Base de dados : MEDLINE
Pesquisa : A10.165.265.521 [Categoria DeCS]
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[PMID]:29179049
[Au] Autor:Michael AR
[Ad] Endereço:Idaho State University, Department of Anthropology, 921S. 8th Avenue, Stop 8005, Pocatello, ID 83209, USA. Electronic address: michamy@isu.edu.
[Ti] Título:Histological estimation of age at death in amputated lower limbs: Issues of disuse, advanced age, and disease in the analysis of pathological bone.
[So] Source:J Forensic Leg Med;53:58-61, 2018 Jan.
[Is] ISSN:1878-7487
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Histological studies of healed bone tissue following amputation are relatively rare in the literature. This study describes the histomorphological features of femoral thin sections from six uni- and bi-lateral amputees of documented age and sex. Thin sections were cut from the midshaft of both the right and left femora from each amputee and analyzed following standard forensic methods for histological estimation of age at death from the human femur. The histological age at death estimations for the thin sections from amputated bone were consistently lower than the actual chronological age of each individual, suggesting that the effects of amputation prohibit the effective use of age at death estimation methods. The nature of each amputation is unknown, which suggests that alternative factors could be responsible for the slowed bone turnover seen in the thin sections from the amputated bone. First, it is reasonable to assume that the amputations in this sample could have resulted from complications of diabetes mellitus rather than trauma so the possible effects on bone remodeling due to disease are explored. Second, the mobility of the decedents following their amputations is unknown so the histomorphological results could be due to disuse osteoporosis.
[Mh] Termos MeSH primário: Amputação
Amputados
Fêmur/patologia
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Reabsorção Óssea
Osso Cortical/patologia
Feminino
Patologia Legal
Osteon/patologia
Seres Humanos
Masculino
Porosidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE


  2 / 169 MEDLINE  
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[PMID]:28463314
[Au] Autor:Tavera R CG; De la Torre-I MH; Flores-M JM; Hernandez M MDS; Mendoza-Santoyo F; Briones-R MJ; Sanchez-P J
[Ti] Título:Surface structural damage study in cortical bone due to medical drilling.
[So] Source:Appl Opt;56(13):F179-F188, 2017 May 01.
[Is] ISSN:1539-4522
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A bone's fracture could be produced by an excessive, repetitive, or sudden load. A regular medical practice to heal it is to fix it in two possible ways: external immobilization, using a ferule, or an internal fixation, using a prosthetic device commonly attached to the bone by means of surgical screws. The bone's volume loss due to this drilling modifies its structure either in the presence or absence of a fracture. To observe the bone's surface behavior caused by the drilling effects, a digital holographic interferometer is used to analyze the displacement surface's variations in nonfractured post-mortem porcine femoral bones. Several nondrilled post-mortem bones are compressed and compared to a set of post-mortem bones with a different number of cortical drillings. During each compression test, a series of digital interferometric holograms were recorded using a high-speed CMOS camera. The results are presented as pseudo 3D mesh displacement maps for comparisons in the physiological range of load (30 and 50 lbs) and beyond (100, 200, and 400 lbs). The high resolution of the optical phase gives a better understanding about the bone's microstructural modifications. Finally, a relationship between compression load and bone volume loss due to the drilling was observed. The results prove that digital holographic interferometry is a viable technique to study the conditions that avoid the surgical screw from loosening in medical procedures of this kind.
[Mh] Termos MeSH primário: Parafusos Ósseos/efeitos adversos
Osso Cortical/lesões
Fêmur/lesões
Holografia/instrumentação
Imagem Tridimensional/métodos
[Mh] Termos MeSH secundário: Animais
Osso Cortical/química
Consolidação da Fratura/fisiologia
Interferometria
Suínos
Suporte de Carga
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180206
[Lr] Data última revisão:
180206
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.1364/AO.56.00F179


  3 / 169 MEDLINE  
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[PMID]:28464615
[Au] Autor:Nygren H; Bigdeli N; Ilver L; Malmberg P
[Ad] Endereço:Department of Medical Chemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, POB 440, 40530 Gothenburg, Sweden.
[Ti] Título:Mg-corrosion, hydroxyapatite, and bone healing.
[So] Source:Biointerphases;12(2):02C407, 2017 05 02.
[Is] ISSN:1559-4106
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The different capacities of magnesium in the metallic form (Mg-metal) and magnesium oxide (MgO) to stimulate bone healing are possible clues in the search for products that may promote bone healing. Since both Mg-metal and MgO can be assumed to release comparable amounts of Mg ions during their reactions in the tissue where they have been implanted, it is of some importance to follow this process and analyze the resulting mineral formation in the tissue at the implantation site. Implants of MgO were inserted into rat tibia, and the bone healing was compared with sham-operated controls. Samples were taken after 1 week of healing and analyzed by histology, environmental scanning electron microscopy equipped with an energy dispersive x-ray spectroscopy analyzer, and time-of-flight secondary ion mass spectrometry (ToF-SIMS). Callus bone was seen in sham-operated controls after 1 week of healing. Implantation of MgO impaired the callus bone formation by replacing bone with apparently mineralized areas, lacking osteocytes and were denoted, amorphous bodies. Elemental analysis showed increased levels of Ca (7.1%), P (3.7%), and Mg (0.2%) in the bone marrow of MgO-treated animals versus sham-operated controls Ca (2.4%), P (2.3%), and Mg (0.1%). The Ca content of the cortical bone was also significantly increased (Ca, 29% increase) in MgO-treated animals compared to sham-operated controls. The Ca content of the cortical bone of sham-operated animals was also significantly (p < 0.05) higher than the corresponding value of untreated animals, which means that the surgical trauma induces an altered composition of the bone mineral. The Ca/P ratio was 1.26-1.68, which is compatible with that of mineralized bone with different contents of organic materials. Analysis of bone sections using ToF-SIMS showed the presence of hydroxyapatite (HA) and MgCO in the bone marrow and in cortical bone. Analysis using x-ray photoelectron spectroscopy of Mg, MgO, and MgCO after incubation with cell culture medium (DMEM), in vitro, showed binding of CaPO at the Mg and MgO samples. The Ca/P ratio was 0.8, indicating a higher P content than that expected for HA. Exposure of human embryonic stem cells to Mg species preincubated in DMEM resulted in HA production by the cells. Thus, two sources of CaPO in the bone marrow of MgO-treated bone were defined, catalytic formation on Mg-species and synthesis from activated stem-cells. The presented data suggest that bone healing near Mg implants is congruent with the fracture healing of bone, boosted by high HA levels in the bone marrow. In this context, the different capacities of Mg-metal and MgO to catalyse the formation of HA can be important clues to their different bone promoting effects.
[Mh] Termos MeSH primário: Calo Ósseo/metabolismo
Osso Cortical/lesões
Osso Cortical/metabolismo
Durapatita/farmacologia
Consolidação da Fratura/efeitos dos fármacos
Óxido de Magnésio/farmacologia
[Mh] Termos MeSH secundário: Animais
Calo Ósseo/patologia
Linhagem Celular
Corrosão
Osso Cortical/patologia
Células-Tronco Embrionárias Humanas
Seres Humanos
Magnésio/farmacologia
Masculino
Teste de Materiais
Ratos
Ratos Sprague-Dawley
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
3A3U0GI71G (Magnesium Oxide); 91D9GV0Z28 (Durapatite); I38ZP9992A (Magnesium)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180201
[Lr] Data última revisão:
180201
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE
[do] DOI:10.1116/1.4982601


  4 / 169 MEDLINE  
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[PMID]:27777119
[Au] Autor:Poole KES; Skingle L; Gee AH; Turmezei TD; Johannesdottir F; Blesic K; Rose C; Vindlacheruvu M; Donell S; Vaculik J; Dungl P; Horak M; Stepan JJ; Reeve J; Treece GM
[Ad] Endereço:Department of Medicine, University of Cambridge and Addenbrooke's Hospital, Hills Road, Cambridge, UK. Electronic address: Kenneth.poole@nhs.net.
[Ti] Título:Focal osteoporosis defects play a key role in hip fracture.
[So] Source:Bone;94:124-134, 2017 01.
[Is] ISSN:1873-2763
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Hip fractures are mainly caused by accidental falls and trips, which magnify forces in well-defined areas of the proximal femur. Unfortunately, the same areas are at risk of rapid bone loss with ageing, since they are relatively stress-shielded during walking and sitting. Focal osteoporosis in those areas may contribute to fracture, and targeted 3D measurements might enhance hip fracture prediction. In the FEMCO case-control clinical study, Cortical Bone Mapping (CBM) was applied to clinical computed tomography (CT) scans to define 3D cortical and trabecular bone defects in patients with acute hip fracture compared to controls. Direct measurements of trabecular bone volume were then made in biopsies of target regions removed at operation. METHODS: The sample consisted of CT scans from 313 female and 40 male volunteers (158 with proximal femoral fracture, 145 age-matched controls and 50 fallers without hip fracture). Detailed Cortical Bone Maps (c.5580 measurement points on the unfractured hip) were created before registering each hip to an average femur shape to facilitate statistical parametric mapping (SPM). Areas where cortical and trabecular bone differed from controls were visualised in 3D for location, magnitude and statistical significance. Measures from the novel regions created by the SPM process were then tested for their ability to classify fracture versus control by comparison with traditional CT measures of areal Bone Mineral Density (aBMD). In women we used the surgical classification of fracture location ('femoral neck' or 'trochanteric') to discover whether focal osteoporosis was specific to fracture type. To explore whether the focal areas were osteoporotic by histological criteria, we used micro CT to measure trabecular bone parameters in targeted biopsies taken from the femoral heads of 14 cases. RESULTS: Hip fracture patients had distinct patterns of focal osteoporosis that determined fracture type, and CBM measures classified fracture type better than aBMD parameters. CBM measures however improved only minimally on aBMD for predicting any hip fracture and depended on the inclusion of trabecular bone measures alongside cortical regions. Focal osteoporosis was confirmed on biopsy as reduced sub-cortical trabecular bone volume. CONCLUSION: Using 3D imaging methods and targeted bone biopsy, we discovered focal osteoporosis affecting trabecular and cortical bone of the proximal femur, among men and women with hip fracture.
[Mh] Termos MeSH primário: Fraturas do Quadril/etiologia
Osteoporose/complicações
[Mh] Termos MeSH secundário: Idoso
Área Sob a Curva
Biópsia
Osso Cortical/patologia
Feminino
Colo do Fêmur/patologia
Fraturas do Quadril/patologia
Seres Humanos
Masculino
Razão de Chances
Osteoporose/patologia
Curva ROC
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171223
[Lr] Data última revisão:
171223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161107
[St] Status:MEDLINE


  5 / 169 MEDLINE  
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[PMID]:28977604
[Au] Autor:Bornstein S; Moschetta M; Kawano Y; Sacco A; Huynh D; Brooks D; Manier S; Fairfield H; Falank C; Roccaro AM; Nagano K; Baron R; Bouxein M; Vary C; Ghobrial IM; Rosen CJ; Reagan MR
[Ad] Endereço:Maine Medical Center Research Institute, Scarborough, Maine 04074.
[Ti] Título:Metformin Affects Cortical Bone Mass and Marrow Adiposity in Diet-Induced Obesity in Male Mice.
[So] Source:Endocrinology;158(10):3369-3385, 2017 Oct 01.
[Is] ISSN:1945-7170
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Obesity during maturation can affect the growing skeleton directly and indirectly, although these effects and the mechanisms behind them are not fully understood. Our objective was to determine how a high-fat diet with or without metformin treatment affects skeletal development. We also sought to characterize changes that occur in white adipose tissue, circulating metabolites, lipids, and gut microbiota. A diet-induced obesity C57BL/6J mouse model was used to test the effects of obesity and metformin on bone using bone histomorphometry and microcomputed tomography. Bone marrow adipose tissue was quantified with osmium tetroxide microcomputed tomography and histology. Dual-energy x-ray absorptiometry was used to analyze body composition. Hematoxylin and eosin staining was used to assess changes in white adipose depots, mass spectrometry was used for circulating lipids and protein metabolite analysis, and ribosomal RNA sequencing was used for gut microbiome analysis. Mice fed a high fat-diet since wean displayed increased medullary areas and decreased osteoblast numbers in the long bones; this phenotype was partially normalized by metformin. Marrow and inguinal adipose expansion was also noted in obese mice, and this was partially normalized by metformin. A drug-by-diet interaction was noted for circulating lipid molecules, protein metabolites, and gut microbiome taxonomical units. Obesity was not detrimental to trabecular bone in growing mice, but bone marrow medullary expansion was observed, likely resulting from inhibition of osteoblastogenesis, and this was partially reversed by metformin treatment.
[Mh] Termos MeSH primário: Adiposidade/efeitos dos fármacos
Medula Óssea/efeitos dos fármacos
Osso Cortical/efeitos dos fármacos
Metformina/farmacologia
Obesidade
[Mh] Termos MeSH secundário: Absorciometria de Fóton
Tecido Adiposo Branco/efeitos dos fármacos
Animais
Composição Corporal
Contagem de Células
Cromatografia Líquida
Osso Cortical/patologia
Dieta Hiperlipídica
Microbioma Gastrointestinal/efeitos dos fármacos
Microbioma Gastrointestinal/genética
Imuno-Histoquímica
Metabolismo dos Lipídeos/efeitos dos fármacos
Masculino
Espectrometria de Massas
Metabolômica
Camundongos
Camundongos Endogâmicos C57BL
Tamanho do Órgão
Osteoblastos/efeitos dos fármacos
Fenótipo
RNA Bacteriano/genética
RNA Ribossômico 16S/genética
Espectrometria de Massas em Tandem
Microtomografia por Raio-X
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Bacterial); 0 (RNA, Ribosomal, 16S); 9100L32L2N (Metformin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171115
[Lr] Data última revisão:
171115
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171005
[St] Status:MEDLINE
[do] DOI:10.1210/en.2017-00299


  6 / 169 MEDLINE  
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[PMID]:28880868
[Au] Autor:Vogl F; Bernet B; Bolognesi D; Taylor WR
[Ad] Endereço:Institute for Biomechanics, ETH Zurich, Zurich, Switzerland.
[Ti] Título:Towards assessing cortical bone porosity using low-frequency quantitative acoustics: A phantom-based study.
[So] Source:PLoS One;12(9):e0182617, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Cortical porosity is a key characteristic governing the structural properties and mechanical behaviour of bone, and its quantification is therefore critical for understanding and monitoring the development of various bone pathologies such as osteoporosis. Axial transmission quantitative acoustics has shown to be a promising technique for assessing bone health in a fast, non-invasive, and radiation-free manner. One major hurdle in bringing this approach to clinical application is the entanglement of the effects of individual characteristics (e.g. geometry, porosity, anisotropy etc.) on the measured wave propagation. In order to address this entanglement problem, we therefore propose a systematic bottom-up approach, in which only one bone property is varied, before addressing interaction effects. This work therefore investigated the sensitivity of low-frequency quantitative acoustics to changes in porosity as well as individual pore characteristics using specifically designed cortical bone phantoms. MATERIALS AND METHODS: 14 bone phantoms were designed with varying pore size, axial-, and radial pore number, resulting in porosities (bone volume fraction) between 0% and 15%, similar to porosity values found in human cortical bone. All phantoms were manufactured using laser sintering, measured using axial-transmission acoustics and analysed using a full-wave approach. Experimental results were compared to theoretical predictions based on a modified Timoshenko theory. RESULTS: A clear dependence of phase velocity on frequency and porosity produced by increasing pore size or radial pore number was demonstrated, with the velocity decreasing by between 2-5 m/s per percent of additional porosity, which corresponds to -0.5% to -1.0% of wave speed. While the change in phase velocity due to axial pore number was consistent with the results due to pore size and radial pore number, the relative uncertainties for the estimates were too high to draw any conclusions for this parameter. CONCLUSIONS: This work has shown the capability of low-frequency quantitative acoustics to reflect changes in porosity and individual pore characteristics and demonstrated that additive manufacturing is an appropriate method that allows the influence of individual bone properties on the wave propagation to be systematically assessed. The results of this work opens perspectives for the efficient development of a multi-frequency, multi-mode approach to screen, diagnose, and monitor bone pathologies in individuals.
[Mh] Termos MeSH primário: Acústica
Osso Cortical/diagnóstico por imagem
Osso Cortical/metabolismo
Imagens de Fantasmas
[Mh] Termos MeSH secundário: Anisotropia
Simulação por Computador
Seres Humanos
Modelos Teóricos
Porosidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170908
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0182617


  7 / 169 MEDLINE  
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[PMID]:28863910
[Au] Autor:Nguyen MV; Codrington J; Fletcher L; Dreyer CW; Sampson WJ
[Ad] Endereço:Department of Orthodontics, University of Adelaide, Adelaide, South Australia, Australia. Electronic address: drmvnguyen@gmail.com.
[Ti] Título:Influence of cortical bone thickness on miniscrew microcrack formation.
[So] Source:Am J Orthod Dentofacial Orthop;152(3):301-311, 2017 Sep.
[Is] ISSN:1097-6752
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: The aim of this in-vitro study was to investigate the influence of cortical bone thickness on the amount of surface microdamage produced after insertion of orthodontic miniscrews (OM) in porcine tibia bone. METHODS: Aarhus OMs (Medicon, Tuttlingen, Germany; diameter, 1.5 mm; length, 6 mm) were inserted into 1.0 mm (group A; n = 10), 1.5 mm (group B; n = 10), and 2.0 mm (group C; n = 10) of porcine cortical bone using a torque-limiting hand screwdriver set at 18 Ncm. A sequential staining technique was used to identify microdamage under laser confocal microscopy. Virtual slices were stitched together using ImageJ software (National Institutes of Health, Bethesda, Md) to form a compressed 2-dimensional composition of the microdamage. The ImageJ software was used to quantify the total damage area, diffuse damage area, maximum crack length, maximum damage radius, and maximum diffuse damage radius. Kruskal-Wallis tests and Wilcoxon rank sum tests were used to analyze the data. RESULTS: All OMs in group A (1.0 mm) were inserted completely; however, 2 OMs from group B (1.5 mm) and all OMs in group C (2.0 mm) failed to insert completely. The entry surface of group C (2.0 mm) exhibited significantly higher amounts of total damage, diffuse damage area, maximum crack length, and maximum crack damage radius compared with groups A (1.0 mm) and B (1.5 mm). The maximum crack length observed on the entry and exit surfaces ranged from 1.03 to 3.06 mm. CONCLUSIONS: In this study, we demonstrated a higher level of microdamage after the insertion of OMs into 2.0-mm thick cortical bone compared with 1.0-mm thick cortical bone. Therefore, clinicians need to consider the thickness of the cortical bone at the insertion site, because mechanisms to reduce cortical bone thickness would likely reduce the amount of microdamage formed. A safety zone of 3.5 mm from the OM is also recommended for OMs inserted into 1.0- and 1.5-mm cortical bone thicknesses to minimize any detrimental effects after targeted remodeling.
[Mh] Termos MeSH primário: Parafusos Ósseos/efeitos adversos
Osso Cortical/lesões
Tíbia/lesões
[Mh] Termos MeSH secundário: Animais
Remodelação Óssea
Osso Cortical/ultraestrutura
Microscopia Confocal
Suínos
Tíbia/ultraestrutura
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170915
[Lr] Data última revisão:
170915
[Sb] Subgrupo de revista:D; IM
[Da] Data de entrada para processamento:170903
[St] Status:MEDLINE


  8 / 169 MEDLINE  
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[PMID]:28832945
[Au] Autor:Andronowski JM; Pratt IV; Cooper DML
[Ad] Endereço:Department of Biology, University of Akron, Akron, Ohio 44325-3908.
[Ti] Título:Occurrence of osteon banding in adult human cortical bone.
[So] Source:Am J Phys Anthropol;164(3):635-642, 2017 Nov.
[Is] ISSN:1096-8644
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: Differentiating human from nonhuman fragmented bone is often accomplished using histological methods if the observation of gross morphology proves insufficient. Linearly oriented primary and/or secondary osteonal systems, commonly referred to as osteon bands, are described as a strong indicator of nonhuman bone, particularly the occurrence of multiple bands. This phenomenon has been conventionally documented using two-dimensional (2D) histology, but such analyses are destructive and typically limited to a single cross-section. Progressive developments in high-resolution X-ray imaging, however, allow for the nondestructive three-dimensional (3D) visualization of bone microarchitecture. The primary objective of the current research was to visualize and document the occurrence of osteon banding in adult human cortical bone using high-resolution synchrotron radiation-based micro-Computed Tomography (SR micro-CT). MATERIALS AND METHODS: Synchrotron radiation-based micro-CT scanning was carried out at the Canadian Light Source (CLS) national synchrotron facility. The presence or absence of osteon banding was visualized in human skeletal elements from three adult males with representative samples from all regions of the skeleton (n = 129). If present, osteon banding was described and quantified. RESULTS: Results indicated that 23 of 129 human cortical bone specimens exhibited osteon banding, representing 18% of the sample. Linear arrangements of primary and/or secondary osteons were observed in the following skeletal elements: temporal, parietal, frontal, occipital, clavicle, mandible, femur, tibia, ulna, second metatarsal, and sacrum. DISCUSSION: The present work represents the first 3D examination of inter-element variation in osteon banding in adult human cortical bone. Findings indicate that the presence of multiple osteon bands in a single specimen is not diagnostic of nonhuman bone. As such, osteon banding categorically should not be taken as evidence of nonhuman bone in forensic and archaeological contexts.
[Mh] Termos MeSH primário: Osso Cortical/anatomia & histologia
Osteon/anatomia & histologia
[Mh] Termos MeSH secundário: Adulto
Antropologia Física
Osso Cortical/diagnóstico por imagem
Osteon/diagnóstico por imagem
Seres Humanos
Masculino
Microtomografia por Raio-X
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170824
[St] Status:MEDLINE
[do] DOI:10.1002/ajpa.23297


  9 / 169 MEDLINE  
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[PMID]:28825716
[Au] Autor:Farr JN; Xu M; Weivoda MM; Monroe DG; Fraser DG; Onken JL; Negley BA; Sfeir JG; Ogrodnik MB; Hachfeld CM; LeBrasseur NK; Drake MT; Pignolo RJ; Pirtskhalava T; Tchkonia T; Oursler MJ; Kirkland JL; Khosla S
[Ad] Endereço:Robert and Arlene Kogod Center on Aging and Division of Endocrinology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
[Ti] Título:Targeting cellular senescence prevents age-related bone loss in mice.
[So] Source:Nat Med;23(9):1072-1079, 2017 Sep.
[Is] ISSN:1546-170X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Aging is associated with increased cellular senescence, which is hypothesized to drive the eventual development of multiple comorbidities. Here we investigate a role for senescent cells in age-related bone loss through multiple approaches. In particular, we used either genetic (i.e., the INK-ATTAC 'suicide' transgene encoding an inducible caspase 8 expressed specifically in senescent cells) or pharmacological (i.e., 'senolytic' compounds) means to eliminate senescent cells. We also inhibited the production of the proinflammatory secretome of senescent cells using a JAK inhibitor (JAKi). In aged (20- to 22-month-old) mice with established bone loss, activation of the INK-ATTAC caspase 8 in senescent cells or treatment with senolytics or the JAKi for 2-4 months resulted in higher bone mass and strength and better bone microarchitecture than in vehicle-treated mice. The beneficial effects of targeting senescent cells were due to lower bone resorption with either maintained (trabecular) or higher (cortical) bone formation as compared to vehicle-treated mice. In vitro studies demonstrated that senescent-cell conditioned medium impaired osteoblast mineralization and enhanced osteoclast-progenitor survival, leading to increased osteoclastogenesis. Collectively, these data establish a causal role for senescent cells in bone loss with aging, and demonstrate that targeting these cells has both anti-resorptive and anabolic effects on bone. Given that eliminating senescent cells and/or inhibiting their proinflammatory secretome also improves cardiovascular function, enhances insulin sensitivity, and reduces frailty, targeting this fundamental mechanism to prevent age-related bone loss suggests a novel treatment strategy not only for osteoporosis, but also for multiple age-related comorbidities.
[Mh] Termos MeSH primário: Osso e Ossos/efeitos dos fármacos
Senescência Celular/efeitos dos fármacos
Janus Quinases/antagonistas & inibidores
Osteoblastos/efeitos dos fármacos
Osteoclastos/efeitos dos fármacos
Osteócitos/efeitos dos fármacos
Osteoporose/metabolismo
Pirazóis/farmacologia
[Mh] Termos MeSH secundário: Absorciometria de Fóton
Animais
Apoptose/genética
Osso e Ossos/metabolismo
Osso Esponjoso/efeitos dos fármacos
Osso Esponjoso/metabolismo
Caspase 8/genética
Diferenciação Celular
Senescência Celular/genética
Osso Cortical/efeitos dos fármacos
Osso Cortical/metabolismo
Meios de Cultivo Condicionados
Citometria de Fluxo
Perfilação da Expressão Gênica
Técnicas In Vitro
Camundongos
Camundongos Transgênicos
Osteoblastos/citologia
Osteoclastos/citologia
Osteoporose/genética
Reação em Cadeia da Polimerase em Tempo Real
Suporte de Carga
beta-Galactosidase
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Culture Media, Conditioned); 0 (INCB018424); 0 (Pyrazoles); EC 2.7.10.2 (Janus Kinases); EC 3.2.1.23 (beta-Galactosidase); EC 3.4.22.- (Casp8 protein, mouse); EC 3.4.22.- (Caspase 8)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170822
[St] Status:MEDLINE
[do] DOI:10.1038/nm.4385


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[PMID]:28797125
[Au] Autor:Hemmatian H; Laurent MR; Ghazanfari S; Vanderschueren D; Bakker AD; Klein-Nulend J; van Lenthe GH
[Ad] Endereço:Biomechanics Section, Department of Mechanical Engineering, KU Leuven, Leuven, Belgium.
[Ti] Título:Accuracy and reproducibility of mouse cortical bone microporosity as quantified by desktop microcomputed tomography.
[So] Source:PLoS One;12(8):e0182996, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Bone's microporosity plays important roles in bone biology and bone mechanical quality. In this study, we explored the accuracy and reproducibility of nondestructive desktop µCT for 3D visualization and subsequent morphometric analysis of mouse cortical bone microporosity including the vascular canal network and osteocyte lacunae. The accuracy of measurements was evaluated in five murine fibula using confocal laser scanning microscopy (CLSM) in conjunction with Fluorescein isothiocyanate (FITC) staining as the reference method. The reproducibility of µCT-derived cortical bone microstructural indices was examined in 10 fibulae of C57Bl/6J male mice at a nominal resolution of 700 nanometer. Three repeated measurements were made on different days. An excellent correlation between µCT and CLSM was observed for both mean lacuna volume (r = 0.98, p = 0.002) and for mean lacuna orientation (r = 0.93, p = 0.02). Whereas the two techniques showed no significant differences for these parameters, the mean lacuna sphericity acquired from µCT was significantly higher than CLSM (p = 0.01). Reproducibility was high, with precision errors (PE) of 1.57-4.69% for lacuna parameters, and of 1.01-9.45% for vascular canal parameters. Intraclass correlation coefficient (ICC) showed a high reliability of the measurements, ranging from 0.998-1.000 for cortical parameters, 0.973-0.999 for vascular canal parameters and 0.755-0.991 for lacuna parameters. In conclusion, desktop µCT is a valuable tool to quantify the 3D characteristics of bone vascular canals as well as lacunae which can be applied to intact murine bones with high accuracy and reproducibility. Thus, µCT might be an important tool to improve our understanding of the physiological and biomechanical significance of these cannular and lacunar structure in cortical bone.
[Mh] Termos MeSH primário: Osso Cortical/diagnóstico por imagem
[Mh] Termos MeSH secundário: Algoritmos
Animais
Densidade Óssea
Feminino
Imagem Tridimensional/métodos
Masculino
Camundongos Endogâmicos C57BL
Microscopia Confocal/métodos
Reprodutibilidade dos Testes
Microtomografia por Raio-X/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171004
[Lr] Data última revisão:
171004
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170811
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0182996



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