANKL+, OPG+, and sclerostin+ osteocytes was also higher in SCI rats. At the cortical midshaft, osteocyte TNF-α, IL-6, and sclerostin were statistically higher in SCI vs. CON. With regression analysis, inflammatory factors were associated with changes in bone turnover. In conclusion, inflammatory factors as well as altered mechanical loading influence bone turnover following a moderate SCI. Treatments aimed at minimizing fracture risk after SCI may need to target both the chronically altered inflammatory state as well as disuse-induced bone loss.


Assuntos
Inflamação/patologia , Osteócitos/patologia , Traumatismos da Medula Espinal/patologia , Animais , Proteínas Morfogenéticas Ósseas/metabolismo , Osso Cortical/patologia , Osso Cortical/fisiopatologia , Modelos Animais de Doenças , Fêmur/patologia , Fêmur/fisiopatologia , Marcadores Genéticos , Membro Posterior/fisiopatologia , Inflamação/complicações , Modelos Lineares , Masculino , Tamanho do Órgão , Osteócitos/metabolismo , Osteogênese , Periósteo/patologia , Periósteo/fisiopatologia , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/diagnóstico por imagem , Tíbia/patologia , Tíbia/fisiopatologia , Suporte de Carga
8.
Bone ; 112: 97-106, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29680264

RESUMO

INTRODUCTION: Aminocaproic acid is approved as an anti-fibrinolytic for use in joint replacement and spinal fusion surgeries to limit perioperative blood loss. Previous animal studies have demonstrated a pro-osteogenic effect of aminocaproic acid in spine fusion models. Here, we tested if aminocaproic acid enhances appendicular bone healing and we sought to uncover the effect of aminocaproic acid on osteoprogenitor cells (OPCs) during bone regeneration. METHODS: We employed a well-established murine femur fracture model in adult C57BL/6J mice after receiving two peri-operative injections of aminocaproic acid. Routine histological assays, biomechanical testing and micro-CT analyses were utilized to assess callus volume, and strength, progenitor cell proliferation, differentiation, and remodeling in vivo. Two disparate ectopic transplantation models were used to study the effect of the growth factor milieu within the early fracture hematoma on osteoprogenitor cell fate decisions. RESULTS: Aminocaproic acid treated femur fractures healed with a significantly smaller cartilaginous callus, and this effect was also observed in the ectopic transplantation assays. We hypothesized that aminocaproic acid treatment resulted in a stabilization of the early fracture hematoma, leading to a change in the growth factor milieu created by the early hematoma. Gene and protein expression analysis confirmed that aminocaproic acid treatment resulted in an increase in Wnt and BMP signaling and a decrease in TGF-ß-signaling, resulting in a shift from chondrogenic to osteogenic differentiation in this model of endochondral bone formation. CONCLUSION: These experiments demonstrate for the first time that inhibition of the plasminogen activator during fracture healing using aminocaproic acid leads to a change in cell fate decision of periosteal osteoprogenitor cells, with a predominance of osteogenic differentiation, resulting in a larger and stronger bony callus. These findings may offer a promising new use of aminocaproic acid, which is already FDA-approved and offers a very safe risk profile.


Assuntos
Condrogênese , Fraturas do Fêmur/patologia , Consolidação da Fratura , Osteogênese , Periósteo/patologia , Ativadores de Plasminogênio/antagonistas & inibidores , Ácido Aminocaproico/farmacologia , Animais , Fenômenos Biomecânicos/efeitos dos fármacos , Coagulação Sanguínea/efeitos dos fármacos , Calo Ósseo/patologia , Microambiente Celular/efeitos dos fármacos , Condrogênese/efeitos dos fármacos , Fraturas do Fêmur/sangue , Fraturas do Fêmur/diagnóstico por imagem , Consolidação da Fratura/efeitos dos fármacos , Hematoma/patologia , Masculino , Camundongos Endogâmicos C57BL , Osteogênese/efeitos dos fármacos , Periósteo/diagnóstico por imagem , Periósteo/efeitos dos fármacos , Periósteo/fisiopatologia , Ativadores de Plasminogênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Microtomografia por Raio-X
9.
Int Orthop ; 40(10): 2191-2197, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27277947

RESUMO

BACKGROUND: A peculiarity of non-vascularized fibular harvest is that the donor site regenerates new bone provided periosteum is preserved. We prospectively investigated the regenerated fibula quantitatively and studied clinical implications of non-regeneration. MATERIAL AND METHODS: The fibula was harvested using a periosteum preserving technique. Only fibulae from healthy legs were harvested. X-rays were done pre- and post-operatively at three and six months. Clinical assessment of donor limb included pain, gait, motor and sensory examination. Fibular regeneration was quantified using defined length and width criteria. RESULTS: There were 16 children with 21 harvested fibula. About 65 % of total fibular length was available for use as graft. There was regeneration of fibula similar to the pre-operative dimensions as early as six months in 71 % of cases. There were no clinical morbid findings as assessed at six months follow up despite non-continuity being observed in 29 % of cases. The predominant site for non-continuity was middle third-distal third junction. CONCLUSIONS: Periosteal preserving non-vascularized fibula grafting was a low morbidity procedure. In two-third of the cases, there was regeneration of fibula comparable to pre-operative dimensions as early as six months. The non-continuous regeneration had no clinical implications.


Assuntos
Regeneração Óssea/fisiologia , Transplante Ósseo/métodos , Fíbula/fisiopatologia , Fíbula/transplante , Criança , Humanos , Periósteo/fisiopatologia , Estudos Prospectivos , Coleta de Tecidos e Órgãos , Sítio Doador de Transplante
10.
Bone ; 88: 138-145, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27143110

RESUMO

Mechanical signal transduction in bone tissue begins with load-induced activation of several cellular pathways in the osteocyte population. A key pathway that participates in mechanotransduction is Wnt/Lrp5 signaling. A putative downstream mediator of activated Lrp5 is the nucleocytoplasmic shuttling protein ß-catenin (ßcat), which migrates to the nucleus where it functions as a transcriptional co-activator. We investigated whether osteocytic ßcat participates in Wnt/Lrp5-mediated mechanotransduction by conducting ulnar loading experiments in mice with or without chemically induced ßcat deletion in osteocytes. Mice harboring ßcat floxed loss-of-function alleles (ßcat(f/f)) were bred to the inducible osteocyte Cre transgenic (10)(kb)Dmp1-CreERt2. Adult male mice were induced to recombine the ßcat alleles using tamoxifen, and intermittent ulnar loading sessions were applied over the following week. Although adult-onset deletion of ßcat from Dmp1-expressing cells reduced skeletal mass, the bone tissue was responsive to mechanical stimulation as indicated by increased relative periosteal bone formation rates in recombined mice. However, load-induced improvements in cross sectional geometric properties were compromised in recombined mice. The collective results indicate that the osteoanabolic response to loading can occur on the periosteal surface when ß-cat levels are significantly reduced in Dmp1-expressing cells, suggesting that either (i) only low levels of ß-cat are required for mechanically induced bone formation on the periosteal surface, or (ii) other additional downstream mediators of Lrp5 might participate in transducing load-induced Wnt signaling.


Assuntos
Adaptação Fisiológica , Proteínas da Matriz Extracelular/metabolismo , Deleção de Genes , Osteoblastos/metabolismo , Osteócitos/metabolismo , Osteogênese , Periósteo/fisiopatologia , beta Catenina/metabolismo , Absorciometria de Fóton , Alelos , Animais , Animais Recém-Nascidos , Densidade Óssea , Osso Cortical/patologia , Camundongos , Músculos/patologia , Periósteo/patologia , Transgenes , Suporte de Carga
11.
Bone ; 84: 279-288, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26709236

RESUMO

The mammalian skeleton stores calcium and phosphate ions in bone matrix. Osteocytes in osteocyte lacunae extend numerous dendrites into canaliculi less than a micron in diameter and which are distributed throughout bone matrix. Although osteoclasts are the primary bone-resorbing cells, osteocytes also reportedly dissolve hydroxyapatite at peri-lacunar bone matrix. However, robust three-dimensional evidence for peri-canalicular bone mineral dissolution has been lacking. Here we applied a previously reported Talbot-defocus multiscan tomography method for synchrotron X-ray microscopy and analyzed the degree of bone mineralization in mouse cortical bone around the lacuno-canalicular network, which is connected both to blood vessels and the peri- and endosteum. We detected cylindrical low mineral density regions spreading around canaliculi derived from a subset of osteocytes. Transmission electron microscopy revealed both intact and demineralized bone matrix around the canaliculus. Peri-canalicular low mineral density regions were also observed in osteopetrotic mice lacking osteoclasts, indicating that osteoclasts are dispensable for peri-canalicular demineralization. These data suggest demineralization can occur from within bone through the canalicular system, and that peri-canalicular demineralization occurs not uniformly but directed by individual osteocytes. Blockade of peri-canalicular demineralization may be a therapeutic strategy to increase bone mass and quality.


Assuntos
Desmineralização Patológica Óssea/patologia , Osteócitos/patologia , Animais , Desmineralização Patológica Óssea/fisiopatologia , Densidade Óssea/efeitos dos fármacos , Diáfises/efeitos dos fármacos , Diáfises/patologia , Feminino , Humanos , Lactação/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Osteócitos/efeitos dos fármacos , Osteócitos/metabolismo , Osteopetrose/patologia , Osteopetrose/fisiopatologia , Hormônio Paratireóideo/farmacologia , Periósteo/patologia , Periósteo/fisiopatologia , Proteínas Proto-Oncogênicas c-fos/deficiência , Proteínas Proto-Oncogênicas c-fos/metabolismo , Síncrotrons , Tomografia , Raios X
12.
Morfologiia ; 147(2): 69-74, 2015.
Artigo em Russo | MEDLINE | ID: mdl-26234044

RESUMO

Histogenesis of bone tissue was studied in 25 adult mongrel dogs under conditions of automatic shin lengthening by the technique of transosseous distraction osteosynthesis with the daily rate of 3 mm in 120 repeats using the methods of light, scanning electron microscopy, electron probe microanalysis, immunohistochemistry and morphometry. During the distraction period, cellular heteromorphism and proliferative activity of the cells of connective tissue interlayer and periosteum were clearly detected in the interfragmental diastasis. In the post-distraction period, the reduction of cellular heteromorphism and the increase of the biosynthetic activity of the osteoblastic cells were observed while the provisional endosteal bone regenerate of normotrophic type with the signs of organotypic reorganization was formed. Intramembranous osteogenesis was noted at all the stages of the experiment. The organ-specific nature of the newly formed bone occured by 30 days after the apparatus removal. Bone tissue plasticity and the conditions of high-fractional distraction allow to increase the daily rate of leg lengthening up to 3 mm, as well as to provide the formation of weight-bearing bone part during 45 days, thereby reducing by 31% the duration of the period of fixator use for shin lengthening in comparison with that one adopted in classic technique with the daily rate not exceeding 1 mm.


Assuntos
Regeneração Óssea , Proliferação de Células , Osteoblastos , Osteogênese por Distração , Periósteo , Animais , Cães , Osteoblastos/metabolismo , Osteoblastos/patologia , Periósteo/metabolismo , Periósteo/patologia , Periósteo/fisiopatologia
13.
J Bone Miner Res ; 29(9): 2118-29, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24644043

RESUMO

In this cross-sectional study, we investigated volumetric bone mineral density (vBMD), bone microstructure, and biomechanical competence of the distal radius in male patients with rheumatoid arthritis (RA). The study cohort comprised 50 male RA patients of average age of 61.1 years and 50 age-matched healthy males. Areal BMD (aBMD) of the hip, lumbar spine, and distal radius was measured by dual-energy X-ray absorptiometry. High-resolution peripheral quantitative computed tomography (HR-pQCT) of the distal radius provided measures of cortical and trabecular vBMD, microstructure, and biomechanical indices. aBMD of the hip but not the lumbar spine or ultradistal radius was significantly lower in RA patients than controls after adjustment for body weight. Total, cortical, and trabecular vBMD at the distal radius were, on average, -3.9% to -23.2% significantly lower in RA patients, and these differences were not affected by adjustment for body weight, testosterone level, or aBMD at the ultradistal radius. Trabecular microstructure indices were, on average, -8.1% (trabecular number) to 28.7% (trabecular network inhomogeneity) significantly inferior, whereas cortical pore volume and cortical porosity index were, on average, 80.3% and 63.9%, respectively, significantly higher in RA patients. RA patients also had significantly lower whole-bone stiffness, modulus, and failure load, with lower and more unevenly distributed cortical and trabecular stress. Density and microstructure indices significantly correlated with disease activity, severity, and levels of pro-inflammatory cytokines (interleukin [IL] 12p70, tumor necrosis factor, IL-6 and IL-1ß). Ten RA patients had focal periosteal bone apposition most prominent at the ulnovolar aspect of the distal radius. These patients had shorter disease duration and significantly higher cortical porosity. In conclusion, HR-pQCT reveals significant alterations of bone density, microstructure, and strength of the distal radius in male RA patients and provides new insight into the microstructural basis of bone fragility accompanying chronic inflammation.


Assuntos
Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/fisiopatologia , Densidade Óssea , Rádio (Anatomia)/patologia , Rádio (Anatomia)/fisiopatologia , Tomografia Computadorizada por Raios X , Artrite Reumatoide/patologia , Fenômenos Biomecânicos , Estudos de Casos e Controles , Estudos Transversais , Citocinas/metabolismo , Análise de Elementos Finitos , Humanos , Mediadores da Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Periósteo/diagnóstico por imagem , Periósteo/patologia , Periósteo/fisiopatologia , Rádio (Anatomia)/diagnóstico por imagem
14.
Orthop Traumatol Surg Res ; 100(1 Suppl): S139-48, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24394918

RESUMO

Significant changes have occurred recently in fixation methods following fracture or osteotomy in children and teenagers. Children have benefited the most from these advances. A child's growth is anatomically and physiologically ensured by the growth plate and periosteum. The need to keep the periosteum intact during trauma cases has led to the introduction of flexible intramedullary nailing. We will review the basic principles of this safe, universally adopted technique, and also describe available material, length and diameter options. The problems and the limitations of this method will be discussed extensively. In orthopedics, the desire to preserve the periosteum has led to the use of locking compression plates. Because of their low profile and high stability, they allow the micromovements essential for bone union. These new methods reduce the immobilization period and allow autonomy to be regained more quickly, which is especially important in children with neurological impairment. The need to preserve the growth plate, which is well known in pediatric surgery, is reviewed with the goal of summarizing current experimental data on standard fracture and osteotomy fixation methods. Adjustable block stop wires provide better control over compression. These provide an alternate means of fixation between K-wires and screws (now cannulated) and have contributed to the development of minimally invasive surgical techniques. The aim of this lecture is to provide a rationale for the distinct technical features of pediatric surgery, while emphasizing the close relationship between the physiology of growth, bone healing and technical advances.


Assuntos
Fixação de Fratura/métodos , Fraturas Ósseas/cirurgia , Osteotomia/métodos , Adolescente , Desenvolvimento Ósseo/fisiologia , Placas Ósseas , Criança , Fixação Intramedular de Fraturas/métodos , Consolidação da Fratura/fisiologia , Fraturas Ósseas/fisiopatologia , Lâmina de Crescimento/fisiopatologia , Lâmina de Crescimento/cirurgia , Humanos , Periósteo/fisiopatologia , Periósteo/cirurgia
15.
J Craniomaxillofac Surg ; 42(5): 661-7, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24161467

RESUMO

Abnormal elongation of the styloid process, or Eagle syndrome, can be painful, and is associated with differential diagnoses including cranio-facial malformations and vasculo-neurological disturbances. The precise molecular mechanism leading to styloid process elongation is unknown. In this study, elongated styloid processes with periosteal fibrous ligament tissue were obtained from three patients with Eagle syndrome and examined by immunohistochemical methods using different antisera. In all cases, marked bony deposition was found at the apex of the styloid process. The osteogenetic proteins, such as osteonectin, osteocalcin, BMP-2, BMP-4, and RANKL were strongly positive by immunohistochemistry in both the ligament fibers and the periosteal membrane attached to the styloid process apex. Staining for protective proteins, HO-1, HSP-70, and HSP-90 was also positive. These results suggest that styloid process elongation is related to increased expression of osteogenetic and protective proteins. Therefore, we propose that Eagle syndrome results from a protective response to increased tensile stress in the ligament attached to the styloid process, which could also signal osteogenetic protein expression in the periosteal fibrous tissue.


Assuntos
Ossificação Heterotópica/fisiopatologia , Osteogênese/fisiologia , Osso Temporal/anormalidades , Adulto , Fenômenos Biomecânicos , Proteína Morfogenética Óssea 2/análise , Proteína Morfogenética Óssea 4/análise , Proteínas de Choque Térmico HSP70/análise , Proteínas de Choque Térmico HSP90/análise , Heme Oxigenase-1/análise , Humanos , Imuno-Histoquímica , Ligamentos/química , Ligamentos/fisiopatologia , Masculino , Ossificação Heterotópica/metabolismo , Osteocalcina/análise , Osteonectina/análise , Periósteo/química , Periósteo/fisiopatologia , Ligante RANK/análise , Estresse Mecânico , Osso Temporal/química , Osso Temporal/metabolismo , Osso Temporal/fisiopatologia , Adulto Jovem
16.
J Bone Miner Res ; 28(7): 1631-40, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23426919

RESUMO

Osteonecrosis of the jaw (ONJ) is a well-recognized complication of antiresorptive medications, such as bisphosphonates (BPs). Although ONJ is most common after tooth extractions in patients receiving high-dose BPs, many patients do not experience oral trauma. Animal models using tooth extractions and high BP doses recapitulate several clinical, radiographic, and histologic findings of ONJ. We and others have reported on rat models of ONJ using experimental dental disease in the absence of tooth extraction. These models emphasize the importance of dental infection/inflammation for ONJ development. Here, we extend our original report in the rat, and present a mouse model of ONJ in the presence of dental disease. Mice were injected with high dose zoledronic acid and pulpal exposure of mandibular molars was performed to induce periapical disease. After 8 weeks, quantitative and qualitative radiographic and histologic analyses of mouse mandibles were done. Periapical lesions were larger in vehicle-treated versus BP-treated mice. Importantly, radiographic features resembling clinical ONJ, including thickening of the lamina dura, periosteal bone deposition, and increased trabecular density, were seen in the drilled site of BP-treated animals. Histologically, osteonecrosis, periosteal thickening, periosteal bone apposition, epithelial migration, and bone exposure were present in the BP-treated animals in the presence of periapical disease. No difference in tartrate-resistant acid phosphatase (TRAP)+ cell numbers was observed, but round, detached, and removed from the bone surface cells were present in BP-treated animals. Although 88% of the BP-treated animals showed areas of osteonecrosis in the dental disease site, only 33% developed bone exposure, suggesting that osteonecrosis precedes bone exposure. Our data further emphasize the importance of dental disease in ONJ development, provide qualitative and quantitative measures of ONJ, and present a novel mouse ONJ model in the absence of tooth extraction that should be useful in further exploring ONJ pathophysiological mechanisms.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Conservadores da Densidade Óssea/efeitos adversos , Difosfonatos/efeitos adversos , Imidazóis/efeitos adversos , Mandíbula , Dente Molar , Doenças Periapicais , Animais , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/patologia , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/fisiopatologia , Conservadores da Densidade Óssea/farmacologia , Difosfonatos/farmacologia , Modelos Animais de Doenças , Imidazóis/farmacologia , Masculino , Mandíbula/patologia , Mandíbula/fisiopatologia , Camundongos , Dente Molar/patologia , Dente Molar/fisiopatologia , Doenças Periapicais/induzido quimicamente , Doenças Periapicais/patologia , Doenças Periapicais/fisiopatologia , Periósteo/patologia , Periósteo/fisiopatologia , Ratos , Ácido Zoledrônico
17.
J Orthop Res ; 31(5): 800-6, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23280449

RESUMO

To examine bone remodeling following implant placement, 88 female Sprague-Dawley rats underwent either sham ovariectomy (sham-ovx) or ovariectomy (ovx) at 4.5 months. At 11 months, 17 baseline control animals were euthanized, while 71 rats received bilateral intramedullary femoral implants. Implanted rats were randomized to 4-, 8-, or 12-week follow-up times. Microcomputed tomography was used to assess cortical area and trabecular architecture in all rats. Dynamic and static histomorphometry were performed in a subset to examine the trabecular and endocortical bone in the distal femoral metaphysis adjacent to the implant and the periosteal surface at the midshaft superior to the implant (n = 59). Implantation did not affect bone volume in either sham-ovx or ovx rats compared to baseline controls. Implant placement significantly increased mineralizing surface, mineral apposition rate, and bone formation rate in both sham-ovx and ovx rats at the trabecular and endocortical surfaces at four and sometimes 8 weeks, with a return to baseline values by 12 weeks. At the periosteal surface, implant placement increased bone formation at 4 weeks with a return to baseline levels by 8 weeks. Thus, implant placement increases bone remodeling transiently without affecting bone volume in sham-ovx and ovx rats.


Assuntos
Remodelação Óssea/fisiologia , Osseointegração/fisiologia , Osteoporose/fisiopatologia , Osteoporose/cirurgia , Próteses e Implantes , Animais , Modelos Animais de Doenças , Feminino , Fêmur/diagnóstico por imagem , Fêmur/fisiopatologia , Fêmur/cirurgia , Teste de Materiais , Osteoporose/diagnóstico por imagem , Ovariectomia , Periósteo/diagnóstico por imagem , Periósteo/fisiopatologia , Periósteo/cirurgia , Radiografia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
18.
J Biomed Mater Res A ; 101(1): 167-75, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22829533

RESUMO

The purpose of this report was to develop biodegradable balloon-expandable self-locking poly(ε-caprolactone) (PCL) stents for the treatment of retinal detachment. To create the biodegradable stents, polycaprolactone components were first fabricated by a laboratory-scale microinjection molding machine. The components were then assembled into mesh-like stents of 6 and 8 mm in diameter. A special geometry of the components was designed to self-lock the assembled stents after being expanded by balloons. Characterization of the biodegradable PCL stents was carried out. PCL stents exhibited comparable mechanical properties with that of silicone sponge. Neither significant amount of collapse pressure reduction nor weight loss of the stents was observed after being submerged in phosphate buffered saline for 30 days. In addition, the stents were also implanted in the episcleral space of 10 New Zealand white rabbits. The stents were placed in radial direction and left unsutured after balloon expansion. The stents achieved an efficient buckling effect in echographic and fundus photographic examinations. The ocular pressure was significantly elevated after stent implantation and gradually normalized after the second week. The computed tomography studies verified the hypothesis of minimal migration of the PCL stents. The in vivo result suggests that balloon-expandable biodegradable stents can potentially serve as an ideal indenting biomaterial in retinal detachment surgery.


Assuntos
Materiais Biocompatíveis/farmacologia , Implantes Experimentais , Poliésteres/farmacologia , Descolamento Retiniano/terapia , Stents , Animais , Materiais Biocompatíveis/química , Biodegradação Ambiental , Força Compressiva/efeitos dos fármacos , Imageamento Tridimensional , Pressão Intraocular/efeitos dos fármacos , Órbita/diagnóstico por imagem , Órbita/efeitos dos fármacos , Órbita/patologia , Órbita/cirurgia , Periósteo/efeitos dos fármacos , Periósteo/patologia , Periósteo/fisiopatologia , Periósteo/cirurgia , Poliésteres/química , Coelhos , Descolamento Retiniano/diagnóstico por imagem , Descolamento Retiniano/patologia , Descolamento Retiniano/cirurgia , Tomografia Computadorizada por Raios X , Ultrassonografia
19.
J Bone Miner Res ; 28(4): 794-806, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23090909

RESUMO

The purpose of this work was to investigate the volumetric bone mineral density (vBMD), bone microstructure, and mechanical indices of the distal radius in female patients with rheumatoid arthritis (RA). We report a cross-sectional study of 66 middle-aged female RA patients and 66 age-matched healthy females. Areal BMD (aBMD) of the hip, lumbar spine, and distal radius was measured by dual-energy X-ray absorptiometry (DXA). High-resolution peripheral quantitative computed tomography (HR-pQCT) was performed at the distal radius, yielding vBMD, bone microstructure, and mechanical indices. Cortical and trabecular vBMD were 3.5% and 10.7% lower, respectively, in RA patients than controls, despite comparable aBMD. Trabecular microstructural indices were -5.7% to -23.1% inferior, respectively, in RA patients compared to controls, with significant differences in trabecular bone volume fraction, separation, inhomogeneity, and structural model index. Cortical porosity volume and percentage were 128% and 93% higher, respectively, in RA patients, with stress being distributed more unevenly. Fourteen RA patients had exaggerated periosteal bone apposition primarily affecting the ulnovolar aspect of the distal radius. These particular patients were more likely to have chronic and severe disease and coexisting wrist deformity. The majority of the differences in density and microstructure between RA patients and controls did not depend on menstrual status. Recent exposure to glucocorticoids did not significantly affect bone density and microstructure. HR-pQCT provides new insight into inflammation-associated bone fragility in RA. It detects differences in vBMD, bone microstructure, and mechanical indices that are not captured by DXA. At the distal radius, deterioration in density and microstructure in RA patients involved both cortical and trabecular compartments. Excessive bone resorption appears to affect cortical more than trabecular bone at distal radius, particularly manifested as increased cortical porosity. Ulnovolar periosteal apposition of the distal radius is a feature of chronic, severe RA with wrist deformity.


Assuntos
Artrite Reumatoide/patologia , Artrite Reumatoide/fisiopatologia , Rádio (Anatomia)/patologia , Rádio (Anatomia)/fisiopatologia , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/tratamento farmacológico , Fenômenos Biomecânicos/efeitos dos fármacos , Densidade Óssea/efeitos dos fármacos , Estudos de Casos e Controles , Densitometria , Feminino , Glucocorticoides/farmacologia , Glucocorticoides/uso terapêutico , Humanos , Menstruação/efeitos dos fármacos , Pessoa de Meia-Idade , Periósteo/diagnóstico por imagem , Periósteo/patologia , Periósteo/fisiopatologia , Rádio (Anatomia)/diagnóstico por imagem , Rádio (Anatomia)/efeitos dos fármacos , Tomografia Computadorizada por Raios X , Punho/patologia , Punho/fisiopatologia
20.
J Bone Joint Surg Br ; 94(10): 1427-32, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23015573

RESUMO

Periosteum is important for bone homoeostasis through the release of bone morphogenetic proteins (BMPs) and their effect on osteoprogenitor cells. Smoking has an adverse effect on fracture healing and bone regeneration. The aim of this study was to evaluate the effect of smoking on the expression of the BMPs of human periosteum. Real-time polymerase chain reaction was performed for BMP-2,-4,-6,-7 gene expression in periosteal samples obtained from 45 fractured bones (19 smokers, 26 non-smokers) and 60 non-fractured bones (21 smokers, 39 non-smokers). A hierarchical model of BMP gene expression (BMP-2 > BMP-6 > BMP-4 > BMP-7) was demonstrated in all samples. When smokers and non-smokers were compared, a remarkable reduction in the gene expression of BMP-2, -4 and -6 was noticed in smokers. The comparison of fracture and non-fracture groups demonstrated a higher gene expression of BMP-2, -4 and -7 in the non-fracture samples. Within the subgroups (fracture and non-fracture), BMP gene expression in smokers was either lower but without statistical significance in the majority of BMPs, or similar to that in non-smokers with regard to BMP-4 in fracture and BMP-7 in non-fracture samples. In smokers, BMP gene expression of human periosteum was reduced, demonstrating the effect of smoking at the molecular level by reduction of mRNA transcription of periosteal BMPs. Among the BMPs studied, BMP-2 gene expression was significantly higher, highlighting its role in bone homoeostasis.


Assuntos
Proteínas Morfogenéticas Ósseas/biossíntese , Fraturas Ósseas/genética , Periósteo/metabolismo , Fumar/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas Morfogenéticas Ósseas/genética , Feminino , Fraturas Ósseas/metabolismo , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Periósteo/fisiopatologia , RNA Mensageiro/biossíntese , Adulto Jovem
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