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Sample records for human trabecular meshwork

  1. Aberrant Glycosylation in the Human Trabecular Meshwork

    PubMed Central

    Sienkiewicz, Adam E.; Rosenberg, Brandon N.; Edwards, Genea; Carreon, Teresia A.; Bhattacharya, Sanjoy K.

    2014-01-01

    Purpose To determine the difference in protein glycosylation and glycosylation enzyme levels between glaucomatous and control trabecular meshwork (TM). Experimental design Glaucomatous and normal donor (n=12 each) TM tissues, Lectin-fluorescence, fluorophore assisted carbohydrate analyses, and quantitative mass spectrometry were used to determine the glycosylation levels. Primary TM cells and glycosylation inhibitors were used to determine their effect on cell shape and motility. Results In contrast to elevated levels of glycoproteins determined by lectin-fluorescence, simultaneous hyper and hypo-glycosylation in glaucomatous trabecular meshwork was revealed by fluorophore assisted carbohydrate analyses. Analyses of enzymes showed elevation of Beta-glycosidase 1 and decrease in Galactosyltransferase family 6 domain containing protein 1 in the glaucomatous trabecular meshwork. Quantitative mass spectrometry identified select protein level changes between glaucomatous and normal trabecular meshwork. Primary trabecular meshwork cells were treated with inhibitors to elicit hypo-glycosylation, which affected cell shape, motility, and fluorescent tracer transport across a layer of trabecular meshwork cells. Conclusions and clinical relevance Global protein glycosylation is aberrant in glaucomatous trabecular meshwork compared to controls. The results presented here suggest that the alteration in global TM protein glycosylation encompassing cellular and extracellular matrix proteins contributes to glaucoma pathology likely mediated through changes in properties of TM cells. PMID:24458570

  2. Effects of elastase on cultured human trabecular meshwork.

    PubMed

    Hoya, T

    1992-01-01

    We evaluated the effect of elastase, a proteolytic enzyme, on the endothelial meshwork of cultured human trabecular meshwork using a solid agar method. The tissues were obtained from 3 postmortem eyes, aged 64, 71 and 77 years. Elastase was added to the culture medium for 24 h at a concentration of 1 x 10(-1)-10(-4) mg/ml. The cultured specimens were then processed for transmission electron microscopy. We evaluated the electron micrographs to determine the percent area occupied by the cells and the extracellular materials and by the empty space in the endothelial meshwork using computer-assisted morphometry. A statistically significant decrease in extracellular materials with intact trabecular cells was confirmed 24 h following the administration of elastase at the concentration of 1 x 10(-1)-10(-3) mg/ml. PMID:1630765

  3. Isolation and culture of human trabecular meshwork cells by extracellular matrix digestion.

    PubMed

    Stamer, W D; Seftor, R E; Williams, S K; Samaha, H A; Snyder, R W

    1995-07-01

    Like corneal endothelial cells, human trabecular meshwork cells are believed to be of neural crest origin, but demonstrate physiological properties and an antithrombogenic surface similar to vascular endothelial cells. One current method for isolating trabecular meshwork cells utilizes the motile nature of these cells to migrate away from a trabecular meshwork explant in culture to more distal regions of the culture dish. This 'outgrowth' technique is limited in practice by the relatively small number of cells that migrate per explant per unit time, thus hindering the ability to gather sufficient numbers of cells for comprehensive experimentation. For this reason, we have modified an extracellular matrix digestion technique in current use for the isolation of microvascular endothelial cells to isolate human trabecular meshwork cells. This procedure is both efficient and rapid for isolating large numbers of trabecular meshwork cells and results in the availability of trabecular meshwork cells in sufficient quantities for subsequent experimentation. PMID:7587308

  4. Dexamethasone induced ultrastructural changes in cultured human trabecular meshwork cells.

    PubMed

    Wilson, K; McCartney, M D; Miggans, S T; Clark, A F

    1993-09-01

    Glucocorticoid-induced ocular hypertension has been demonstrated in both animals and humans. It is possible that glucocorticoid-induced changes in trabecular meshwork (TM) cells are responsible for this hypertension. In order to elaborate further the effect of glucocorticoids on the trabecular meshwork, the ultrastructural consequences of dexamethasone (DEX) treatment were examined in three different human TM cell lines. Confluent TM cells were treated with 0.1 microM of DEX for 14 days, and then processed for light, epifluorescent microscopy or transmission electron microscopy (TEM). The effect of DEX treatment on TM cell and nuclear size was quantified using computer assisted morphometrics. Morphometric analysis showed a significant increase in both TM cell and nuclear size after 14 days of DEX treatment. Epifluorescent microscopy of rhodamine-phalloidin stained, control TM cells showed the normal arrangement of stress fibers. In contrast, DEX-treated TM cells showed unusual geodesic dome-like cross-linked actin networks. Control TM cells had the normal complement and arrangement of organelles as well as electron dense inclusions and large vacuoles. DEX-treated TM cells showed stacked arrangements of smooth and rough endoplasmic reticulum, proliferation of the Golgi apparatus, pleomorphic nuclei and increased amounts of extracellular matrix material. The DEX-induced alterations observed in the present study may be an indication of the processes that are occurring in the in vivo disease process. PMID:8261790

  5. Constitutive secretion of chemokines by cultured human trabecular meshwork cells.

    PubMed

    Shifera, Amde Selassie; Trivedi, Sheetal; Chau, Phuonglan; Bonnemaison, Lucia H; Iguchi, Rumiko; Alvarado, Jorge A

    2010-07-01

    Trabecular meshwork endothelial (TME) cells secrete a number of factors, such as enzymes and cytokines, which modulate the functions of the cells and the extracellular matrix of the conventional aqueous outflow pathway. TME cells usually secrete these factors in response to stimuli such as mechanical stretching, laser irradiation and pro-inflammatory cytokines. Here, we report that cultured human TME cells isolated from two non-glaucomatous individuals secrete significant quantities of the chemotactic cytokines IL8, CXCL6 and MCP1 in the absence of any stimulation. The secretion of these chemokines was augmented by treatment with the pro-inflammatory cytokines TNFalpha and IL1beta. By way of comparison, there was little or very low production of the three chemokines by human non-pigmented ciliary epithelial cells in the absence of stimulation. Our findings provide support to our recent observations that monocytes, presumably under the influence of chemotactic signals, circulate through the trabecular meshwork in the normal state and also that cytokines regulate the permeability of Schlemm's canal endothelial cells. In addition, the fact that normal TME cells constitutively secrete chemotactic cytokines strengthens the notion that cytokines play a key role in the homeostasis of the outflow of the aqueous humor and, possibly, in the pathogenesis of glaucoma. PMID:20403352

  6. Oxidative Damage and Autophagy in the Human Trabecular Meshwork as Related with Ageing

    PubMed Central

    Pulliero, Alessandra; Seydel, Anke; Camoirano, Anna; Saccà, Sergio Claudio; Sandri, Marco; Izzotti, Alberto

    2014-01-01

    Autophagy is an intracellular lysosomal degradation process induced under stress conditions. Autophagy also plays a major role in ocular patho-physiology. Molecular aging does occur in the trabecular meshwork, the main regulator of aqueous humor outflow, and trabecular meshwork senescence is accompanied by increased oxidative stress. However, the role of autophagy in trabecular meshwork patho-physiology has not yet been examined in vivo in human ocular tissues. The purpose of the herein presented study is to evaluate autophagy occurrence in ex-vivo collected human trabecular meshwork specimens and to evaluate the relationship between autophagy, oxidative stress, and aging in this tissue. Fresh trabecular meshwork specimens were collected from 28 healthy corneal donors devoid of ocular pathologies and oxidative DNA damage, and LC3 and p62 protein expression analyzed. In a subset of 10 subjects, further to trabecular meshwork proteins, the amounts of cathepesin L and ubiquitin was analyzed by antibody microarray in aqueous humor. Obtained results demonstrate that autophagy activation, measured by LC3II/I ratio, is related with. oxidative damage occurrence during aging in human trabecular meshwork. The expression of autophagy marker p62 was lower in subjects older than 60 years as compared to younger subjects. These findings reflect the occurrence of an agedependent increase in the autophagy as occurring in the trabecular meshwork. Furthermore, we showed that aging promotes trabecular-meshwork senescence due to increased oxidative stress paralleled by autophagy increase. Indeed, both oxidative DNA damage and autophagy were more abundant in subjects older than 60 years. These findings shed new light on the role of oxidative damage and autophagy during trabecular-meshwork aging. PMID:24945152

  7. Extracellular materials in the endothelial meshwork of organcultured human trabecular meshwork. Morphologic and morphometric study.

    PubMed

    Urakawa, Y

    1991-01-01

    Twenty-three normal cadaver eyes were used in this study. Eight trabecular meshwork explants were dissected at 45-degree intervals from a 77-year-old donor eye and cultured for 2 weeks for studying circumferential differences in the amount of extracellular materials in the endothelial meshwork. One trabecular meshwork explant was dissected from each of 22 individual eyes (age range: 64-89 years) and cultured for 2 weeks to study the effect of age on the amount of the extracellular materials. Then, 5 consecutive electron micrographs in the endothelial meshwork were obtained from the individual specimens and subjected to morphometric studies. In the endothelial meshwork, the results revealed: (1) no statistically significant circumferential differences in the amount of extracellular materials and (2) no statistically significant changes associated with aging in the amount of these materials. PMID:1923311

  8. Tissue-based imaging model of human trabecular meshwork.

    PubMed

    Chu, Edward R; Gonzalez, Jose M; Tan, James C H

    2014-01-01

    We have developed a tissue-based model of the human trabecular meshwork (TM) using viable postmortem corneoscleral donor tissue. Two-photon microscopy is used to optically section and image deep in the tissue to analyze cells and extracellular matrix (ECM) within the original three-dimensional (3D) environment of the TM. Multimodal techniques, including autofluorescence (AF), second harmonic generation (SHG), intravital dye fluorescence, and epifluorescence, are combined to provide unique views of the tissue at the cellular and subcellular level. SHG and AF imaging are non-invasive tissue imaging techniques with potential for clinical application, which can be modeled in the system. We describe the following in the tissue-based model: analysis of live cellularity to determine tissue viability; characteristics of live cells based on intravital labeling; features and composition of the TM's structural ECM; localization of specific ECM proteins to regions such as basement membrane; in situ induction and expression of tissue markers characteristic of cultured TM cells relevant to glaucoma; analysis of TM actin and pharmacological effects; in situ visualization of TM, inner wall endothelium, and Schlemm's canal; and application of 3D reconstruction, modeling, and quantitative analysis to the TM. The human model represents a cost-effective use of valuable and scarce yet available human tissue that allows unique cell biology, pharmacology, and translational studies of the TM. PMID:24517246

  9. Comparative Phospholipid Profiles of Control and Glaucomatous Human Trabecular Meshwork

    PubMed Central

    Aribindi, Katyayini; Guerra, Yenifer; Lee, Richard K.; Bhattacharya, Sanjoy K.

    2013-01-01

    Purpose. We compared phospholipid (phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine, and phosphatidylinositol) profiles of control and glaucomatous trabecular meshwork (TM) derived from human donors. Methods. Control TM and most primary open angle glaucoma (POAG) TM were collected from cadaver donors. A select subset of POAG surgical TM samples also were collected for analyses. Lipid extraction was performed using a modification of the Bligh and Dyer method, protein concentrations were determined using the Bradford method, and for select samples confirmed with densitometry of PHAST gels. Lipids were identified and subjected to ratiometric quantification using a TSQ quantum Access Max triple quadrupole mass spectrometer with precursor ion scan (PIS) or neutral ion loss scan (NLS), using appropriate class specific lipid standards. Results. The comparative profiles of phosphatidylcholine, phosphatidylserine, phosphoethanolamine, and phosphatidylinositol between control and glaucomatous TM showed several species common between them. A number of unique lipids in all four phospholipid classes also were identified in control TM that were absent in glaucoma TM and vice versa. Conclusions. A number of phospholipids were found to be uniquely present in control but absent in glaucomatous TM and vice versa. Compared to a previous study of control and POAG blood, a number of these phospholipids are absent locally (TM), as well as systemically (in blood). PMID:23557733

  10. Elastic Modulus Determination of Normal and Glaucomatous Human Trabecular Meshwork

    PubMed Central

    Last, Julie A.; Pan, Tingrui; Ding, Yuzhe; Reilly, Christopher M.; Keller, Kate; Acott, Ted S.; Fautsch, Michael P.; Murphy, Christopher J.; Russell, Paul

    2011-01-01

    Purpose. Elevated intraocular pressure (IOP) is a risk factor for glaucoma. The principal outflow pathway for aqueous humor in the human eye is through the trabecular meshwork (HTM) and Schlemm's canal (SC). The junction between the HTM and SC is thought to have a significant role in the regulation of IOP. A possible mechanism for the increased resistance to flow in glaucomatous eyes is an increase in stiffness (increased elastic modulus) of the HTM. In this study, the stiffness of the HTM in normal and glaucomatous tissue was compared, and a mathematical model was developed to predict the impact of changes in stiffness of the juxtacanalicular layer of HTM on flow dynamics through this region. Methods. Atomic force microscopy (AFM) was used to measure the elastic modulus of normal and glaucomatous HTM. According to these results, a model was developed that simulated the juxtacanalicular layer of the HTM as a flexible membrane with embedded pores. Results. The mean elastic modulus increased substantially in the glaucomatous HTM (mean = 80.8 kPa) compared with that in the normal HTM (mean = 4.0 kPa). Regional variation was identified across the glaucomatous HTM, possibly corresponding to the disease state. Mathematical modeling suggested an increased flow resistance with increasing HTM modulus. Conclusions. The data indicate that the stiffness of glaucomatous HTM is significantly increased compared with that of normal HTM. Modeling exercises support substantial impairment in outflow facility with increased HTM stiffness. Alterations in the biophysical attributes of the HTM may participate directly in the onset and progression of glaucoma. PMID:21220561

  11. Distribution of proteoglycans in the human trabecular meshwork: histochemical electron microscopic findings with cuprolinic blue.

    PubMed

    Ko, M K; Kim, D S; Shin, J C

    1999-06-01

    The distribution of sulfated proteoglycans (PGs) in the normal human trabecular meshwork was studied by histochemical electron microscopy using the cationic dye, cuprolinic blue (CB).. The trabecular meshwork was obtained from human enucleated eyes and incubated for three days. After incubation, they were stained with 0.2% CB at a critical electrolyte concentration and prepared for histochemical electron microscopy. Ultrastructurally, PG-CB complexes were found as small punctate or filamentous structures, and were associated with collagen fibrils in the cores of the trabecular beams and the basal laminae of trabecular endothelial cells. In addition, large filamentous PG-CB complexes were mainly associated with areas of amorphous extracellular matrix between the collagen fiber bundles and in the fine fibrillar material near the basal laminae of endothelial cells of Schlemm's canal. This investigation resulted in an illustration of the ultrastructural distribution of PGs in the human trabecular meshwork. Further studies will be needed to specify the nature of PGs and their role in the aqueous outflow system. PMID:10761390

  12. [Electron microscopic histochemical study in human trabecular meshwork--Second report: location of glycoconjugate residues using lectins].

    PubMed

    Nagata, S

    1994-01-01

    The location of fourteen lectins in normal human trabecular meshworks were investigated with the electron microscope. The specimens were embedded in Lowicryl K4M at low temperature. Ultrathin sections were stained with biotin labeled lectins and colloidal gold labeled streptoavidin and observed with the electron microscope. ABA, ConA, DSA, PHA-E1, PHA-L4, WGA, LCA, and RCA120 were localized around fine fibrils underneath the endothelium of the trabecular wall of the Schlemm's canal (type I plaque) and collagenous fibers in the corneoscleral meshworks. ABA, ConA, and DSA were localized on the long-spacing collagens, basal membrane, microfibrils of elastic fiber (type II plaque), and fine granular (type III plaque). The present study indicated that extracellular matrices of normal human trabecular meshworks contained specific glycoconjugate residues. PMID:8109442

  13. Human trabecular meshwork cells express BMP antagonist mRNAs and proteins.

    PubMed

    Tovar-Vidales, Tara; Fitzgerald, Ashley M; Clark, Abbot F

    2016-06-01

    Glaucoma patients have elevated aqueous humor and trabecular meshwork (TM) levels of transforming growth factor-beta2 (TGF-β2). TGF-β2 has been associated with increased extracellular matrix (ECM) deposition (i.e. fibronectin), which is attributed to the increased resistance of aqueous humor outflow through the TM. We have previously demonstrated that bone morphogenetic protein (BMP) 4 selectively counteracts the profibrotic effect of TGF-β2 with respect to ECM synthesis in the TM, and this action is reversed by the BMP antagonist gremlin. Thus, the BMP and TGF-β signaling pathways antagonize each other's antifibrotic and profibrotic roles. The purpose of this study was to determine whether cultured human TM cells: (a) express other BMP antagonists including noggin, chordin, BMPER, BAMBI, Smurf1 and 2, and (b) whether expression of these proteins is regulated by exogenous TGF-β2 treatment. Primary human trabecular meshwork (TM) cells were grown to confluency and treated with TGF-β2 (5 ng/ml) for 24 or 48 h in serum-free medium. Untreated cell served as controls. qPCR and Western immunoblots (WB) determined that human TM cells expressed mRNAs and proteins for the BMP antagonist proteins: noggin, chordin, BMPER, BAMBI, and Smurf1/2. Exogenous TGF-β2 decreased chordin, BMPER, BAMBI, and Smurf1 mRNA and protein expression. In contrast, TGF-β2 increased secreted noggin and Smurf2 mRNA and protein levels. BMP antagonist members are expressed in the human TM. These molecules may be involved in the normal function of the TM as well as TM pathogenesis. Altered expression of BMP antagonist members may lead to functional changes in the human TM. PMID:27167364

  14. Dexamethasone Stiffens Trabecular Meshwork, Trabecular Meshwork Cells, and Matrix

    PubMed Central

    Raghunathan, Vijay Krishna; Morgan, Joshua T.; Park, Shin Ae; Weber, Darren; Phinney, Brett S.; Murphy, Christopher J.; Russell, Paul

    2015-01-01

    Purpose Treatment with corticosteroids can result in ocular hypertension and may lead to the development of steroid-induced glaucoma. The extent to which biomechanical changes in trabecular meshwork (TM) cells and extracellular matrix (ECM) contribute toward this dysfunction is poorly understood. Methods Primary human TM (HTM) cells were cultured for either 3 days or 4 weeks in the presence or absence of dexamethasone (DEX), and cell mechanics, matrix mechanics and proteomics were determined, respectively. Adult rabbits were treated topically with either 0.1% DEX or vehicle over 3 weeks, and mechanics of the TM were determined. Results Treatment with DEX for 3 days resulted in a 2-fold increase in HTM cell stiffness, and this correlated with activation of extracellular signal-related kinase 1/2 (ERK1/2) and overexpression of α-smooth muscle actin (αSMA). Further, the matrix deposited by HTM cells chronically treated with DEX is approximately 4-fold stiffer, more organized, and has elevated expression of matrix proteins commonly implicated in glaucoma (decorin, myocilin, fibrillin, secreted frizzle-related protein [SFRP1], matrix-gla). Also, DEX treatment resulted in a 3.5-fold increase in stiffness of the rabbit TM. Discussion This integrated approach clearly demonstrates that DEX treatment increases TM cell stiffness concurrent with elevated αSMA expression and activation of the mitogen-activated protein kinase (MAPK) pathway, stiffens the ECM in vitro along with upregulation of Wnt antagonists and fibrotic markers embedded in a more organized matrix, and increases the stiffness of TM tissues in vivo. These results demonstrate glucocorticoid treatment can initiate the biophysical alteration associated with increased resistance to aqueous humor outflow and the resultant increase in IOP. PMID:26193921

  15. Murine trabecular meshwork cells in tissue culture.

    PubMed

    Begley, C G; Yue, B Y; Hendricks, R L

    1991-11-01

    Trabecular meshwork cells from an inbred strain of mice (A/J) were established in tissue culture. Within 1 hour of enucleation, tissue containing the cornea and the chamber angle was excised and placed in tissue culture. Two to five days later, three cell types grew from the explants. Two of these cell types, corneal endothelium and fibroblasts, grew together, with the fibroblasts preferentially spreading on top of the endothelial cells. The trabecular meshwork cells extended from the explant as a distinct morphological type. The corneal endothelium and its associated fibroblasts were then removed from the culture flask with a sterile cotton swab, leaving a monolayer of pure trabecular meshwork cells. These cells required 3-4 weeks to reach confluency and could be passaged five times. They were actively phagocytic in culture and exhibited immunoreactivity to antibodies against two extracellular matrix components, laminin and collagen type IV. Mouse trabecular meshwork cells also expressed receptors for acetylated low-density lipoprotein, a property shared by trabecular meshwork cells derived from other species. The availability of trabecular meshwork cells from an inbred strain of mice will facilitate future in vivo functional studies of these cells in a syngeneic system, as well as investigations of potential immunoregulatory properties of the trabecular meshwork. PMID:1782800

  16. Non-housekeeping genes expressed in human trabecular meshwork cell cultures

    PubMed Central

    Paylakhi, Seyed Hassan; Yazdani, Shahin; April, Craig; Fan, Jian-Bing; Moazzeni, Hamidreza; Ronaghi, Mostafa

    2012-01-01

    Purpose To identify non-housekeeping genes definitively expressed in the human trabecular meshwork (TM). Methods Microarray gene expression data on TM cultured cells from four studies were compared. Genes that were queried in at least three studies and assessed to be expressed in at least three studies were considered definitively expressed genes of the human TM. Housekeeping genes were removed from this set of genes. The non-housekeeping TM gene profile was analyzed for pathway enrichment and microRNA targeting, using bioinformatics tools. The results were compared with results of previous non-array based studies. Results Nine hundred and sixty-two genes were identified as non-housekeeping TM expressed genes. Analysis of these by Kyoto Encyclopedia of Genes and Genomes led to identification of two enriched biologic pathways that achieved a highly significant Bonferroni p-value (p≤0.01): focal adhesion and extracellular matrix (ECM)-receptor interaction. Many of the genes were previously implicated in TM-related functions and the TM-associated disease glaucoma; however, some are novel. MicroRNAs known to be expressed in the trabecular meshwork were predicted to target some of the genes. Ten genes identified here, ALDH1A1 (aldehyde dehydrogenase 1 family, member A1), CDH11 (cadherin 11, type 2, OB-cadherin), CXCR7 (chemokine (C-X-C motif) receptor 7), CHI3L1 (chitinase 3-like 1), FGF2 (fibroblast growth factor 2), GNG11 (guanine nucleotide binding protein [G protein], gamma 11), IGFBP5 (insulin-like growth factor binding protein 5), PTPRM (protein tyrosine phosphatase, receptor type, M), RGS5 (regulator of G-protein signaling 5), and TUSC3 (tumor suppressor candidate 3), were also reported as TM expressed genes in three earlier non-microarray based studies. Conclusions A transcriptome consisting of 962 non-housekeeping genes definitively expressed in the human TM was identified. Multiple genes and microRNAs are proposed for further study for a better understanding

  17. Trabecular Meshwork Response to Pressure Elevation in the Living Human Eye.

    PubMed

    Kagemann, Larry; Wang, Bo; Wollstein, Gadi; Ishikawa, Hiroshi; Mentley, Brandon; Sigal, Ian; Bilonick, Richard A; Schuman, Joel S

    2015-01-01

    The mechanical characteristics of the trabecular meshwork (TM) are linked to outflow resistance and intraocular pressure (IOP) regulation. The rationale behind this technique is the direct observation of the mechanical response of the TM to acute IOP elevation. Prior to scanning, IOP is measured at baseline and during IOP elevation. The limbus is scanned by spectral-domain optical coherence tomography at baseline and during IOP elevation (ophthalmodynamometer (ODM) applied at 30 g force). Scans are processed to enhance visualization of the aqueous humor outflow pathway using ImageJ. Vascular landmarks are used to identify corresponding locations in baseline and IOP elevation scan volumes. Schlemm canal (SC) cross-sectional area (SC-CSA) and SC length from anterior to posterior along its long axis are measured manually at 10 locations within a 1 mm segment of SC. Mean inner to outer wall distance (short axis length) is calculated as the area of SC divided by its long axis length. To examine the contribution of adjacent tissues to the effect IOP elevations, measurements are repeated without and with smooth muscle relaxation with instillation of tropicamide. TM migration into SC is resisted by TM stiffness, but is enhanced by the support of its attachment to adjacent smooth muscle within the ciliary body. This technique is the first to measure the living human TM response to pressure elevation in situ under physiological conditions within the human eye. PMID:26132890

  18. The intrinsic stiffness of human trabecular meshwork cells increases with senescence

    PubMed Central

    Chang, Yow-Ren; Murphy, Christopher J.; Russell, Paul

    2015-01-01

    Dysfunction of the human trabecular meshwork (HTM) plays a central role in the age-associated disease glaucoma, a leading cause of irreversible blindness. The etiology remains poorly understood but cellular senescence, increased stiffness of the tissue, and the expression of Wnt antagonists such as secreted frizzled related protein-1 (SFRP1) have been implicated. However, it is not known if senescence is causally linked to either stiffness or SFRP1 expression. In this study, we utilized in vitro HTM senescence to determine the effect on cellular stiffening and SFRP1 expression. Stiffness of cultured cells was measured using atomic force microscopy and the morphology of the cytoskeleton was determined using immunofluorescent analysis. SFRP1 expression was measured using qPCR and immunofluorescent analysis. Senescent cell stiffness increased 1.88±0.14 or 2.57±0.14 fold in the presence or absence of serum, respectively. This was accompanied by increased vimentin expression, stress fiber formation, and SFRP1 expression. In aggregate, these data demonstrate that senescence may be a causal factor in HTM stiffening and elevated SFRP1 expression, and contribute towards disease progression. These findings provide insight into the etiology of glaucoma and, more broadly, suggest a causal link between senescence and altered tissue biomechanics in aging-associated diseases. PMID:25915531

  19. Bioengineered glaucomatous 3D human trabecular meshwork as an in vitro disease model.

    PubMed

    Torrejon, Karen Y; Papke, Ellen L; Halman, Justin R; Stolwijk, Judith; Dautriche, Cula N; Bergkvist, Magnus; Danias, John; Sharfstein, Susan T; Xie, Yubing

    2016-06-01

    Intraocular pressure (IOP) is mostly regulated by aqueous humor outflow through the human trabecular meshwork (HTM) and represents the only modifiable risk factor of glaucoma. The lack of IOP-modulating therapeutics that targets HTM underscores the need of engineering HTM for understanding the outflow physiology and glaucoma pathology in vitro. Using a 3D HTM model that allows for regulation of outflow in response to a pharmacologic steroid, a fibrotic state has been induced resembling that of glaucomatous HTM. This disease model exhibits HTM marker expression, ECM overproduction, impaired HTM cell phagocytic activity and outflow resistance, which represent characteristics found in steroid-induced glaucoma. In particular, steroid-induced ECM alterations in the glaucomatous model can be modified by a ROCK inhibitor. Altogether, this work presents a novel in vitro disease model that allows for physiological and pathological studies pertaining to regulating outflow, leading to improved understanding of steroid-induced glaucoma and accelerated discovery of new therapeutic targets. Biotechnol. Bioeng. 2016;113: 1357-1368. © 2015 Wiley Periodicals, Inc. PMID:26615056

  20. Tissue-based multiphoton analysis of actomyosin and structural responses in human trabecular meshwork

    PubMed Central

    Gonzalez, Jose M.; Ko, Minhee K.; Pouw, Andrew; Tan, James C. H.

    2016-01-01

    The contractile trabecular meshwork (TM) modulates aqueous humor outflow resistance and intraocular pressure. The primary goal was to visualize and quantify human TM contractile state by analyzing actin polymerization (F-actin) by 2-photon excitation fluorescence imaging (TPEF) in situ. A secondary goal was to ascertain if structural extracellular matrix (ECM) configuration changed with contractility. Viable ex vivo human TM was incubated with latrunculin-A (Lat-A) or vehicle prior to Alexa-568-phalloidin labeling and TPEF. Quantitative image analysis was applied to 2-dimensional (2D) optical sections and 3D image reconstructions. After Lat-A exposure, (a) the F-actin network reorganized as aggregates; (b) F-actin-associated fluorescence intensity was reduced by 48.6% (mean; p = 0.007; n = 8); (c) F-actin 3D distribution was reduced by 68.9% (p = 0.040); (d) ECM pore cross-sectional area and volume were larger by 36% (p = 0.032) and 65% (p = 0.059) respectively and pores appeared more interconnected; (e) expression of type I collagen and elastin, key TM structural ECM proteins, were unaltered (p = 0.54); and (f) tissue viability was unchanged (p = 0.39) relative to vehicle controls. Thus Lat-A-induced reduction of actomyosin contractility was associated with TM porous expansion without evidence of reduced structural ECM protein expression or cellular viability. These important subcellular-level dynamics could be visualized and quantified within human tissue by TPEF. PMID:26883567

  1. Optimizing two-photon multiple fluorophore imaging of the human trabecular meshwork

    PubMed Central

    Gonzalez, Jose M.; Ammar, Michael J.; Ko, MinHee K.

    2016-01-01

    Purpose Advances in two-photon (2P) deep tissue imaging provide powerful options for simultaneously viewing multiple fluorophores within tissues. We determined imaging parameters for optimally visualizing three fluorophores in the human trabecular meshwork (TM) to simultaneously detect broad-spectrum autofluorescence and multiple fluorophores through a limited number of emission filters. Methods 2P imaging of viable human postmortem TM was conducted to detect Hoechst 33342–labeled nuclei, Alexa-568-conjugated phalloidin labeling of filamentous actin, and autofluorescence of the structural extracellular matrix (ECM). Emission detection through green (500–550 nm), near-red (565–605 nm), and far-red (590–680 nm) filters following 2P excitation at 750, 800, 850, and 900 nm was analyzed. Region-of-interest (ROI) image analysis provided fluorescence intensity values for each fluorophore. Results Red-channel Alexa 568 fluorescence was of highest intensity with 2P 750 nm and 800 nm excitation. Alexa 568 was imperceptible with 900 nm excitation. With excitation at 750 nm and 800 nm, Hoechst 33,342 intensity swamped autofluorescence in the green channel, and marked bleed-through into red channels was seen. 850 nm excitation yielded balanced Hoechst 33342 and autofluorescence intensities, minimized their bleed-through into the far-red channel, and produced reasonable Alexa 568 intensities in the far-red channel. Conclusions 2P excitation at 850 nm and long-wavelength emission detection in the far-red channel allowed simultaneous visualization of the specific mix of endogenous and exogenous fluorophores with reasonably balanced intensities while minimizing bleed-through when imaging the human TM. PMID:27122962

  2. Regulation of Myocilin-Associated Exosome Release from Human Trabecular Meshwork Cells

    PubMed Central

    Hoffman, Emely A.; Perkumas, Kristin M.; Highstrom, Lindsey M.; Stamer, W. Daniel

    2009-01-01

    Purpose The goal of the present study was to determine whether the release of exosomes containing MYOC from trabecular meshwork (TM) cells is constitutive or regulated. Methods Conditioned media from TM cells were analyzed for MYOC-associated exosomes after treatment with IFN-γ, porcine aqueous humor, dexamethasone, or a calcium ionophore in cells pretreated with dexamethasone. Aqueous humor was tested whole or fractionated by size exclusion filters. Exosomes from conditioned media were purified by differential centrifugation. Proteins in whole, exosome, and soluble fractions were separated by SDS-PAGE and analyzed for MYOC content by Western blot and densitometry. Results Although treatment of TM cells with IFN-γ increased the appearance of extracellular MYOC-associated exosomes, results were not significantly different from those of control (P = 0.13). In contrast, treatment with dexamethasone increased the appearance of MYOC in the exosome fraction by 376% (P < 0.01). The increase in MYOC-associated exosomes caused by dexamethasone was enhanced by an additional 379% after short-term exposure to ionomycin (P < 0.05). When cultured in media containing aqueous humor, MYOC-associated exosomes increased 514% over control (P < 0.01). Such an increase was diminished in cells treated with aqueous humor that was first passed through a 3-kDa or a 30-kDa, but not a 100-kDa, size exclusion filter. Conclusions The appearance of MYOC-associated exosomes in conditioned media from human TM cells is regulated by a corticosteroid, a calcium ionophore, and a component of aqueous humor, suggesting that TM cells respond to environmental cues by releasing MYOC-associated exosomes. PMID:18952916

  3. Crosstalk between TGFβ and Wnt signaling pathways in the human trabecular meshwork.

    PubMed

    Webber, Hannah C; Bermudez, Jaclyn Y; Sethi, Anirudh; Clark, Abbot F; Mao, Weiming

    2016-07-01

    Primary Open Angle Glaucoma (POAG) is an irreversible, vision-threatening disease that affects millions worldwide. The principal risk factor of POAG is increased intraocular pressure (IOP) due to pathological changes in the trabecular meshwork (TM). The TGFβ signaling pathway activator TGFβ2 and the Wnt signaling pathway inhibitor secreted frizzled-related protein 1 (sFRP1) are elevated in the POAG TM. In this study, we determined whether there is a crosstalk between the TGFβ/Smad pathway and the canonical Wnt pathway using luciferase reporter assays. Lentiviral luciferase reporter vectors for studying the TGFβ/Smad pathway or the canonical Wnt pathway were transduced into primary human non-glaucomatous TM (NTM) cells. Cells were treated with or without a combination of 5 μg/ml TGFβ2 and/or 100 ng/ml Wnt3a recombinant proteins, and luciferase levels were measured using a plate reader. We found that TGFβ2 inhibited Wnt3a-induced canonical Wnt pathway activation, while Wnt3a inhibited TGFβ2-induced TGFβ/Smad pathway activation (n = 6, p < 0.05) in 3 NTM cell strains. We also found that knocking down of Smad4 or β-catenin using siRNA in HTM5 cells transfected with similar luciferase reporter plasmids abolished the inhibitory effect of TGFβ2 and/or Wnt3a on the other pathway (n = 6). Our results suggest the existence of a cross-inhibition between the TGFβ/Smad and canonical Wnt pathways in the TM, and this cross-inhibition may be mediated by Smad4 and β-catenin. PMID:27091054

  4. Trabecular meshwork cell culture in glaucoma research: evaluation of biological activity and structural properties of human trabecular cells in vitro.

    PubMed

    Polansky, J R; Wood, I S; Maglio, M T; Alvarado, J A

    1984-06-01

    The propagation of human trabecular cells in culture allows the study of the structural and functional properties of this distinct cell type under reproducible experimental conditions. Human trabecular cells can be effectively grown from dissected explants of trabecullar tissue, and the cultured cells can maintain the distinctive ultrastructural features of uncultured trabecular cells through at least five passages in vitro. The trabecular cell possesses a wide range of biochemical and structural properties that may be important for the maintenance of the aqueous outflow pathway. These properties include the growth of trabecular cells as an endothelial monolayer with a nonthrombogenic cell surface, the production of plasminogen activator, avid phagocytosis, and the ability to synthesize glycosaminoglycans, collagen, fibronectin, and other connective tissue elements. The presence of hyaluronidase and other lysosomal enzymes emphasizes that human trabecular cells are capable of metabolizing hyaluronic acid and other extracellular materials. Potential mechanisms of trabecular cell damage in vitro are examined by evaluating the effects of extended passage, peroxide exposure, and laser treatment on cellular morphology. PMID:6540429

  5. Protein expression in human trabecular meshwork: downregulation of RhoGDI by dexamethasone in vitro

    PubMed Central

    Yu, Minbin; Sun, Jing; Peng, Wei; Chen, Ziyan; Lin, Xianchai; Liu, Xuyang; Li, Mingtao

    2010-01-01

    Purpose The characterization of the human trabecular meshwork (TM) proteome is a valuable step toward understanding its role under normal and glaucomatous conditions. This study uses proteomic techniques to investigate the set of proteins expressed in normal human TM and to identify those differentially expressed in response to dexamethasone (DEX) treatment of TM cells (TMCs) in vitro. Methods TM tissue (TMT) was isolated from human donor eyes and pooled. Immortalized human TMCs were cultured with or without DEX. Protein extracts from each were separated by two-dimensional electrophoresis (2-DE). Protein spots in TMT gel were excised, destained, and subjected to in-gel tryptic digestion and identification with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). To determine those proteins whose expression patterns were affected by glucocorticoids, TMCs were treated with DEX and assayed by 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) dye and 2-DE. A differentially expressed protein, RhoGDI, was validated by both western blotting and immunocytological staining. Results The comprehensive protein set included more than 850 protein spots from both the TMT and TMCs, as visualized on 2-DE gel. Two-hundred-and-thirty-five spots were successfully identified in the TMT gel. The functional categories of the identified proteins were mainly comprised of metabolic process, cell adhesion, anti-apoptosis, cell motility, carbohydrate metabolic process, signal transduction, and regulation of transcription. During three days of DEX treatment, TMCs’ proliferation was inhibited in a time- and dose-dependent manner, as evidenced by MTT assay. In the 48 h cultured cell group, RhoGDI expression was reduced, as detected by 2-DE, western blotting, and immunocytological staining. In contrast, the expression of RhoA, a target of RhoGDI, increased in response to DEX treatment. Conclusions Using the classic proteomic workflow

  6. Surgery on the Trabecular Meshwork: Histopathological Evidence

    PubMed Central

    Bhartiya, Shibal; Ichhpujani, Parul

    2015-01-01

    ABSTRACT Juxtacanalicular (JXT) trabecular meshwork and endothelial lining of Schlemm’s canal have been cited as the loci of aqueous outflow resistance, both in a normal as well as a glaucomatous eye. In this review, we attempt to understand the currently available surgical modalities in light of the available histopathological evidence, regarding localization of outflow resistance. How to cite this article: Bhartiya S, Ichhpujani P, Shaarawy T. Surgery on the Trabecular Meshwork: Histopathological Evidence. J Curr Glaucoma Pract 2015;9(2):51-61. PMID:26997835

  7. OCT Study of Mechanical Properties Associated with Trabecular Meshwork and Collector Channel Motion in Human Eyes.

    PubMed

    Xin, Chen; Johnstone, Murray; Wang, Ningli; Wang, Ruikang K

    2016-01-01

    We report the use of a high-resolution optical coherence tomography (OCT) imaging platform to identify and quantify pressure-dependent aqueous outflow system (AOS) tissue relationships and to infer mechanical stiffness through examination of tissue properties in ex vivo human eyes. Five enucleated human eyes are included in this study, with each eye prepared with four equal-sized quadrants, each encompassing 90 degrees of the limbal circumference. In radial limbal segments perfusion pressure within Schlemm's canal (SC) is controlled by means of a perfusion cannula inserted into the canal lumen, while the other end of the cannula leads to a reservoir at a height that can control the pressure in the cannula. The OCT system images the sample with a spatial resolution of about 5 μm from the trabecular meshwork (TM) surface. Geometric parameters are quantified from the 2D OCT images acquired from the sample subjected to controlled changes in perfusion pressures; parameters include area and height of the lumen of SC, collector channel entrances (CCE) and intrascleral collector channels (ISCC). We show that 3D OCT imaging permits the identification of 3-D relationships of the SC, CCE and ISCC lumen dimensions. Collagen flaps or leaflets are found at CCE that are attached or hinged at only one end, whilst the flaps are connected to the TM by cylindrical structures spanning SC. Increasing static SC pressures resulted in SC lumen enlargement with corresponding enlargement of the CCE and ISCC lumen. Pressure-dependent SC lumen area and height changes are significant at the 0.01 levels for ANOVA, and at the 0.05 for both polynomial curves and Tukey paired comparisons. Dynamic measurements demonstrate a synchronous increase in SC, CCE and ISCC lumen height in response to pressure changes from 0 to 10, 30 or 50 mm Hg, respectively, and the response time is within the 50-millisecond range. From the measured SC volume and corresponding IOP values, we demonstrate that an elastance

  8. Effect of PITX2 knockdown on transcriptome of primary human trabecular meshwork cell cultures

    PubMed Central

    Paylakhi, Seyed Hassan; Fan, Jian-Bing; Mehrabian, Mohadeseh; Sadeghizadeh, Majid; Yazdani, Shahin; Katanforoush, Ali; Kanavi, Mozhgan Rezaei; Ronaghi, Mostafa

    2011-01-01

    Purpose To identify genes whose expressions in primary human trabecular meshwork (TM) cell cultures are affected by the transcription factor pituitary homeobox 2 (PITX2) and to identify genes that may have roles in glaucoma. Known glaucoma causing genes account for disease in a small fraction of patients, and we aimed at identification of other genes that may have subtle and accumulative effects not easily identifiable by a genetic approach. Methods Expression profiles derived using microarrays were compared between TM control cells and cells treated with PITX2 siRNAs using three protocols so as to minimize false positive and negative results. The first protocol was based on the commonly used B statistic. The second and third protocols were based on fold change in expression. The second protocol used a threshold of at least 2 fold change in expression, whereas the third protocol used ranking in fold change without setting a threshold. The likelihood of a selected gene being a true positive was considered to correlate with the number of protocols by which it was selected. By considering all genes that were selected by at least one protocol, the likelihood of false negatives was expected to decrease. Effects on a subset of selected genes were verified by real time PCR, western blots, and immunocytochemistry. Effects on ALDH1A1, were further pursued because its protein product, aldehyde dehydrogenase 1 family, member A1, has roles in oxidative stress and because oxidative stress is known to be relevant to the etiology of glaucoma. Results The expression level of 41 genes was assessed by to be possibly affected by PITX2 knockdown. Twenty one genes were down-regulated and twenty were upregulated. The expression of five genes was assessed to be altered by all three analysis protocols. The five genes were DIRAS3 (DIRAS family, GTP-binding RAS-like 3), CXCL6 (chemokine (C-X-C motif) ligand 6), SAMD5 (sterile alpha motif domain containing 5), CBFB (core-binding factor, beta

  9. Rho GTPase signaling promotes constitutive expression and release of TGF-β2 by human trabecular meshwork cells.

    PubMed

    Pervan, Cynthia L; Lautz, Jonathan D; Blitzer, Andrea L; Langert, Kelly A; Stubbs, Evan B

    2016-05-01

    Elevated intraocular pressure (IOP) is causally implicated in the pathophysiology of primary open-angle glaucoma (POAG). The molecular mechanisms responsible for elevated IOP remain elusive, but may involve aberrant expression and signaling of transforming growth factor (TGF)-β2 within the trabecular meshwork (TM). Consistent with previously published studies, we show here that exogenous addition of TGF-β2 to cultured porcine anterior segments significantly attenuates outflow facility in a time-dependent manner. By comparison, perfusing segments with a TGFβRI/ALK-5 antagonist (SB-431542) unexpectedly elicited a significant and sustained increase in outflow facility, implicating a role for TM-localized constitutive expression and release of TGF-β2. Consistent with this thesis, cultured primary or transformed (GTM3) quiescent human TM cells were found to constitutively express and secrete measurable amounts of biologically-active TGF-β2. Disrupting monomeric GTPase post-translational prenylation and activation with lovastatin or GGTI-298 markedly reduced constitutive TGF-β2 expression and release. Specifically, inhibiting the Rho subfamily of GTPases with C3 exoenzyme similarly reduced constitutive expression and secretion of TGF-β2. These findings suggest that Rho GTPase signaling, in part, regulates constitutive expression and release of biologically-active TGF-β2 from human TM cells. Localized constitutive expression and release of TGF-β2 by TM cells may promote or exacerbate elevation of IOP in POAG. PMID:26743044

  10. Mapping Molecular Differences and Extracellular Matrix Gene Expression in Segmental Outflow Pathways of the Human Ocular Trabecular Meshwork

    PubMed Central

    Vranka, Janice A.; Bradley, John M.; Yang, Yong-Feng; Keller, Kate E.; Acott, Ted S.

    2015-01-01

    Elevated intraocular pressure (IOP) is the primary risk factor for glaucoma, and lowering IOP remains the only effective treatment for glaucoma. The trabecular meshwork (TM) in the anterior chamber of the eye regulates IOP by generating resistance to aqueous humor outflow. Aqueous humor outflow is segmental, but molecular differences between high and low outflow regions of the TM are poorly understood. In this study, flow regions of the TM were characterized using fluorescent tracers and PCR arrays. Anterior segments from human donor eyes were perfused at physiological pressure in an ex vivo organ culture system. Fluorescently-labeled microspheres of various sizes were perfused into anterior segments to label flow regions. Actively perfused microspheres were segmentally distributed, whereas microspheres soaked passively into anterior segments uniformly labeled the TM and surrounding tissues with no apparent segmentation. Cell-tracker quantum dots (20 nm) were localized to the outer uveal and corneoscleral TM, whereas larger, modified microspheres (200 nm) localized throughout the TM layers and Schlemm’s canal. Distribution of fluorescent tracers demonstrated a variable labeling pattern on both a macro- and micro-scale. Quantitative PCR arrays allowed identification of a variety of extracellular matrix genes differentially expressed in high and low flow regions of the TM. Several collagen genes (COL16A1, COL4A2, COL6A1 and 2) and MMPs (1, 2, 3) were enriched in high, whereas COL15A1, and MMP16 were enriched in low flow regions. Matrix metalloproteinase activity was similar in high and low regions using a quantitative FRET peptide assay, whereas protein levels in tissues showed modest regional differences. These gene and protein differences across regions of the TM provide further evidence for a molecular basis of segmental flow routes within the aqueous outflow pathway. New insight into the molecular mechanisms of segmental aqueous outflow may aid in the design

  11. Potential regulatory molecules in the human trabecular meshwork of patients with glaucoma: immunohistochemical profile of a number of inflammatory cytokines.

    PubMed

    Taurone, Samanta; Ripandelli, Guido; Pacella, Elena; Bianchi, Enrica; Plateroti, Andrea Maria; De Vito, Stefania; Plateroti, Pasquale; Grippaudo, Francesca Romana; Cavallotti, Carlo; Artico, Marco

    2015-02-01

    Glaucoma occurs when there are imbalances between the production and the drainage of the eye liquid. The vast majority of the aqueous humor leaves the eye through the trabecular meshwork (TM). The cause of hypertonicity may be due to an alteration in the thickness of the TM. In the majority of cases the molecular changes that determine primary open‑angle glaucoma (POAG) are unclear. However, it has been hypothesized that the significant increase in the extracellular matrix (ECM) of the fibrillary bands in the TM is associated with possible inflammatory conditions. In this study the tissue distribution of interleukin (IL)‑6, IL‑1β, transforming growth factor-β1 (TGF‑β1), vascular endothelial growth factor (VEGF) and tumor necrosis factor α (TNF‑α) was analyzed in TM samples from patients with POAG by immunohistochemistry. Seven specimens from patients with POAG and three control tissues were analyzed by immunohistochemistry using specific antibodies against these cytokines. Morphological changes in the TM, such as increased cell content, macrophages, fibrosis and accumulation of neutrophils, were observed by transmission electron microscopy. In human TM tissues, an evident immunoreactivity for IL‑6, IL‑1β and TNF‑α was observed in patients with POAG when compared with the control subjects, indicating that these cytokines may be correlated with disease activity. TM endothelial cells secrete a number of factors and cytokines that modulate the functions of the cells and the ECM of the conventional outflow pathway. In the TM in glaucoma, macrophages produce cytokines, including IL‑6, IL‑1β and TNF‑α, leading to an acute inflammatory response and recruitment of other immune cells, including T lymphocytes. In addition, TGF‑β1 regulates and induces the expression of IL‑6 in TM that indirectly induces angiogenesis by stimulating VEGF expression. The present results support previous evidence that suggests that growth factors and cytokines

  12. Autophagic Dysregulation in Glaucomatous Trabecular Meshwork Cells

    PubMed Central

    Porter, Kristine; Hirt, Joshua; Stamer, W. Daniel; Liton, Paloma B.

    2014-01-01

    Primary open angle glaucoma (POAG) is a degenerative disease commonly associated with aging and elevated intraocular pressure (IOP). Higher resistance to aqueous humor (AH) outflow through the trabecular meshwork (TM) generates the elevated IOP in POAG; unfortunately the underlying molecular mechanisms responsible for elevated resistance are unknown. It is widely accepted, however, that differences between normal and POAG TM tissues are presumably a consequence of cellular dysfunction. Here, we investigated the autophagic function and response to chronic oxidative stress in TM cells isolated from glaucomatous and age-matched donor eyes. Glaucomatous TM cells showed elevated senescence-associated-beta-galactosidase (SA-β-Gal) and cellular lipofuscin, together with decreased steady-state levels of LC3B-II, decreased levels of pRPS6K-T389 and reduced proteolysis of long-live proteins. Moreover, the glaucomatous cultures failed to activate autophagy when exposed to hyperoxic conditions. These results strongly suggest mTORdependent dysregulation of the autophagic pathway in cells isolated from the glaucomatous TM. Such dysregulated autophagic capacity can have a detrimental impact in outflow pathway tissue, i.e mechanotransduction, and thus represent an important factor contributing to the progression of the disease. PMID:25483712

  13. Effects of benzalkonium chloride- or polyquad-preserved fixed combination glaucoma medications on human trabecular meshwork cells

    PubMed Central

    Ammar, David A.

    2011-01-01

    Purpose We investigated the potential short and long-term effects in cultured human trabecular meshwork (TM) cells of various topical glaucoma formulations containing different preservatives. Methods We tested the fixed combination medications 0.004% travoprost plus 0.5% timolol preserved with either 0.015% benzalkonium chloride (BAK; DuoTrav®), or with 0.001% polyquad (PQ; DuoTrav® BAK-free); and 0.005% latanoprost plus 0.5% timolol preserved with 0.020% BAK (Xalacom®). Also tested was a range of BAK concentrations (0.001%–0.020%) in balanced salt solution (BSS). Cells were treated for 25 min at 37 °C with solutions diluted 1:10 and 1:100 to mimic the reduced penetration of topical preparations to the anterior chamber. The percentage of live cells was determined immediately after treatment through the uptake of the fluorescent vital dye calcein-AM. To determine any long-term effects, we assayed release of matrix metalloproteinase 9 (MMP-9) and apoptosis 24 h after treatments. Results BAK demonstrated a dose-dependent reduction in TM cell viability, ranging from 71±5% live cells at 0.001% BAK (diluted 1:10) to 33±3% live cells at 0.020% BAK (diluted 1:10). Travoprost (0.004%) plus 0.5% timolol preserved with 0.015% BAK had statistically fewer live TM cells (79±7%) than the same preparation preserved with 0.001% polyquad® (PQ; 93±1%; p<0.001). Latanoprost plus timolol preserved with 0.020% BAK (29±9% live cells) was similar to the 0.020% BAK (33±3%) treatment. However, travoprost plus timolol preserved in 0.015% BAK had significantly more live cells (83±12%) than the 1:10 dilution of 0.015% BAK (49±10%). We also found 0.020% BAK (diluted 1:100) resulted in elevated levels of extracellular MMP-9 at 24 h. Conclusions These results demonstrate that the substitution of the preservative BAK from topical ophthalmic drugs results in greater in vitro viability of TM cells. Travoprost with timolol, but not latanoprost with timolol, countered some of the toxic

  14. Hypoxia-Induced Changes in DNA Methylation Alter RASAL1 and TGFβ1 Expression in Human Trabecular Meshwork Cells

    PubMed Central

    Irnaten, Mustapha; Clark, Abbot F.; O’Brien, Colm J.; Wallace, Deborah M.

    2016-01-01

    Purpose Fibrosis and a hypoxic environment are associated with the trabecular meshwork (TM) region in the blinding disease glaucoma. Hypoxia has been shown to alter DNA methylation, an epigenetic mechanism involved in regulating gene expression such as the pro-fibrotic transforming growth factor (TGF) β1 and the anti-fibrotic Ras protein activator like 1 (RASAL1). The purpose of this study was to compare DNA methylation levels, and the expression of TGFβ1 and RASAL1 in primary human normal (NTM) with glaucomatous (GTM) cells and in NTM cells under hypoxic conditions. Methods Global DNA methylation was assessed by ELISA in cultured age-matched NTM and GTM cells. qPCR was conducted for TGFβ1, collagen 1α1 (COL1A1), and RASAL1 expression. Western immunoblotting was used to determine protein expression. For hypoxia experiments, NTM cells were cultured in a 1%O2, 5%CO2 and 37°C environment. NTM and GTM cells were treated with TGFβ1 (10ng/ml) and the methylation inhibitor 5-azacytidine (5-aza) (0.5μM) respectively to determine their effects on DNA Methyltransferase 1 (DNMT1) and RASAL1 expression. Results We found increased DNA methylation, increased TGFβ1 expression and decreased RASAL1 expression in GTM cells compared to NTM cells. Similar results were obtained in NTM cells under hypoxic conditions. TGFβ1 treatment increased DNMT1 and COL1A1, and decreased RASAL1 expression in NTM cells. 5-aza treatment decreased DNMT1, TGFβ1 and COL1A1 expression, and increased RASAL1 expression in GTM cells. Conclusions TGFβ1 and RASAL1 expression, global DNA methylation, and expression of associated methylation enzymes were altered between NTM and GTM cells. We found that hypoxia in NTM cells induced similar results to the GTM cells. Furthermore, DNA methylation, TGFβ1 and RASAL1 appear to have an interacting relationship that may play a role in driving pro-fibrotic disease progression in the glaucomatous TM. PMID:27124111

  15. Genomic and post-genomic effects of anti-glaucoma drugs preservatives in trabecular meshwork.

    PubMed

    Izzotti, Alberto; La Maestra, Sebastiano; Micale, Rosanna Tindara; Longobardi, Maria Grazia; Saccà, Sergio Claudio

    2015-02-01

    Oxidative stress plays an important role in glaucoma. Some preservatives of anti-glaucoma drugs, commonly used in glaucoma therapy, can prevent or induce oxidative stress in the trabecular meshwork. The aim of this study is to evaluate cellular and molecular damage induced in trabecular meshwork by preservatives contained in anti-glaucoma drugs. Cell viability (MTT test), DNA fragmentation (Comet test), oxidative DNA damage (8-oxo-dG), and gene expression (cDNA microarray) have been evaluated in trabecular meshwork specimens and in human trabecular meshwork cells treated with benzalkonium chloride, polyQuad, purite, and sofzia-like mixture. Moreover, antimicrobial effectiveness and safety of preservative contents in drugs was tested. In ex vivo experiments, benzalkonium chloride and polyQuad induced high level of DNA damage in trabecular meshwork specimens, while the effect of purite and sofzia were more attenuated. The level of DNA fragmentation induced by benzalkonium chloride was 2.4-fold higher in subjects older than 50 years than in younger subjects. Benzalkonium chloride, and polyQuad significantly increased oxidative DNA damage as compared to sham-treated specimens. Gene expression was altered by benzalkonium chloride, polyQuad, and purite but not by sofzia. In in vitro experiments, benzalkonium chloride and polyQuad dramatically decreased trabecular meshwork cell viability, increased DNA fragmentation, and altered gene expression. A lesser effect was also exerted by purite and sofzia. Genes targeted by these alterations included Fas and effector caspase-3. The efficacy of the preservatives in inhibiting bacterial growth increased the adverse effects in trabecular meshwork in terms of DNA damage and alteration of gene expression. Presented data indicates the delicate balance between efficacy and safety of drug preservatives as not yet optimized. PMID:25772104

  16. A new view of the human trabecular meshwork using quick-freeze, deep-etch electron microscopy.

    PubMed

    Gong, Haiyan; Ruberti, Jeffrey; Overby, Darryl; Johnson, Mark; Freddo, Thomas F

    2002-09-01

    Conventional transmission electron microscopic (TEM) images of the juxtacanalicular tissue (JCT) region of the trabecular meshwork (TM) show flow passages that are much too large to generate significant outflow resistance. The goal of the current study was to use quick-freeze/deep-etch (QF/DE), a technique that better preserves extracellular matrices, to determine if extracellular matrix material fills all the apparently 'open-spaces' that were observed using conventional TEM. Normal adult human eyes were fixed by immersion or under flow at pressures of 15 or 45 mmHg. The TM and the inner wall of Schlemm's canal (SC) were examined using QF/DE and compared to the observations using conventional TEM. The structure of the TM, as seen using QF/DE, showed much greater three dimensional ultrastructural detail than was seen with conventional TEM. Open space was confirmed to be present between the trabecular beams. Although significantly more extracellular matrix was observed in the JCT region using QF/DE than by conventional TEM, some micron-sized open-spaces were still present immediately beneath the inner wall of SC. Consistent with prior reports, the basement membrane of the cells lining the inner wall of SC exhibited discontinuities but the basement membrane as seen by QF/DE was much more elaborate and complex than was evident in conventional TEM of immersion-fixed eyes. This basal lamina became less continuous with increasing perfusion pressure.QF/DE, although difficult and very labor-intensive when used to examine the TM, offers several clear advantages over conventional methods of tissue preparation for ultrastructural study. Although a more complex and less open extracellular matrix structure was seen in the JCT using QF/DE compared with conventional TEM, some open-spaces, similar in size to those seen by TEM, were still observed in this region. The continued presence of such open-spaces in QF/DE images suggests that either the JCT may not generate a significant

  17. Functional morphology of the trabecular meshwork in primate eyes.

    PubMed

    Lütjen-Drecoll, E

    1999-01-01

    The trabecular meshwork forms most of the resistance to aqueous humor outflow needed for maintenance of a pressure gradient between intraocular pressure of approximately 17 mmHg and venous pressure of approximately 10 mmHg. The composition of the extracellular material in the subendothelial or cribriform layer seems to be mainly responsible for outflow resistance. The aqueous humor pathways through the subendothelial layer can be influenced by ciliary muscle contraction and presumably also by contractile elements recently found both in trabecular meshwork and scleral spur. Pharmacologically induced disconnection of inner wall and cribriform cells leads to wash out of extracellular material through breaks of the endothelial lining of Schlemm's canal and to increase of outflow facility. In glaucomatous eyes the resistance to aqueous humor outflow is increased due to an increase in different forms of extracellular material deposited within the cribriform layer. The amount of this newly developed extracellular material is correlated with loss of axons in the optic nerve, indicating that a common factor is responsible for both changes. To investigate the effect of various factors on the biology of trabecular cells monolayer cultures derived from cribriform and corneoscleral trabecular meshwork have been established. The two cell lines can be differentiated because cribriform cells in vivo as in vitro stain for alphabeta-crystallin whereas the corneoscleral cells remain unstained. The effect of TGFbeta, a growth factor increased in aqueous humor of glaucomatous eyes and glycocorticoids on trabecular meshwork cells show typical changes in formation of extracellular matrix components and of stress proteins. Dexamethasone and oxidative damage also lead to increase of trabecular meshwork inducible glucocorticoid response (TIGR) protein. A mutation of the TIGR-gene family has recently been found in families with juvenile and chronic simple glaucoma. Future research has to

  18. Collagen fibrils as skeletal frame in monkey trabecular meshwork.

    PubMed

    Nishida, S; Mizutani, S

    1994-01-01

    In an attempt to identify the characteristic skeletal frame of the trabecular meshwork, the three-dimensional architecture of collagen fibrillar bundles (collagen bundles) was studied by applying the NaOH cell-maceration method to the anterior segment of cynomolgus monkey eyes. Collagen bundles in the trabecular meshwork were found to be continuous with thinner collagen lamellae in the peripheral cornea and with the collagen fibril plexus in the ciliary body. The collagen core in the uveal cord was columnar in shape and was arranged parallel to the long axis. Collagen bundles were arranged as the layered network forming the fundamental framework of the trabecular meshwork. Most collagen bundles of the corneoscleral sheet were arranged circularly, parallel to the circumference of the limbus, and numerous slender bundles were observed side by side, forming the flat and membranous configuration of the sheet. The endothelial meshwork consisted of a network of fine and sparse collagen fibrils forming extracellular spaces and intercommunicating openings. The inner wall of the canal of Schlemm was seen as a netlike surface of sparse collagen fibrils with variously sized circular openings. The openings suggested the possibility that development of giant vacuoles corresponds to the circular openings under the inner endothelial cell lining. PMID:7933694

  19. Effects of chondroitin sulfate on trabecular meshwork in rabbit eyes: an electron microscopic study.

    PubMed

    Fei, P F; Yue, B Y; Tso, M O

    1984-11-01

    The intraocular pressure of four New Zealand albino rabbit eyes was elevated when we replaced the aqueous humor of these eyes repeatedly with a chondroitin sulfate solution. Seen by electron microscopy, the trabecular meshwork of these eyes showed moderately increased collagen fibers, elastic fibers, and fine fibrils, and thickening of basement membrane. The amount of extracellular material present was markedly increased when compared with control eyes. Three types of basement membranes were noted. Compact multilaminated basement membrane and placoid accumulations of filamentous material with a granular background were found adjacent to the endothelial cells of the trabecular meshwork, and fine fibrils were observed around the angular aqueous veins. The ultrastructural alterations we observed were similar to those seen in some human glaucoma cases. The metabolism of trabecular meshwork cells may be affected by the long-term chondroitin sulfate treatment. As a result, extracellular matrix material appears to be accumulated in the trabecular meshwork, which may then contribute to an increased outflow resistance and a mild intraocular pressure elevation. PMID:6440803

  20. The trabecular meshwork outflow pathways: structural and functional aspects.

    PubMed

    Tamm, Ernst R

    2009-04-01

    The major drainage structures for aqueous humor (AH) are the conventional or trabecular outflow pathways, which are comprised of the trabecular meshwork (made up by the uveal and corneoscleral meshworks), the juxtacanalicular connective tissue (JCT), the endothelial lining of Schlemm's canal (SC), the collecting channels and the aqueous veins. The trabecular meshwork (TM) outflow pathways are critical in providing resistance to AH outflow and in generating intraocular pressure (IOP). Outflow resistance in the TM outflow pathways increases with age and primary open-angle glaucoma. Uveal and corneoscleral meshworks form connective tissue lamellae or beams that are covered by flat TM cells which rest on a basal lamina. TM cells in the JCT are surrounded by fibrillar elements of the extracellular matrix (ECM) to form a loose connective tissue. In contrast to the other parts of the TM, JCT cells and ECM fibrils do not form lamellae, but are arranged more irregularly. SC inner wall endothelial cells form giant vacuoles in response to AH flow, as well as intracellular and paracellular pores. In addition, minipores that are covered with a diaphragm are observed. There is considerable evidence that normal AH outflow resistance resides in the inner wall region of SC, which is formed by the JCT and SC inner wall endothelium. Modulation of TM cell tone by the action of their actomyosin system affects TM outflow resistance. In addition, the architecture of the TM outflow pathways and consequently outflow resistance appear to be modulated by contraction of ciliary muscle and scleral spur cells. The scleral spur contains axons that innervate scleral spur cells or that have the ultrastructural characteristics of mechanosensory nerve endings. PMID:19239914

  1. Low dose latrunculin-A inhibits dexamethasone-induced changes in the actin cytoskeleton and alters extracellular matrix protein expression in cultured human trabecular meshwork cells.

    PubMed

    Liu, X; Wu, Z; Sheibani, N; Brandt, C R; Polansky, J R; Kaufman, P L

    2003-08-01

    We determined the effects of a low dose of the actin-disrupting agent latrunculin (LAT)-A on dexamethasone (DEX)-induced changes in actin organization, focal adhesions, and production of extracellular matrix proteins in cultured human trabecular meshwork (HTM) cells. HTM cells were cultured to a highly confluent stage with stable endothelium-like morphology and incubated with 0.1 or 0.2 microM DEX and/or 0.1 microM LAT-A. Changes in the actin cytoskeleton and vinculin-containing focal contacts were evaluated by immunofluorescence microscopy. Expression of thrombospondin-1 (TSP1) and fibronectin (FN) in HTM cells was evaluated by Western blot analysis. The results showed that DEX induced morphological changes and actin reorganization in HTM cells. The cells partly recovered after DEX withdrawal, but the addition of low dose LAT-A hastened the recovery. In addition, DEX failed to induce changes when co-incubated with LAT-A for at least 4 weeks, and for at least 2 weeks when cells were pre-treated with LAT-A for 2 weeks. HTM cells treated with 0.1 microM LAT-A only for 5 days showed mild disorganization of the actin cytoskeleton and focal adhesions, which persisted during the 4 weeks of treatment. DEX stimulated production of FN in HTM cells independent of LAT-A treatment. LAT-A and, to a lesser extent, DEX inhibited production of TSP1 by HTM cells. Although LAT-A is not a DEX receptor antagonist, it is able to prevent the effects of DEX on the actin cytoskeleton in cultured HTM cells at a dose subthreshold for increasing outflow facility in monkeys. This suggests that LAT-A at low doses may be useful in treating steroid and other glaucomas. TSP1 may be an important target of LAT-A in HTM cells and modulation of TSP may influence the actin cytoskeleton of the trabecular meshwork (TM), and consequently, intraocular pressure. PMID:12873448

  2. Role of miR-29b on the regulation of the extracellular matrix in human trabecular meshwork cells under chronic oxidative stress

    PubMed Central

    Luna, Coralia; Li, Guorong; Qiu, Jianmimg; Epstein, David L.

    2009-01-01

    Purpose To investigate the role of miR-29b on the changes in expression of genes involved in the synthesis and deposition of extracellular matrix (ECM) induced by chronic oxidative stress in human trabecular meshwork cells (HTM). Methods Changes in gene expression induced by miR-29b in HTM cells were evaluated by gene array analysis using Affymetrix U133A2 arrays and confirmed by quantitative–PCR. Pathway analysis was conducted using Metacore. Targeting of miR-29b to the 3’-untranslated region of three novel putative targets was evaluated using the Psicheck luciferase system. Chronic oxidative stress was induced by incubation at 40% oxygen for 4–5 days, using cultures incubated at 5% oxygen as controls. Changes in expression in microRNA or gene expression were analyzed by Q-PCR. Cell viability was measured by lactate dehydrogenase release. Results Transfection of HTM cells with miR-29b mimic resulted in downregulation of multiple ECM components, including collagens (COL1A1, COL1A2, COL4A1, COL5A1, COL5A2, COL3A1) LAMC1, and FBN as well as several genes involved in ECM deposition and remodeling, such as SPARC/osteonectin. Three additional genes, BMP1, ADAM12, and NKIRAS2, were identified as direct targets of miR-29b. Chronic oxidative stress induced a significant downregulation of miR-29b in two HTM cell lines that was associated with increased expression of several ECM genes known to be regulated by miR-29b. The increase in expression of these genes was inhibited by transfection with miR-29b mimic. MiR-29b increased cell viability under both chronic oxidative stress and physiologic oxygen concentrations. Conclusions MiR-29b negatively regulates the expression of multiple genes involved in the synthesis and deposition of ECM in trabecular meshwork (TM) cells. Downregulation of miR-29b might contribute to increased expression of several ECM genes under chronic oxidative stress conditions. The balance between the activation of ECM production induced by oxidative

  3. Direct trabecular meshwork imaging in porcine eyes through multiphoton gonioscopy

    NASA Astrophysics Data System (ADS)

    Masihzadeh, Omid; Ammar, David A.; Kahook, Malik Y.; Gibson, Emily A.; Lei, Tim C.

    2013-03-01

    The development of technologies to characterize the ocular aqueous outflow system (AOS) is important for the understanding of the pathophysiology of glaucoma. Multiphoton microscopy (MPM) offers the advantage of high-resolution, label-free imaging with intrinsic image contrast because the emitted signals result from the specific biomolecular content of the tissue. Previous attempts to use MPM to image the murine irido-corneal region directly through the sclera have suffered from degradation in image resolution due to scattering of the focused laser light. As a result, transscleral MPM has limited ability to observe fine structures in the AOS. In this work, the porcine irido-corneal angle was successfully imaged through the transparent cornea using a gonioscopic lens to circumvent the highly scattering scleral tissue. The resulting high-resolution images allowed the detailed structures in the trabecular meshwork (TM) to be observed. Multimodal imaging by two-photon autofluorescence and second harmonic generation allowed visualization of different features in the TM without labels and without disruption of the TM or surrounding tissues. MPM gonioscopy is a promising noninvasive imaging tool for high-resolution studies of the AOS, and research continues to explore the potential for future clinical applications in humans.

  4. A Porcine Anterior Segment Perfusion and Transduction Model With Direct Visualization of the Trabecular Meshwork

    PubMed Central

    Loewen, Ralitsa T.; Roy, Pritha; Park, Daniel B.; Jensen, Adrianna; Scott, Gordon; Cohen-Karni, Devora; Fautsch, Michael P.; Schuman, Joel S.; Loewen, Nils A.

    2016-01-01

    Purpose To establish a consistent and affordable, high quality porcine anterior segment perfusion and transduction model that allows direct visualization of the trabecular meshwork. Methods Porcine anterior segments were cultured within 2 hours of death by removing lens and uvea and securing in a specially designed petri dish with a thin bottom to allow direct visualization of the trabecular meshwork with minimal distortion. Twenty-two control eyes (CO) with a constant flow rate were compared to eight gravity perfused eyes (COgr, 15 mm Hg). We established gene delivery to the TM using eGFP expressing feline immunodeficiency virus (FIV) vector GINSIN at 108 transducing units (TU) per eye (GINSIN_8, n = 8) and 107 TU (GINSIN_7, n = 8). Expression was assessed for 14 days before histology was obtained. Results Pig eyes were a reliable source for consistent and high quality anterior segment cultures with a low failure rate of 12%. Control eyes had an intraocular pressure (IOP) of 15.8 ± 1.9 mm Hg at fixed pump perfusion with 3 μL/min compared to gravity perfused COgr with imputed 3.7 ± 1.6 μL/min. Vector GINSIN_8 eyes experienced a transient posttransduction IOP increase of 44% that resolved at 48 hours; this was not observed in GINSIN_7 eyes. Expression was higher in GINSIN_8 than in GINSIN_7 eyes. Trabecular meshwork architecture was well preserved. Conclusions Compared with previously used human donor eyes, this inexpensive porcine anterior segment perfusion model is of sufficient, repeatable high quality to develop strategies of TM bioengineering. Trabecular meshwork could be observed directly. Despite significant anatomic differences, effects of transduction replicate the main aspects of previously explored human, feline and rodent models. PMID:27002293

  5. Quantitative Proteomics: TGFβ2 Signaling in Trabecular Meshwork Cells

    PubMed Central

    Bollinger, Kathryn E.; Crabb, John S.; Yuan, Xianglin; Putliwala, Tasneem; Clark, Abbot F.

    2011-01-01

    Purpose. Transforming growth factor beta 2 (TGFβ2) is often elevated in the aqueous humor (AH) and trabecular meshwork (TM) of patients with primary open-angle glaucoma (POAG) and appears to contribute to POAG pathogenesis. To better understand TGFβ2 signaling in the eye, TGFβ2-induced proteomic changes were identified in cells cultured from the TM, a tissue involved in intraocular pressure (IOP) elevation in glaucoma. Methods. Primary cultures of human TM cells from four donors were treated with or without TGFβ2 (5 ng/mL) for 48 hours; then cellular protein was analyzed by liquid chromatography–mass spectrometry iTRAQ (isobaric tags for relative and absolute quantitation) technology. Results. A total of 853 proteins were quantified. TGFβ2 treatment significantly altered the abundance of 47 proteins, 40 of which have not previously been associated with TGFβ2 signaling in the eye. More than half the 30 elevated proteins support growing evidence that TGFβ2 induces extracellular matrix remodeling and abnormal cytoskeletal interactions in the TM. The levels of 17 proteins were reduced, including four cytoskeletal and six regulatory proteins. Both elevated and decreased regulatory proteins implicate TGFβ2-altered processes involving transcription, translation, and the glutamate/glutamine cycle. Altered levels of eight mitochondrial proteins support TGFβ2-induced mitochondrial dysfunction in the TM that in POAG could contribute to oxidative damage in the AH outflow pathway, TM senescence, and elevated IOP. Conclusions. The results expand the repertoire of proteins known to participate in TGFβ2 signaling, provide new molecular insight into POAG, and establish a quantitative proteomics database for the TM that includes candidate glaucoma biomarkers for future validation studies. PMID:21917933

  6. FOXC1 in human trabecular meshwork cells is involved in regulatory pathway that includes miR-204, MEIS2, and ITGβ1.

    PubMed

    Paylakhi, Seyed Hassan; Moazzeni, Hamidreza; Yazdani, Shahin; Rassouli, Paniz; Arefian, Ehsan; Jaberi, Elham; Arash, Emad Heidari; Gilani, Ahmad Sadighi; Fan, Jian-Bing; April, Craig; Amin, Sadaf; Suri, Fatemeh; Elahi, Elahe

    2013-06-01

    Forkhead box C1 (FOXC1) is a transcription factor that affects eye development. FOXC1 is implicated in the etiology of glaucoma because mutations in the gene are among the causes of Axenfeld-Rieger syndrome which is often accompanied by glaucoma. Glaucoma is the second leading cause of blindness. It is a complex disorder whose genetic basis in most patients remains unknown. Microarrays expression analysis was performed to identify genes in human trabecular meshwork (TM) primary cultures that are affected by FOXC1 and genes that may have roles in glaucoma. This represents the first genome wide analysis of FOXC1 target genes in any tissue. FOXC1 knock down by siRNAs affected the expression of 849 genes. Results on selected genes were confirmed by real time PCR, immunoblotting, and dual luciferase reporter assays. Observation of MEIS2 as a FOXC1 target and consideration of FOXC1 as a potential target of miR-204 prompted testing the effect of this micro RNA on expression of FOXC1 and several genes identified by array analysis as FOXC1 target genes. It was observed that miR-204 caused decreased expression of FOXC1 and the FOXC1 target genes CLOCK, PLEKHG5, ITGβ1, and MEIS2 in the TM cultures. Expression of CLOCK, PLEKHG5, ITGβ1 has not previously been reported to be affected by miR-204. The data suggest existence of a complex regulatory pathway in the TM part of which includes interactions between FOXC1, miR-204, MEIS2, and ITGβ1. All these molecules are known to have TM relevant functions, and the TM is strongly implicated in the etiology of glaucoma. PMID:23541832

  7. β1 and β3 Integrins Cooperate to Induce Syndecan-4-Containing Cross-linked Actin Networks in Human Trabecular Meshwork Cells

    PubMed Central

    Filla, Mark S.; Woods, Anne; Kaufman, Paul L.; Peters, Donna M.

    2006-01-01

    Purpose To characterize the molecular composition of cross-linked actin networks (CLANs) and the regulation of their formation by integrins in normal human trabecular meshwork (TM) cells. CLANs have been observed in steroid-treated and glaucomatous TM cells and have been suggested to contribute to decreased outflow facility by altering the contractility of the TM. Methods Immunofluorescence microscopy was used to identify molecular components of CLANs and quantitate CLAN formation in HTM cells plated on coverslips coated with various extracellular matrix (ECM) proteins (fibronectin, types I and IV collagen, and vitronectin), vascular cell adhesion molecule (VCAM)-1, or activating antibodies against β1, β3, or α2β1 integrins. These integrin antibodies were also used as soluble ligands. Results CLAN vertices contained the actin-binding proteins α-actinin and filamin and the signaling molecules syndecan-4 and PIP2. CLANs lacked Arp3 and cortactin. CLAN formation was dependent on the ECM substrate and was significantly higher on fibronectin and VCAM-1 compared with vitronectin, types I or IV collagen. Adsorbed β1 integrin antibodies also induced CLANs, whereas adsorbed β3 or α2β1 integrin antibodies did not. Soluble β3 integrin antibodies, however, induced CLANs and actually enhanced CLAN formation in cells spread on fibronectin, VCAM-1, type I or type IV collagen, or β1 integrin antibodies. Conclusions CLANs are unique actin-branched networks whose formation can be regulated by β1 and β3 integrin signaling pathways. Thus, integrin-mediated signaling events can modulate the organization of the actin cytoskeleton in TM cells and hence could participate in regulating cytoskeletal events previously demonstrated to be involved in controlling outflow facility. PMID:16639003

  8. The Role of Integrins in the Trabecular Meshwork

    PubMed Central

    Gagen, Debjani; Faralli, Jennifer A.; Filla, Mark S.

    2014-01-01

    Abstract Integrins are a family of heterodimeric transmembrane receptors that mediate adhesion to the extracellular matrix (ECM). However, integrins are not just adhesion receptors. They can act as “bidirectional signal transducers” that coordinate a large number of cellular activities in response to the extracellular environment and intracellular signaling events. Among the activities regulated by integrins are cell adhesion, assembly of the ECM, growth factor signaling, apoptosis, organization of the cytoskeleton, and cytoskeleton-mediated processes such as contraction, endocytosis, and phagocytosis. Integrins regulate these activities through a complex network of intracellular signaling kinases and adaptor proteins that associate with the transmembrane and cytoplasmic domains of the integrin subunits. In this review, we will discuss how some of the known integrin-mediated activities can control the function of the trabecular meshwork. We will also discuss how integrin activity is a tightly regulated process that involves conformation changes within the heterodimer which are mediated by specific integrin-binding proteins. PMID:24266581

  9. The trabecular meshwork in normal eyes and in exfoliation glaucoma.

    PubMed

    Rasmussen, Carol A; Kaufman, Paul L

    2014-01-01

    Trabecular meshwork (TM) and ciliary muscle contraction and relaxation function together to provide control of outflow. The active role the TM plays in the regulation of intraocular pressure (IOP) is mediated by cytoskeletal and contractility mechanisms as well as signal/transduction factors that mediate its response to stressors. This complex system is altered with age and the glaucomas, and it can be difficult to differentiate between the various etiological effects/agents. Factors such as a compromised antioxidant defense system and altered extracellular matrix metabolism are known to contribute to impaired outflow and may be common to primary open-angle glaucoma, exfoliation syndrome, and exfoliation glaucoma (XFG). Genes differentially expressed in diseased ocular tissue or in cultured HTM cell models, and thus implicated in the disease process, include SOD2, ALDH1A1, MGST1, LOX, and LOXL1, elements of the transforming growth factor-β/bone morphogenetic protein/SMAD signaling pathways, connective tissue growth factor, matrix metalloproteinase-2, a tissue inhibitor of metalloproteinases also known as TIMP-2, and endothelin-1 (ET-1). In exfoliation syndrome and XFG fibrillar, proteinaceous extracellular material is produced in excess and accumulates in both outflow pathways but does not always lead to elevated IOP. Locally produced material may accumulate in the intertrabecular spaces, juxtacanalicular (JCT) meshwork, and the inner wall of Schlemm's canal as a result of a combination of both excessive synthesis and insufficient degradation. An increase in JCT plaque and decreased cellularity in the TM are thought to contribute to decreased outflow facility in glaucoma patients, but XFG patient specimens show reduced extracellular plaque material in the JCT, and the structural integrity of trabecular endothelial cells is mostly retained and cellularity remains unchanged. The distinctions between causes/effects of structural changes leading to reduced outflow

  10. Monkey trabecular meshwork cells in culture: growth, morphologic, and biochemical characteristics.

    PubMed

    Yue, B Y; Kurosawa, A; Elvart, J L; Elner, V M; Tso, M O

    1988-01-01

    We established tissue cultures of trabecular meshwork cells from cynomolgus monkey eyes. The cultures were initiated within 4 h of enucleation on Falcon Primaria flasks. Using medium containing 10% fetal bovine serum and 5% calf serum, trabecular meshwork cells could be grown for up to eight passages without additional growth factors. The growth pattern and cell morphology were distinct from those seen in fibroblastic or endothelial cultures derived from neighboring tissues. Ultrastructurally, our cells showed the characteristics of trabecular meshwork cells, exhibiting prominent basement membranes, intercellular junctions, pinocytotic vesicles, microvillous projections, and branched cell extensions. These cells were grown mostly as monolayers. However, they also appeared to form multi-layered arrays in densely confluent areas when plated at a high density. The extracellular matrix material was surrounded by cells and cell processes, simulating in vivo trabecular beam formation. Radiolabeling experiments demonstrated that our trabecular meshwork cells had the capacity to produce collagen. These results indicated that our cultured cells retain many in vivo characteristics and may be used for various biologic studies of trabecular meshwork. PMID:3042523

  11. Multiphoton gonioscopy to image the trabecular meshwork of porcine eyes

    NASA Astrophysics Data System (ADS)

    Masihzadeh, Omid; Ammar, David A.; Kahook, Malik Y.; Gibson, Emily A.; Lei, Tim C.

    2013-03-01

    The aqueous outflow system (AOS), including the trabecular meshwork (TM), the collector channels (CC) and the Schlemm's canal (SC), regulates intraocular pressure (IOP) through the drainage of the aqueous humor (AH). Abnormal IOP elevation leads to increased pressure stress to retinal ganglion cells, resulting in cell loss that can ultimately lead to complete loss of eyesight. Therefore, development of imaging tools to detect abnormal structural and functional changes of the AOS is important in early diagnosis and prevention of glaucoma. Multiphoton microscopy (MPM), including twophoton autofluorescence (TPAF) and second harmonic generation (SHG), is a label-free microscopic technique that allows molecular specific imaging of biological tissues like the TM. Since the TM and other AOS structures are located behind the highly scattering scleral tissue, transscleral imaging of the TM does not provide enough optical resolution. In this work, a gonioscopic lens is used to allow direct optical access of the TM through the cornea for MPM imaging. Compared to transscleral imaging, the acquired MPM images show improved resolution as individual collagen fiber bundles of the TM can be observed. MPM gonioscopy may have the potential to be developed as a future clinical imaging tool for glaucoma diagnostics.

  12. Stem Cells in the Trabecular Meshwork for Regulating Intraocular Pressure.

    PubMed

    Yun, Hongmin; Zhou, Yi; Wills, Andrew; Du, Yiqin

    2016-06-01

    Intraocular pressure (IOP) is still the main treatment target for glaucoma. Outflow resistance mainly exists at the trabecular meshwork (TM) outflow pathway, which is responsible for IOP regulation. Changes of TM cellularity and TM extracellular matrix turnover may play important roles in IOP regulation. In this article, we review basic anatomy and physiology of the outflow pathway and TM stem cell characteristics regarding the location, isolation, identification and function. TM stem cells are localized at the insert region of the TM and are label-retaining in vivo. They can be isolated by side-population cell sorting, cloning culture, or sphere culture. TM stem cells are multipotent with the ability to home to the TM region and differentiate into TM cells in vivo. Other stem cell types, such as adipose-derived stem cells, mesenchymal stem cells and induced pluripotent stem cells have been discovered for TM cell differentiation and TM regeneration. We also review glaucomatous animal models, which are suitable to study stem cell-based therapies for TM regeneration. PMID:27183473

  13. Prostaglandin EP2 receptor signaling protects human trabecular meshwork cells from apoptosis induced by ER stress through down-regulation of p53.

    PubMed

    Kalouche, Georges; Boucher, Céline; Coste, Annick; Debussche, Laurent; Orsini, Cécile; Baudouin, Christophe; Debeir, Thomas; Vigé, Xavier; Rostène, William

    2016-09-01

    E-prostanoid receptor subtype 2 (EP2) agonists are currently under clinical development as hypotensive agents for the treatment of ocular hypertension. However, the effects of EP2 receptor agonists on trabecular meshwork (TM) alterations leading to primary open-angle glaucoma (POAG) are still unknown. Here, we evaluated whether EP2 receptor activation exhibits protective functions on TM cell death induced by endoplasmic reticulum (ER) stress. We show that the EP2 receptor agonist butaprost protects TM cell death mediated by the ER stress inducer tunicamycin through a cyclic AMP (cAMP)-dependent mechanism, but independent of the classical cAMP sensors, protein kinase A and exchange proteins activated by cAMP. The ER stress-induced intrinsic apoptosis inhibited by the EP2 receptor agonist was correlated with a decreased accumulation of the cellular stress sensor p53. In addition, p53 down-regulation was associated with inhibition of its transcriptional activity, which led to decreased expression of the pro-apoptotic p53-upregulated modulator of apoptosis (PUMA). The stabilization of p53 by nutlin-3a abolished butaprost-mediated cell death protection. In conclusion, we showed that EP2 receptor activation protects against ER stress-dependent mitochondrial apoptosis through down-regulation of p53. The specific inhibition of this pathway could reduce TM alterations observed in POAG patients. PMID:27321910

  14. Glycans of the trabecular meshwork in primary open angle glaucoma.

    PubMed Central

    Chapman, S A; Bonshek, R E; Stoddart, R W; O'Donoghue, E; Goodall, K; McLeod, D

    1996-01-01

    AIMS: Glycan expression was compared in glaucomatous trabecular meshwork (TM) and normal TM in order to determine any differences which may reflect pathological changes underlying primary open angle glaucoma (POAG). METHODS: Resin embedded TM from trabeculectomy specimens from 15 eyes with POAG and from 12 eyes with normal anterior segments were probed with a panel of biotinylated lectins and an avidin-peroxidase revealing system at the light microscope level. Statistical analyses were performed on the comparative staining results. RESULTS: The lectins ConA and ePHA showed strong staining in all areas of both glaucomatous and normal TM; ePHA staining of Schlemm's canal (SC) from POAG TM was significantly less than that from normal TM (ePHA-SC p = 0.04). The lectins PSA, LCA, and SNA bound moderately strongly to SC endothelium and weakly to the endothelium of the corneoscleral meshwork (CSM); glaucomatous SC endothelial binding was significantly less than that of normal SC endothelium for PSA and LCA (PSA-SC p = 0.002, LCA-SC p = 0.002). STA and DSA showed moderately strong binding while WGA, ECA, AHA, and MPA bound weakly throughout the TM; for DSA and MPA this staining was significantly greater in POAG than in normal TM (DSA-SC p = 0.001, DSA-CSM p = 0.002, MPA-SC p = 0.01, MPA-CSM p = 0.02). Jac stained strongly throughout the TM and showed no significant difference in POAG compared with normal TM (Jac-SC p = 0.6, Jac-CSM p = 1). 1PHA, SBA, DBA, CTA, UEA-1 and LTA did not bind to glaucomatous TM or normal TM. There were no age-related changes seen. CONCLUSIONS: The expression of some complex and hybrid, bisected and non-bisected N-linked glycans is significantly diminished in glaucomatous TM compared with normal TM. Some glycans with multiple N-acetylglucosamine residues and O-linked glycans with terminal and subterminal galactosyl groups are significantly increased in POAG TM. Glycan expression does not change significantly with age in POAG or normal TM. Images

  15. Sustained stress response after oxidative stress in trabecular meshwork cells

    PubMed Central

    Li, Guorong; Luna, Coralia; Liton, Paloma B.; Navarro, Iris; Epstein, David L.

    2007-01-01

    Purpose To investigate the mechanisms by which chronic oxidative stress may lead to a sustained stress response similar to that previously observed in the trabecular meshwork (TM) of glaucoma donors. Methods Porcine TM cells were treated with 200 μM H2O2 twice a day for four days and were allowed to recover for three additional days. After the treatment, TM cells were analyzed for generation of intracellular reactive oxygen species (iROS), mitochondrial potential, activation of NF-κB, and the expression of inflammatory markers IL-1α, IL-6, IL-8, and ELAM-1. Potential sources of iROS were evaluated using inhibitors for nitric oxide, nitric oxide synthetase, cyclooxygenase, xanthine oxidase, NADPH oxidase, mitochondrial ROS, and PKC. The role of NF-κB activation in the induction of inflammatory markers was evaluated using the inhibitors Lactacystin and BAY11–7082. Results Chronic oxidative stress simulated by H2O2 exposure of porcine TM cells resulted in the sustained production of iROS by the mitochondria. Inhibition of mitochondrial iROS had a significant inhibitory effect on the activation of NF-κB and the induction of IL-1α, IL-6, IL-8, and ELAM-1 triggered by chronic oxidative stress. Inhibition of NF-κB partially prevented the induction of IL-1α, IL-8, and ELAM-1, but not IL-6. Conclusions Chronic oxidative stress in TM cells induced iROS production in mitochondria. This increase in iROS may contribute to the pathogenesis of the TM in glaucoma by inducing the expression of inflammatory mediators previously observed in glaucoma donors as well as the levels of oxidative damage in the tissue. PMID:18199969

  16. Tetramethylpyrazine (TMP), an Active Ingredient of Chinese Herb Medicine Chuanxiong, Attenuates the Degeneration of Trabecular Meshwork through SDF-1/CXCR4 Axis

    PubMed Central

    Chen, Pei; Zhong, Yimin; Cai, Xiaoxiao; Hu, Huan; Yang, Ying; Zhang, Jing; Li, Kaijing; Ge, Jian; Yu, Keming; Liu, Xing; Zhuang, Jing

    2015-01-01

    Background A traditional Chinese medicine, Tetramethylpyrazine (TMP), has been prescribed as a complementary treatment for glaucoma to improve patient prognosis. However, the pharmacological mechanism of action of TMP is poorly understood. In previous studies, we demonstrated that TMP exerts potent inhibitory effects on neovascularization, suppresses the tumorigenic behavior of glioma cells, and protects neural cells by regulating CXCR4 expression. Here, we further investigated whether the SDF-1/CXCR4 pathway is also involved in the TMP-mediated activity in trabecular meshwork cells. Methodology/Principal Findings CXCR4 expression was examined by quantitative real-time PCR in trabecular and iris specimens from 54 primary open-angle glaucoma (POAG) patients who required surgery and 19 non-glaucomatous donors. Our data revealed markedly elevated CXCR4 expression in the trabecular meshwork of POAG patients compared with that of controls. Consistently, CXCR4 expression was much higher in glaucomatous trabecular meshwork cells than in normal trabecular meshwork cells. Using RT-PCR and western blot assays, we determined that glaucoma-related cytokines and dexamethasone (DEX) also significantly up-regulated CXCR4 expression in primary human trabecular meshwork (PHTM) cells. Moreover, the TGF-β1-mediated induction of CXCR4 expression in PHTM cells was markedly down-regulated by TMP compared with control treatment (PBS) and the CXCR4 antagonist AMD3100. In addition, TMP could counteract the TGF-β1-induced effects on stress fiber accumulation and expansion of PHTM cells. TMP markedly suppressed the migration of PHTM cells stimulated by TGF-β1 in transwell and scratch wound assays. TMP also suppressed the extracellular matrix (ECM) accumulation induced by TGF-β2. Conclusions Our findings demonstrate that CXCR4 might be involved in the pathogenetic changes in the trabecular meshwork of patients with POAG. Additionally, TMP might exert its beneficial effects in POAG

  17. ETX1 is over-expressed in the glaucomatous trabecular meshwork

    PubMed Central

    Algeciras, Mabel E.; Lee, Richard K.; Bhattacharya, Sanjoy K.

    2009-01-01

    Purpose To determine whether exon-trapped X chromosome clone 1 (ETX1) is overexpressed in the trabecular meshwork (TM) of glaucomatous human eyes compared to controls. Methods Immunohistochemical, western blot, and enzyme-linked immunosorbent assay analysis were used with human tissues and TM protein extracts. Reverse transcription-PCR was performed on isolated mRNA-derived cDNA preparations. Results Elevated expression levels of ETX1 were detected in glaucomatous compared to control TM tissue. This corroborates previous detection of ETX1 in glaucomatous TM by proteomic analysis. ETX1 mRNA is present in TM tissue, suggesting ETX1 protein is locally produced within TM cells. Conclusions This is the first report demonstrating overexpression of ETX1 in glaucomatous TM. ETX1 expression may regulate TM protein interactions involved in cell adhesion, and its aberrant overexpression may be part of the pathophysiological pathway in the development of glaucoma. PMID:19862339

  18. Phase-sensitive optical coherence tomography characterization of pulse-induced trabecular meshwork displacement in ex vivo non-human primate eyes

    NASA Astrophysics Data System (ADS)

    Li, Peng; Reif, Roberto; Zhi, Zhongwei; An, Lin; Martin, Elizabeth; Shen, Tueng T.; Johnstone, Murray; Wang, Ruikang K.

    2013-03-01

    Purpose. It is suspected that the abnormalities of aqueous outflow pump composed of trabecular meshwork (TM) and Schlemm's canal (SC) results in the increased outflow resistance and then elevated intraocular pressure (IOP) in initial glaucoma. In order to explore the casual mechanism and the early diagnosis of glaucoma, the dynamic characterizations of aqueous outflow pump were explored. Methods. As a functional extension of optical coherence tomography (OCT), tissue Doppler OCT (tissue-DOCT) method capable of measuring the slow tissue movement was developed. The tissue-DOCT imaging was conducted on the corneo-scleral limbus of 4 monkey eyes. The eye was mounted in an anterior segment holder, together with a perfusion system to control the mean IOP and to induce the cyclic IOP transients with amplitude 3 mm Hg at frequency 1 pulse/second. IOP was monitored on-line by a pressure transducer. Tissue-DOCT data and pressure data were recorded simultaneously. The IOP-transient induced Doppler velocity, displacement and strain rate of TM and the normalized area of SC were quantified at 7 different mean IOPs (5, 8, 10, 20, 30, 40, 50 mm Hg). Results. The outflow system, including TM, SC and CCs, was visualized in the micro-structural imaging. The IOP-transient induced pulsatile TM movement and SC deformation were detected and quantified by tissue-DOCT. The TM movement was depth-dependent and the largest movement was located in the area closest to SC endothelium (SCE). Both the pulsations of TM and SC were found to be synchronous with the IOP pulse wave. At 8 mm Hg IOP, the global TM movement was around 0.65μm during one IOP transient. As IOP elevated, a gradual attenuation of TM movement and SC deformation was observed. Conclusions. The observed pulsation of TM and SC induced by the pulsatile IOP transients was in good agreement with the predicated role of TM and SC acting as a biomechanical pump (pumping

  19. Interleukin-20 Receptor Expression in the Trabecular Meshwork and Its Implication in Glaucoma

    PubMed Central

    Keller, Kate E.; Yang, Yong-Feng; Sun, Ying Ying; Sykes, Renee; Gaudette, Natalie Donna; Samples, John R.; Acott, Ted S.

    2014-01-01

    Abstract Purpose: To determine whether interleukin-20 receptors (IL-20R) are expressed in trabecular meshwork cells and the effect of a T104M mutation in IL-20R2 on downstream cellular functions. Methods: Evaluation of signal transducer and activator of transcription (STAT)3 phosphorylation and generic matrix metalloproteinase (MMP) activity in primary open angle glaucoma (POAG) dermal fibroblasts (pHDF) with the T104M IL-20R2 mutation were compared with normal human dermal fibroblasts (HDF). Expression of IL-20R1 and IL-20R2 in human trabecular meshwork (HTM) cells was determined by immunohistochemistry and western immunoblotting. Results: A T104M mutation in IL20-R2 was identified in a large POAG family in which the GLC1C locus was originally mapped. pHDFs harboring this mutation had significantly increased phosphorylated STAT3 (pSTAT3) activity compared with normal HDFs. However, stimulation with either IL-19 or IL-20 for 15 min resulted in significantly decreased levels of pSTAT3 in pHDFs compared with controls. Generic MMP activity was significantly decreased in pHDFs compared with controls after stimulation with IL-20 for 24 h. Both IL-20R1 and IL-20R2 receptors were expressed in HTM cells by western immunoblot and immunofluorescence, and they appeared to be up-regulated in response to cytokine treatment. Conclusions: A T104M mutation in IL-20R2 significantly impacts the function of this receptor as shown by decreased pSTAT3 levels and generic MMP activity. Reduced MMP activity may affect the ability of glaucoma patients to alter outflow resistance in response to elevated intraocular pressure. PMID:24455976

  20. From DNA damage to functional changes of the trabecular meshwork in aging and glaucoma.

    PubMed

    Saccà, Sergio Claudio; Gandolfi, Stefano; Bagnis, Alessandro; Manni, Gianluca; Damonte, Gianluca; Traverso, Carlo Enrico; Izzotti, Alberto

    2016-08-01

    Glaucoma is a degenerative disease of the eye. Both the anterior and posterior segments of the eye are affected, extensive damage being detectable in the trabecular meshwork and the inner retina-central visual pathway complex. Oxidative stress is claimed to be mainly responsible for molecular damage in the anterior chamber. Indeed, oxidation harms the trabecular meshwork, leading eventually to endothelial cell decay, tissue malfunction, subclinical inflammation, changes in the extracellular matrix and cytoskeleton, altered motility, reduced outflow facility and (ultimately) increased IOP. Moreover, free radicals are involved in aging and can be produced in the brain (as well as in the eye) as a result of ischemia, leading to oxidation of the surrounding neurons. Glaucoma-related cell death occurs by means of apoptosis, and apoptosis is triggered by oxidative stress via (a) mitochondrial damage, (b) inflammation, (c) endothelial dysregulation and dysfunction, and (d) hypoxia. The proteomics of the aqueous humor is significantly altered in glaucoma as a result of oxidation-induced trabecular damage. Those proteins whose aqueous humor levels are increased in glaucoma are biomarkers of trabecular meshwork impairment. Their diffusion from the anterior to the posterior segment of the eye may be relevant in the cascade of events triggering apoptosis in the inner retinal layers, including the ganglion cells. PMID:27242026

  1. Extracellular matrix in the trabecular meshwork: Intraocular pressure regulation and dysregulation in glaucoma

    PubMed Central

    Vranka, Janice A.; Kelley, Mary J.; Acott, Ted S.; Keller, Kate E.

    2014-01-01

    The trabecular meshwork (TM) is located in the anterior segment of the eye and is responsible for regulating the outflow of aqueous humor. Increased resistance to aqueous outflow causes intraocular pressure to increase, which is the primary risk factor for glaucoma. TM cells reside on a series of fenestrated beams and sheets through which the aqueous humor flows to exit the anterior chamber via Schlemm’s canal. The outer trabecular cells are phagocytic and are thought to function as a pre-filter. However, most of the outflow resistance is thought to be from the extracellular matrix (ECM) of the juxtacanalicular region, the deepest portion of the TM, and from the inner wall basement membrane of Schlemm’s canal. It is becoming increasingly evident that the extracellular milieu is important in maintaining the integrity of the TM. Not only have ultrastructural changes been observed in the ECM of the TM in glaucoma, and a significant number of mutations in ECM genes are known to be associated with glaucoma, but the stiffness of glaucomatous TM appears to be greater than that of normal tissue. Additionally, TGFβ2 has been found to be elevated in the aqueous humor of glaucoma patients and is assumed to be involved in ECM changes deep with the juxtacanalicular region of the TM. This review summarizes the current literature on trabecular ECM as well as the development and function of the TM. Animal models and organ culture models targeting specific ECM molecules to investigate the mechanisms of glaucoma are described. Finally, the growing number of mutations that have been identified in ECM genes and genes that modulate ECM in humans with glaucoma are documented. PMID:25819459

  2. A syndecan-4 binding peptide derived from laminin 5 uses a novel PKCε pathway to induce cross-linked actin network (CLAN) formation in human trabecular meshwork (HTM) cells.

    PubMed

    Filla, Mark S; Clark, Ross; Peters, Donna M

    2014-10-01

    In this study, we examined the role(s) of syndecan-4 in regulating the formation of an actin geodesic dome structure called a cross-linked actin network (CLAN) in which syndecan-4 has previously been localized. CLANs have been described in several different cell types, but they have been most widely studied in human trabecular meshwork (HTM) cells where they may play a key role in controlling intraocular pressure by regulating aqueous humor outflow from the eye. In this study we show that a loss of cell surface synedcan-4 significantly reduces CLAN formation in HTM cells. Analysis of HTM cultures treated with or without dexamethasone shows that laminin 5 deposition within the extracellular matrix is increased by glucocorticoid treatment and that a laminin 5-derived, syndecan-4-binding peptide (PEP75), induces CLAN formation in TM cells. This PEP75-induced CLAN formation was inhibited by heparin and the broad spectrum PKC inhibitor Ro-31-7549. In contrast, the more specific PKCα inhibitor Gö 6976 had no effect, thus excluding PKCα as a downstream effector of syndecan-4 signaling. Analysis of PKC isozyme expression showed that HTM cells also expressed both PKCγ and PKCε. Cells treated with a PKCε agonist formed CLANs while a PKCα/γ agonist had no effect. These data suggest that syndecan-4 is essential for CLAN formation in HTM cells and that a novel PKCε-mediated signaling pathway can regulate formation of this unique actin structure. PMID:25128150

  3. A syndecan-4 binding peptide derived from laminin 5 uses a novel PKCε pathway to induce cross-linked actin network (CLAN) formation in human trabecular meshwork (HTM) cells

    PubMed Central

    Filla, Mark S.; Clark, Ross; Peters, Donna M.

    2014-01-01

    In this study, we examined the role(s) of syndecan-4 in regulating the formation of an actin geodesic dome structure called a cross-linked actin network (CLAN) in which syndecan-4 has previously been localized. CLANs have been described in several different cell types, but they have been most widely studied in human trabecular meshwork (HTM) cells where they may play a key role in controlling intraocular pressure by regulating aqueous humor outflow from the eye. In this study we show that a loss of cell surface synedcan-4 significantly reduces CLAN formation in HTM cells. Analysis of HTM cultures treated with or without dexamethasone shows that laminin 5 deposition within the extracellular matrix is increased by glucocorticoid treatment and that a laminin 5-derived, syndecan-4-binding peptide (PEP75), induces CLAN formation in TM cells. This PEP75-induced CLAN formation was inhibited by heparin and the broad spectrum PKC inhibitor Ro-31-7549. In contrast, the more specific PKCα inhibitor Go 6976 had no effect, thus excluding PKCα as a downstream effector of syndecan-4 signaling. Analysis of PKC isozyme expression showed that HTM cells also expressed both PKCγ and PKCε. Cells treated with a PKCε agonist formed CLANs while a PKCα/γ agonist had no effect. These data suggest that syndecan-4 is essential for CLAN formation in HTM cells and that a novel PKCε-mediated signaling pathway can regulate formation of this unique actin structure. PMID:25128150

  4. Ultrastructural abnormalities of the trabecular meshwork extracellular matrix in Cyp1b1-deficient mice.

    PubMed

    Teixeira, L B C; Zhao, Y; Dubielzig, R R; Sorenson, C M; Sheibani, N

    2015-03-01

    Cytochrome P450 1B1 (CYP1B1) is highly expressed in human and murine ocular tissues during development. Mutations in this gene are implicated in the development of primary congenital glaucoma (PCG) in humans. Mice deficient in Cyp1b1 (Cyp1b1(-/-) ) present developmental abnormalities similar to human primary congenital glaucoma. The present work describes the ultrastructural morphology of the iridocorneal angle of 21 eyes from 1-week-old to 8-month-old Cyp1b1(-/-) mice. Morphometric and semiquantitative analysis of the data revealed that 3-week-old Cyp1b1(-/-) mice present a significantly (P < .005) decreased amount of trabecular meshwork (TM) collagen and higher TM endothelial cell and collagen lesion scores (P < .005) than age-matched controls. Collagen loss and lesion scores were progressively increased in older animals, with 8-month-old animals presenting severe atrophy of the TM. Our findings advance the understanding of the effects of CYP1B1 mutations in TM development and primary congenital glaucoma, as well as suggest a link between TM morphologic alterations and increased intraocular pressure. PMID:24879660

  5. Cyp1b1 Mediates Periostin Regulation of Trabecular Meshwork Development by Suppression of Oxidative Stress

    PubMed Central

    Zhao, Yun; Wang, Shoujian; Sorenson, Christine M.; Teixeira, Leandro; Dubielzig, Richard R.; Peters, Donna M.; Conway, Simon J.; Jefcoate, Colin R.

    2013-01-01

    Mutation in CYP1B1 has been reported for patients with congenital glaucoma. However, the underlying mechanisms remain unknown. Here we show increased diurnal intraocular pressure (IOP) in Cyp1b1-deficient (Cyp1b1−/−) mice. Cyp1b1−/− mice presented ultrastructural irregular collagen distribution in their trabecular meshwork (TM) tissue along with increased oxidative stress and decreased levels of periostin (Postn). Increased levels of oxidative stress and decreased levels of Postn were also detected in human glaucomatous TM tissues. Furthermore, Postn-deficient mice exhibited TM tissue ultrastructural abnormalities similar to those of Cyp1b1−/− mice. Administration of the antioxidant N-acetylcysteine (NAC) restored structural abnormality of TM tissue in Cyp1b1−/− mice. In addition, TM cells prepared from Cyp1b1−/− mice exhibited increased oxidative stress, altered adhesion, and decreased levels of Postn. These aberrant cellular responses were reversed in the presence of NAC or by restoration of Cyp1b1 expression. Cyp1b1 knockdown or inhibition of CYP1B1 activity in Cyp1b1+/+ TM cells resulted in a Cyp1b1−/− phenotype. Thus, metabolic activity of CYP1B1 contributes to oxidative homeostasis and ultrastructural organization and function of TM tissue through modulation of Postn expression. PMID:23979599

  6. Endothelial nitric oxide synthase deficiency influences normal cell cycle progression and apoptosis in trabecular meshwork cells

    PubMed Central

    Liao, Qiong; Huang, Yan-Ming; Fan, Wei; Li, Chan; Yang, Hong

    2016-01-01

    AIM To clarify how the endothelial nitric oxide synthase (eNOS, NOS3) make effect on outflow facility through the trabecular meshwork (TM). METHODS Inhibition of NOS3 gene expression in human TM cells were conducted by three siRNAs. Then the mRNA and protein levels of NOS3 in siRNA-treated and negative control (NC) cells were determined, still were the collagen, type IV, alpha 1 (COL4A1) and fibronectin 1 by real-time PCR and Western blot analysis. In addition, NOS3 concentrations in culture supernatant fluids of TM cells were measured. Cell cycle and cell apoptosis analysis were performed using flow cytometry. RESULTS The mRNA level of NOS3 was decreased by three different siRNA interference, similar results were obtained not only of the relative levels of NOS3 protein, but also the expression levels of COL4A1 and fibronectin 1. The number of cells in S phase was decreased, while contrary result was obtained in G2 phase. The number of apoptotic cells in siRNA-treated groups were significant increased compared to the NC samples. CONCLUSION Abnormal NOS3 expression can make effects on the proteins levels of extracellular matrix component (e.g. fibronectin 1 and COL4A1). Reduced NOS3 restrains the TM cell cycle progression at the G2/M-phase transition and induced cell apoptosis. PMID:27366677

  7. Regulation of myosin light chain phosphorylation in the trabecular meshwork: role in aqueous humour outflow facility.

    PubMed

    Rao, P Vasantha; Deng, Peifeng; Sasaki, Yasuharu; Epstein, David L

    2005-02-01

    Cellular contraction and relaxation and integrity of the actin cytoskeleton in trabecular meshwork (TM) tissue have been thought to influence aqueous humour outflow. However, the cellular pathways that regulate these events in TM cells are not well understood. In this study, we investigated physiological agonist-mediated regulation of myosin light chain (MLC) phosphorylation in the TM, and correlated such effects with alterations in aqueous outflow facility, since MLC phosphorylation is a critical biochemical determinant of cellular contraction in TM cells. Treatment of serum starved human TM cells with endothelin-1 (0.1 microM), thromboxane A2 mimetic U-46619 (1.0 microM), or angiotensin II (1 microM), all of which are agonists of G-protein coupled receptors, triggered activation of MLC phosphorylation, as determined by urea/glycerol-based Western blot analysis. Agonist-stimulated increase in MLC phosphorylation was associated with activation of Rho GTPase in TM cells, as determined in pull-down assays. In contrast, treatment of human TM cells with a novel Rho-kinase inhibitor H-1152 (0.1-2 microM), in the presence of serum reduced basal MLC phosphorylation. H-1152 also increased aqueous outflow facility significantly in a dose-dependent fashion, in perfusion studies with cadaver porcine eyes. This effect of H-1152 on outflow facility was associated with decreased MLC phosphorylation in TM tissue of drug-perfused eyes. Collectively, this study identifies potential physiological regulators of MLC phosphorylation in human TM cells and demonstrates the significance of Rho/Rho-kinase pathway-mediated MLC phosphorylation in modulation of aqueous outflow facility through TM. PMID:15670798

  8. Regulation of plasticity and fibrogenic activity of trabecular meshwork cells by Rho GTPase signaling.

    PubMed

    Pattabiraman, Padmanabhan P; Maddala, Rupalatha; Rao, Ponugoti Vasantha

    2014-07-01

    Glaucoma, a prevalent blinding disease is commonly associated with increased intraocular pressure due to impaired aqueous humor (AH) drainage through the trabecular meshwork (TM). Although increased TM tissue contraction and stiffness in association with accumulation of extracellular matrix (ECM) are believed to be partly responsible for increased resistance to AH outflow, the extracellular cues and intracellular mechanisms regulating TM cell contraction and ECM production are not well defined. This study tested the hypothesis that sustained activation of Rho GTPase signaling induced by lysophosphatidic acid (LPA), TGF-β, and connective tissue growth factor (CTGF) influences TM cell plasticity and fibrogenic activity which may eventually impact resistance to AH outflow. Various experiments performed using human TM cells revealed that constitutively active RhoA (RhoAV14), TGF-β2, LPA, and CTGF significantly increase the levels and expression of Fibroblast Specific Protein-1 (FSP-1), α-smooth muscle actin (αSMA), collagen-1A1 and secretory total collagen, as determined by q-RT-PCR, immunofluorescence, immunoblot, flow cytometry and the Sircol assay. Significantly, these changes appear to be mediated by Serum Response Factor (SRF), myocardin-related transcription factor (MRTF-A), Slug, and Twist-1, which are transcriptional regulators known to control cell plasticity, myofibroblast generation/activation and fibrogenic activity. Additionally, the Rho kinase inhibitor-Y27632 and anti-fibrotic agent-pirfenidone were both found to suppress the TGF-β2-induced expression of αSMA, FSP-1, and collagen-1A1. Taken together, these observations demonstrate the significance of RhoA/Rho kinase signaling in regulation of TM cell plasticity, fibrogenic activity, and myofibroblast activation, events with potential implications for the pathobiology of elevated intraocular pressure in glaucoma patients. PMID:24318513

  9. Effect of persistent high intraocular pressure on microstructure and hydraulic permeability of trabecular meshwork

    NASA Astrophysics Data System (ADS)

    Mei, Xi; Ren, Lin; Xu, Qiang; Zheng, Wei; Liu, Zhi-Cheng

    2015-05-01

    As the aqueous humor leaves the eye, it first passes through the trabecular meshwork (TM). Increased flow resistance in this region causes elevation of intraocular pressure (IOP), which leads to the occurrence of glaucoma. To quantitatively evaluate the effect of high IOP on the configuration and hydraulic permeability of the TM, second harmonic generation (SHG) microscopy was used to image the microstructures of the TM and adjacent tissues in control (normal) and high IOP conditions. Enucleated rabbit eyes were perfused at a pressure of 60 mmHg to achieve the high IOP. Through the anterior chamber of the eye, in situ images were obtained from different depths beneath the surface of the TM. Porosity and specific surface area of the TM in control and high IOP conditions were then calculated to estimate the effect of the high pressure on the permeability of tissue in different depths. We further photographed the histological sections of the TM and compared the in situ images. The following results were obtained in the control condition, where the region of depth was less than 55 μm with crossed branching beams and large pores in the superficial TM. The deeper meshwork is a silk-like tissue with abundant fluorescence separating the small size of pores. The total thickness of pathway tissues composed of TM and juxtacanalicular (JCT) is more than 100 μm. After putting a high pressure on the inner wall of the eye, the TM region progressively collapses and decreases to be less than 40 μm. Fibers of the TM became dense, and the porosity at 34 μm in the high IOP condition is comparable to that at 105 μm in the control condition. As a consequent result, the permeability of the superficial TM decreases rapidly from 120 μm2 to 49.6 μm2 and that of deeper TM decreases from 1.66 μm2 to 0.57 μm2. Heterogeneity reflected by descent in permeability reduces from 12.4 μm of the control condition to 3.74 μm of the high IOP condition. The persistently high IOP makes the TM

  10. Effect of Nitric Oxide on the Expression of Matrix Metalloproteinase and Its Association with Migration of Cultured Trabecular Meshwork Cells

    PubMed Central

    2016-01-01

    Purpose To determine the effect of exogenous nitric oxide (NO) on the migration of trabecular meshwork (TM) cells and its association with expression of matrix metalloproteinases (MMPs). Methods Primary human TM cells treated with 1 or 10 µM S-nitroso-N-acetyl-penicillamine (SNAP) and examined for changes in adherence. TM cells were seeded onto transwell culture inserts, and changes in their migratory activity were quantified. Reverse transcription polymerase chain reaction was performed to determine the relative changes in mRNA expression of MMPs and tissue inhibitor of metalloproteinases (TIMPs). Results Treatment with SNAP did not significantly suppress TM cell adhesion or migration (p > 0.05). Treatment of TM cells with 10 µM SNAP decreased expression of MMP-2 and increased expression of membrane type MMP-1 and TIMP-2. Treatment with interleukin-1α triggered MMP-3 expression but did not exert significant effects on MMP-3 activation in response to SNAP. Conclusions These data suggest that NO revealed no significant effect on the migration of TM cells because NO decreased MMP-2 and increased TIMP-2 expression. Although expression of certain MMPs and TIMPs change in response to NO donors, NO may modulate trabecular outflow by changing the cellular production of extracellular matrix without having a significant effect on the migration of TM cells. PMID:26865806

  11. Elevated Intraocular Pressure Induces Rho GTPase Mediated Contractile Signaling in the Trabecular Meshwork

    PubMed Central

    Pattabiraman, Padmanabhan P; Inoue, Toshihiro; Rao, P. Vasantha

    2015-01-01

    Rho GTPase regulated contractile signaling in the trabecular meshwork (TM) has been shown to modulate aqueous humor (AH) outflow and intraocular pressure (IOP). To explore whether elevated IOP, a major risk factor for primary open angle glaucoma (POAG) influences Rho GTPase signaling in the TM, we recorded AH outflow in enucleated contralateral porcine eyes perfused for 4–5 hours at either 15 mm or 50 mm Hg pressure. After perfusion, TM tissue extracted from perfused eyes was evaluated for the activation status of Rho GTPase, myosin light chain (MLC), myosin phosphatase target substrate 1 (MYPT1), myristoylated alanine-rich C-kinase substrate (MARCKS) and paxillin. Eyes perfused at 50 mm Hg exhibited a significant decrease in AH outflow facility compared with those perfused at 15 mm Hg. Additionally, TM tissue from eyes perfused at 50 mm Hg revealed significantly increased levels of activated RhoA and phosphorylated MLC, MYPT1, MARCKS and paxillin compared to TM tissue derived from eyes perfused at 15 mm Hg. Taken together, these observations indicate that elevated IOP-induced activation of Rho GTPase-dependent contractile signaling in the TM is associated with increased resistance to AH outflow through the trabecular pathway, and demonstrate the sensitivity of Rho GTPase signaling to mechanical force in the AH outflow pathway. PMID:25956210

  12. Structural changes of the trabecular meshwork in different kinds of glaucoma.

    PubMed

    Tektas, Ozan-Yüksel; Lütjen-Drecoll, Elke

    2009-04-01

    The morphology of the trabecular meshwork in three types of open angle glaucoma: primary open angle glaucoma (POAG), corticosteroid-induced glaucoma and pigmentary glaucoma (PG) are described. Ageing is one major risk factor for development of POAG. It is assumed that preexisting age-related changes of the trabecular meshwork (TM) play a role for the development of increased outflow resistance and intraocular pressure (IOP) in various types of glaucoma. These age-related changes in the TM develop concomitant with that of presbyopia. Therefore the functional relationship between ciliary muscle (CM) and TM and the age-related changes in morphology of the outflow system are described first. One main finding in the ageing TM concerns changes of the elastic fiber network and the anterior elastic tendons of the CM. There is an increase in thickness of the sheath of the elastic fibers. Cross-sections through these fibers with their sheath appear as extracellular plaques and were therefore termed "sheath derived plaques" (SD-plaques). Morphologically, the TM changes in POAG resemble that of the ageing TM, but in POAG there is a significant increase in SD-plaques compared to age-matched controls. This increase is due to fine fibrils and other components of the extracellular matrix (ECM) that adhere to the sheaths of the elastic fibers and their connections to the inner wall endothelium. In POAG eyes there is also a marked loss of TM cells, at places leading to fusion and thickening of trabecular lamellae. In steroid-induced glaucoma there is also an increase in fine fibrillar material in the subendothelial region of SC. In contrast to POAG eyes these fibrils do not adhere to the sheath of the elastic fibers but are deposited underneath the inner wall endothelium. The main finding in steroid-induced glaucoma is an accumulation of basement membrane-like material staining for type IV collagen. These accumulations are found throughout all layers of the TM. In pigmentary

  13. Latrunculin B effects on trabecular meshwork and corneal endothelial morphology in monkeys.

    PubMed

    Sabanay, Ilana; Tian, Baohe; Gabelt, B'Ann T; Geiger, Benjamin; Kaufman, Paul L

    2006-02-01

    To determine the mechanism of latrunculin B (LAT-B)-induced decrease in outflow resistance and the effect of LAT-B on the cornea, structural changes of the trabecular meshwork (TM) and the corneal endothelium following LAT-B were studied in the live monkey eye. LAT-B (0.5 microM) and vehicle were administered by anterior chamber exchange and infusion with cationized and non-cationized gold solution in opposite eyes. The eyes were fixed by infusing Ito's solution and enucleated. Anterior segments were quadrisected and embedded in Epon-Embed 812. Morphology of the TM and the corneal endothelium was studied by light and electron microscopy. LAT-B-induced morphological changes in the TM included: (1) loss of microfilament integrity in cells, especially in TM cells on the collagen beams; (2) development of numerous cytoplasmic projections of the sub-canalicular cells (SUB); (3) reorganization of intermediate filaments in Schlemm's canal inner wall (IW) cells; (4) massive 'ballooning' of the juxtacanalicular (JXT) region, leading to a substantial expansion of the space between the IW of Schlemm's canal and the trabecular collagen beams; and (5) retention of extracellular matrix (ECM), trapped between the SUB cell layer and IW cells. No detrimental effects on tight junctions, giant vacuoles, and cell-cell and cell-ECM adhesions were observed. Endocytosis of gold particles was not affected. Morphology of the corneal endothelium of the LAT-B-treated eye was unchanged. In conclusion, TM changes in the LAT-B-treated eye suggest that the expansion of the JXT space may account for the decrease in outflow resistance induced by latrunculins. The outflow-effective concentration of LAT-B administered intracamerally does not significantly affect the corneal endothelium. PMID:16054137

  14. Targeting the ER-autophagy system in the trabecular meshwork to treat glaucoma.

    PubMed

    Stothert, Andrew R; Fontaine, Sarah N; Sabbagh, Jonathan J; Dickey, Chad A

    2016-03-01

    A major drainage network involved in aqueous humor dynamics is the conventional outflow pathway, which is gated by the trabecular meshwork (TM). The TM acts as a molecular sieve, providing resistance to aqueous outflow, which is responsible for regulating intraocular pressure (IOP). If the TM is damaged, aqueous outflow is impaired, IOP increases and glaucoma can manifest. Mutations in the MYOC gene cause hereditary primary open-angle glaucoma (POAG) by promoting the abnormal amyloidosis of the myocilin protein in the endoplasmic reticulum (ER), leading to ER stress-induced TM cell death. Myocilin accumulation is observed in approximately 70-80% of all glaucoma cases suggesting that environmental or other genetic factors may also promote myocilin toxicity. For example, simply preventing myocilin glycosylation is sufficient to promote its abnormal accretion. These myocilin amyloids are unique as there are no other known pathogenic proteins that accumulate within the ER of TM cells and cause toxicity. Moreover, this pathogenic accumulation only kills TM cells, despite expression of this protein in other cell types, suggesting that another modifier exclusive to the TM participates in the proteotoxicity of myocilin. ER autophagy (reticulophagy) is one of the pathways essential for myocilin clearance that can be impacted dramatically by aging and other environmental factors such as nutrition. This review will discuss the link between myocilin and autophagy, evaluating the role of this degradation pathway in glaucoma as well as its potential as a therapeutic target. PMID:26302411

  15. MTOR-independent induction of autophagy in trabecular meshwork cells subjected to biaxial stretch.

    PubMed

    Porter, Kristine M; Jeyabalan, Nallathambi; Liton, Paloma B

    2014-06-01

    The trabecular meshwork (TM) is part of a complex tissue that controls the exit of aqueous humor from the anterior chamber of the eye, and therefore helps maintaining intraocular pressure (IOP). Because of variations in IOP with changing pressure gradients and fluid movement, the TM and its contained cells undergo morphological deformations, resulting in distention and stretching. It is therefore essential for TM cells to continuously detect and respond to these mechanical forces and adapt their physiology to maintain proper cellular function and protect against mechanical injury. Here we demonstrate the activation of autophagy, a pro-survival pathway responsible for the degradation of long-lived proteins and organelles, in TM cells when subjected to biaxial static stretch (20% elongation), as well as in high-pressure perfused eyes (30mmHg). Morphological and biochemical markers for autophagy found in the stretched cells include elevated LC3-II levels, increased autophagic flux, and the presence of autophagic figures in electron micrographs. Furthermore, our results indicate that the stretch-induced autophagy in TM cells occurs in an MTOR- and BAG3-independent manner. We hypothesize that activation of autophagy is part of the physiological response that allows TM cells to cope and adapt to mechanical forces. PMID:24583119

  16. Laser Trabeculoplasty Induces Changes in the Trabecular Meshwork Glycoproteome: A pilot study

    PubMed Central

    Amelinckx, Adriana; Castello, Maria; Arrieta-Quintero, Esdras; Lee, Tinthu; Salas, Nelson; Hernandez, Eleut; Lee, Richard K.; Bhattacharya, Sanjoy K.; Parel, Jean-Marie A

    2009-01-01

    Laser trabeculoplasty (LT) is a commonly used modality of treatment for glaucoma. The mechanism by which LT lowers the intraocular pressure (IOP) is unknown. Using cat eyes, selective laser trabeculoplasty (SLT) with a Q-switched frequency doubled Nd:YAG laser was used to treat the trabecular meshwork (TM). Laser treated TM was then subjected to proteomic analysis for detection of molecular changes and histological analysis for the detection of structural and protein expression patterns. In addition, the protein glycosylation patterns of laser treated and non-treated TM was assessed and differentially glycosylated proteins were proteomically identified. SLT laser treatment to the TM resulted in elevated glycosylation levels compared to non-lasered TM. TM laser treatment also resulted in protein expression levels changes of several proteins. Elevated levels of biglycan, keratocan and prolargin were detected in laser treated TM compared to non-lasered controls. Further investigation is anticipated to provide insight into how glycosylation changes affect TM proteins and TM regulation of aqueous outflow in response to laser trabeculoplasty. PMID:19432485

  17. Schlemm’s Canal and Trabecular Meshwork in Eyes with Primary Open Angle Glaucoma: A Comparative Study Using High-Frequency Ultrasound Biomicroscopy

    PubMed Central

    Yan, Xiaoqin; Li, Mu; Chen, Zhiqi; Zhu, Ying; Song, Yinwei; Zhang, Hong

    2016-01-01

    We investigated in vivo changes in Schlemm’s canal and the trabecular meshwork in eyes with primary open angle glaucoma (POAG). Relationships between Schlemm’s canal diameter, trabecular meshwork thickness, and intraocular pressure (IOP) were examined. Forty POAG patients and 40 normal individuals underwent 80-MHz Ultrasound Biomicroscopy examinations. The Schlemm’s canal and trabecular meshwork were imaged in superior, inferior, nasal and temporal regions. Normal individuals had an observable Schlemm’s canal in 80.3% of sections, a meridional canal diameter of 233.0±34.5 μm, a coronal diameter of 44.5±12.6 μm and a trabecular meshwork thickness of 103.9±11.1 μm, in POAG patients, Schlemm’s canal was observable in 53.1% of sections, a meridional canal diameter of 195.6±31.3 μm, a coronal diameter of 35.7±8.0 μm, and a trabecular meshwork thickness of 88.3±13.2 μm, which significantly differed from normal (both p <0.001). Coronal canal diameter (r = -0.623, p < 0.001) and trabecular meshwork thickness (r = -0.663, p < 0.001) were negatively correlated with IOP, but meridional canal diameter was not (r = -0.160, p = 0.156). Schlemm’s canal was observable in 50.5% and 56.6% of POAG patients with normal (<21 mmHg) and elevated (>21 mmHg) IOP, respectively (χ = 1.159, p = 0.282). Coronal canal diameter was significantly lower in the elevated IOP group (32.6±4.9 μm) than in the normal IOP group (35.7±8.0 μm, p < 0.001). This was also true of trabecular meshwork thickness (81.9±10.0 μm vs. 97.1±12.0 μm, p < 0.001). In conclusion, eyes with POAG had fewer sections with an observable Schlemm’s canal. Canal diameter and trabecular meshwork thickness were also lower than normal in POAG patients. Schlemm’s canal coronal diameter and trabecular meshwork thickness were negatively correlated with IOP. PMID:26726880

  18. Schlemm's Canal and Trabecular Meshwork in Eyes with Primary Open Angle Glaucoma: A Comparative Study Using High-Frequency Ultrasound Biomicroscopy.

    PubMed

    Yan, Xiaoqin; Li, Mu; Chen, Zhiqi; Zhu, Ying; Song, Yinwei; Zhang, Hong

    2016-01-01

    We investigated in vivo changes in Schlemm's canal and the trabecular meshwork in eyes with primary open angle glaucoma (POAG). Relationships between Schlemm's canal diameter, trabecular meshwork thickness, and intraocular pressure (IOP) were examined. Forty POAG patients and 40 normal individuals underwent 80-MHz Ultrasound Biomicroscopy examinations. The Schlemm's canal and trabecular meshwork were imaged in superior, inferior, nasal and temporal regions. Normal individuals had an observable Schlemm's canal in 80.3% of sections, a meridional canal diameter of 233.0±34.5 μm, a coronal diameter of 44.5±12.6 μm and a trabecular meshwork thickness of 103.9±11.1 μm, in POAG patients, Schlemm's canal was observable in 53.1% of sections, a meridional canal diameter of 195.6±31.3 μm, a coronal diameter of 35.7±8.0 μm, and a trabecular meshwork thickness of 88.3±13.2 μm, which significantly differed from normal (both p <0.001). Coronal canal diameter (r = -0.623, p < 0.001) and trabecular meshwork thickness (r = -0.663, p < 0.001) were negatively correlated with IOP, but meridional canal diameter was not (r = -0.160, p = 0.156). Schlemm's canal was observable in 50.5% and 56.6% of POAG patients with normal (<21 mmHg) and elevated (>21 mmHg) IOP, respectively (χ = 1.159, p = 0.282). Coronal canal diameter was significantly lower in the elevated IOP group (32.6±4.9 μm) than in the normal IOP group (35.7±8.0 μm, p < 0.001). This was also true of trabecular meshwork thickness (81.9±10.0 μm vs. 97.1±12.0 μm, p < 0.001). In conclusion, eyes with POAG had fewer sections with an observable Schlemm's canal. Canal diameter and trabecular meshwork thickness were also lower than normal in POAG patients. Schlemm's canal coronal diameter and trabecular meshwork thickness were negatively correlated with IOP. PMID:26726880

  19. In Vitro and in Vivo Experimental Studies on Trabecular Meshwork Degeneration Induced by Benzalkonium Chloride (An American Ophthalmological Society Thesis)

    PubMed Central

    Baudouin, Christophe; Denoyer, Alexandre; Desbenoit, Nicolas; Hamm, Gregory; Grise, Alice

    2012-01-01

    Purpose: Long-term antiglaucomatous drug administration may cause irritation, dry eye, allergy, subconjunctival fibrosis, or increased risk of glaucoma surgery failure, potentially due to the preservative benzalkonium chloride (BAK), whose toxic, proinflammatory, and detergent effects have extensively been shown experimentally. We hypothesize that BAK also influences trabecular meshwork (TM) degeneration. Methods: Trabecular specimens were examined using immunohistology and reverse transcriptase–polymerase chain reaction. A trabecular cell line was stimulated by BAK and examined for apoptosis, oxidative stress, fractalkine and SDF-1 expression, and modulation of their receptors. An experimental model was developed with BAK subconjunctival injections to induce TM degeneration. Mass spectrometry (MS) imaging assessed BAK penetration after repeated instillations in rabbit eyes. Results: Trabecular specimens showed extremely low densities of trabecular cells and presence of cells expressing fractalkine and fractalkine receptor and their respective mRNAs. Benzalkonium in vitro induced apoptosis, oxidative stress, and fractalkine expression and inhibited the protective chemokine SDF-1 and Bcl2, also inducing a sustained intraocular pressure (IOP) increase, with dramatic apoptosis of trabecular cells and reduction of aqueous outflow. MS imaging showed that BAK could access the TM at measurable levels after repeated instillations. Conclusion: BAK enhances all characteristics of TM degeneration typical of glaucoma—trabecular apoptosis, oxidative stress, induction of inflammatory chemokines—and causes degeneration in acute experimental conditions, potentially mimicking long-term accumulation. BAK was also shown to access the TM after repeated instillations. These findings support the hypothesis that antiglaucoma medications, through toxicity of their preservative, may cause further long-term trabecular degeneration and therefore enhance outflow resistance, reducing the

  20. Intraocular Pressure and the Mechanisms Involved in Resistance of the Aqueous Humor Flow in the Trabecular Meshwork Outflow Pathways.

    PubMed

    Tamm, Ernst R; Braunger, Barbara M; Fuchshofer, Rudolf

    2015-01-01

    Intraocular pressure (IOP), the critical risk factor for glaucoma, is generated and maintained by the aqueous humor circulation system. Aqueous humor is secreted from the epithelial layers of the ciliary body and exits the eye through the trabecular meshwork or the uveoscleral outflow pathways. IOP builds up in response to a resistance to aqueous humor flow in the trabecular outflow pathways. The trabecular outflow resistance is localized in the inner wall region, which comprises the juxtacanalicular connective tissue (JCT) and the inner wall endothelium of Schlemm's canal (SC). Outflow resistance in this region is lowered through the relaxation of contractile myofibroblast-like cells in trabecular meshwork and the adjacent scleral spur, or the contraction of the ciliary muscle. In primary open-angle glaucoma, the most frequent form of glaucoma, outflow resistance of the inner wall region is typically higher than normal. There is evidence that the increase in resistance is related to characteristic biological changes in the resident cells of the JCT, which more and more acquire the structural and functional characteristics of contractile myofibroblasts. The changes involve an augmentation of their actin cytoskeleton and of their surrounding fibrillary extracellular matrix, which connects to JCT cells via integrins. This scenario leads to an overall stiffening of the inner wall region, and is modulated by transforming growth factor-β/connective tissue growth factor signaling. Essentially comparable changes appear to occur in SC endothelial cells. Stiffening of JCT and SC cells is very likely a critical causative factor for the increase in trabecular outflow resistance in POAG. PMID:26310162

  1. Ascorbic Acid Modulation of Iron Homeostasis and Lysosomal Function in Trabecular Meshwork Cells

    PubMed Central

    Xu, Ping; Lin, Yizhi; Porter, Kristine

    2014-01-01

    Abstract Purpose: To investigate the antioxidant properties and biological functions of ascorbic acid (AA) on trabecular meshwork (TM) cells. Methods: Primary cultures of porcine TM cells were supplemented for 10 days with increasing concentrations of AA. Antioxidant properties against cytotoxic effect of H2O2 were evaluated by monitoring cell viability. Redox-active iron was quantified using calcein-AM. Intracellular reactive oxygen species (iROS) production was quantified using H2DCFDA. Ferritin and cathepsin protein levels were analyzed by Western blot. Autophagy was evaluated by monitoring lipidation of LC3-I to LC3-II. Lysosomal proteolysis and cathepsins activities were quantified using specific fluorogenic substrates. Results: AA exerts a dual effect against oxidative stress in TM cells, acting as an anti-oxidant or a pro-oxidant, depending on the concentration used. The pro-oxidant effect of AA was mediated by free intracellular iron and correlated with increased protein levels of ferritin and elevated iROS. In contrast, antioxidant properties correlated with lower ferritin and basal iROS content. Ascorbic acid supplementation also caused induction of autophagy, as well as increased lysosomal proteolysis, with the latter resulting from higher proteolytic activation of lysosomal cathepsins in treated cultures. Conclusions: Our results suggest that the reported decrease of AA levels in plasma and aqueous humor can compromise lysosomal degradation in the outflow pathway cells with aging and contribute to the pathogenesis of glaucoma. Restoration of physiological levels of vitamin C inside the cells might improve their ability to degrade proteins within the lysosomal compartment and recover tissue function. PMID:24552277

  2. Hic-5 Regulates Actin Cytoskeletal Reorganization and Expression of Fibrogenic Markers and Myocilin in Trabecular Meshwork Cells

    PubMed Central

    Pattabiraman, Padmanabhan Paranji; Rao, Ponugoti Vasantha

    2015-01-01

    Purpose To explore the role of inducible focal adhesion (FA) protein Hic-5 in actin cytoskeletal reorganization, FA formation, fibrogenic activity, and expression of myocilin in trabecular meshwork (TM) cells. Methods Using primary cultures of human TM (HTM) cells, the effects of various external factors on Hic-5 protein levels, as well as the effects of recombinant Hic-5 and Hic-5 small interfering RNA (siRNA) on actin cytoskeleton, FAs, myocilin, α-smooth muscle actin (αSMA), and collagen-1 were determined by immunofluorescence and immunoblot analyses. Results Hic-5 distributes discretely to the FAs in HTM cells and throughout the TM and Schlemm's canal of the human aqueous humor (AH) outflow pathway. Transforming growth factor-β2 (TGF-β2), endothelin-1, lysophosphatidic acid, hydrogen peroxide, and RhoA significantly increased Hic-5 protein levels in HTM cells in association with reorganization of actin cytoskeleton and FAs. While recombinant Hic-5 induced actin stress fibers, FAs, αv integrin redistribution to the FAs, increased levels of αSMA, collagen-1, and myocilin, Hic-5 siRNA suppressed most of these responses in HTM cells. Hic-5 siRNA also suppressed TGF-β2-induced fibrogenic activity and dexamethasone-induced myocilin expression in HTM cells. Conclusions Taken together, these results reveal that Hic-5, whose levels were increased by various external factors implicated in elevated intraocular pressure, induces actin cytoskeletal reorganization, FAs, expression of fibrogenic markers, and myocilin in HTM cells. These characteristics of Hic-5 in TM cells indicate its importance in regulation of AH outflow through the TM in both normal and glaucomatous eyes. PMID:26313302

  3. Regulation of Adherens Junctions in Trabecular Meshwork Cells by Rac GTPase and their influence on Intraocular Pressure

    PubMed Central

    Pattabiraman, Padmanabhan P; Epstein, David L; Rao, Ponugoti Vasantha

    2013-01-01

    Intercellular adherens junctions and cell-extracellular matrix interactions are presumed to influence aqueous humor (AH) drainage via the conventional route, however, their direct role in modulation of intraocular pressure (IOP) is not well understood. Here, we investigated the role of Rac GTPase signaling in basal and growth factor-induced formation of adherens junctions in human trabecular meshwork (HTM) cells as compared to human umbilical vascular endothelial cells, and evaluated the effects of inhibition of Rac GTPase activity on IOP in rabbits. Expression of a constitutively active Rac1 GTPase or treatment with platelet derived growth factor (PDGF), a known activator of Rac GTPase, induced formation of β-catenin-based adherens junctions, actin cytoskeletal reorganization and membrane ruffle in HTM cells. In contrast, treatment of HTM cells with inhibitors of Rac GTPase caused cell-cell separation, a decrease in adherens junctions, and reorganization of actin stress fibers to the cell cortical regions and focal adhesion to the cell leading edges. Both, constitutively active Rac1 and PDGF stimulated generation of Reactive Oxygen Species (ROS) in HTM cells, and ROS were found to increase adherens junction formation and transendothelial electrical resistance (TEER) in HTM cells. Topical application of Rac GTPase inhibitors (EHT1864 and NSC23766), however, only marginally influenced IOP in rabbit eyes. Taken together, these data reveal that while Rac GTPase signaling plays a significant role in regulation of adherens junctions, ROS production and TEER in cells of the AH outflow pathway, Rac inhibitors showed only a marginal influence on IOP in live rabbits. PMID:24932460

  4. Regulation of Adherens Junctions in Trabecular Meshwork Cells by Rac GTPase and their influence on Intraocular Pressure.

    PubMed

    Pattabiraman, Padmanabhan P; Epstein, David L; Rao, Ponugoti Vasantha

    2013-06-01

    Intercellular adherens junctions and cell-extracellular matrix interactions are presumed to influence aqueous humor (AH) drainage via the conventional route, however, their direct role in modulation of intraocular pressure (IOP) is not well understood. Here, we investigated the role of Rac GTPase signaling in basal and growth factor-induced formation of adherens junctions in human trabecular meshwork (HTM) cells as compared to human umbilical vascular endothelial cells, and evaluated the effects of inhibition of Rac GTPase activity on IOP in rabbits. Expression of a constitutively active Rac1 GTPase or treatment with platelet derived growth factor (PDGF), a known activator of Rac GTPase, induced formation of β-catenin-based adherens junctions, actin cytoskeletal reorganization and membrane ruffle in HTM cells. In contrast, treatment of HTM cells with inhibitors of Rac GTPase caused cell-cell separation, a decrease in adherens junctions, and reorganization of actin stress fibers to the cell cortical regions and focal adhesion to the cell leading edges. Both, constitutively active Rac1 and PDGF stimulated generation of Reactive Oxygen Species (ROS) in HTM cells, and ROS were found to increase adherens junction formation and transendothelial electrical resistance (TEER) in HTM cells. Topical application of Rac GTPase inhibitors (EHT1864 and NSC23766), however, only marginally influenced IOP in rabbit eyes. Taken together, these data reveal that while Rac GTPase signaling plays a significant role in regulation of adherens junctions, ROS production and TEER in cells of the AH outflow pathway, Rac inhibitors showed only a marginal influence on IOP in live rabbits. PMID:24932460

  5. Imaging the Effects of Prostaglandin Analogues on Cultured Trabecular Meshwork Cells by Coherent Anti-Stokes Raman Scattering

    PubMed Central

    Lei, Tim C.; Masihzadeh, Omid; Kahook, Malik Y.; Ammar, David A.

    2013-01-01

    Purpose. The aim of this study was to nondestructively monitor morphological changes to the lipid membranes of primary cultures of living human trabecular meshwork cells (hTMC) without the application of exogenous label. Methods. Live hTMC were imaged using two nonlinear optical techniques: coherent anti-Stokes Raman scattering (CARS) and two-photon autofluorescence (TPAF). The hTMC were treated with a commercial formulation of latanoprost (0.5 μg/mL) for 24 hours before imaging. Untreated cells and cells treated with vehicle containing the preservative benzalkonium chloride (BAK; 2 μg/mL) were imaged as controls. After CARS/TPAF imaging, hTMC were fixed, stained with the fluorescent lipid dye Nile Red, and imaged by conventional confocal microscopy to verify lipid membrane structures. Results. Analysis of CARS/TPAF images of hTMC treated with latanoprost revealed multiple intracellular lipid membranes absent from untreated or BAK-treated hTMC. Treatment of hTMC with sodium fluoride or ouabain, agents shown to cause morphological changes to hTMC, also did not induce formation of intracellular lipid membranes. Conclusions. CARS microscopy detected changes in living hTMC morphology that were validated by subsequent histological stain. Prostaglandin-induced changes to hTMC involved rearrangement of lipid membranes within these cells. These in vitro results identify a novel biological response to a class of antiglaucoma drugs, and further experiments are needed to establish how this effect is involved in the hypotensive action of prostaglandin analogues in vivo. PMID:23900606

  6. Non-contact high resolution Bessel beam probe for diagnostic imaging of cornea and trabecular meshwork region in eye

    NASA Astrophysics Data System (ADS)

    Murukeshan, V. M.; Jesmond, Hong Xun J.; Shinoj, V. K.; Baskaran, M.; Tin, Aung

    2015-07-01

    Primary angle closure glaucoma is a major form of disease that causes blindness in Asia and worldwide. In glaucoma, irregularities in the ocular aqueous outflow system cause an elevation in intraocular pressure (IOP) with subsequent death of retinal ganglion cells, resulting in loss of vision. High resolution visualization of the iridocorneal angle region has great diagnostic value in understanding the disease condition which enables monitoring of surgical interventions that decrease IOP. None of the current diagnostic techniques such as goniophotography, ultrasound biomicroscopy (UBM), anterior segment optical coherence tomography (AS-OCT) and RetCam™ can image with molecular specificity and required spatial resolution that can delineate the trabecular meshwork structures. This paper in this context proposes new concepts and methodology using Bessel beams based illumination and imaging for such diagnostic ocular imaging applications. The salient features using Bessel beams instead of the conventional Gaussian beam, and the optimization challenges in configuring the probe system will be illustrated with porcine eye samples.

  7. Effects of K-115 (Ripasudil), a novel ROCK inhibitor, on trabecular meshwork and Schlemm’s canal endothelial cells

    PubMed Central

    Kaneko, Yoshio; Ohta, Masayuki; Inoue, Toshihiro; Mizuno, Ken; Isobe, Tomoyuki; Tanabe, Sohei; Tanihara, Hidenobu

    2016-01-01

    Ripasudil hydrochloride hydrate (K-115), a specific Rho-associated coiled-coil containing protein kinase (ROCK) inhibitor, was the first ophthalmic solution developed for the treatment of glaucoma and ocular hypertension in Japan. Topical administration of K-115 decreased intraocular pressure (IOP) and increased outflow facility in rabbits. This study evaluated the effect of K-115 on monkey trabecular meshwork (TM) cells and Schlemm’s canal endothelial (SCE) cells. K-115 induced retraction and rounding of cell bodies as well as disruption of actin bundles in TM cells. In SCE-cell monolayer permeability studies, K-115 significantly decreased transendothelial electrical resistance (TEER) and increased the transendothelial flux of FITC-dextran. Further, K-115 disrupted cellular localization of ZO-1 expression in SCE-cell monolayers. These results indicate that K-115 decreases IOP by increasing outflow facility in association with the modulation of TM cell behavior and SCE cell permeability in association with disruption of tight junction. PMID:26782355

  8. Phase-sensitive optical coherence tomography characterization of pulse-induced trabecular meshwork displacement in ex vivo nonhuman primate eyes

    NASA Astrophysics Data System (ADS)

    Li, Peng; Reif, Roberto; Zhi, Zhongwei; Martin, Elizabeth; Shen, Tueng T.; Johnstone, Murray; Wang, Ruikang K.

    2012-07-01

    Glaucoma is a blinding disease for which intraocular pressure (IOP) is the only treatable risk factor. The mean IOP is regulated through the aqueous outflow system, which contains the trabecular meshwork (TM). Considerable evidence indicates that trabecular tissue movement regulates the aqueous outflow and becomes abnormal during glaucoma; however, such motion has thus far escaped detection. The purpose of this study is to describe anovel use of a phase-sensitive optical coherence tomography (PhS-OCT) method to assess pulse-dependent TM movement. For this study, we used enucleated monkey eyes, each mounted in an anterior segment holder. A perfusion system was used to control the mean IOP as well as to provide IOP sinusoidal transients (amplitude 3 mmHg, frequency 1 pulse/second) in all experiments. Measurements were carried out at seven graded mean IOPs (5, 8, 10, 20, 30, 40, and 50 mm Hg). We demonstrate that PhS-OCT is sensitive enough to image/visualize TM movement synchronous with the pulse-induced IOP transients, providing quantitative measurements of dynamic parameters such as velocity, displacement, and strain rate that are important for assessing the biomechanical compliance of the TM. We find that the largest TM displacement is in the area closest to Schlemm's canal (SC) endothelium. While maintaining constant ocular pulse amplitude, an increase of mean IOP results in a decrease of TM displacement and mean size of the SC. These results demonstrate that the PhS-OCT is a useful imaging technique capable of assessing functional properties necessary to maintain IOP in a healthy range, offering a new diagnostic alternative for glaucoma.

  9. Pro-fibrotic pathway activation in trabecular meshwork and lamina cribrosa is the main driving force of glaucoma.

    PubMed

    Zhavoronkov, Alex; Kanherkar, Riya R; Izumchenko, Evgeny; Teka, Mahder; Cantor, Charles; Manaye, Kebreten; Sidransky, David; West, Michael D; Makarev, Eugene; Csoka, Antonei Benjamin

    2016-06-17

    While primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide, it still does not have a clear mechanism that can explain all clinical cases of the disease. Elevated IOP is associated with increased accumulation of extracellular matrix (ECM) proteins in the trabecular meshwork (TM) that prevents normal outflow of aqueous humor (AH) and has damaging effects on the fine mesh-like lamina cribrosa (LC) through which the optic nerve fibers pass. Applying a pathway analysis algorithm, we discovered that an elevated level of TGFβ observed in glaucoma-affected tissues could lead to pro-fibrotic pathway activation in TM and in LC. In turn, activated pro-fibrotic pathways lead to ECM remodeling in TM and LC, making TM less efficient in AH drainage and making LC more susceptible to damage from elevated IOP via ECM transformation in LC. We propose pathway targets for potential therapeutic interventions to delay or avoid fibrosis initiation in TM and LC tissues. PMID:27229292

  10. Pro-fibrotic pathway activation in trabecular meshwork and lamina cribrosa is the main driving force of glaucoma

    PubMed Central

    Zhavoronkov, Alex; Izumchenko, Evgeny; Kanherkar, Riya R.; Teka, Mahder; Cantor, Charles; Manaye, Kebreten; Sidransky, David; West, Michael D.; Makarev, Eugene; Csoka, Antonei Benjamin

    2016-01-01

    ABSTRACT While primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide, it still does not have a clear mechanism that can explain all clinical cases of the disease. Elevated IOP is associated with increased accumulation of extracellular matrix (ECM) proteins in the trabecular meshwork (TM) that prevents normal outflow of aqueous humor (AH) and has damaging effects on the fine mesh-like lamina cribrosa (LC) through which the optic nerve fibers pass. Applying a pathway analysis algorithm, we discovered that an elevated level of TGFβ observed in glaucoma-affected tissues could lead to pro-fibrotic pathway activation in TM and in LC. In turn, activated pro-fibrotic pathways lead to ECM remodeling in TM and LC, making TM less efficient in AH drainage and making LC more susceptible to damage from elevated IOP via ECM transformation in LC. We propose pathway targets for potential therapeutic interventions to delay or avoid fibrosis initiation in TM and LC tissues. PMID:27229292

  11. Bovine Posterior Limbus: An Evaluation of an Alternative Source for Corneal Endothelial and Trabecular Meshwork Stem/Progenitor Cells

    PubMed Central

    Yu, Wing Yan; Grierson, Ian; Sheridan, Carl; Lo, Amy Cheuk-Yin

    2015-01-01

    A growing body of evidence has revealed that stem-like cells in the posterior limbus of the eye between the corneal endothelium (CE) and trabecular meshwork (TM) may be able to rejuvenate these tissues in disease. However, these cells have not been clearly defined and we have named them PET cells (progenitor cells of the endothelium and trabeculum). A good and inexpensive animal model for PET cells is lacking, so we investigated bovine eyes as an effective large tissue source. We showed the presence of stem/progenitor cells in the bovine CE, transition zone, and TM in situ. Floating spheres cultured from the CE and TM showed similar stem cell marker expression patterns. Both the CE and TM spheres were bipotent and highly proliferative, but with limited secondary sphere-forming capability. They were highly prone to differentiate back into the cell type of their tissue of origin. It is speculated that the PET cells become more tissue-specific as they migrate away from their niche. Here, we showed that PET cells are present in the posterior limbus of bovine eyes and that they can be successfully cultured and expanded. PET cells represent an attractive target for developing new treatments to regenerate both the CE and TM, thereby reducing the requirement for donor tissue for corneal transplant and invasive treatments for glaucomatous patients. PMID:25323922

  12. Effects of induction and inhibition of matrix cross-linking on remodeling of the aqueous outflow resistance by ocular trabecular meshwork cells

    PubMed Central

    Yang, Yong-Feng; Sun, Ying Ying; Acott, Ted S.; Keller, Kate E.

    2016-01-01

    The trabecular meshwork (TM) tissue controls drainage of aqueous humor from the anterior chamber of the eye primarily by regulating extracellular matrix (ECM) remodeling by matrix metalloproteinases (MMPs). Glaucomatous TM tissue is stiffer than age-matched controls, which may be due to alterations in ECM cross-linking. In this study, we used genipin or beta-aminopropionitrile (BAPN) agents to induce or inhibit matrix cross-linking, respectively, to investigate the effects on outflow resistance and ECM remodeling. Treatment with BAPN increased outflow rates in perfused human and porcine anterior segments, whereas genipin reduced outflow. Using a fluorogenic peptide assay, MMP activity was increased with BAPN treatment, but reduced with genipin treatment. In genipin-treated TM cells, Western immunoblotting showed a reduction of active MMP2 and MMP14 species and the presence of TIMP2-MMP14 higher molecular weight complexes. BAPN treatment increased collagen type I mRNA and protein levels, but genipin reduced the levels of collagen type I, tenascin C, elastin and versican. CD44 and fibronectin levels were unaffected by either treatment. Collectively, our results show that matrix cross-linking has profound effects on outflow resistance and ECM composition and are consistent with the emerging paradigm that the stiffer the ECM, the lower the aqueous outflow facility through the TM. PMID:27465745

  13. The Role of TGF-β2 and Bone Morphogenetic Proteins in the Trabecular Meshwork and Glaucoma

    PubMed Central

    Sharma, Tasneem; Clark, Abbot F.

    2014-01-01

    Abstract Primary open-angle glaucoma (POAG) is the second leading cause of blindness worldwide. Elevated intraocular pressure (IOP) is a primary risk factor associated with POAG. Increased aqueous humor (AH) outflow resistance through the trabecular meshwork (TM) results in elevated IOP in POAG patients. Resistance to AH outflow is associated with increased accumulation of extracellular matrix (ECM) proteins in the TM. In addition, levels of transforming growth factor-beta2 (TGF-β2) are elevated in the AH and TM tissue of POAG patients. Elevated levels of TGF-β2 in other tissues have been associated with fibrosis and increased tissue stiffness. However, locally produced effectors that maintain homeostatic relationships must also be present. Bone morphogenetic proteins (BMPs) serve this purpose in the TM as they inhibit TGF-β2-induced ECM changes in TM cells. This review article first describes the TGF-β superfamily of growth factors including BMPs and their canonical and noncanonical signaling pathways. The article then addresses the role of TGF-β2 in the pathophysiology of POAG as related to the ECM and ECM crosslinking enzymes. This is followed by a discussion of potential homeostatic control mechanisms of TGF-β2 signaling in the TM including the inhibitory role of BMP-4 and BMP-7. We then describe the relationship of TGF-β2 and BMPs in TM fibrosis including the role of antagonists. Lastly, in future directions, we identify potential future studies that explore new and unique cellular interactions within the TM for potential therapeutic interventions. PMID:24517218

  14. Intraocular Pressure Regulation: Findings of Pulse-Dependent Trabecular Meshwork Motion Lead to Unifying Concepts of Intraocular Pressure Homeostasis

    PubMed Central

    2014-01-01

    Abstract Intraocular pressure (IOP) is the only treatable risk factor in glaucoma, one of the world's leading causes of blindness. Mechanisms that maintain IOP within a normal range have been poorly understood in contrast to intrinsic mechanisms that regulate systemic blood pressure. Vessel walls experience continuous pulse-induced cyclic pressure and flow. Pressure-dependent wall stress and flow-dependent shear stress provide sensory signals that initiate mechanotransduction responses. The responses optimize vessel wall elasticity, compliance and lumen size, providing a feedback loop to maintain intrinsic pressure homeostasis. Aqueous humor is part of a vascular circulatory loop, being secreted into the anterior chamber of the eye from the vasculature, then returning to the vasculature by passing through the trabecular meshwork (TM), a uniquely modified vessel wall interposed between the anterior chamber and a vascular sinus called Schlemm's canal (SC). Since pressure in circulatory loops elsewhere is modulated by cyclic stresses, one might predict similar pressure modulation in the aqueous outflow system. Recent laboratory evidence in fact demonstrates that cyclic IOP changes alter aqueous outflow while increasing cellularity and contractility of TM cells. Cyclic changes also lead to alterations in gene expression, changes in cytoskeletal networks and modulation of signal transduction. A new technology, phase-based optical coherence tomography, demonstrates in vivo pulse-dependent TM motion like that elsewhere in the vasculature. Recognition of pulse-dependent TM motion provides a linkage to well-characterized mechanisms that provide pressure homeostasis in the systemic vasculature. The linkage may permit unifying concepts of pressure control and provide new insights into IOP homeostatic mechanisms. PMID:24359130

  15. The role of calcium-independent phospholipase A2γ in modulation of aqueous humor drainage and Ca2+ sensitization of trabecular meshwork contraction

    PubMed Central

    Pattabiraman, Padmanabhan P.; Lih, Fred B.; Tomer, Kenneth B.

    2012-01-01

    The contractile and relaxation characteristics of trabecular meshwork (TM) are presumed to influence aqueous humor (AH) drainage and intraocular pressure. The mechanisms underlying regulation of TM cell contractile properties, however, are not well understood. This study investigates the role of calcium-independent phospholipase A2 (iPLA2), which controls eicosanoid synthesis, in regulation of TM cell contraction and AH outflow using mechanism-based isoform specific inhibitors (R)-bromoenol lactone (R-BEL, iPLA2γ specific) and (S)-bromoenol lactone (S-BEL, iPLA2β specific). Immunohistochemical analysis revealed intense staining for both iPLA2β and γ isoforms throughout the TM, juxtacanalicular tissue, and Schlemm's canal of human eye. Inhibition of iPLA2γ by R-BEL or small interfering RNA-mediated silencing of iPLA2γ expression induced dramatic changes in TM cell morphology, and decreased actin stress fibers, focal adhesions, and myosin light-chain (MLC) phosphorylation. AH outflow facility increased progressively and significantly in enucleated porcine eyes perfused with R-BEL. This response was associated with a significant decrease in TM tissue MLC phosphorylation and alterations in the morphology of aqueous plexi in R-BEL-perfused eyes. In contrast, S-BEL did not affect either of these parameters. Additionally, R-BEL-induced cellular relaxation of the TM was associated with a significant decrease in the levels of active Rho GTPase, phospho-MLC phosphatase, phospho-CPI-17, and arachidonic acid. Taken together, these observations demonstrate that iPLA2γ plays a significant and isoform-specific role in regulation of AH outflow facility by altering the contractile characteristics of the TM. The effects of iPLA2γ on TM contractile status appear to involve arachidonic acid and Rho GTPase signaling pathways. PMID:22237407

  16. Progenitors for the corneal endothelium and trabecular meshwork: a potential source for personalized stem cell therapy in corneal endothelial diseases and glaucoma.

    PubMed

    Yu, Wing Yan; Sheridan, Carl; Grierson, Ian; Mason, Sharon; Kearns, Victoria; Lo, Amy Cheuk Yin; Wong, David

    2011-01-01

    Several adult stem cell types have been found in different parts of the eye, including the corneal epithelium, conjunctiva, and retina. In addition to these, there have been accumulating evidence that some stem-like cells reside in the transition area between the peripheral corneal endothelium (CE) and the anterior nonfiltering portion of the trabecular meshwork (TM), which is known as the Schwalbe's Ring region. These stem/progenitor cells may supply new cells for the CE and TM. In fact, the CE and TM share certain similarities in terms of their embryonic origin and proliferative capacity in vivo. In this paper, we discuss the putative stem cell source which has the potential for replacement of lost and nonfunctional cells in CE diseases and glaucoma. The future development of personalized stem cell therapies for the CE and TM may reduce the requirement of corneal grafts and surgical treatments in glaucoma. PMID:22187525

  17. Glaucomatous MYOC mutations activate the IL-1/NF-κB inflammatory stress response and the glaucoma marker SELE in trabecular meshwork cells

    PubMed Central

    Itakura, Tatsuo; Peters, Donna M.

    2015-01-01

    Purpose Activation of the IL-1/NF-κB inflammatory stress pathway and induction of SELE expression in the trabecular meshwork (TBM) is a marker for high-tension glaucomas of diverse etiology. Pathway activation stimulates aqueous outflow and protects against oxidative stress, but may be damaging in the long-term. MYOC mutations have been causally linked to high-tension forms of primary open angle glaucoma (POAG). This study investigated a possible link between MYOC mutations and activation of the IL-1/NF-κB pathway and expression of SELE. Methods We constructed MYOC expression vectors with mutations at sites that cause POAG. Mutations (Q368X, Y437H, A427T) were selected to represent proteins with differing POAG-causing potency (Q368X > Y437H > A427T) and intracellular retention behavior (Q368X and Y437H retained, A427T released). The constructs were made in two different kinds of vectors; one a plasmid designed for transient transfection (pCMV6), and one a doxycycline-inducible lentiviral vector (pSLIK) for stable cell transduction. The immortalized human trabecular meshwork line TM-1 was used for all expression studies. Expression of IL1A mRNA was determined by reverse transcription (RT)–PCR, as well as a set of five other genes associated with signaling pathways linked to glaucoma: IL1B and IL6 (NF-κB pathway), TGFB2 and ACTA2 (TGF-β pathway) and FOXO1 (E2F1 apoptotic pathway). An ELISA was used to quantify IL1A protein released into culture media. To quantify intracellular NF-κB activity, we transiently transfected stably transduced cell lines with a luciferase expression vector under control of the IL8 promoter (containing an NF-κB response element). Results Transiently expressed wild-type MYOC was released into cell culture media, whereas mutant MYOCs Q368X and Y437H remained within cells. Both mutant MYOCs activated the IL-1/ NF-κB pathway, significantly stimulating expression of IL1A and IL1B. However Y437H, which causes a severe glaucoma phenotype

  18. Trabecular Plates and Rods Determine Elastic Modulus and Yield Strength of Human Trabecular Bone

    PubMed Central

    Wang, Ji; Zhou, Bin; Liu, X. Sherry; Fields, Aaron J.; Sanyal, Arnav; Shi, Xiutao; Adams, Mark; Keaveny, Tony M.; Guo, X. Edward

    2014-01-01

    The microstructure of trabecular bone is usually perceived as a collection of plate-like and rod-like trabeculae, which can be determined from the emerging high-resolution skeletal imaging modalities such as micro computed tomography (μCT) or clinical high-resolution peripheral quantitative CT (HR-pQCT) using the individual trabecula segmentation (ITS) technique. It has been shown that the ITS-based plate and rod parameters are highly correlated with elastic modulus and yield strength of human trabecular bone. In the current study, plate-rod (PR) finite element (FE) models were constructed completely based on ITS-identified individual trabecular plates and rods. We hypothesized that PR FE can accurately and efficiently predict elastic modulus and yield strength of human trabecular bone. Human trabecular bone cores from proximal tibia (PT), femoral neck (FN) and greater trochanter (GT) were scanned by micro computed tomography (μCT). Specimen-specific ITS-based PR FE models were generated for each μCT image and corresponding voxel-based FE models were also generated in comparison. Both types of specimen-specific models were subjected to nonlinear FE analysis to predict the apparent elastic modulus and yield strength using the same trabecular bone tissue properties. Then, mechanical tests were performed to experimentally measure the apparent modulus and yield strength. Strong linear correlations for both elastic modulus (r2=0.97) and yield strength (r2=0.96) were found between the PR FE model predictions and experimental measures, suggesting that trabecular plates and rods morphology adequately captures three-dimensional (3D) microarchitecture of human trabecular bone. In addition, the PR FE model predictions in both elastic modulus and yield strength were highly correlated with the voxel-based FE models (r2=0.99, r2=0.98, respectively), resulted from the original 3D images without the PR segmentation. In conclusion, the ITS-based PR models predicted accurately

  19. A Novel Mgp-Cre Knock-In Mouse Reveals an Anticalcification/Antistiffness Candidate Gene in the Trabecular Meshwork and Peripapillary Scleral Region

    PubMed Central

    Borrás, Teresa; Smith, Matthew H.; Buie, LaKisha K.

    2015-01-01

    Purpose. Soft tissue calcification is a pathological condition. Matrix Gla (MGP) is a potent mineralization inhibitor secreted by cartilage chondrocytes and arteries' vascular smooth muscle cells. Mgp knock-out mice die at 6 weeks due to massive arterial calcification. Arterial calcification results in arterial stiffness and higher systolic blood pressure. Intriguingly, MGP was highly abundant in trabecular meshwork (TM). Because tissue stiffness is relevant to glaucoma, we investigated which additional eye tissues use Mgp's function using knock-in mice. Methods. An Mgp–Cre-recombinase coding sequence (Cre) knock-in mouse, containing Mgp DNA plus an internal ribosomal entry site (IRES)-Cre-cassette was generated by homologous recombination. Founders were crossed with Cre-mediated reporter mouse R26R-lacZ. Their offspring expresses lacZ where Mgp is transcribed. Eyes from MgpCre/+;R26RlacZ/+ (Mgp-lacZ knock-in) and controls, 1 to 8 months were assayed for β-gal enzyme histochemistry. Results. As expected, Mgp-lacZ knock-in's TM was intensely blue. In addition, this mouse revealed high specific expression in the sclera, particularly in the peripapillary scleral region (ppSC). Ciliary muscle and sclera above the TM were also positive. Scleral staining was located immediately underneath the choroid (chondrocyte layer), began midsclera and was remarkably high in the ppSC. Cornea, iris, lens, ciliary body, and retina were negative. All mice exhibited similar staining patterns. All controls were negative. Conclusions. Matrix Gla's restricted expression to glaucoma-associated tissues from anterior and posterior segments suggests its involvement in the development of the disease. Matrix Gla's anticalcification/antistiffness properties in the vascular tissue, together with its high TM and ppCS expression, place this gene as a strong candidate for TM's softness and sclera's stiffness regulation in glaucoma. PMID:25711639

  20. Isolation of osteocytes from human trabecular bone.

    PubMed

    Prideaux, Matthew; Schutz, Christine; Wijenayaka, Asiri R; Findlay, David M; Campbell, David G; Solomon, Lucian B; Atkins, Gerald J

    2016-07-01

    Osteocytes are essential regulators of bone homeostasis. However, they are difficult to study due to their location within the bone mineralised matrix. Although several techniques have been published for the isolation of osteocytes from mouse bone, no such technique has been described for human osteocytes. We have therefore developed a protocol for the isolation of osteocytes from human trabecular bone samples acquired during surgery. The cells were digested from the bone matrix by sequential collagenase and ethylenediaminetetraacetic acid (EDTA) digestions and the cells from later digests displayed characteristic dendritic osteocyte morphology when cultured ex vivo. Furthermore, the cells expressed characteristic osteocyte marker genes, such as E11, dentin matrix protein 1 (DMP1), SOST, matrix extracellular phosphoglycoprotein (MEPE) and phosphate regulating endopeptidase homologue, X-linked (PHEX). In addition, genes associated with osteocyte perilacunar remodelling, including matrix metallopeptidase-13 (MMP13), cathepsin K (CTSK) and carbonic anhydrase 2 (CAR2) were expressed. The cells also responded to parathyroid hormone (PTH) by downregulating SOST mRNA expression and to 1α,25-dihydroxyvitamin D3 (1,25D) by upregulating fibroblast growth factor 23 (FGF23) mRNA expression. Therefore, the cells behave in a similar manner to osteocytes in vivo. These cells represent an important tool in enhancing current knowledge in human osteocyte biology. PMID:27109824

  1. Trabecular bone structural variation throughout the human lower limb.

    PubMed

    Saers, Jaap P P; Cazorla-Bak, Yasmin; Shaw, Colin N; Stock, Jay T; Ryan, Timothy M

    2016-08-01

    differences in habitual activity when inferring behaviour from the trabecular structure of hominin fossils through comparisons with modern humans. PMID:27457548

  2. Scanning acoustic microscopy study of human cortical and trabecular bone.

    PubMed

    Bumrerraj, S; Katz, J L

    2001-12-01

    Scanning acoustic microscopy (SAM) has been used in the burst mode to study the properties of human cortical and trabecular bone. An Olympus UH3 SAM (Olympus Co., Tokyo, Japan) was used with a 400 MHz burst mode lens (120 degrees aperture, nominal lateral resolution 2.5 microm). The human cortical bone was from the midshaft of a femur from a 60+ male cadaver; the trabecular bone specimens were obtained from the distal femoral condyles of another 60+ human male cadaver. Elastic moduli for both trabecular and cortical bone were obtained by means of a series of calibration curves correlating SAM gray levels of known materials with their elastic moduli; specimens included: polypropylene, PMMA, Teflon, aluminum, Pyrex glass, titanium, and stainless steel. Values obtained by this method are in good agreement with those obtained by nanoindentation techniques. The three critical findings earlier by Katz and Meunier were observed here as well in both the cortical and trabecular bone samples. PMID:11853252

  3. Recent origin of low trabecular bone density in modern humans.

    PubMed

    Chirchir, Habiba; Kivell, Tracy L; Ruff, Christopher B; Hublin, Jean-Jacques; Carlson, Kristian J; Zipfel, Bernhard; Richmond, Brian G

    2015-01-13

    Humans are unique, compared with our closest living relatives (chimpanzees) and early fossil hominins, in having an enlarged body size and lower limb joint surfaces in combination with a relatively gracile skeleton (i.e., lower bone mass for our body size). Some analyses have observed that in at least a few anatomical regions modern humans today appear to have relatively low trabecular density, but little is known about how that density varies throughout the human skeleton and across species or how and when the present trabecular patterns emerged over the course of human evolution. Here, we test the hypotheses that (i) recent modern humans have low trabecular density throughout the upper and lower limbs compared with other primate taxa and (ii) the reduction in trabecular density first occurred in early Homo erectus, consistent with the shift toward a modern human locomotor anatomy, or more recently in concert with diaphyseal gracilization in Holocene humans. We used peripheral quantitative CT and microtomography to measure trabecular bone of limb epiphyses (long bone articular ends) in modern humans and chimpanzees and in fossil hominins attributed to Australopithecus africanus, Paranthropus robustus/early Homo from Swartkrans, Homo neanderthalensis, and early Homo sapiens. Results show that only recent modern humans have low trabecular density throughout the limb joints. Extinct hominins, including pre-Holocene Homo sapiens, retain the high levels seen in nonhuman primates. Thus, the low trabecular density of the recent modern human skeleton evolved late in our evolutionary history, potentially resulting from increased sedentism and reliance on technological and cultural innovations. PMID:25535354

  4. Recent origin of low trabecular bone density in modern humans

    PubMed Central

    Chirchir, Habiba; Kivell, Tracy L.; Ruff, Christopher B.; Hublin, Jean-Jacques; Carlson, Kristian J.; Zipfel, Bernhard; Richmond, Brian G.

    2015-01-01

    Humans are unique, compared with our closest living relatives (chimpanzees) and early fossil hominins, in having an enlarged body size and lower limb joint surfaces in combination with a relatively gracile skeleton (i.e., lower bone mass for our body size). Some analyses have observed that in at least a few anatomical regions modern humans today appear to have relatively low trabecular density, but little is known about how that density varies throughout the human skeleton and across species or how and when the present trabecular patterns emerged over the course of human evolution. Here, we test the hypotheses that (i) recent modern humans have low trabecular density throughout the upper and lower limbs compared with other primate taxa and (ii) the reduction in trabecular density first occurred in early Homo erectus, consistent with the shift toward a modern human locomotor anatomy, or more recently in concert with diaphyseal gracilization in Holocene humans. We used peripheral quantitative CT and microtomography to measure trabecular bone of limb epiphyses (long bone articular ends) in modern humans and chimpanzees and in fossil hominins attributed to Australopithecus africanus, Paranthropus robustus/early Homo from Swartkrans, Homo neanderthalensis, and early Homo sapiens. Results show that only recent modern humans have low trabecular density throughout the limb joints. Extinct hominins, including pre-Holocene Homo sapiens, retain the high levels seen in nonhuman primates. Thus, the low trabecular density of the recent modern human skeleton evolved late in our evolutionary history, potentially resulting from increased sedentism and reliance on technological and cultural innovations. PMID:25535354

  5. Gene expression profiling of TGFβ2- and/or BMP7-treated trabecular meshwork cells: Identification of Smad7 as a critical inhibitor of TGF-β2 signaling

    PubMed Central

    Fuchshofer, Rudolf; Stephan, Dietrich A.; Russell, Paul; Tamm, Ernst R.

    2009-01-01

    A distinct structural change in the trabecular meshwork (TM) of patients with primary open-angle glaucoma (POAH) is the increase in fibrillar extracellular matrix (ECM) in the juxtacanalicular region of the TM. Transforming growth factor (TGF)-β2 signaling may be involved, as TGF-β2 is significantly increased in the aqueous humor of patients with POAG. In cultured human TM cells, TGF-β2 causes an increase in ECM deposition, an effect that is blunted or prevented, if BMP7 is added in combination with TGF-β2. In order to know more about the signaling network that is induced in HTM cells treated with BMP7, TGF-β2 or the combination of both factors, we identified differentially regulated genes by microarray analysis, and confirmed selected genes by quantitative RT-PCR, Western blotting, or immunohistochemistry. We observed multiple effects of both TGF-β2 and BMP7 on the expression of a considerable number of genes involved in growth factor signaling, ECM structure and turnover, and modification of the cytoskeleton. Among the genes that were found to be regulated were CAPZA1, CDC42BPB, EFEMP1, FGF5, FSTL3, HBEGF, LTBP1, LTBP2, MATN2, NRP1, SERPINE1, SH3MD1, SMTN, SMAD7, TFPI2, TNFAIP6, and VEGF. Since SMAD7 encodes for Smad7, an inhibitory Smad that acts in a negative feedback loop to inhibit TGF-β activity, we silenced Smad7 mRNA in cultured human TM cells by a specific small interfering RNA. Silencing of its mRNA caused a substantial knock down of Smad7 in TM cells. Following combined BMP7/TGF-β2 treatment, the antagonizing effect of BMP7 on TGF-β2 induced CTGF expression was abolished. We conclude that Smad7 is the key molecular switch that inhibits TGF-β2 signaling, and mediates the blunting effects of BMP7 on TGF-β2 in TM cells. A therapeutic modulation of Smad7 might be a promising approach to influence ECM turnover in the TM and to treat POAG. PMID:19450457

  6. Determinants of Microdamage in Elderly Human Vertebral Trabecular Bone

    PubMed Central

    Follet, Hélène; Farlay, Delphine; Bala, Yohann; Viguet-Carrin, Stéphanie; Gineyts, Evelyne; Burt-Pichat, Brigitte; Wegrzyn, Julien; Delmas, Pierre; Boivin, Georges; Chapurlat, Roland

    2013-01-01

    Previous studies have shown that microdamage accumulates in bone as a result of physiological loading and occurs naturally in human trabecular bone. The purpose of this study was to determine the factors associated with pre-existing microdamage in human vertebral trabecular bone, namely age, architecture, hardness, mineral and organic matrix. Trabecular bone cores were collected from human L2 vertebrae (n = 53) from donors 54–95 years of age (22 men and 30 women, 1 unknown) and previous cited parameters were evaluated. Collagen cross-link content (PYD, DPD, PEN and % of collagen) was measured on surrounding trabecular bone. We found that determinants of microdamage were mostly the age of donors, architecture, mineral characteristics and mature enzymatic cross-links. Moreover, linear microcracks were mostly associated with the bone matrix characteristics whereas diffuse damage was associated with architecture. We conclude that linear and diffuse types of microdamage seemed to have different determinants, with age being critical for both types. PMID:23457465

  7. Determinants of microdamage in elderly human vertebral trabecular bone.

    PubMed

    Follet, Hélène; Farlay, Delphine; Bala, Yohann; Viguet-Carrin, Stéphanie; Gineyts, Evelyne; Burt-Pichat, Brigitte; Wegrzyn, Julien; Delmas, Pierre; Boivin, Georges; Chapurlat, Roland

    2013-01-01

    Previous studies have shown that microdamage accumulates in bone as a result of physiological loading and occurs naturally in human trabecular bone. The purpose of this study was to determine the factors associated with pre-existing microdamage in human vertebral trabecular bone, namely age, architecture, hardness, mineral and organic matrix. Trabecular bone cores were collected from human L2 vertebrae (n = 53) from donors 54-95 years of age (22 men and 30 women, 1 unknown) and previous cited parameters were evaluated. Collagen cross-link content (PYD, DPD, PEN and % of collagen) was measured on surrounding trabecular bone. We found that determinants of microdamage were mostly the age of donors, architecture, mineral characteristics and mature enzymatic cross-links. Moreover, linear microcracks were mostly associated with the bone matrix characteristics whereas diffuse damage was associated with architecture. We conclude that linear and diffuse types of microdamage seemed to have different determinants, with age being critical for both types. PMID:23457465

  8. Interrelationships between electrical properties and microstructure of human trabecular bone

    NASA Astrophysics Data System (ADS)

    Sierpowska, J.; Hakulinen, M. A.; Töyräs, J.; Day, J. S.; Weinans, H.; Kiviranta, I.; Jurvelin, J. S.; Lappalainen, R.

    2006-10-01

    Microstructural changes, such as reduction of trabecular thickness and number, are characteristic signs of osteoporosis leading to diminished bone strength. Electrical and dielectric parameters might provide diagnostically valuable information on trabecular bone microstructure not extractable from bone mineral density measurements. In this study, structural properties of human trabecular bone samples (n = 26) harvested from the distal femur and proximal tibia were investigated using the computed microtomography (microCT) technique. Quantitative parameters, e.g. structural model index (SMI) or trabecular bone volume fraction (BV/TV), were calculated. In addition, the samples were examined electrically over a wide frequency range (50 Hz-5 MHz) using a two-electrode impedance spectroscopy set-up. Relative permittivity, loss factor, conductivity, phase angle, specific impedance and dissipation factor were determined. Significant linear correlations were obtained between the dissipation factor and BV/TV or SMI (|r| >= 0.70, p < 0.01, n = 26). Principal component analyses, conducted on electrical and structural parameters, revealed that the high frequency principal component of the dissipation factor was significantly related to SMI (r = 0.72, p < 0.01, n = 26). The linear combination of high and low frequency relative permittivity predicted 73% of the variation in BV/TV. To conclude, electrical and dielectric parameters of trabecular bone, especially relative permittivity and dissipation factor, were significantly and specifically related to a trabecular microstructure as characterized with microCT. The data gathered in this study constitute a useful basis for theoretical and experimental work towards the development of impedance spectroscopy techniques for detection of bone quality in vitro or in special cases of open surgery.

  9. Limited Trabecular Bone Density Heterogeneity in the Human Skeleton

    PubMed Central

    Chirchir, Habiba

    2016-01-01

    There is evidence for variation in trabecular bone density and volume within an individual skeleton, albeit in a few anatomical sites, which is partly dependent on mechanical loading. However, little is known regarding the basic variation in trabecular bone density throughout the skeleton in healthy human adults. This is because research on bone density has been confined to a few skeletal elements, which can be readily measured using available imaging technology particularly in clinical settings. This study comprehensively investigates the distribution of trabecular bone density within the human skeleton in nine skeletal sites (femur, proximal and distal tibia, third metatarsal, humerus, ulna, radius, third metacarpal, and axis) in a sample of N = 20 individuals (11 males and 9 females). pQCT results showed that the proximal ulna (mean = 231.3 mg/cm3) and axis vertebra (mean = 234.3 mg/cm3) displayed significantly greater (p < 0.01) trabecular bone density than other elements, whereas there was no significant variation among the rest of the elements (p > 0.01). The homogeneity of the majority of elements suggests that these sites are potentially responsive to site-specific genetic factors. Secondly, the lack of correlation between elements (p > 0.05) suggests that density measurements of one anatomical region are not necessarily accurate measures of other anatomical regions. PMID:27148458

  10. The 3D structure of the collagen fibril network in human trabecular bone: relation to trabecular organization.

    PubMed

    Reznikov, Natalie; Chase, Hila; Brumfeld, Vlad; Shahar, Ron; Weiner, Steve

    2015-02-01

    Trabecular bone is morphologically and functionally different from compact bone at the tissue level, but both are composed of lamellae at the micrometer-scale level. We present a three-dimensional study of the collagenous network of human trabecular lamellar bone from the proximal femur using the FIB-SEM serial surface view method. The results are compared to human compact lamellar bone of the femoral shaft, studied by the same method. Both demineralized trabecular and compact lamellar bone display the same overall structural organization, namely the presence of ordered and disordered materials and the confinement of the canalicular network to the disordered material. However, in trabecular bone lamellae a significant proportion of the ordered collagen fibril arrays is aligned with the long axis of the trabecula and, unlike in compact bone, is not related to the anatomical axis of the whole femur. The remaining ordered collagen fibrils are offset from the axis of a trabecula either by about 30° or 70°. Interestingly, at the tissue scale of millimeters, the most abundant angles between any two connected trabeculae - the inter-trabecular angles - center around 30° and 70°. This implies that within a framework of interconnected trabeculae the same lamellar structure will always have a significant component of the fibrils aligned with the long axes of connected trabeculae. This structural complementarity at different hierarchical levels presumably reflects an adaptation of trabecular bone to function. PMID:25445457

  11. Creep of trabecular bone from the human proximal tibia

    PubMed Central

    Novitskaya, Ekaterina; Zin, Carolyn; Chang, Neil; Cory, Esther; Chen, Peter; D'Lima, Darryl; Sah, Robert L.; McKittrick, Joanna

    2014-01-01

    Creep is the deformation that occurs under a prolonged, sustained load and can lead to permanent damage in bone. Creep in bone is a complex phenomenon and varies with type of loading and local mechanical properties. Human trabecular bone samples from proximal tibia were harvested from a 71-year old female cadaver with osteoporosis. The samples were initially subjected to one cycle load up to 1% strain to determine the creep load. Samples were then loaded in compression under a constant stress for two hours and immediately unloaded. All tests were conducted with the specimens soaked in phosphate buffered saline with proteinase inhibitors at 37°C. Steady state creep rate and final creep strain were estimated from mechanical testing and compared with published data. The steady state creep rate correlated well with values obtained from bovine tibial and human vertebral trabecular bone, and was higher for lower density samples. Tissue architecture was analyzed by micro-computed tomography (μCT) both before and after creep testing to assess creep deformation and damage accumulated. Quantitative morphometric analysis indicated that creep induced changes in trabecular separation and the structural model index. A main mode of deformation was bending of trabeculae. PMID:24857486

  12. Elastic Anisotropy of Trabecular Bone in the Elderly Human Vertebra.

    PubMed

    Unnikrishnan, Ginu U; Gallagher, John A; Hussein, Amira I; Barest, Glenn D; Morgan, Elise F

    2015-11-01

    Knowledge of the nature of the elastic symmetry of trabecular bone is fundamental to the study of bone adaptation and failure. Previous studies have classified human vertebral trabecular bone as orthotropic or transversely isotropic but have typically obtained samples from only selected regions of the centrum. In this study, the elastic symmetry of human vertebral trabecular bone was characterized using microfinite element (μFE) analyses performed on 1019 cubic regions of side length equal to 5 mm, obtained via thorough sampling of the centrums of 18 human L1 vertebrae (age = 81.17 ± 7.7 yr; eight males and ten females). An optimization procedure was used to find the closest orthotropic representation of the resulting stiffness tensor for each cube. The orthotropic elastic constants and orientation of the principal elastic axes were then recorded for each cube and were compared to the constants predicted from Cowin's fabric-based constitutive model (Cowin, 1985, "The Relationship Between the Elasticity Tensor and the Fabric Tensor," Mech. Mater., 4(2), pp. 137-147.) and the orientation of the principal axes of the fabric tensor, respectively. Deviations from orthotropy were quantified by the "orthotropic error" (van Rietbergen et al., 1996, "Direct Mechanics Assessment of Elastic Symmetries and Properties of Trabecular Bone Architecture," J. Biomech., 29(12), pp. 1653-1657), and deviations from transverse isotropy were determined by statistical comparison of the secondary and tertiary elastic moduli. The orthotropic error was greater than 50% for nearly half of the cubes, and the secondary and tertiary moduli differed from one another (p < 0.0001). Both the orthotropic error and the difference between secondary and tertiary moduli decreased with increasing bone volume fraction (BV/TV; p ≤ 0.007). Considering only the cubes with an orthotropic error less than 50%, only moderate correlations were observed between the fabric-based and the

  13. Topology optimization of trabecular bone in the human spine

    NASA Astrophysics Data System (ADS)

    Elbanna, Ahmed

    2015-03-01

    It is widely believed in the realm of biology that the trabecular structure of long bones self-optimizes in response to mechanical loads, in accordance with Wolff's law. Here, we examine this idea by applying techniques from topology optimization the human spine. We consider different domain geometries as well as different load cases to account for the various loading conditions and changes in shape that take place within the spine during day-to-day activities and over the years. We show that the classical approach of minimizing compliance subject to a volume constraint does not yield a sponge-like architecture but results in only vertical trabeculae. Additional constraints/objective functions have to be considered simultaneously. We show that more realistic trabecular geometries may be produced by taking into consideration the function of trabecular bone as a reservoir for minerals and bone marrow production. By maximizing the surface area of the generated voids while minimizing the total volume of the trabeculae subject to a constraint on their buckling strength, we recover the sponge-like structure. Our results shed light on the optimizing conditions for bone structure beyond Wolff's law and provide guidelines for biomimetic material design.

  14. High-Speed Photography during Compression Testing Human Trabecular Bone

    NASA Astrophysics Data System (ADS)

    Thurner, Philipp; Langan, John; Erickson, Blake

    2005-03-01

    The mechanical properties of healthy and diseased bone are extensively studied. Most of this research is motivated by the immense costs in health care due to osteoporosis. To address the problem of assessing bone microarchitecture and concomitant microcracking behavior, we recently combined mechanical compression testing of trabecular bone with high-speed photography. In an exemplary study, we investigated healthy, osteoarthritic, and osteoporotic human vertebral trabecular bone. Bone samples were loaded along their principal load-bearing axis at high strain rates simulating boundary conditions as experienced in individuals during falls. Even at small global strains huge local deformations could be seen in the recorded high-speed photography frames. Moreover, strained trabeculae were seen to whiten with increasing strain, which could be associated with areas of high deformation using a motion energy filter. Presumably the effect seen is due to microcrack formation in these areas, similar to stress whitening in synthetic polymers. This hypothesis is currently tested applying en bloc microcrack staining and histology.

  15. The dependence of ultrasonic backscatter on trabecular thickness in human calcaneus: theoretical and experimental results.

    PubMed

    Wear, Keith A; Laib, Andres

    2003-08-01

    Trabecular thickness within cancellous bone is an important determinant of osteoporotic fracture risk. Noninvasive assessment of trabecular thickness potentially could yield useful diagnostic information. Faran's theory of elastic scattering from a cylindrical object immersed in a fluid has been used to predict the dependence of ultrasonic backscatter on trabecular thickness. The theory predicts that, in the range of morphological and material properties expected for trabecular bone, the backscatter coefficient at 500 kHz should be approximately proportional to trabecular thickness to the power of 2.9. Experimental measurements of backscatter coefficient were performed on 43 human calcaneus samples in vitro. Mean trabecular thicknesses on the 43 samples were assessed using micro computed tomography (CT). A power law fit to the data showed that the backscatter coefficient empirically varied as trabecular thickness to the 2.8 power. The 95% confidence interval for this exponent was 1.7 to 3.9. The square of the correlation coefficient for the linear regression to the log transformed data was 0.40. This suggests that 40% of variations in backscatter may be attributed to variations in trabecular thickness. These results reinforce previous studies that offered validation for the Faran cylinder model for prediction of scattering properties of cancellous bone, and provide added evidence for the potential diagnostic utility of the backscatter measurement. PMID:12952089

  16. A comparative study of the trabecular bony architecture of the talus in humans, non-human primates, and Australopithecus.

    PubMed

    DeSilva, Jeremy M; Devlin, Maureen J

    2012-09-01

    This study tested the hypothesis that talar trabecular microarchitecture reflects the loading patterns in the primate ankle joint, to determine whether talar trabecular morphology might be useful for inferring locomotor behavior in fossil hominins. Trabecular microarchitecture was quantified in the anteromedial, anterolateral, posteromedial, and posterolateral quadrants of the talar body in humans and non-human primates using micro-computed tomography. Trabecular bone parameters, including bone volume fraction, trabecular number and thickness, and degree of anisotropy differed between primates, but not in a manner entirely consistent with hypotheses derived from locomotor kinematics. Humans have highly organized trabecular struts across the entirety of the talus, consistent with the compressive loads incurred during bipedal walking. Chimpanzees possess a high bone volume fraction, consisting of plate-like trabecular struts. Orangutan tali are filled with a high number of thin, connected trabeculae, particularly in the anterior portion of the talus. Gorillas and baboons have strikingly similar internal architecture of the talus. Intraspecific analyses revealed no regional differences in trabecular architecture unique to bipedal humans. Of the 22 statistically significant regional differences in the human talus, all can also be found in other primates. Trabecular thickness, number, spacing, and connectivity density had the same regional relationship in the talus of humans, chimpanzees, gorillas, and baboons, suggesting a deeply conserved architecture in the primate talus. Australopithecus tali are human-like in most respects, differing most notably in having more oriented struts in the posteromedial quadrant of the body compared with the posterolateral quadrant. Though this result could mean that australopiths loaded their ankles in a unique manner during bipedal gait, the regional variation in degree of anisotropy was similar in humans, chimpanzees, and gorillas

  17. Pore cross-section area on predicting elastic properties of trabecular bovine bone for human implants.

    PubMed

    Maciel, Alfredo; Presbítero, Gerardo; Piña, Cristina; del Pilar Gutiérrez, María; Guzmán, José; Munguía, Nadia

    2015-01-01

    A clear understanding of the dependence of mechanical properties of bone remains a task not fully achieved. In order to estimate the mechanical properties in bones for implants, pore cross-section area, calcium content, and apparent density were measured in trabecular bone samples for human implants. Samples of fresh and defatted bone tissue, extracted from one year old bovines, were cut in longitudinal and transversal orientation of the trabeculae. Pore cross-section area was measured with an image analyzer. Compression tests were conducted into rectangular prisms. Elastic modulus presents a linear tendency as a function of pore cross-section area, calcium content and apparent density regardless of the trabecular orientation. The best variable to estimate elastic modulus of trabecular bone for implants was pore cross-section area, and affirmations to consider Nukbone process appropriated for marrow extraction in trabecular bone for implantation purposes are proposed, according to bone mechanical properties. Considering stress-strain curves, defatted bone is stiffer than fresh bone. Number of pores against pore cross-section area present an exponential decay, consistent for all the samples. These graphs also are useful to predict elastic properties of trabecular samples of young bovines for implants. PMID:25585977

  18. Biomarkers and special features of oxidative stress in the anterior segment of the eye linked to lens cataract and the trabecular meshwork injury in primary open-angle glaucoma: challenges of dual combination therapy with N-acetylcarnosine lubricant eye drops and oral formulation of nonhydrolyzed carnosine.

    PubMed

    Babizhayev, Mark A

    2012-02-01

    The implication of oxidative stress associated with increased oxidant production in mammalian and human cells characterized by the release of free radicals, resulting in cellular degeneration, is involved in many ocular diseases, such as age-related macular degeneration, retinopathy of prematurity, retinal light damage, primary open-angle glaucoma (POAG), and cataract. Cataract is the leading cause of blindness, accounting for 50% of blindness worldwide. Glaucoma, the leading cause of irreversible blindness, is considered as a progressive optic neuropathy often caused by elevated intraocular pressure (IOP) consequent to abnormally high resistance to aqueous humor (AH) drainage via the trabecular meshwork (TM) and Schlemm's canal. Morphological and biochemical analyses of the TM of patients with POAG revealed the loss of cells, increased accumulation of extracellular matrix proteins (ECM), changes in the cytoskeleton, cellular senescence, and the process of subclinical inflammation. The TM is the target tissue of glaucoma in the anterior chamber, and the development and progression of glaucoma are accompanied by the accumulation of oxidative damage in this tissue. The separate studies were conducted to comparatively evaluate the sensitivity to oxidative stress and lipid peroxidation (LPO) of anterior chamber tissues including TM. Accumulation of the primary, secondary, and end products of LPO (diene and triene conjugates, Schiff's bases) was noted in the studied extracts. Significant differences in the levels of all mentioned LPO products in comparison with the control were observed. The data may be considered as an evidence of LPO participation in the destruction of the trabecule and Schlemm's canal in POAG. Treatment of TM cells with oxidative stress induced POAG-typical changes such as ECM accumulation, cell death, disarrangement of the cytoskeleton, advanced senescence, and the release of inflammatory markers. By pretreatment with antioxidants, prostaglandin

  19. Mapping trabecular disconnection "hotspots" in aged human spine and hip.

    PubMed

    Aaron, Jean E; Shore, Patricia A; Itoda, Mizuo; Morrison, Rory J M; Hartopp, Andrew; Hensor, Elizabeth M A; Hordon, Lesley D

    2015-09-01

    Trabecular bone disconnection is an independent factor in age-related skeletal failure where real termini (ReTm; rare in youth) may cause weakness disproportionate to tissue loss, yet their structural contribution at vulnerable locations remains uncertain. ReTm (previously recorded at the iliac crest) were mapped in "normal" aged vertebral bodies (T11-L5 autopsy; 20 females, 10 males) and corresponding proximal femora (autopsy; 10 females). Results were compared with biomechanically failed femora from orthopaedic subjects aged >58 yr (osteoporosis OP, 10 females; osteoarthritis OA, 10 females). A novel direct 2D/3D histological method was applied to large, thick (300 μm) slices superficially silver-stained to separate ReTm (unstained) from apparent termini (planar artefacts, brown). Light microscope field co-ordinates enabled ReTm mapping and statistical testing relative to i) sex, ii) tissue sector and iii) slicing plane. In men ReTm populations were small and random while in women they were large and sector-specific. In vertebrae they clustered anterior/superior being rare posterior/inferior; in the femoral head they concentrated distal/superior and also near the fovea, being fewer distal/inferior. A distribution polarity was evident with 100% more ReTm observed transversely (i.e., on tensile-related cross struts) than longitudinally (i.e., on compression-related vertical struts). Their numbers rose in OP (BV/TV<14%, microCT) and in OA (BV/TV>14%), remaining polarised and sector-specific in OP only. Comparative experimentation by marrow elution of an OP animal model demonstrated "floating segments" as a possible outcome. Conclusions were supported statistically that trabecular disconnection "hotspots" at vulnerable locations are sex- and sector-specific, mainly transaxial, and subject to disease modulation. PMID:25874446

  20. The role of fabric in the large strain compressive behavior of human trabecular bone.

    PubMed

    Charlebois, Mathieu; Pretterklieber, Michael; Zysset, Philippe K

    2010-12-01

    Osteoporosis-related vertebral body fractures involve large compressive strains of trabecular bone. The small strain mechanical properties of the trabecular bone such as the elastic modulus or ultimate strength can be estimated using the volume fraction and a second order fabric tensor, but it remains unclear if similar estimations may be extended to large strain properties. Accordingly, the aim of this work is to identify the role of volume fraction and especially fabric in the large strain compressive behavior of human trabecular bone from various anatomical locations. Trabecular bone biopsies were extracted from human T12 vertebrae (n=31), distal radii (n=43), femoral head (n=44), and calcanei (n=30), scanned using microcomputed tomography to quantify bone volume fraction (BV/TV) and the fabric tensor (M), and tested either in unconfined or confined compression up to very large strains (∼70%). The mechanical parameters of the resulting stress-strain curves were analyzed using regression models to examine the respective influence of BV/TV and fabric eigenvalues. The compressive stress-strain curves demonstrated linear elasticity, yielding with hardening up to an ultimate stress, softening toward a minimum stress, and a steady rehardening followed by a rapid densification. For the pooled experiments, the average minimum stress was 1.89 ± 1.77 MPa, while the corresponding mean strain was 7.15 ± 1.84%. The minimum stress showed a weaker dependence with fabric as the elastic modulus or ultimate strength. For the confined experiments, the stress at a logarithmic strain of 1.2 was 8.08 ± 7.91 MPa, and the dissipated energy density was 5.67 ± 4.42 MPa. The latter variable was strongly related to the volume fraction (R(2)=0.83) but the correlation improved only marginally with the inclusion of fabric (R(2)=0.84). The influence of fabric on the mechanical properties of human trabecular bone decreases with increasing strain, while the role of volume fraction remains

  1. Aqueous Angiography–Mediated Guidance of Trabecular Bypass Improves Angiographic Outflow in Human Enucleated Eyes

    PubMed Central

    Huang, Alex S.; Saraswathy, Sindhu; Dastiridou, Anna; Begian, Alan; Mohindroo, Chirayu; Tan, James C. H.; Francis, Brian A.; Hinton, David R.; Weinreb, Robert N.

    2016-01-01

    Purpose To assess the ability of trabecular micro-bypass stents to improve aqueous humor outflow (AHO) in regions initially devoid of AHO as assessed by aqueous angiography. Methods Enucleated human eyes (14 total from 7 males and 3 females [ages 52–84]) were obtained from an eye bank within 48 hours of death. Eyes were oriented by inferior oblique insertion, and aqueous angiography was performed with indocyanine green (ICG; 0.4%) or fluorescein (2.5%) at 10 mm Hg. With an angiographer, infrared and fluorescent images were acquired. Concurrent anterior segment optical coherence tomography (OCT) was performed, and fixable fluorescent dextrans were introduced into the eye for histologic analysis of angiographically positive and negative areas. Experimentally, some eyes (n = 11) first received ICG aqueous angiography to determine angiographic patterns. These eyes then underwent trabecular micro-bypass sham or stent placement in regions initially devoid of angiographic signal. This was followed by fluorescein aqueous angiography to query the effects. Results Aqueous angiography in human eyes yielded high-quality images with segmental patterns. Distally, angiographically positive but not negative areas demonstrated intrascleral lumens on OCT images. Aqueous angiography with fluorescent dextrans led to their trapping in AHO pathways. Trabecular bypass but not sham in regions initially devoid of ICG aqueous angiography led to increased aqueous angiography as assessed by fluorescein (P = 0.043). Conclusions Using sequential aqueous angiography in an enucleated human eye model system, regions initially without angiographic flow or signal could be recruited for AHO using a trabecular bypass stent. PMID:27588614

  2. Relationships between tissue composition and viscoelastic properties in human trabecular bone.

    PubMed

    Ojanen, X; Isaksson, H; Töyräs, J; Turunen, M J; Malo, M K H; Halvari, A; Jurvelin, J S

    2015-01-21

    Trabecular bone is a metabolically active tissue with a high surface to volume ratio. It exhibits viscoelastic properties that may change during aging. Changes in bone properties due to altered metabolism are sensitively revealed in trabecular bone. However, the relationships between material composition and viscoelastic properties of bone, and their changes during aging have not yet been elucidated. In this study, trabecular bone samples from the femoral neck of male cadavers (n=21) aged 17-82 years were collected and the tissue level composition and its associations with the tissue viscoelastic properties were evaluated by using Raman microspectroscopy and nanoindentation, respectively. For composition, collagen content, mineralization, carbonate substitution and mineral crystallinity were evaluated. The calculated mechanical properties included reduced modulus (Er), hardness (H) and the creep parameters (E1, E2, η1and η2), as obtained by fitting the experimental data to the Burgers model. The results indicated that the creep parameters, E1, E2, η1and η2, were linearly correlated with mineral crystallinity (r=0.769-0.924, p<0.001). Creep time constant (η2/E2) tended to increase with crystallinity (r=0.422, p=0.057). With age, the mineralization decreased (r=-0.587, p=0.005) while the carbonate substitution increased (r=0.728, p<0.001). Age showed no significant associations with nanoindentation parameters. The present findings suggest that, at the tissue-level, the viscoelastic properties of trabecular bone are related to the changes in characteristics of bone mineral. This association may be independent of human age. PMID:25498367

  3. Trabecular Evidence for a Human-Like Gait in Australopithecus africanus

    PubMed Central

    Raichlen, David; Pontzer, Herman; Warrener, Anna G.; Hublin, Jean-Jacques

    2013-01-01

    Although the earliest known hominins were apparently upright bipeds, there has been mixed evidence whether particular species of hominins including those in the genus Australopithecus walked with relatively extended hips, knees and ankles like modern humans, or with more flexed lower limb joints like apes when bipedal. Here we demonstrate in chimpanzees and humans a highly predictable and sensitive relationship between the orientation of the ankle joint during loading and the principal orientation of trabecular bone struts in the distal tibia that function to withstand compressive forces within the joint. Analyses of the orientation of these struts using microCT scans in a sample of fossil tibiae from the site of Sterkfontein, of which two are assigned to Australopithecus africanus, indicate that these hominins primarily loaded their ankles in a relatively extended posture like modern humans and unlike chimpanzees. In other respects, however, trabecular properties in Au africanus are distinctive, with values that mostly fall between those of chimpanzees and humans. These results indicate that Au. africanus, like Homo, walked with an efficient, extended lower limb. PMID:24223719

  4. Trabecular evidence for a human-like gait in Australopithecus africanus.

    PubMed

    Barak, Meir M; Lieberman, Daniel E; Raichlen, David; Pontzer, Herman; Warrener, Anna G; Hublin, Jean-Jacques

    2013-01-01

    Although the earliest known hominins were apparently upright bipeds, there has been mixed evidence whether particular species of hominins including those in the genus Australopithecus walked with relatively extended hips, knees and ankles like modern humans, or with more flexed lower limb joints like apes when bipedal. Here we demonstrate in chimpanzees and humans a highly predictable and sensitive relationship between the orientation of the ankle joint during loading and the principal orientation of trabecular bone struts in the distal tibia that function to withstand compressive forces within the joint. Analyses of the orientation of these struts using microCT scans in a sample of fossil tibiae from the site of Sterkfontein, of which two are assigned to Australopithecus africanus, indicate that these hominins primarily loaded their ankles in a relatively extended posture like modern humans and unlike chimpanzees. In other respects, however, trabecular properties in Au africanus are distinctive, with values that mostly fall between those of chimpanzees and humans. These results indicate that Au. africanus, like Homo, walked with an efficient, extended lower limb. PMID:24223719

  5. Local measurements of the diffusion constant in multiple scattering media: Application to human trabecular bone imaging

    NASA Astrophysics Data System (ADS)

    Aubry, Alexandre; Derode, Arnaud; Padilla, Frédéric

    2008-03-01

    We present local measurements of the diffusion constant for ultrasonic waves undergoing multiple scattering. The experimental setup uses a coherent array of programmable transducers. By achieving Gaussian beamforming at emission and reception, an array of virtual sources and receivers located in the near field is constructed. A matrix treatment is proposed to separate the incoherent intensity from the coherent backscattering peak. Local measurements of the diffusion constant D are then achieved. This technique is applied to a real case: a sample of human trabecular bone for which the ultrasonic characterization of multiple scattering is an issue.

  6. Distinct Tissue Mineral Density in Plate- and Rod-like Trabeculae of Human Trabecular Bone.

    PubMed

    Wang, Ji; Kazakia, Galateia J; Zhou, Bin; Shi, X Tony; Guo, X Edward

    2015-09-01

    Trabecular bone quality includes both microstructural and intrinsic tissue mineralization properties. However, the tissue mineralization in individual trabeculae of different trabecular types and orientations has not yet been investigated. The aim of this study was to develop an individual trabecula mineralization (ITM) analysis technique to determine tissue mineral density (TMD) distributions in plate- and rod-like trabeculae, respectively, and to compare the TMD of trabeculae along various orientations in micro-computed tomography (μCT) images of trabecular bone samples from the femoral neck, greater trochanter, and proximal tibia. ITM analyses indicated that trabecular plates, on average, had significantly higher TMD than trabecular rods. In addition, the distribution of TMD in trabecular plates depended on trabecular orientation with the lowest TMD in longitudinal plates and the highest TMD in transverse plates. Conversely, there was a relatively uniform distribution of TMD among trabecular rods, with respect to trabecular orientation. Further analyses of TMD distribution revealed that trabecular plates had higher mean and peak TMD, whereas trabecular rods had a wider TMD distribution and a larger portion of low mineralized trabeculae. Comparison of apparent Young's moduli derived from micro-finite element models with and without heterogeneous TMD demonstrated that heterogeneous TMD in trabecular plates had a significant influence on the elastic mechanical property of trabecular bone. In conclusion, this study revealed differences in TMD between plate- and rod-like trabeculae and among various trabecular orientations. The observation of less mineralized longitudinal trabecular plates suggests interesting implications of these load-bearing plates in bone remodeling. The newly developed ITM analysis can be a valuable technique to assess the influence of metabolic bone diseases and their pharmaceutical treatments on not only microstructure of trabecular bone but

  7. Optimal sample volumes of human trabecular bone in μCT analysis within vertebral body and femoral head

    PubMed Central

    Wen, Xin-Xin; Zong, Chun-Lin; Xu, Chao; Ma, Xiang-Yu; Wang, Fa-Qi; Feng, Ya-Fei; Yan, Ya-Bo; Lei, Wei

    2015-01-01

    Trabecular bones of different skeletal sites have different bone morphologies. How to select an appropriate volume of region of interest (ROI) to reflect the microarchitecture of trabecular bone in different skeletal sites was an interesting problem. Therefore, in this study, the optimal volumes of ROI within vertebral body and femoral head, and if the relationships between volumes of ROI and microarchitectural parameters were affected by trabecular bone morphology were studied. Within vertebral body and femoral head, different cubic volumes of ROI (from (1 mm)3 to (20 mm)3) were set to compare with control groups(whole volume of trabecular bone). Five microarchitectural parameters (BV/TV, Tb.N, Tb.Th, Tb.Sp, and BS/BV) were obtained. Nonlinear curve fitting functions were used to explore the relationships between the microarchitectural parameters and the volumes of ROI. The volumes of ROI could affect the microarchitectural parameters when the volume was smaller than (8 mm)3 within the vertebral body and smaller than (13 mm)3 within the femoral head. As the volume increased, the variable tendencies of BV/TV, Tb.N, and Tb.Sp were different between these two skeletal sites. The curve fitting functions between these two sites were also different. The relationships between volumes of ROI and microarchitectural parameters were affected by the different trabecular bone morphologies within lumbar vertebral body and femoral head. When depicting the microarchitecture of human trabecular bone within lumbar vertebral body and femoral head, the volume of ROI would be larger than (8 mm)3 and (13 mm)3. PMID:26770381

  8. Influence of object location in different FOVs on trabecular bone microstructure measurements of human mandible: a cone beam CT study

    PubMed Central

    Parsa, A; Hassan, B; van der Stelt, P; Aartman, I H A; Nambiar, P

    2014-01-01

    The aim of this study was to assess the influence of different object locations in different fields of view (FOVs) of two cone beam CT (CBCT) systems on trabecular bone microstructure measurements of a human mandible. A block of dry human mandible was scanned at five different locations (centre, left, right, anterior and posterior) using five different FOVs of two CBCT systems (NewTom™ 5G; QR Verona, Verona, Italy and Accuitomo 170; Morita, Kyoto, Japan). Image analysis software (CTAn software v. 1.1; SkyScan, Kontich, Belgium) was used to assess the trabecular bone microstructural parameters (thickness, Tb.Th; spacing, Tb.Sp; number, Tb.N; bone volume density, BV/TV). All measurements were taken twice by one trained observer. Tb.Th, Tb.Sp and Tb.N varied significantly across different FOVs in the NewTom 5G (p < 0.001) and the Accuitomo 170 (p < 0.001). For location, a significant difference was observed only when measuring BV/TV (p = 0.03) using the NewTom 5G. The trabecular bone microstructural measurements obtained from CBCT systems are influenced by the size of FOVs. Not all trabecular bone parameters measured using different CBCT systems are affected when varying the object location within the FOVs. PMID:24265395

  9. Role of trabecular microfractures in failure of human vertebrae estimated by the finite element method

    NASA Astrophysics Data System (ADS)

    Sidorenko, Irina N.; Bauer, Jan; Monetti, Roberto; Müller, Dirk; Rummeny, Ernst J.; Eckstein, Felix; Matsuura, Maiko; Lochmüller, Eva-Maria; Zysset, Philippe K.; Räth, Christoph W.

    2009-02-01

    Spine fractures are the most frequent complication of osteoporosis, a disease characterized by low bone mass and structural deterioration of bone tissue. In case of the spine, the trabecular network plays the main role in load carrying and distribution. A correct description of mechanical properties of this bone structure helps to differentiate between strong and weak bones and can be useful for fracture prediction and treatment monitoring. By means of the finite element method (FEM), applied to μCT images, we modelled biomechanical processes in probes during loading and correlated the estimated failure load with the maximum compressive strength (MCS), obtained in real biomechanical tests. We studied a sample of 151 specimens taken from the trabecular part of human vertebrae in vitro, visualised using μCT imaging at an isotropic resolution of 26μm and tested by uniaxial compression. Besides the standard way of estimating failure load, which takes into account only strong micro-fractures, we also included small micro-fractures, what improved the correlation with MCS (Pearson's correlation coefficient r=0.78 vs. r=0.58). This correlation coefficient was larger than that for both the standard morphometric parameters (r=0.73 for bone volume fraction) and for texture measures defined by the local (an-) isotropic scaling indices method (r=0.55) and Minkowski Functionals (r=0.61). However, the performance of the FEM was different for subsamples selected according to the MCS value. The correlation increased for strong specimens (r=0.88), slightly decreased for weak specimens (r=0.68) and markedly dropped for specimens with medium MCS, e.g. between 60

  10. Insight into the 3D-trabecular architecture of the human patella.

    PubMed

    Hoechel, Sebastian; Schulz, Georg; Müller-Gerbl, Magdalena

    2015-07-01

    The subchondral bone plate (SBP), a dynamic component of the osteochondral unit, shows functional adaptation to long-term loading by distribution of the mineral content in a manner best serving the mechanical demands. Since the received joint-load is transmitted into the trabecular system, the spongy bone also exhibits differences in strain energy density which models it for optimal support. To evaluate the regional variations in trabecular architecture, in accordance with the density distribution of the SBP revealing its long-term load intake, CT- and μCT-datasets of ten physiologic patellae were analysed for defined parameters of bony structure. For the SBP, the density distributions as well as area measurements were used. The trabecular architecture was described using parameters of bone morphology comprising the first 5mm (examined in 1mm steps) below the SBP. The obtained measurements are: Bone volume fraction (BV/TV); Bone surface density (BS/TV); Trabecular number (Tb.N); Trabecular separation (Tb.Sp); Trabecular thickness (Tb.Th); structure model index (SMI); and the Degree of anisotropy (DA). The evaluated architectural parameters varied within the trabecular system and showed an inhomogeneous distribution pattern. It proved to be distinctive with maxima of material and stability situated below areas of the highest long-term load intake. With increasing depth, the pattern of distribution was persistent but lessened in intensity. The parameters significantly correlated with the density distribution of the SBP within the first and second millimetres. With increasing depth down to the fifth millimetre, the coefficients of correlation decreased for all values. The trabecular network adapts to its mechanical needs and is therefore not homogenously built. Dependent upon the long-term load intake, the trabecular model optimizes the support with significant correlation to the density distribution of the SBP. PMID:25835353

  11. Ex vivo human trabecular bone model for biocompatibility evaluation of calcium phosphate composites modified with spray dried biodegradable microspheres.

    PubMed

    Schnieders, Julia; Gbureck, Uwe; Germershaus, Oliver; Kratz, Marita; Jones, David B; Kissel, Thomas

    2013-10-01

    Our aim was to study the suitability of the ex-vivo human trabecular bone bioreactor ZetOS to test the biocompatibility of calcium phosphate bone cement composites modified with spray dried, drug loaded microspheres. We hypothesized, that this bone bioreactor could be a promising alternative to in vivo assessment of biocompatibility in living human bone over a defined time period. Composites consisting of tetracycline loaded poly(lactic-co-glycolic acid) microspheres and calcium phosphate bone cement, were inserted into in vitro cultured human femora head trabecular bone and incubated over 30 days at 37°C in the incubation system. Different biocompatibility parameters, such as lactate dehydrogenase activity, alkaline phosphatase release and the expression of relevant cytokines, IL-1β, IL-6, and TNF-α, were measured in the incubation medium. No significant differences in alkaline phosphatase, osteocalcin, and lactate dehydrogenase activity were measured compared to control samples. Tetracycline was released from the microspheres, delivered and incorporated into newly formed bone. In this study we demonstrated that ex vivo biocompatibility testing using human trabecular bone in a bioreactor is a potential alternative to animal experiments since bone metabolism is still maintained in a physiological environment ex vivo. PMID:23568426

  12. Variation of bone layer thicknesses and trabecular volume fraction in the adult male human calvarium.

    PubMed

    Boruah, Sourabh; Paskoff, Glenn R; Shender, Barry S; Subit, Damien L; Salzar, Robert S; Crandall, Jeff R

    2015-08-01

    The human calvarium is a sandwich structure with two dense layers of cortical bone separated by porous cancellous bone. The variation of the three dimensional geometry, including the layer thicknesses and the volume fraction of the cancellous layer across the population, is unavailable in the current literature. This information is of particular importance to mathematical models of the human head used to simulate mechanical response. Although the target geometry for these models is the median geometry of the population, the best attempt so far has been the scaling of a unique geometry based on a few median anthropometric measurements of the head. However, this method does not represent the median geometry. This paper reports the average three dimensional geometry of the calvarium from X-ray computed tomography (CT) imaging and layer thickness and trabecular volume fraction from micro CT (μCT) imaging of ten adult male post-mortem human surrogates (PMHS). Skull bone samples have been obtained and μCT imaging was done at a resolution of 30 μm. Monte Carlo simulation was done to estimate the variance in these measurements due to the uncertainty in image segmentation. The layer thickness data has been averaged over areas of 5mm(2). The outer cortical layer was found to be significantly (p < 0.01; Student's t test) thicker than the inner layer (median of thickness ratio 1.68). Although there was significant location to location difference in all the layer thicknesses and volume fraction measurements, there was no trend. Average distribution and the variance of these metrics on the calvarium have been shown. The findings have been reported as colormaps on a 2D projection of the cranial vault. PMID:25920690

  13. Osteoblast-Specific Overexpression of Human WNT16 Increases Both Cortical and Trabecular Bone Mass and Structure in Mice.

    PubMed

    Alam, Imranul; Alkhouli, Mohammed; Gerard-O'Riley, Rita L; Wright, Weston B; Acton, Dena; Gray, Amie K; Patel, Bhavmik; Reilly, Austin M; Lim, Kyung-Eun; Robling, Alexander G; Econs, Michael J

    2016-02-01

    Previous genome-wide association studies have identified common variants in genes associated with bone mineral density (BMD) and risk of fracture. Recently, we identified single nucleotide polymorphisms (SNPs) in Wingless-type mouse mammary tumor virus integration site (WNT)16 that were associated with peak BMD in premenopausal women. To further identify the role of Wnt16 in bone mass regulation, we created transgenic (TG) mice overexpressing human WNT16 in osteoblasts. We compared bone phenotypes, serum biochemistry, gene expression, and dynamic bone histomorphometry between TG and wild-type (WT) mice. Compared with WT mice, WNT16-TG mice exhibited significantly higher whole-body areal BMD and bone mineral content (BMC) at 6 and 12 weeks of age in both male and female. Microcomputer tomography analysis of trabecular bone at distal femur revealed 3-fold (male) and 14-fold (female) higher bone volume/tissue volume (BV/TV), and significantly higher trabecular number and trabecular thickness but lower trabecular separation in TG mice compared with WT littermates in both sexes. The cortical bone at femur midshaft also displayed significantly greater bone area/total area and cortical thickness in the TG mice in both sexes. Serum biochemistry analysis showed that male TG mice had higher serum alkaline phosphatase, osteocalcin, osteoprotegerin (OPG), OPG to receptor activator of NF-kB ligand (tumor necrosis family ligand superfamily, number 11; RANKL) ratio as compared with WT mice. Also, lower carboxy-terminal collagen cross-link (CTX) to tartrate-resistant acid phosphatase 5, isoform b (TRAPc5b) ratio was observed in TG mice compared with WT littermates in both male and female. Histomorphometry data demonstrated that both male and female TG mice had significantly higher cortical and trabecular mineralizing surface/bone surface and bone formation rate compared with sex-matched WT mice. Gene expression analysis demonstrated higher expression of Alp, OC, Opg, and Opg to

  14. In vivo microdamage is an indicator of susceptibility to initiation and propagation of microdamage in human femoral trabecular bone.

    PubMed

    Wu, Ziheng; Laneve, Anthony J; Niebur, Glen L

    2013-07-01

    Microdamage has been cited as an important element of trabecular bone quality and fracture risk, as materials with flaws have lower modulus and strength than equivalent undamaged materials. However, the magnitude of the effect of damage on failure properties depends on its tendency to propagate. Human femoral trabecular bone from the neck and greater trochanter was subjected to one of compressive, torsional, or combined compression and torsion. The in vivo, new, and propagating damage were then quantified in thick sections under epifluorescent microscopy. Multiaxial loading, which was intended to represent an off-axis load such as a fall or accident, caused much more damage than either simple compression or shear, and similarly caused the greatest stiffness loss. In all cases, initiation of new damage far exceeded the propagation of existing damage. This may reflect stress redistribution away from damaged trabeculae, resulting in new damage sites. However, the accumulation of new damage was positively correlated with quantity of pre-existing damage in all loading modes, indicating that damaged bone is inherently more prone to further damage formation. Moreover, about 50% of in vivo microcracks propagated under each type of loading. Finally, damage formation was positively correlated to decreased compressive stiffness following both axial and shear loading. Taken together, these results demonstrate that damage in trabecular bone adversely affects its mechanical properties, and is indicative of bone that is more susceptible to further damage. PMID:23459314

  15. Human trabecular bone microarchitecture can be assessed independently of density with second generation HR-pQCT.

    PubMed

    Manske, Sarah L; Zhu, Ying; Sandino, Clara; Boyd, Steven K

    2015-10-01

    The second generation HR-pQCT scanner (XtremeCTII, Scanco Medical) can assess human bone microarchitecture of peripheral limbs with a 61 μm nominal isotropic voxel size. This is a marked improvement from the first generation HR-pQCT that had a nominal isotropic voxel size of 82 μm, which is at the limit to accurately determine the thickness of individual human trabeculae. We sought to determine the accuracy of a direct morphometric approach to measure trabecular bone microarchitecture with three-dimensional morphological techniques using second generation HR-pQCT, and to compare this with the approach currently applied by the first generation HR-pQCT scanner based on derived indices using ex vivo scans of human cadaveric radii. We also compared images acquired and resampled to mimic the first generation HR-pQCT with those obtained directly from the first generation HR-pQCT. We evaluated 20 human cadaveric radii and a micro-CT performance phantom using the first (XtremeCT, Scanco Medical) and second generation HR-pQCT scanner (XtremeCTII) and compared a patient evaluation (XCTII, 61 μm) with a high resolution ex vivo protocol (HR, 30μm). We generated 82 μm scans of the same specimens to mimic a first-generation HR-pQCT evaluation (XCTIM, 82 μm) and compared these with a first-generation patient evaluation (XCTI, 82 μm). A standard structural extraction approach was applied to both XCTII and HR evaluations for assessment of bone volume fraction (BV/TV), and a distance transform was used to assess trabecular number (Tb.N), trabecular thickness (Tb.Th) and trabecular separation (Tb.Sp). For XCTI and XCTIM evaluations we followed the manufacturer's standard procedure and assessed bone mineral density (BMD), Tb.N with a distance transform, and then derived bone volume ratio (BV/TV(d)), trabecular thickness (Tb.Th(d)) and separation (Tb.Sp(d)). The spatial resolution (10% MTF) was 142.2 μm for XCTI, 108.9 μm for XCTIM, 95.2μm for XCTII, and 55.9 μm for HR. XCTI

  16. Comparison of synchrotron radiation and conventional x-ray microcomputed tomography for assessing trabecular bone microarchitecture of human femoral heads

    SciTech Connect

    Chappard, Christine; Basillais, Armelle; Benhamou, Laurent; Bonassie, Alexandra; Brunet-Imbault, Barbara; Bonnet, Nicolas; Peyrin, Francoise

    2006-09-15

    Microcomputed tomography ({mu}CT) produces three-dimensional (3D) images of trabecular bone. We compared conventional {mu}CT (C{mu}CT) with a polychromatic x-ray cone beam to synchrotron radiation (SR) {mu}CT with a monochromatic parallel beam for assessing trabecular bone microarchitecture of 14 subchondral femoral head specimens from patients with osteoarthritis (n=10) or osteoporosis (n=4). SR{mu}CT images with a voxel size of 10.13 {mu}m were reconstructed from 900 2D radiographic projections (angular step, 0.2 deg. ). C{mu}CT images with a voxel size of 10.77 {mu}m were reconstructed from 205, 413, and 825 projections obtained using angular steps of 0.9 deg., 0.45 deg., and 0.23 deg., respectively. A single threshold was used to binarize the images. We computed bone volume/tissue volume (BV/TV), bone surface/bone volume (BS/BV), trabecular number (Tb.N), trabecular thickness (Tb.Th and Tb.Th*), trabecular spacing (Tb.Sp), degree of anisotropy (DA), and Euler density. With the 0.9 deg. angular step, all C{mu}CT values were significantly different from SR{mu}CT values. With the 0.23 deg. and 0.45 deg. rotation steps, BV/TV, Tb.Th, and BS/BV by C{mu}CT differed significantly from the values by SR{mu}CT. The error due to slice matching (visual site matching {+-}10 slices) was within 1% for most parameters. Compared to SR{mu}CT, BV/TV, Tb.Sp, and Tb.Th by C{mu}CT were underestimated, whereas Tb.N and Tb.Th* were overestimated. A Bland and Altman plot showed no bias for Tb.N or DA. Bias was -0.8{+-}1.0%, +5.0{+-}1.1 {mu}m, -5.9{+-}6.3 {mu}m, and -5.7{+-}29.1 {mu}m for BV/TV, Tb.Th*, Tb.Th, and Tb.Sp, respectively, and the differences did not vary over the range of values. Although systematic differences were noted between SR{mu}CT and C{mu}CT values, correlations between the techniques were high and the differences would probably not change the discrimination between study groups. C{mu}CT provides a reliable 3D assessment of human defatted bone when working at the 0

  17. Anisotropic analysis of trabecular architecture in human femur bone radiographs using quaternion wavelet transforms.

    PubMed

    Sangeetha, S; Sujatha, C M; Manamalli, D

    2014-01-01

    In this work, anisotropy of compressive and tensile strength regions of femur trabecular bone are analysed using quaternion wavelet transforms. The normal and abnormal femur trabecular bone radiographic images are considered for this study. The sub-anatomic regions, which include compressive and tensile regions, are delineated using pre-processing procedures. These delineated regions are subjected to quaternion wavelet transforms and statistical parameters are derived from the transformed images. These parameters are correlated with apparent porosity, which is derived from the strength regions. Further, anisotropy is also calculated from the transformed images and is analyzed. Results show that the anisotropy values derived from second and third phase components of quaternion wavelet transform are found to be distinct for normal and abnormal samples with high statistical significance for both compressive and tensile regions. These investigations demonstrate that architectural anisotropy derived from QWT analysis is able to differentiate normal and abnormal samples. PMID:25571265

  18. Quantifying trabecular orientation in the pelvic cancellous bone of modern humans, chimpanzees, and the Kebara 2 Neanderthal.

    PubMed

    Martinón-Torres, María

    2003-01-01

    The adaptive nature of bone lies in its ability to respond to the environment by conforming and reshaping itself constantly to accommodate life-time stresses experienced throughout daily activities. In order to keep strains within the bone as uniform and isotropic as possible, the trabecular orientation is determined by forces acting on the bone through adaptive remodeling. Hence, the preserved structure of bones may contain direct information about the forces they may have undergone. Some authors (Correnti [1952], Atti Acc Naz Lincei 12:518-523, [1955] Riv Antrop 42:289-336; Macchiarelli et al. [1999] J Hum Evol 36:211-232, [2001] Cambridge, UK: Cambridge University Press) have described in detail the trabecular systems of the hip bone in different primate species and have identified a gait-related system above the acetabulum with substantial differences across species (Macchiarelli et al. [1999]; Rook et al. [1999] Proc Natl Acad Sci USA 96:8875-8879). The aim of this study was to quantify trabecular orientation above the acetabulum to test the hypothesis that hominoid biomechanical behavior is recorded in the cancellous bone. The pelvic bones of 23 archaeological adult modern humans (12 females, 11 males), 20 adult Pan troglodytes (10 females, 10 males), and one adult male Neanderthal were radiographed and digitized. Fast Fourier transforms (FFTs) of the regions of interest in the corpus of the ilium were performed, with the angular distribution of the trabeculae quantified. All species displayed a constant and periodic orthogonal arrangement in the trabeculae with differences in the pattern of dominance between the arcades oriented along the 0 degrees or the 90 degrees axes. The variation in the FFT spectrum between species is discussed in the light of distinctive biomechanical features. PMID:12953177

  19. Regional variations in human patellar trabecular architecture and the structure of the proximal patellar tendon enthesis

    PubMed Central

    Toumi, H; Higashiyama, I; Suzuki, D; Kumai, T; Bydder, G; McGonagle, D; Emery, P; Fairclough, J; Benjamin, M

    2006-01-01

    Proximal patellar tendinopathy occurs as an overuse injury in sport and is also characteristic of ankylosing spondylitis patients. It particularly affects the posteromedial part of the patellar tendon enthesis, although the reason for this is unclear. We investigated whether there are regional differences in the trabecular architecture of the patella or in the histology of the patellar tendon enthesis that could suggest unequal force transmission from bone to tendon. Trabecular architecture was analysed from X-rays taken with a Faxitron radiography system of the patellae of dissecting room cadavers and in magnetic resonance images of the knees of living volunteers. Structural and fractal analyses were performed on the Faxitron digital images using MatLab software. Regional differences at the enthesis in the thickness of the uncalcified fibrocartilage and the subchondral plate were evaluated histologically in cadaveric material. The radiological studies showed that the quantity of bone and the apparent trabecular thickness in the patella were greatest medially, and that in the lateral part of the patella there were fewer trabeculae which were orientated either antero-posteriorly or superiorly inferiorly. The histological study showed that the uncalcified fibrocartilage was most prominent medially and that the subchondral plate was thinner laterally. Overall, the results indicate that mechanical stress at the proximal patellar tendon enthesis is asymmetrically distributed and greater on the medial than on the lateral side. Thus, we suggest that the functional anatomy of the knee is closely related to regional variations in force transmission, which in turn relates to the posteromedial site of pathology in proximal patellar tendinopathy. PMID:16420378

  20. Early Trabecular Development in Human Vertebrae: Overproduction, Constructive Regression, and Refinement

    PubMed Central

    Acquaah, Frank; Robson Brown, Katharine A.; Ahmed, Farah; Jeffery, Nathan; Abel, Richard L.

    2015-01-01

    Early bone development may have a significant impact upon bone health in adulthood. Bone mineral density (BMD) and bone mass are important determinants of adult bone strength. However, several studies have shown that BMD and bone mass decrease after birth. If early development is important for strength, why does this reduction occur? To investigate this, more data characterizing gestational, infant, and childhood bone development are needed in order to compare with adults. The aim of this study is to document early vertebral trabecular bone development, a key fragility fracture site, and infer whether this period is important for adult bone mass and structure. A series of 120 vertebrae aged between 6 months gestation and 2.5 years were visualized using microcomputed tomography. Spherical volumes of interest were defined, thresholded, and measured using 3D bone analysis software (BoneJ, Quant3D). The findings showed that gestation was characterized by increasing bone volume fraction whilst infancy was defined by significant bone loss (≈2/3rds) and the appearance of a highly anisotropic trabecular structure with a predominantly inferior–superior direction. Childhood development progressed via selective thickening of some trabeculae and the loss of others; maintaining bone volume whilst creating a more anisotropic structure. Overall, the pattern of vertebral development is one of gestational overproduction followed by infant “sculpting” of bone tissue during the first year of life (perhaps in order to regulate mineral homeostasis or to adapt to loading environment) and then subsequent refinement during early childhood. Comparison of early bone developmental data in this study with adult bone volume values taken from the literature shows that the loss in bone mass that occurs during the first year of life is never fully recovered. Early development could therefore be important for developing bone strength, but through structural changes in trabecular

  1. Early Trabecular Development in Human Vertebrae: Overproduction, Constructive Regression, and Refinement.

    PubMed

    Acquaah, Frank; Robson Brown, Katharine A; Ahmed, Farah; Jeffery, Nathan; Abel, Richard L

    2015-01-01

    Early bone development may have a significant impact upon bone health in adulthood. Bone mineral density (BMD) and bone mass are important determinants of adult bone strength. However, several studies have shown that BMD and bone mass decrease after birth. If early development is important for strength, why does this reduction occur? To investigate this, more data characterizing gestational, infant, and childhood bone development are needed in order to compare with adults. The aim of this study is to document early vertebral trabecular bone development, a key fragility fracture site, and infer whether this period is important for adult bone mass and structure. A series of 120 vertebrae aged between 6 months gestation and 2.5 years were visualized using microcomputed tomography. Spherical volumes of interest were defined, thresholded, and measured using 3D bone analysis software (BoneJ, Quant3D). The findings showed that gestation was characterized by increasing bone volume fraction whilst infancy was defined by significant bone loss (≈2/3rds) and the appearance of a highly anisotropic trabecular structure with a predominantly inferior-superior direction. Childhood development progressed via selective thickening of some trabeculae and the loss of others; maintaining bone volume whilst creating a more anisotropic structure. Overall, the pattern of vertebral development is one of gestational overproduction followed by infant "sculpting" of bone tissue during the first year of life (perhaps in order to regulate mineral homeostasis or to adapt to loading environment) and then subsequent refinement during early childhood. Comparison of early bone developmental data in this study with adult bone volume values taken from the literature shows that the loss in bone mass that occurs during the first year of life is never fully recovered. Early development could therefore be important for developing bone strength, but through structural changes in trabecular

  2. Trabecular trajectory in the articular processes of the human fourth cervical vertebra

    PubMed Central

    HERRERA, M.; PANCHÓN, A.; PEREZ-BACETE, M.

    2001-01-01

    The articular processes (AP) of the neural arch have been implicated in weight transmission through the cervical spine. To analyse the mechanism of weight transmission in the AP, we studied the direction of forces within it, in particular, the pattern of trabecular trajectories. Twenty-two AP from C4 vertebrae were studied in anatomical sections, and corresponding photoelastic models from selected sections were constructed and analysed. Anatomical and photoelastic findings show the subarticular spongiosa of the superior articular process (SAP) to be orthogonally arranged with vertical and oblique trabeculae in the direction of compressive forces and additional trabeculae always oriented perpendicular to the former. Vertical and oblique trabeculae are divided into rostral, middle and posterior groups. Rostral and middle trabeculae end in the anterior wall of the SAP and the transitional zone with the pedicle. Posterior trabeculae end in the subarticular spongiosa of the inferior articular process (IAP). The findings relating to trabecular trajectories in the SAP differ from previous descriptions and instead suggest that a part of the weight forces distributed within the AP transmit to the subchondral zone of the IAP. Knowledge of the trajectorial architecture of the AP may contribute to refining finite element analytical models for investigating its weight-bearing function. PMID:11554512

  3. Relationship between sample volumes and modulus of human vertebral trabecular bone in micro-finite element analysis.

    PubMed

    Wen, Xin-Xin; Xu, Chao; Zong, Chun-Lin; Feng, Ya-Fei; Ma, Xiang-Yu; Wang, Fa-Qi; Yan, Ya-Bo; Lei, Wei

    2016-07-01

    Micro-finite element (μFE) models have been widely used to assess the biomechanical properties of trabecular bone. How to choose a proper sample volume of trabecular bone, which could predict the real bone biomechanical properties and reduce the calculation time, was an interesting problem. Therefore, the purpose of this study was to investigate the relationship between different sample volumes and apparent elastic modulus (E) calculated from μFE model. 5 Human lumbar vertebral bodies (L1-L5) were scanned by micro-CT. Cubic concentric samples of different lengths were constructed as the experimental groups and the largest possible volumes of interest (VOI) were constructed as the control group. A direct voxel-to-element approach was used to generate μFE models and steel layers were added to the superior and inferior surface to mimic axial compression tests. A 1% axial strain was prescribed to the top surface of the model to obtain the E values. ANOVA tests were performed to compare the E values from the different VOIs against that of the control group. Nonlinear function curve fitting was performed to study the relationship between volumes and E values. The larger cubic VOI included more nodes and elements, and more CPU times were needed for calculations. E values showed a descending tendency as the length of cubic VOI decreased. When the volume of VOI was smaller than (7.34mm(3)), E values were significantly different from the control group. The fit function showed that E values approached an asymptotic values with increasing length of VOI. Our study demonstrated that apparent elastic modulus calculated from μFE models were affected by the sample volumes. There was a descending tendency of E values as the length of cubic VOI decreased. Sample volume which was not smaller than (7.34mm(3)) was efficient enough and timesaving for the calculation of E. PMID:26999702

  4. Occlusal load distribution through the cortical and trabecular bone of the human mid-facial skeleton in natural dentition: a three-dimensional finite element study.

    PubMed

    Janovic, Aleksa; Saveljic, Igor; Vukicevic, Arso; Nikolic, Dalibor; Rakocevic, Zoran; Jovicic, Gordana; Filipovic, Nenad; Djuric, Marija

    2015-01-01

    Understanding of the occlusal load distribution through the mid-facial skeleton in natural dentition is essential because alterations in magnitude and/or direction of occlusal forces may cause remarkable changes in cortical and trabecular bone structure. Previous analyses by strain gauge technique, photoelastic and, more recently, finite element (FE) methods provided no direct evidence for occlusal load distribution through the cortical and trabecular bone compartments individually. Therefore, we developed an improved three-dimensional FE model of the human skull in order to clarify the distribution of occlusal forces through the cortical and trabecular bone during habitual masticatory activities. Particular focus was placed on the load transfer through the anterior and posterior maxilla. The results were presented in von Mises stress (VMS) and the maximum principal stress, and compared to the reported FE and strain gauge data. Our qualitative stress analysis indicates that occlusal forces distribute through the mid-facial skeleton along five vertical and two horizontal buttresses. We demonstrated that cortical bone has a priority in the transfer of occlusal load in the anterior maxilla, whereas both cortical and trabecular bone in the posterior maxilla are equally involved in performing this task. Observed site dependence of the occlusal load distribution may help clinicians in creating strategies for implantology and orthodontic treatments. Additionally, the magnitude of VMS in our model was significantly lower in comparison to previous FE models composed only of cortical bone. This finding suggests that both cortical and trabecular bone should be modeled whenever stress will be quantitatively analyzed. PMID:25458179

  5. Distribution of proteoglycans in the trabecular tissue of eyes with neovascular glaucoma.

    PubMed

    Kubota, T; Tawara, A; Khalil, A; Honda, M; Inomata, H

    1996-11-01

    We investigated histo-chemically the composition and distribution of proteoglycans in the trabecular tissue of eyes with neovascular glaucoma. Cupromeronic blue in combination with a series of enzyme digestions and nitrous acid treatment were used. The spaces between the trabecular beams were lined by a single layer of vascular endothelium and were filled with red blood cells. A basal lamina and microfibrils were detected just beneath the newly formed vascular endothelial cells. Chondroitin-sulfate- and dermatan-sulfate-type proteoglycans were present in association with collagen fibrils in the extracellular matrix. Heparan-sulfate-type proteoglycans were present in association with the basal lamina of both the vascular endothelial cells and the trabecular cells. It is unlikely that these abnormalities in the type or distribution of proteoglycans in the trabecular meshwork have a major role in the pathogenesis of glaucoma. PMID:9479524

  6. Tomography of human trabecular bone with a laser-wakefield driven x-ray source

    NASA Astrophysics Data System (ADS)

    Cole, J. M.; Wood, J. C.; Lopes, N. C.; Poder, K.; Abel, R. L.; Alatabi, S.; Bryant, J. S. J.; Jin, A.; Kneip, S.; Mecseki, K.; Parker, S.; Symes, D. R.; Sandholzer, M. A.; Mangles, S. P. D.; Najmudin, Z.

    2016-01-01

    A laser-wakefield driven x-ray source is used for the radiography of human bone. The betatron motion of accelerated electrons generates x-rays which are hard (critical energy {{E}\\text{crit}}>30 keV), have small source size (<3 μm) and high average brightness. The x-rays are generated from a helium gas cell which is near-instantly replenishable, and thus the average photon flux is limited by the repetition rate of the driving laser rather than the breakdown of the x-ray source. A tomograph of a human bone sample was recorded with a resolution down to 50 μm. The photon flux was sufficiently high that a radiograph could be taken with each laser shot, and the fact that x-ray beams were produced on 97% of shots minimised failed shots and facilitated full micro-computed tomography in a reasonable time scale of several hours, limited only by the laser repetition rate. The x-ray imaging beamline length (not including the laser) is shorter than that of a synchrotron source due to the high accelerating fields and small source size. Hence this interesting laboratory-based source may one day bridge the gap between small microfocus x-ray tubes and large synchrotron facilities.

  7. Synchrotron radiation micro-CT at the micrometer scale for the analysis of the three-dimensional morphology of microcracks in human trabecular bone.

    PubMed

    Larrue, Aymeric; Rattner, Aline; Peter, Zsolt-Andrei; Olivier, Cécile; Laroche, Norbert; Vico, Laurence; Peyrin, Françoise

    2011-01-01

    Bone quality is an important concept to explain bone fragility in addition to bone mass. Among bone quality factors, microdamage which appears in daily life is thought to have a marked impact on bone strength and plays a major role in the repair process. The starting point for all studies designed to further our understanding of how bone microdamage initiate or dissipate energy, or to investigate the impact of age, gender or disease, remains reliable observation and measurement of microdamage. In this study, 3D Synchrotron Radiation (SR) micro-CT at the micrometric scale was coupled to image analysis for the three-dimensional characterization of bone microdamage in human trabecular bone specimens taken from femoral heads. Specimens were imaged by 3D SR micro-CT with a voxel size of 1.4 µm. A new tailored 3D image analysis technique was developed to segment and quantify microcracks. Microcracks from human trabecular bone were observed in different tomographic sections as well as from 3D renderings. New 3D quantitative measurements on the microcrack density and morphology are reported on five specimens. The 3D microcrack density was found between 3.1 and 9.4/mm3 corresponding to a 2D density between 0.55 and 0.76 /mm2. The microcrack length and width measured in 3D on five selected microcrack ranged respectively from 164 µm to 209 µm and 100 µm to 120 µm. This is the first time that various microcracks in unloaded human trabecular bone--from the simplest linear crack to more complex cross-hatch cracks--have been examined and quantified by 3D imaging at this scale. The suspected complex morphology of microcracks is here considerably more evident than in the 2D observations. In conclusion, this technique opens new perspective for the 3D investigation of microcracks and the impact of age, disease or treatment. PMID:21750707

  8. Electron absorbed fractions of energy and S-values in an adult human skeleton based on µCT images of trabecular bone

    NASA Astrophysics Data System (ADS)

    Kramer, R.; Richardson, R. B.; Cassola, V. F.; Vieira, J. W.; Khoury, H. J.; Lira, C. A. B. de O.; Robson Brown, K.

    2011-03-01

    When the human body is exposed to ionizing radiation, among the soft tissues at risk are the active marrow (AM) and the bone endosteum (BE) located in tiny, irregular cavities of trabecular bone. Determination of absorbed fractions (AFs) of energy or absorbed dose in the AM and the BE represent one of the major challenges of dosimetry. Recently, at the Department of Nuclear Energy at the Federal University of Pernambuco, a skeletal dosimetry method based on µCT images of trabecular bone introduced into the spongiosa voxels of human phantoms has been developed and applied mainly to external exposure to photons. This study uses the same method to calculate AFs of energy and S-values (absorbed dose per unit activity) for electron-emitting radionuclides known to concentrate in skeletal tissues. The modelling of the skeletal tissue regions follows ICRP110, which defines the BE as a 50 µm thick sub-region of marrow next to the bone surfaces. The paper presents mono-energetic AFs for the AM and the BE for eight different skeletal regions for electron source energies between 1 keV and 10 MeV. The S-values are given for the beta emitters 14C, 59Fe, 131I, 89Sr, 32P and 90Y. Comparisons with results from other investigations showed good agreement provided that differences between methodologies and trabecular bone volume fractions were properly taken into account. Additionally, a comparison was made between specific AFs of energy in the BE calculated for the actual 50 µm endosteum and the previously recommended 10 µm endosteum. The increase in endosteum thickness leads to a decrease of the endosteum absorbed dose by up to 3.7 fold when bone is the source region, while absorbed dose increases by ~20% when the beta emitters are in marrow.

  9. Improving bone strength prediction in human proximal femur specimens through geometrical characterization of trabecular bone microarchitecture and support vector regression

    PubMed Central

    Huber, Markus B.; Carballido-Gamio, Julio; Bauer, Jan S.; Baum, Thomas; Eckstein, Felix; Lochmüller, Eva; Majumdar, Sharmila; Link, Thomas M.; Wismüller, Axel

    2014-01-01

    We investigate the use of different trabecular bone descriptors and advanced machine learning tech niques to complement standard bone mineral density (BMD) measures derived from dual-energy x-ray absorptiometry (DXA) for improving clinical assessment of osteoporotic fracture risk. For this purpose, volumes of interest were extracted from the head, neck, and trochanter of 146 ex vivo proximal femur specimens on multidetector computer tomography. The trabecular bone captured was characterized with (1) statistical moments of the BMD distribution, (2) geometrical features derived from the scaling index method (SIM), and (3) morphometric parameters, such as bone fraction, trabecular thickness, etc. Feature sets comprising DXA BMD and such supplemental features were used to predict the failure load (FL) of the specimens, previously determined through biomechanical testing, with multiregression and support vector regression. Prediction performance was measured by the root mean square error (RMSE); correlation with measured FL was evaluated using the coefficient of determination R2. The best prediction performance was achieved by a combination of DXA BMD and SIM-derived geometric features derived from the femoral head (RMSE: 0.869 ± 0.121, R2: 0.68 ± 0.079), which was significantly better than DXA BMD alone (RMSE: 0.948 ± 0.119, R2: 0.61 ± 0.101) (p < 10−4). For multivariate feature sets, SVR outperformed multiregression (p < 0.05). These results suggest that supplementing standard DXA BMD measurements with sophisticated femoral trabecular bone characterization and supervised learning techniques can significantly improve biomechanical strength prediction in proximal femur specimens. PMID:24860245

  10. St. John's Wort (Hypericum perforatum) stimulates human osteoblastic MG-63 cell proliferation and attenuates trabecular bone loss induced by ovariectomy

    PubMed Central

    You, Mi-kyoung; Kim, Du-Woon; Jeong, Kyu-Shik; Bang, Mi-Ae; Kim, Hwan-Seon; Rhuy, Jin

    2015-01-01

    BACKGROUND/OBJECFTIVES The effect of St. John's Wort extract (SJW) on MG-63 cell proliferation and trabecular bone loss induced by ovariectomy was examined. MATERIALS/METHODS Proliferation, expression of estrogen receptor (ER) α and ER β, and gene expressions of osteoprotegerin (OPG), osteocalcin (OC) and alkaline phosphatase (ALP) were examined in MG-63 cells treated with or without SJW. Ovariectomized rats were treated with SJW at the dose of 100 or 200 mg/kg/day, β-estradiol-3-benzoate (E2), or vehicle only (OVX-C), and sham operated rats were treated with vehicle only (Sham-C). Serum ALP and C-telopeptide (CTX), and femoral trabecular bone loss were examined. RESULTS SJW increased MG-63 cell proliferation and expression of ER α and ER β, and positive effect was shown on gene expressions of ALP, OC and OPG. SJW also showed estrogen like effect on bone associated with slowing down in trabecular bone loss. Histopathology by H&E showed rats treated with SJW displayed denser structure in metaphyseal region of distal femur compared with rats in OVX-C. SJW was shown to reduce serum CTX in OVX rats. CONCLUSION The present study provides new insight in preventing estrogen deficiency induced bone loss of SJW and possibility for its application in bone health supplement. PMID:26425274

  11. An Orientation Distribution Function for Trabecular Bone

    SciTech Connect

    Lawrence Livermore National Laboratory

    2004-10-08

    We describe a new method for quantifying the orientation of trabecular bone from three-dimensional images. Trabecular lattices from five human vertebrae were decomposed into individual trabecular elements, and the orientation, mass, and thickness of each element were recorded. Continuous functions that described the total mass (M({var_phi},{theta})) and mean thickness ({tau}({var_phi},{theta})) of all trabeculae as a function of orientation were derived. The results were compared with experimental measurements of the elastic modulus in the three principal anatomic directions. A power law scaling relationship between the anisotropies in mass and elastic modulus was observed; the scaling exponent was 1.41 (R{sup 2} = 0.88). As expected, the preponderance of trabecular mass was oriented along the cranial-caudal direction; on average, there was 3.4 times more mass oriented vertically than horizontally. Moreover, the vertical trabeculae were 30% thicker, on average, than the horizontal trabeculae. The vertical trabecular thickness was inversely related to the connectivity (R{sup 2} = 0.70; p = 0.07), suggesting a possible organization into either few, thick trabeculae or many thin trabeculae. The method, which accounts for the mechanical connectedness of the lattice, provides a rapid way to both visualize and quantify the three-dimensional organization of trabecular bone.

  12. AGE-RELATED CHANGES IN HUMAN TRABECULAR BONE: RELATIONSHIP BETWEEN MICROSTRUCTURAL STRESS AND STRAIN AND DAMAGE MORPHOLOGY

    PubMed Central

    O’Neal, Jessica M.; Nagaraja, Srinidhi; Diab, Tamim; Vidakovic, Brani; Guldberg, Robert E.

    2011-01-01

    Accumulation of microdamage in aging and disease can cause skeletal fragility and is one of several factors contributing to osteoporotic fractures. To better understand the role of microdamage in fragility fracture, the mechanisms of bone failure must be elucidated on a tissue-level scale where interactions between bone matrix properties, the local biomechanical environment, and bone architecture are concurrently examined for their contributions to microdamage formation. A technique combining histological damage assessment of individual trabeculae with linear finite element solutions of trabecular von Mises and principal stress and strain was used to compare the damage initiation threshold between pre-menopausal (32–37 years, n=3 donors) and post-menopausal (71–80 years, n=3 donors) femoral cadaveric bone. Strong associations between damage morphology and stress and strain parameters were observed in both groups, and an age-related decrease in undamaged trabecular von Mises stress was detected. In trabeculae from younger donors, the 95% CI for von Mises stress on undamaged regions ranged from 50.7 – 67.9 MPa, whereas in trabeculae from older donors, stresses were significantly lower (38.7 – 50.2, p<0.01). Local microarchitectural analysis indicated that thinner, rod-like trabeculae oriented along the loading axis are more susceptible to severe microdamage formation in older individuals, while only rod-like architecture was associated with severe damage in younger individuals. This study therefore provides insight into how damage initiation and morphology relate to local trabecular microstructure and the associated stresses and strains under loading. Furthermore, by comparison of samples from pre- and post-menopausal women, the results suggest that trabeculae from younger individuals can sustain higher stresses prior to microdamage initiation. PMID:21724189

  13. Human adipose-derived stem cells (hASCs) proliferate and differentiate in osteoblast-like cells on trabecular titanium scaffolds.

    PubMed

    Gastaldi, Giulia; Asti, Annalia; Scaffino, Manuela Federica; Visai, Livia; Saino, Enrica; Cometa, Angela Maria; Benazzo, Francesco

    2010-09-01

    The use of stem cells in regenerative medicine is an appealing area of research that has received a great deal of interest in recent years. The population called human adipose tissue-derived stem cells (hASCs) share many of the characteristic of its counterpart of marrow including extensive proliferative potential and the ability to undergo multilineage differentiation along classical mesenchymal lineages: adipogenesis, chondrogenesis, osteogenesis, and myogenesis. The aim of this study was to evaluate with biochemical and morphological methods the adhesion and differentiation of hASCs grown on trabecular titanium scaffolds. The hASCs isolated from subcutaneous adipose tissue after digestion with collagenase were seeded on monolayer and on trabecular titanium scaffolds and incubated at 37 degrees C in 5% CO(2) with osteogenic medium or control medium.The results showed that hASCs were able to adhere to titanium scaffolds, to proliferate, to acquire an osteoblastic-like phenotype, and to produce a calcified extracellular matrix with protein, such as, decorin, fibronectin, osteocalcin, osteonectin, osteopontin, and type I collagen. These data suggest that this kind of scaffold/cells construct is effective to regenerate damaged tissue and to restore the function of bone tissue. PMID:20336739

  14. Multiple quantitative trait loci for cortical and trabecular bone regulation map to mid-distal mouse chromosome 4 that shares linkage homology to human chromosome 1p36.

    PubMed

    Beamer, Wesley G; Shultz, Kathryn L; Coombs, Harold F; Horton, Lindsay G; Donahue, Leah Rae; Rosen, Clifford J

    2012-01-01

    The mid-distal region of mouse chromosome 4 (Chr 4) is homologous with human Chr 1p36. Previously, we reported that mouse Chr 4 carries a quantitative trait locus (QTL) with strong regulatory effect on volumetric bone mineral density (vBMD). The intent of this study is to utilize nested congenic strains to decompose the genetic complexity of this gene-rich region. Adult females and males from 18 nested congenic strains carrying discrete C3H sequences were phenotyped for femoral mineral and volume by pQCT and for trabecular bone volume (BV), tissue volume (TV), trabecular number (Trab.no), and trabecular thickness (Trab.thk) by MicroCT 40. Our data show that the mouse Chr 4 region consists of at least 10 regulatory QTL regions that affected either or both pQCT and MicroCT 40 phenotypes. The pQCT phenotypes were typically similar between sexes, whereas the MicroCT 40 phenotypes were divergent. Individual congenic strains contained one to seven QTL regions. These regions conferred large positive or negative effects in some congenic strains, depending on the particular bone phenotype. The QTL regions II to X are syntenic with human 1p36, containing from 1 to 102 known genes. We identified 13 candidate genes that can be linked to bone within these regions. Six of these genes were linked to osteoblasts, three linked to osteoclasts, and two linked to skeletal development. Three of these genes have been identified in Genome Wide Association Studies (GWAS) linked to 1p36. In region III, there is only one gene, Lck, which conferred negative pQCT and MicroCT 40 phenotypes in both sexes. This gene is important to development and functioning of T cells, has been associated with osteoclast activity, and represents a novel bone regulatory gene that merits further experimental evaluation. In summary, congenic strains are powerful tools for identifying regulatory regions that influence bone biology and offer models for testing hypotheses about gene-gene and gene

  15. Material Properties of the Mandibular Trabecular Bone

    PubMed Central

    Lakatos, Éva; Magyar, Lóránt; Bojtár, Imre

    2014-01-01

    The present paper introduces a numerical simulation aided, experimental method for the measurement of Young's modulus of the trabecular substance in the human mandible. Compression tests were performed on fresh cadaveric samples containing trabecular bone covered with cortical layer, thus avoiding the destruction caused by the sterilization, preservation, and storage and the underestimation of the stiffness resulting from the individual failure of the trabeculae cut on the surfaces. The elastic modulus of the spongiosa was determined by the numerical simulation of each compression test using a specimen specific finite element model of each sample. The received mandibular trabecular bone Young's modulus values ranged from 6.9 to 199.5 MPa. PMID:27006933

  16. Microcomputed tomographic analysis of human condyles in unilateral condylar hyperplasia: increased cortical porosity and trabecular bone volume fraction with reduced mineralisation.

    PubMed

    Karssemakers, L H E; Nolte, J W; Tuinzing, D B; Langenbach, G E J; Raijmakers, P G; Becking, A G

    2014-12-01

    Unilateral condylar hyperplasia or hyperactivity is a disorder of growth that affects the mandible, and our aim was to visualise the 3-dimensional bony microstructure of resected mandibular condyles of affected patients. We prospectively studied 17 patients with a clinical presentation of progressive mandibular asymmetry and an abnormal single-photon emission computed tomographic (SPECT) scan. All patients were treated by condylectomy to arrest progression. The resected condyles were scanned with micro-CT (18 μm resolution). Rectangular volumes of interest were selected in 4 quadrants (lateromedial and superoinferior) of the trabecular bone of each condyle. Variables of bone architecture (volume fraction, trabecular number, thickness, and separation, degree of mineralisation, and degree of structural anisotrophy) were calculated with routine morphometric software. Eight of the 17 resected condyles showed clear destruction of the subchondral layer of cortical bone. There was a significant superoinferior gradient for all trabecular variables. Mean (SD) bone volume fraction (25.1 (6) %), trabecular number (1.69 (0.26) mm(-1)), trabecular thickness (0.17 (0.03) mm), and degree of mineralisation (695.39 (39.83) mg HA/cm(3)) were higher in the superior region. Trabecular separation (0.6 (0.16) mm) and structural anisotropy (1.84 (0.28)) were higher in the inferior region. The micro-CT analysis showed increased cortical porosity in many of the condyles studied. It also showed a higher bone volume fraction, greater trabecular thickness and trabecular separation, greater trabecular number, and less mineralisation in the condyles of the 17 patients compared with the known architecture of unaffected mandibular condyles. PMID:25219775

  17. Mechanical model of blebbing in nuclear lamin meshworks

    PubMed Central

    Funkhouser, Chloe M.; Sknepnek, Rastko; Shimi, Takeshi; Goldman, Anne E.; Goldman, Robert D.; Olvera de la Cruz, Monica

    2013-01-01

    Much of the structural stability of the nucleus comes from meshworks of intermediate filament proteins known as lamins forming the inner layer of the nuclear envelope called the nuclear lamina. These lamin meshworks additionally play a role in gene expression. Abnormalities in nuclear shape are associated with a variety of pathologies, including some forms of cancer and Hutchinson–Gilford Progeria Syndrome, and often include protruding structures termed nuclear blebs. These nuclear blebs are thought to be related to pathological gene expression; however, little is known about how and why blebs form. We have developed a minimal continuum elastic model of a lamin meshwork that we use to investigate which aspects of the meshwork could be responsible for bleb formation. Mammalian lamin meshworks consist of two types of lamin proteins, A type and B type, and it has been reported that nuclear blebs are enriched in A-type lamins. Our model treats each lamin type separately and thus, can assign them different properties. Nuclear blebs have been reported to be located in regions where the fibers in the lamin meshwork have a greater separation, and we find that this greater separation of fibers is an essential characteristic for generating nuclear blebs. The model produces structures with comparable morphologies and distributions of lamin types as real pathological nuclei. Thus, preventing this opening of the meshwork could be a route to prevent bleb formation, which could be used as a potential therapy for the pathologies associated with nuclear blebs. PMID:23401537

  18. iStent® Trabecular Microbypass Stent: An Update

    PubMed Central

    Resende, Arthur Fernandes; Patel, Neal Sanjay; Waisbourd, Michael; Katz, L. Jay

    2016-01-01

    Due to the high rates of complications and failure experienced with current glaucoma procedures, there is a continuous search for a safer and more effective glaucoma surgery. A new class of procedures termed minimally invasive glaucoma surgeries (MIGS) aim to fill this void by offering an alternative method of IOP reduction associated with markedly reduced complication rates and shorter recovery times. The iStent, a trabecular microbypass stent, is a MIGS device that has quickly gained popularity. The device allows aqueous humor to directly drain from the anterior chamber into Schlemm's canal by bypassing an obstructed trabecular meshwork. This review examines publications about the iStent, focusing on the device's efficacy, safety, and cost when a single iStent or multiple iStents are implanted in combination with cataract surgery or as a solo procedure. Current data suggest that the iStent is a safe and effective tool in the management of mild-to-moderate glaucoma, notable for its limited complications and absence of serious adverse events following implantation. As valuable experience is gained performing ab interno MIGS, increasing familiarity with angle anatomy and iStent placement, and as newer stent designs are developed, there is promise of continual improvement in the surgical management of glaucoma. PMID:27413541

  19. Automated trabecular bone histomorphometry

    NASA Technical Reports Server (NTRS)

    Polig, E.; Jee, W. S. S.

    1985-01-01

    The toxicity of alpha-emitting bone-seeking radionuclides and the relationship between bone tumor incidence and the local dosimetry of radionuclides in bone are investigated. The microdistributions of alpha-emitting radionuclides in the trabecular bone from the proximal humerus, distal humerus, proximal ulna, proximal femur, and distal femur of six young adult beagles injected with Am-241 (three with 2.8 micro-Ci/kg and three with 0.9 micro-Ci/kg) are estimated using a computer-controlled microscope photometer system; the components of the University of Utah Optical Track Scanner are described. The morphometric parameters for the beagles are calculated and analyzed. It is observed that the beagles injected with 0.9 micro-Ci of Am-241/kg showed an increase in the percentage of bone and trabecular bone thickness, and a reduction in the width of the bone marrow space and surface/volume ratio. The data reveal that radiation damage causes abnormal bone structure.

  20. Relationships of trabecular bone structure with quantitative ultrasound parameters: in vitro study on human proximal femur using transmission and backscatter measurements.

    PubMed

    Padilla, F; Jenson, F; Bousson, V; Peyrin, F; Laugier, P

    2008-06-01

    The present study was designed to assess the relationships between QUS parameters and bone density or microarchitecture on samples of human femoral trabecular bone. The normalized slope of the frequency-dependent attenuation (nBUA), the speed of sound (SOS) and the broadband ultrasound backscatter coefficient (BUB) were measured on 37 specimens of pure trabecular bones removed from upper parts of fresh human femurs. Bone mineral density (BMD) was assessed using a clinical scanner. Finally, 8 mm diameter cylindrical cores were extracted from the specimens and their microarchitecture was reconstructed after synchrotron radiation microtomography experiments (isotropic resolution of 10 microm). A large number of microarchitectural parameters were computed, describing morphology, connectivity and geometry of the specimens. BMD correlated with all the microarchitectural parameters and the number of significant correlations was found among the architectural parameters themselves. All QUS parameters were significantly correlated to BMD (R=0.83 for nBUA, R=0.81 for SOS and R=0.69 for BUB) and to microarchitectural parameters (R=-0.79 between nBUA and Tb.Sp, R=-0.81 between SOS and Tb.Sp, R=-0.65 between BUB and BS/BV). Using multivariate model, it was found that microstructural parameters adds 10%, 19%, and 4% to the respective BMD alone contribution for the three variables BUA, SOS and BUB. Moreover, the RMSE was reduced by up to 50% for SOS, by up to 21% for nBUA and up to 11% when adding structural variables to BMD in explaining QUS results. Given the sample, which is not osteoporosis-enriched, the added contribution is quite substantial. The variability of SOS was indeed completely explained by a multivariate model including BMD and independent structural parameters (R(2)=0.94). The inverse problem on the data presented here has been addressed using simple and multiple linear regressions. It was shown that the predictions (in terms of R(2) or RMSE) of microarchitectural

  1. Characterization of micro-invasive trabecular bypass stents by ex vivo perfusion and computational flow modeling

    PubMed Central

    Hunter, Kendall S; Fjield, Todd; Heitzmann, Hal; Shandas, Robin; Kahook, Malik Y

    2014-01-01

    Micro-invasive glaucoma surgery with the Glaukos iStent® or iStent inject® (Glaukos Corporation, Laguna Hills, CA, USA) is intended to create a bypass through the trabecular meshwork to Schlemm’s canal to improve aqueous outflow through the natural physiologic pathway. While the iStent devices have been evaluated in ex vivo anterior segment models, they have not previously been evaluated in whole eye perfusion models nor characterized by computational fluid dynamics. Intraocular pressure (IOP) reduction with the iStent was evaluated in an ex vivo whole human eye perfusion model. Numerical modeling, including computational fluid dynamics, was used to evaluate the flow through the stents over physiologically relevant boundary conditions. In the ex vivo model, a single iStent reduced IOP by 6.0 mmHg from baseline, and addition of a second iStent further lowered IOP by 2.9 mmHg, for a total IOP reduction of 8.9 mmHg. Computational modeling showed that simulated flow through the iStent or iStent inject is smooth and laminar at physiological flow rates. Each stent was computed to have a negligible flow resistance consistent with an expected significant decrease in IOP. The present perfusion results agree with prior clinical and laboratory studies to show that both iStent and iStent inject therapies are potentially titratable, providing clinicians with the opportunity to achieve lower target IOPs by implanting additional stents. PMID:24648713

  2. Comparative forefoot trabecular bone architecture in extant hominids.

    PubMed

    Griffin, Nicole L; D'Août, Kristiaan; Ryan, Timothy M; Richmond, Brian G; Ketcham, Richard A; Postnov, Andrei

    2010-08-01

    The appearance of a forefoot push-off mechanism in the hominin lineage has been difficult to identify, partially because researchers disagree over the use of the external skeletal morphology to differentiate metatarsophalangeal joint functional differences in extant great apes and humans. In this study, we approach the problem by quantifying properties of internal bone architecture that may reflect different loading patterns in metatarsophalangeal joints in humans and great apes. High-resolution x-ray computed tomography data were collected for first and second metatarsal heads of Homo sapiens (n = 26), Pan paniscus (n = 17), Pan troglodytes (n = 19), Gorilla gorilla (n = 16), and Pongo pygmaeus (n = 20). Trabecular bone fabric structure was analyzed in three regions of each metatarsal head. While bone volume fraction did not significantly differentiate human and great ape trabecular bone structure, human metatarsal heads generally show significantly more anisotropic trabecular bone architectures, especially in the dorsal regions compared to the corresponding areas of the great ape metatarsal heads. The differences in anisotropy between humans and great apes support the hypothesis that trabecular architecture in the dorsal regions of the human metatarsals are indicative of a forefoot habitually used for propulsion during gait. This study provides a potential route for predicting forefoot function and gait in fossil hominins from metatarsal head trabecular bone architecture. PMID:20655571

  3. Experimental Study of Diffusion Coefficients of Water through the Collagen: Apatite Porosity in Human Trabecular Bone Tissue

    PubMed Central

    Bini, Fabiano; Marinozzi, Andrea

    2014-01-01

    We firstly measured the swelling of single trabeculae from human femur heads during water imbibition. Since the swelling is caused by water diffusing from external surfaces to the core of the sample, by measuring the sample swelling over time, we obtained direct information about the transport of fluids through the intimate constituents of bone, where the mineralization process takes place. We developed an apparatus to measure the free expansion of the tissue during the imbibition. In particular, we measured the swelling along three natural axes (length L, width W, and thickness T) of plate-like trabeculae. For this aim, we developed a 3D analytical model of the water uptake by the sample that was performed according to Fickian transport mechanism. The results were then utilized to predict the swelling over time along the three sample directions (L, W, T) and the apparent diffusion coefficients DT, DW, and DL. PMID:24967405

  4. Experimental study of diffusion coefficients of water through the collagen: apatite porosity in human trabecular bone tissue.

    PubMed

    Marinozzi, Franco; Bini, Fabiano; Quintino, Alessandro; Corcione, Massimo; Marinozzi, Andrea

    2014-01-01

    We firstly measured the swelling of single trabeculae from human femur heads during water imbibition. Since the swelling is caused by water diffusing from external surfaces to the core of the sample, by measuring the sample swelling over time, we obtained direct information about the transport of fluids through the intimate constituents of bone, where the mineralization process takes place. We developed an apparatus to measure the free expansion of the tissue during the imbibition. In particular, we measured the swelling along three natural axes (length L, width W, and thickness T) of plate-like trabeculae. For this aim, we developed a 3D analytical model of the water uptake by the sample that was performed according to Fickian transport mechanism. The results were then utilized to predict the swelling over time along the three sample directions (L, W, T) and the apparent diffusion coefficients D T, D W, and D L. PMID:24967405

  5. Application of the scaling index method to μCT images of human trabecular bone for the characterization of biomechanical strength

    NASA Astrophysics Data System (ADS)

    Monetti, Roberto A.; Bauer, Jan; Müller, Dirk; Rummeny, Ernst; Matsuura, Maiko; Eckstein, Felix; Link, Thomas; Räth, Christoph

    2007-03-01

    Osteoporosis is a metabolic bone disorder characterized by the loss of bone mineral density (BMD) and the deterioration of the bone micro-architecture. Rarefied bone structures are more susceptible to fractures which are the worst complications of osteoporosis. Here, we apply a structure characterization method, namely the Scaling Index Method, to micro-computed tomographic (μ-CT) images of the distal radius and extract 3D nonlinear structure measures to assess the biomechanical properties of trabecular bone. Biomechanical properties were quantified by the maximum compressive strength (MCS) obtained in a biomechanical test and bone mineral density (BMD) was calculated using dual X-ray absorptiometry (DXA). μ-CT images allow for the application of two different modalities of the SIM which differ in the dimensional embedding of the image. Both representations lead to similar correlation coefficients with MCS which are significantly better than the ones obtained using standard 3D morphometric parameters and comparable to the result given by BMD. The analysis of μ-CT images based on the SIM allows for a sharp distinction of the different structural elements which compose the trabecular bone network.

  6. Distribution of tissue plasminogen activator in human and monkey eyes. An immunohistochemical study.

    PubMed

    Tripathi, B J; Geanon, J D; Tripathi, R C

    1987-11-01

    The authors examined various structures of human and rhesus monkey eyes for the presence of tissue plasminogen activator (t-PA) by using the peroxidase-antiperoxidase immunohistochemical technique with a monoclonal antibody specific for human t-PA. Positive staining for t-PA was observed both intracellularly and in the extracellular matrix of many tissues in both species. The tissues which stained intensely for t-PA included the corneal endothelium, corneal epithelium, trabecular meshwork, lens epithelium, peripheral vitreous, uveal tract, inner retina, and all vascular endothelia. The apparent minor difference in staining intensity between human and monkey eyes may be related to the time-dependent degradation of t-PA, to variations in the tissue content of t-PA, or to the difference in animal species. The discussion includes a consideration of the fibrinolytic activity of t-PA and of its emerging role in the destructive remodeling of the extracellular matrix in various ocular structures. PMID:3120076

  7. [Retinal and trabecular degeneration in glaucoma: new insights into pathogenesis and treatment].

    PubMed

    Denoyer, A; Roubeix, C; Sapienza, A; Réaux-Le Goazigo, A; Mélik-Parsadaniantz, S; Baudouin, C

    2015-04-01

    Academic and industrial research has brought new insights into the pathogenesis of glaucoma, aiming at identifying and targeting specific mechanisms to improve our current therapeutic strategy. Retinal neurodegeneration is still the main focus, whether in terms of extrinsic factors such as neurotrophin deprivation, glutamate toxicity, vascular deficiency and neuro-inflammation from glial cells, or in terms of retinal ganglion cell intrinsic sensibility to proapoptotic signals. However, glaucoma is not solely a retinal disease but also involves retinal and trabecular meshwork degeneration, extending into and/or even originating from the brain. The present review summarizes our current knowledge of key mechanisms involved in glaucoma degeneration, focusing on the direction of current research towards the future of glaucoma therapy. PMID:25659482

  8. A three-scale finite element investigation into the effects of tissue mineralisation and lamellar organisation in human cortical and trabecular bone.

    PubMed

    Vaughan, T J; McCarthy, C T; McNamara, L M

    2012-08-01

    Bone is an exceptional material that is lightweight for efficient movement but also exhibits excellent strength and stiffness imparted by a composite material of organic proteins and mineral crystals that are intricately organised on many scales. Experimental and computational studies have sought to understand the role of bone composition and organisation in regulating the biomechanical behaviour of bone. However, due to the complex hierarchical arrangement of the constituent materials, the reported experimental values for the elastic modulus of trabecular and cortical tissue have conflicted greatly. Furthermore, finite element studies of bone have largely made the simplifying assumption that material behaviour was homogeneous or that tissue variability only occurred at the microscale, based on grey values from micro-CT scans. Thus, it remains that the precise role of nanoscale tissue constituents and microscale tissue organisation is not fully understood and more importantly that these have never been incorporated together to predict bone fracture or implant outcome in a multiscale finite element framework. In this paper, a three-scale finite element homogenisation scheme is presented which enables the prediction of homogenised effective properties of tissue level bone from its fundamental nanoscale constituents of hydroxyapatite mineral crystals and organic collagen proteins. Two independent homogenisation steps are performed on representative volume elements which describe the local morphological arrangement of both the nanostructural and microstructural levels. This three-scale homogenisation scheme predicts differences in the tissue level properties of bone as a function of mineral volume fraction, mineral aspect ratio and lamellar orientation. These parameters were chosen to lie within normal tissue ranges derived from experimental studies, and it was found that the predicted stiffness properties at the lamellar level correlate well with experimental

  9. ENDOTHELIAL PROGENITOR CELL ADHESION, GROWTH AND CHARACTERIZATION ON TRABECULAR TITANIUM AND TRABECULAR TITANIUM COATED WITH COLLAGEN OR DECELLULARIZED ECM.

    PubMed

    Gastaldi, G; Caliogna, L; Botta, L; Ghiara, M; Benazzo, F

    2015-01-01

    Adequate blood supply is essential for prosthesis osteointegration and bone healing as it supplies oxygen, nutrition and progenitor cells. The bone healing process and vascularization depend upon the endothelial cells, which speed up implant osteointegration. Endothelial Progenitor Cells (EPC) are a population of stem cells that can reproduce, migrate and acquire mature endothelial phenotype. Their recruitment occurs in the tissue lesion to enhance neovascularization. Trabecular TitaniumTM (TTTM) is a new biomaterial with very interesting biomechanical characteristics and fast osteointegration. This study has investigated adhesion, proliferation and characteristics of EPC on three types of biomaterial: unmodified trabecular titanium, trabecular titanium coated with the ECM deposited by human mesenchymal stem cells isolated from subcutaneous adipose tissue and decellularized and trabecular titanium coated with type I collagen (control scaffold). MTT assay showed similar percentages of EPCs seeded on the different kinds of scaffold: 67% on TT, 70% on decellularized scaffolds and 82% on collagen-coated scaffolds. There were no statistically significant differences between the three groups. We therefore conclude that TTTM allows EPC adhesion and proliferation and, consequently, by permitting vascularization, it favours prosthesis osteointegration. PMID:26652487

  10. Long-Term Dose Response of Trabecular Bone in Mice to Proton Radiation

    PubMed Central

    Bandstra, Eric R.; Pecaut, Michael J.; Anderson, Erica R.; Willey, Jeffrey S.; De Carlo, Francesco; Stock, Stuart R.; Gridley, Daila S.; Nelson, Gregory A.; Levine, Howard G.; Bateman, Ted A.

    2015-01-01

    Astronauts on exploratory missions will experience a complex environment, including microgravity and radiation. While the deleterious effects of unloading on bone are well established, fewer studies have focused on the effects of radiation. We previously demonstrated that 2 Gy of ionizing radiation has deleterious effects on trabecular bone in mice 4 months after exposure. The present study investigated the skeletal response after total doses of proton radiation that astronauts may be exposed to during a solar particle event. We exposed mice to 0.5, 1 or 2 Gy of whole-body proton radiation and killed them humanely 117 days later. Tibiae and femora were analyzed using microcomputed tomography, mechanical testing, mineral composition and quantitative histomorphometry. Relative to control mice, mice exposed to 2 Gy had significant differences in trabecular bone volume fraction (−20%), trabecular separation (+11%), and trabecular volumetric bone mineral density (−19%). Exposure to 1 Gy radiation induced a nonsignificant trend in trabecular bone volume fraction (−13%), while exposure to 0.5 Gy resulted in no differences. No response was detected in cortical bone. Further analysis of the 1-Gy mice using synchrotron microCT revealed a significantly lower trabecular bone volume fraction (−13%) than in control mice. Trabecular bone loss 4 months after exposure to 1 Gy highlights the importance of further examination of how space radiation affects bone. PMID:18494551

  11. Simulating the transport of heavy charged particles through trabecular spongiosa

    NASA Astrophysics Data System (ADS)

    Gersh, Jacob A.

    As planning continues for manned missions far beyond Low Earth Orbit, a paramount concern remains the flight crew's exposure to galactic cosmic radiation. When humans exit the protective magnetic field of Earth, they become subject to bombardment by highly-reactive heavy charged (HZE) particles. A possible consequence of this two- to three-year-long mission is the onset of radiation-induced leukemia, a disorder with a latency period as short as two to three years. Because data on risk to humans from exposure to HZE particles is non-existent, studies of leukemia in animals are now underway to investigate the relative effectiveness of HZE exposures. Leukemogenesis can result from energy depositions occurring within marrow contained in the trabecular spongiosa. Trabecular spongiosa is found in flat bones and within the ends of long bones, and is characterized by an intricate matrix of interconnected bone tissue forming cavities that house marrow. The microscopic internal dimensions of spongiosa vary between species. As radiation traverses this region, interface-induced dose perturbations that occur at the interfaces between bone and marrow affect the patterns of energy deposition within the region. An aim of this project is to determine the extent by which tissue heterogeneity and microscopic dimensions have on patterns of energy deposition within the trabecular spongiosa. This leads to the development of PATHFIT, a computer code capable of generating simple quadric-based geometric models of trabecular spongiosa for both humans and mice based on actual experimentally-determined internal dimensions of trabecular spongiosa. Following the creation of spongiosa models, focus is placed on the development of HITSPAP, a hybrid Monte Carlo (MC) radiation transport code system that combines capabilities of the MC code PENELOPE and MC code PARTRAC. This code is capable of simulating the transport of HZE particles through accurate models of trabecular spongiosa. The final and

  12. A review of trabecular bone functional adaptation: what have we learned from trabecular analyses in extant hominoids and what can we apply to fossils?

    PubMed

    Kivell, Tracy L

    2016-04-01

    Many of the unresolved debates in palaeoanthropology regarding evolution of particular locomotor or manipulative behaviours are founded in differing opinions about the functional significance of the preserved external fossil morphology. However, the plasticity of internal bone morphology, and particularly trabecular bone, allowing it to respond to mechanical loading during life means that it can reveal greater insight into how a bone or joint was used during an individual's lifetime. Analyses of trabecular bone have been commonplace for several decades in a human clinical context. In contrast, the study of trabecular bone as a method for reconstructing joint position, joint loading and ultimately behaviour in extant and fossil non-human primates is comparatively new. Since the initial 2D studies in the late 1970s and 3D analyses in the 1990 s, the utility of trabecular bone to reconstruct behaviour in primates has grown to incorporate experimental studies, expanded taxonomic samples and skeletal elements, and improved methodologies. However, this work, in conjunction with research on humans and non-primate mammals, has also revealed the substantial complexity inherent in making functional inferences from variation in trabecular architecture. This review addresses the current understanding of trabecular bone functional adaptation, how it has been applied to hominoids, as well as other primates and, ultimately, how this can be used to better interpret fossil hominoid and hominin morphology. Because the fossil record constrains us to interpreting function largely from bony morphology alone, and typically from isolated bones, analyses of trabecular structure, ideally in conjunction with that of cortical structure and external morphology, can offer the best resource for reconstructing behaviour in the past. PMID:26879841

  13. Prediction of mechanical properties of trabecular bone using quantitative MRI

    NASA Astrophysics Data System (ADS)

    Lammentausta, E.; Hakulinen, M. A.; Jurvelin, J. S.; Nieminen, M. T.

    2006-12-01

    Techniques for quantitative magnetic resonance imaging (MRI) have been developed for non-invasive estimation of the mineral density and structure of trabecular bone. The R*2 relaxation rate (i.e. 1/T*2) is sensitive to bone mineral density (BMD) via susceptibility differences between trabeculae and bone marrow, and by binarizing MRI images, structural variables, such as apparent bone volume fraction, can be assessed. In the present study, trabecular bone samples of human patellae were investigated in vitro at 1.5 T to determine the ability of MRI-derived variables (R*2 and bone volume fraction) to predict the mechanical properties (Young's modulus, yield stress and ultimate strength). Further, the MRI variables were correlated with reference measurements of volumetric BMD and bone area fraction as determined with a clinical pQCT system. The MRI variables correlated significantly (p < 0.01) with the mechanical variables (r = 0.32-0.46), BMD (r = 0.56) and bone structure (r = 0.51). A combination of R*2 and MRI-derived bone volume fraction further improved the prediction of yield stress and ultimate strength. Although pQCT showed a trend towards better prediction of the mechanical properties, current results demonstrate the feasibility of combined MR imaging of marrow susceptibility and bone volume fraction in predicting the mechanical strength of trabecular bone and bone mineral density.

  14. [Microradiography in the study of trabecular parameters].

    PubMed

    Flautre, B; Hardouin, P

    1992-01-01

    The intermethod variation in measurement of trabecular bone volume (VTO) and the indirect estimation of its microstructure according to Parfitt MTPT (microns), MTPD (/mm) and MTPS (microns) were evaluated in seven undecalcified bone biopsies by analyzing the microradiograph of a 100-microns-thick section with an automatic method (IBAS II Zeiss, Munich) in addition to reference methods (manual and semiautomatic) described in the literature and performed on 7-microns-thick stained sections. Three consecutive 7-microns-stained sections and one 100-mu-thick microradiographed section were taken in each specimen. The 100 microns-thick section was also superficially stained. Trabecular bone volume was measured with both a manual integrating eyepiece and an automatic method. The automatic method on the microradiograph underestimated the VTO by 24.42%. There was a correlation (r = 0.75; p < 0.02) between the manual and computerized methods. Mean trabecular plate thickness (microns), mean trabecular plate density (/mm) and mean trabecular separation (microns) were measured with both semiautomatic and automatic methods. The automatic method on the microradiograph underestimated the MTPT (microns) by 18.98% and the MTPD (/mm) by 14.14% and overestimated the MTPS (microns) by 23.17%. For the MTPT (microns) there was a correlation (r = 0.88; p < 0.02), between both methods, and the correlation was good for MTPD (/mm) (r = 0.97; p < 0.001), and MTPS (r = 0.86; p < 0.002). PMID:1441965

  15. Tensile strength of bovine trabecular bone.

    PubMed

    Kaplan, S J; Hayes, W C; Stone, J L; Beaupré, G S

    1985-01-01

    Data on the tensile and compressive properties of trabecular bone are needed to define input parameters and failure criteria for modeling total joint replacements. To help resolve differences in reports comparing tensile and compressive properties of trabecular bone, we have developed new methods, based on porous foam technology, for tensile testing of fresh/frozen trabecular bone specimens. Using bovine trabecular bone from an isotropic region from the proximal humerus as a model material, we measured ultimate strengths in tension and compression for two groups of 24 specimens each. The average ultimate strength in tension was 7.6 +/- 2.2 (95% C.I.) MPa and in compression was 12.4 +/- 3.2 MPa. This difference was statistically significant (p = 0.013) and was not related to density differences between the test groups (p = 0.28). Strength was related by a power-law function of the local apparent density, but, even accounting for density influences, isotropic bovine trabecular bone exhibits significantly lower strengths in tension than in compression. PMID:4077868

  16. Hip bone trabecular architecture shows uniquely distinctive locomotor behaviour in South African australopithecines.

    PubMed

    Macchiarelli, R; Bondioli, L; Galichon, V; Tobias, P V

    1999-02-01

    Cancellous bone retains structural and behavioural properties which are time and strain-rate dependent. As the orientation of the trabeculae (trajectories) follows the direction of the principal strains imposed by daily loadings, habitual postural and locomotor behaviours are responsible for a variety of trabecular architectures and site-specific textural arrangements of the pelvic cancellous network. With respect to the great ape condition, the human trabecular pattern is characterized by a distinctive ilioischial bundle, an undivided sacropubic bundle, and a full diagonal crossing (approximately 100 degrees) over the acetabulum between the ilioischial and the sacropubic bundles. Advanced digital image processing (DIP) of hip bone radiographs has revealed that adolescent and adult South African australopithecines retained an incompletely developed human-like trabecular pattern associated with gait-related features that are unique among the extant primates. PMID:10068067

  17. Imaging the Aqueous Humor Outflow Pathway in Human Eyes by Three-dimensional Micro-computed Tomography (3D micro-CT)

    SciTech Connect

    C Hann; M Bentley; A Vercnocke; E Ritman; M Fautsch

    2011-12-31

    The site of outflow resistance leading to elevated intraocular pressure in primary open-angle glaucoma is believed to be located in the region of Schlemm's canal inner wall endothelium, its basement membrane and the adjacent juxtacanalicular tissue. Evidence also suggests collector channels and intrascleral vessels may have a role in intraocular pressure in both normal and glaucoma eyes. Traditional imaging modalities limit the ability to view both proximal and distal portions of the trabecular outflow pathway as a single unit. In this study, we examined the effectiveness of three-dimensional micro-computed tomography (3D micro-CT) as a potential method to view the trabecular outflow pathway. Two normal human eyes were used: one immersion fixed in 4% paraformaldehyde and one with anterior chamber perfusion at 10 mmHg followed by perfusion fixation in 4% paraformaldehyde/2% glutaraldehyde. Both eyes were postfixed in 1% osmium tetroxide and scanned with 3D micro-CT at 2 {mu}m or 5 {mu}m voxel resolution. In the immersion fixed eye, 24 collector channels were identified with an average orifice size of 27.5 {+-} 5 {mu}m. In comparison, the perfusion fixed eye had 29 collector channels with a mean orifice size of 40.5 {+-} 13 {mu}m. Collector channels were not evenly dispersed around the circumference of the eye. There was no significant difference in the length of Schlemm's canal in the immersed versus the perfused eye (33.2 versus 35.1 mm). Structures, locations and size measurements identified by 3D micro-CT were confirmed by correlative light microscopy. These findings confirm 3D micro-CT can be used effectively for the non-invasive examination of the trabecular meshwork, Schlemm's canal, collector channels and intrascleral vasculature that comprise the distal outflow pathway. This imaging modality will be useful for non-invasive study of the role of the trabecular outflow pathway as a whole unit.

  18. Trabecular bone deficits among Vietnamese immigrants

    PubMed Central

    Marquez, M. A.; McCready, L. K.; Achenbach, S. J.; Riggs, B. L.; Amin, S.; Khosla, S.

    2011-01-01

    Summary Compared to white women, lower areal bone mineral density (aBMD) in middle-aged Vietnamese immigrants is due to reduced trabecular volumetric bone mineral density (vBMD), which in turn is associated with greater trabecular separation along with lower estrogen levels. Introduction The epidemiology of osteoporosis in Asian populations is still poorly known, but we previously found a deficit in lumbar spine aBMD among postmenopausal Southeast Asian women, compared to white women, that persisted after correction for bone size. This issue was revisited using more sophisticated imaging techniques. Methods Twenty Vietnamese immigrants (age, 44–79 years) were compared to 162 same-aged white women with respect to aBMD at the hip, spine and wrist, vBMD at the hip and spine by quantitative computed tomography and vBMD and bone microstructure at the ultradistal radius by high-resolution pQCT. Bone turnover and sex steroid levels were assessed in a subset (20 Vietnamese and 40 white women). Results The aBMD was lower at all sites among the Vietnamese women, but femoral neck vBMD did not differ from middle-aged white women. Significant differences in lumbar spine and ultradistal radius vBMD in the Vietnamese immigrants were due to lower trabecular vBMD, which was associated with increased trabecular separation. Bone resorption was elevated and bone formation depressed among the Vietnamese immigrants, although trends were not statistically significant. Serum estradiol was positively associated with trabecular vBMD in the Vietnamese women, but their estrogen levels were dramatically lower compared to white women. Conclusions Although reported discrepancies in aBMD among Asian women are mainly an artifact of smaller bone size, we identified a specific deficit in the trabecular bone among a sample of Vietnamese immigrants that may be related to low estrogen levels and which needs further study. PMID:20658128

  19. Internal channel structures in trabecular bone

    NASA Astrophysics Data System (ADS)

    Scherf, Heike; Beckmann, Felix; Fischer, Jens; Witte, Frank

    2004-10-01

    Material properties of bone are crucial for studies regarding the mechanical behavior of bone. The mechanical behavior depends on the macro- and micro-architecture as well as the organic and mineral content of bone. The marco-architecture of bone is normally analyzed by plane radiographs. The micro-architecture of the trabecular bone can be imaged by high resolution CT imaging techniques using conventional x-ray tubes. However, fine structures in bone architecture cannot be sufficiently analyzed by this technique due to its limited resolution. High resolution CT imaging technique using synchrotron radiation generates images with a high spatial resolution of bone structures on a micron scale. Additionally, this imaging technique provides superior determination of local differences in the bone mineral density. Two microtomography techniques, first: based on conventional x-ray tubes and second: based on synchrotron radiation were compared in this study to detect fine bone structures such as inner trabecular channels. In two red howler monkeys (Alouatta seniculus) femora channel structures were found inside the trabecular bone by both techniques. Only synchrotron-based microtomography was able to detect layers of lower mineral density in the channel walls. The found structures in trabecular bone are normally expected in the Haversian channel walls of the cortical bone. However, the origin of the trabecular channel structure is not fully understood. We found, that synchrotron-based microtomography is a very valuable technique in the research of fine bone structures. Further research should focus on the impact of these findings on the mechanical properties of trabecular bone.

  20. Optimizing the assessment of age-related changes in trabecular bone

    NASA Astrophysics Data System (ADS)

    Kubik, T.; Pasowicz, M.; Tabor, Z.; Rokita, E.

    2002-05-01

    The goal of this study was to develop an optimal procedure to determine age-related changes in trabecular bone. The investigations were based on two-dimensional images of the human vertebral trabecular bone specimens. The following indices of trabecular structure were considered: bone volume/total volume, star volume of the marrow cavity, Euler number and the probability of disconnection (straightforwardly connected with the number of separated parts of the network). To follow precisely the changes in the trabecular structure with age, a computer simulation model was used. Up to 35 years of physiological remodelling were simulated. The validation of the model calculations was based on a quantitative comparison with the data measured for older individuals. The simulations confirmed that the description of the age-related changes in the trabecular bone by means of the architectural parameter (star volume) constitutes a promising tool for subjects older than ~50 years. For individuals younger than ~50 years bone mineral density (bone volume/total volume) seems to be the best suited descriptor. The results suggest that the optimal diagnostic procedure is age-dependent and should not be limited to the bone mineral density measurement. The clinical usefulness of the procedure has been validated by examination of the CT images.

  1. Dependence of ultrasonic scattering on frequency and microarchitecture in trabecular bone: Theory and experiment

    NASA Astrophysics Data System (ADS)

    Wear, Keith A.

    2002-05-01

    Measurements of ultrasonic properties of calcaneus (heel bone) have been shown to be effective for the diagnosis of osteoporosis. However, the mechanisms underlying the interaction between ultrasound and bone are currently not well understood. A model that predicts backscatter from trabecular bone has been developed. Scattering is assumed to originate from the surfaces of trabeculae, which are modeled as long, thin, elastic cylinders with radii small compared with the ultrasonic wavelength. Experimental measurements of backscatter using broadband ultrasound centered at 500 kHz from 43 trabecular bone samples (from human calcaneus) in vitro have been performed. Microcomputed tomography has been performed on all 43 samples in order to measure microarchitectural features. The theory correctly predicts the measured dependences of backscatter on ultrasonic frequency and trabecular thickness. [Funding from the FDA Office of Womens Health is gratefully acknowledged.

  2. Measurement of the speed of sound in trabecular bone by using a time reversal acoustics focusing system

    NASA Astrophysics Data System (ADS)

    Lee, Kang Il; Choi, Bok Kyoung

    2014-10-01

    A new method for measuring the speed of sound (SOS) in trabecular bone by using a time reversal acoustics (TRA) focusing system was proposed and validated with measurements obtained by using the conventional pulse-transmission technique. The SOS measured in 14 bovine femoral trabecular bone samples by using the two methods was highly correlated each other, although the SOS measured by using the TRA focusing system was slightly lower by an average of 2.2 m/s. The SOS measured by using the two methods showed high correlation coefficients of r = 0.92 with the apparent bone density, consistent with the behavior in human trabecular bone in vitro. These results prove the efficacy of the new method based on the principle of TRA to measure the SOS in trabecular bone.

  3. Resolution dependence of the non-metric trabecular structure indices.

    PubMed

    Sode, Miki; Burghardt, Andrew J; Nissenson, Robert A; Majumdar, Sharmila

    2008-04-01

    Non-metric indices of topological features of trabecular bone structure, such as structure model index (SMI), connectivity density (Conn.D), and degree of anisotropy (DA), provide unique information relevant to bone quality. With recent technological advancement, in vivo assessment of these indices may be possible from images acquired using high-resolution imaging techniques such as high-resolution peripheral quantitative computed tomography (HR-pQCT). However, more detailed investigation of the dependence of non-metric indices on spatial resolution is needed to determine their applicability. The purpose of this study was to determine whether these three non-metric indices are affected by the spatial resolution of CT images. First, the SMI, Conn.D, and DA were calculated for trabecular bone specimens with varying plate-like and rod-like structures from resampled muCT images across a range of spatial resolutions and compared to the reference values. To account for differences in size across different species and anatomical sites, the results are reported in normalized resolution units. Next, the impact of resolution on the non-metric indices for cores of human distal tibia trabecular bone from clinical HR-pQCT images was evaluated to determine the applicability of the non-metric indices to in vivo imaging. We found that the non-metric indices of trabecular bone structure were affected by spatial resolution of CT images. Particularly, the SMI deviated from the high-resolution muCT reference value depending on the structure type, whether plate-like or rod-like. Both Conn.D and DA were underestimated in the images obtained at an in vivo resolution. It is not trivial to determine absolute threshold for validity of these non-metric indices without considering a specific study design (e.g. relative resolution, the size of the treatment effect to detect, and specimen type). The results of this study provide an upper bound for the accuracy of the non-metric indices under

  4. Vibrational testing of trabecular bone architectures using rapid prototype models.

    PubMed

    Mc Donnell, P; Liebschner, M A K; Tawackoli, Wafa; Mc Hugh, P E

    2009-01-01

    The purpose of this study was to investigate if standard analysis of the vibrational characteristics of trabecular architectures can be used to detect changes in the mechanical properties due to progressive bone loss. A cored trabecular specimen from a human lumbar vertebra was microCT scanned and a three-dimensional, virtual model in stereolithography (STL) format was generated. Uniform bone loss was simulated using a surface erosion algorithm. Rapid prototype (RP) replicas were manufactured from these virtualised models with 0%, 16% and 42% bone loss. Vibrational behaviour of the RP replicas was evaluated by performing a dynamic compression test through a frequency range using an electro-dynamic shaker. The acceleration and dynamic force responses were recorded and fast Fourier transform (FFT) analyses were performed to determine the response spectrum. Standard resonant frequency analysis and damping factor calculations were performed. The RP replicas were subsequently tested in compression beyond failure to determine their strength and modulus. It was found that the reductions in resonant frequency with increasing bone loss corresponded well with reductions in apparent stiffness and strength. This suggests that structural dynamics has the potential to be an alternative diagnostic technique for osteoporosis, although significant challenges must be overcome to determine the effect of the skin/soft tissue interface, the cortex and variabilities associated with in vivo testing. PMID:18555727

  5. A digital model of trabecular bone.

    PubMed

    Engelke, K; Song, S M; Glüer, C C; Genant, H K

    1996-04-01

    A 3D microCT dataset of bovine bone was used to create a digital 3D model simulating trabecular bone. The model serves a dual purpose: It allows for standard quantitative histomorphometric analysis and it approximates the reality e.g. of high resolution CT in vivo datasets of trabecular bone. Thus the model can potentially be used as a reference to develop 2D and 3D structural analysis algorithms applicable in vivo while it simultaneously allows verification of the results of these algorithms by standard histomorphometry. The model can be used as a standard to evaluate the impact of image processing techniques and of restrictions of imaging systems on the quantitative analysis of structural parameters describing a trabecular network. The model can be used for a comparison of 2D and 3D structural analysis methods and for an analysis of decreasing spatial resolution. The effects of segmentation and filtration can be studied separately and grayscale analysis is possible. As examples standard 2D histomorphometry and the analysis of topological parameters like node number and trabecular network length were applied to the model. The influence of spatial resolution was investigated by decreasing the spatial resolution of the digital model. The bone surface area determined by 3D surface triangulation was only 4% smaller than the surface area determined from the traditional 2D bone histomorphometric parameter bone surface/tissue volume (BS/TV) when 2D results were averaged over all slices of the 3D volume. However, BS/TV showed large (10%) variations among slices within the volume. Both histomorphometric and topological parameters were heavily influenced by spatial resolution and image segmentation. Our initial experience with the digital model indicates a need to investigate bone microstructure based on volume data or to average the 2D results of many slices. PMID:8992879

  6. Trabecular bone texture classification using wavelet leaders

    NASA Astrophysics Data System (ADS)

    Zou, Zilong; Yang, Jie; Megalooikonomou, Vasileios; Jennane, Rachid; Cheng, Erkang; Ling, Haibin

    2016-03-01

    In this paper we propose to use the Wavelet Leader (WL) transformation for studying trabecular bone patterns. Given an input image, its WL transformation is defined as the cross-channel-layer maximum pooling of an underlying wavelet transformation. WL inherits the advantage of the original wavelet transformation in capturing spatial-frequency statistics of texture images, while being more robust against scale and orientation thanks to the maximum pooling strategy. These properties make WL an attractive alternative to replace wavelet transformations which are used for trabecular analysis in previous studies. In particular, in this paper, after extracting wavelet leader descriptors from a trabecular texture patch, we feed them into two existing statistic texture characterization methods, namely the Gray Level Co-occurrence Matrix (GLCM) and the Gray Level Run Length Matrix (GLRLM). The most discriminative features, Energy of GLCM and Gray Level Non-Uniformity of GLRLM, are retained to distinguish two different populations between osteoporotic patients and control subjects. Receiver Operating Characteristics (ROC) curves are used to measure performance of classification. Experimental results on a recently released benchmark dataset show that WL significantly boosts the performance of baseline wavelet transformations by 5% in average.

  7. Trabecular Bone Mechanical Properties and Fractal Dimension

    NASA Technical Reports Server (NTRS)

    Hogan, Harry A.

    1996-01-01

    Countermeasures for reducing bone loss and muscle atrophy due to extended exposure to the microgravity environment of space are continuing to be developed and improved. An important component of this effort is finite element modeling of the lower extremity and spinal column. These models will permit analysis and evaluation specific to each individual and thereby provide more efficient and effective exercise protocols. Inflight countermeasures and post-flight rehabilitation can then be customized and targeted on a case-by-case basis. Recent Summer Faculty Fellowship participants have focused upon finite element mesh generation, muscle force estimation, and fractal calculations of trabecular bone microstructure. Methods have been developed for generating the three-dimensional geometry of the femur from serial section magnetic resonance images (MRI). The use of MRI as an imaging modality avoids excessive exposure to radiation associated with X-ray based methods. These images can also detect trabecular bone microstructure and architecture. The goal of the current research is to determine the degree to which the fractal dimension of trabecular architecture can be used to predict the mechanical properties of trabecular bone tissue. The elastic modulus and the ultimate strength (or strain) can then be estimated from non-invasive, non-radiating imaging and incorporated into the finite element models to more accurately represent the bone tissue of each individual of interest. Trabecular bone specimens from the proximal tibia are being studied in this first phase of the work. Detailed protocols and procedures have been developed for carrying test specimens through all of the steps of a multi-faceted test program. The test program begins with MRI and X-ray imaging of the whole bones before excising a smaller workpiece from the proximal tibia region. High resolution MRI scans are then made and the piece further cut into slabs (roughly 1 cm thick). The slabs are X-rayed again

  8. Trabecular Plate Loss and Deteriorating Elastic Modulus of Femoral Trabecular Bone in Intertrochanteric Hip Fractures

    PubMed Central

    Wang, Ji; Zhou, Bin; Parkinson, Ian; Thomas, C. David L.; Clement, John G.; Fazzalari, Nick; Guo, X. Edward

    2013-01-01

    Osteoporotic hip fracture is associated with significant trabecular bone loss, which is typically characterized as low bone density by dual-energy X-ray absorptiometry (DXA) and altered microstructure by micro-computed tomography (μCT). Emerging morphological analysis techniques, e.g. individual trabecula segmentation (ITS), can provide additional insights into changes in plate-like and rod-like trabeculae, two major microstructural types serving different roles in determining bone strength. Using ITS, we evaluated trabecular microstructure of intertrochanteric bone cores obtained from 23 patients undergoing hip replacement surgery for intertrochanteric fracture and 22 cadaveric controls. Micro-finite element (μFE) analyses were performed to further understand how the abnormalities seen by ITS might translate into effects on bone strength. ITS analyses revealed that, near fracture site, plate-like trabeculae were seriously depleted in fracture patients, but trabecular rod volume was maintained. Besides, decreased plate area and rod length were observed in fracture patients. Fracture patients also showed decreased elastic moduli and shear moduli of trabecular bone. These results provided evidence that in intertrochanteric hip fracture, preferential loss of plate-like trabeculae led to more rod-like microstructure and deteriorated mechanical competence adjacent to the fracture site, which increased our understanding of the biomechanical pathogenesis of hip fracture in osteoporosis. PMID:26273512

  9. Structural adaptation of trabecular bone revealed by position resolved analysis of proximal femora of different primates.

    PubMed

    Saparin, Peter; Scherf, Heike; Hublin, Jean-Jacques; Fratzl, Peter; Weinkamer, Richard

    2011-01-01

    The anisotropic arrangement of trabeculae in the proximal femur of humans and primates is seen as striking evidence for the functional adaptation of trabecular bone architecture. Quantitative evidence to demonstrate this adaptation for trabecular bone is still scarce, because experimental design of controlled load change is difficult. In this work, we use the natural variation of loading caused by a different main locomotor behavior of primates. Using high-resolution computed tomography and advanced image analysis techniques, we analyze the heterogeneity of the architecture in four proximal femora of four primate species. Although the small sample number does not allow an interspecies comparison, the very differently loaded bones are well suited to search for common structural features as a result of adaptation. A cubic volume of interest of size (5 mm)(3) was moved through the proximal femur and a morphometric analysis including local anisotropy was performed on 209 positions on average. The correlation of bone volume fraction (BV/TV) with trabecular number (Tb.N) and trabecular thickness (Tb.Th) leads to the suggestion of two different mechanisms of trabecular bone adaptation. Higher values of BV/TV in highly loaded regions of the proximal femur are due to a thickening of the trabeculae, whereas Tb.N does not change. In less loaded regions, however, lower values of BV/TV are found, caused by a reduction of the number of the trabeculae, whereas Tb.Th remains constant. This reduction in Tb.N goes along with an increase in the degree of anisotropy, indicating an adaptive selection of trabeculae. PMID:21157916

  10. Nonhuman anthropoid primate femoral neck trabecular architecture and its relationship to locomotor mode.

    PubMed

    Fajardo, Roberto J; Müller, Ralph; Ketcham, Rich A; Colbert, Matthew

    2007-04-01

    Functional analyses of human and nonhuman anthropoid primate femoral neck structure have largely ignored the trabecular bone. We tested hypotheses regarding differences in the relative distribution and structural anisotropy of trabecular bone in the femoral neck of quadrupedal and climbing/suspensory anthropoids. We used high-resolution X-ray computed tomography to analyze quantitatively the femoral neck trabecular structure of Ateles geoffroyi, Symphalangus syndactylus, Alouatta seniculus, Colobus guereza, Macaca fascicularis, and Papio cynocephalus (n = 46). We analyzed a size-scaled superior and inferior volume of interest (VOI) in the femoral neck. The ratio of the superior to inferior VOI bone volume fraction indicated that the distribution of trabecular bone was inferiorly skewed in most (but not all) quadrupeds and evenly distributed the climbing/suspensory species, but interspecific comparisons indicated that all taxa overlapped in these measurements. Degree of anisotropy values were generally higher in the inferior VOI of all species and the results for the two climbing/suspensory taxa, A. geoffroyi (1.71 +/- 0.30) and S. syndactylus (1.55 +/- 0.04), were similar to the results for the quadrupedal anthropoids, C. guereza (male = 1.64 +/- 0.13; female = 1.68 +/- 0.07) and P. cynocephalus (1.47 +/- 0.13). These results suggest strong trabecular architecture similarity across body sizes, anthropoid phylogenetic backgrounds, and locomotor mode. This structural similarity might be explained by greater similarity in anthropoid hip joint loading mechanics than previously considered. It is likely that our current models of anthropoid hip joint mechanics are overly simplistic. PMID:17514766

  11. Trabecular architecture in the StW 352 fossil hominin calcaneus.

    PubMed

    Zeininger, Angel; Patel, Biren A; Zipfel, Bernhard; Carlson, Kristian J

    2016-08-01

    Australopithecus africanus has been interpreted as having a rigid lateral foot. One mechanism contributing to a rigid foot during push-off in humans is a calcaneocuboid joint (CCJ) with limited dorsiflexion and a "close-packed" talocalcaneal joint (TCJ). In contrast, apes likely have a greater CCJ range of motion and lack a close-packed TCJ. Differences in tarsal arthrokinematics may result in different joint loading environments. In Homo sapiens, we tested the hypothesis that dorsal and plantar CCJ and the TCJ show evidence of predictable habitual loading. In Pan troglodytes, Gorilla gorilla, Gorilla beringei, and Papio ursinus, we tested the hypothesis that only the dorsal CCJ shows evidence of predictable loading. Specifically, we predicted similarity in trabecular properties across the dorsal and plantar CCJ in H. sapiens, but dissimilarity in non-humans. Additionally, we investigated trabecular properties of an A. africanus calcaneus (StW 352) to evaluate joint loading patterns in this hominin and ultimately address the evolution of these properties in H. sapiens. Contrary to predictions, the H. sapiens dorsal CCJ has a significantly higher elongation index, bone volume fraction, trabecular thickness, and trabecular number than the plantar CCJ, while trabecular properties in non-humans do not always differ as predicted between regions. H. sapiens exhibits trabecular morphology indicative of less variable TCJ loading than other groups, having the most anisotropic and rod-like struts oriented in line with predicted principal loads. Multivariate analysis shows that the StW 352 dorsal CCJ matches P. ursinus best, while the plantar CCJ matches G. beringei best and the TCJ matches that of G. gorilla best. Overall patterns suggest that the StW 352 calcaneus experienced more variable loading than H. sapiens, but less variable loading than P. troglodytes, G. gorilla, G. beringei, and P. ursinus, consistent with a large range of foot movements, probably

  12. High-resolution magnetic resonance imaging: three-dimensional trabecular bone architecture and biomechanical properties.

    PubMed

    Majumdar, S; Kothari, M; Augat, P; Newitt, D C; Link, T M; Lin, J C; Lang, T; Lu, Y; Genant, H K

    1998-05-01

    The purpose of this study was to use high-resolution magnetic resonance (MR) imaging combined with image analysis to investigate the three-dimensional (3D) trabecular structure, anisotropy, and connectivity of human vertebral, femoral, and calcaneal specimens. The goal was to determine whether: (a) MR-derived measures depict known skeletal-site-specific differences in architecture and orientation of trabeculae; (b) 3D architectural parameters combined with bone mineral density (BMD) improve the prediction of the elastic modulus using a fabric tensor formulation; (c) MR-derived 3D architectural parameters combined with BMD improve the prediction of strength using a multiple regression model, and whether these results corresponded to the results obtained using higher resolution depictions of trabecular architecture. A total of 94 specimens (12 x 12 x 12 mm cubes) consisting of trabecular bone only were obtained, of which there were 7 from the calcaneus, 15 from distal femur, 47 from the proximal femur, and 25 from the vertebral bodies. MR images were obtained using a 1.5 Tesla MR scanner at a spatial resolution of 117 x 117 x 300 microm. Additionally, BMD was determined using quantitative computed tomography (QCT), and the specimens were nondestructively tested and the elastic modulus (YM) was measured along three orthogonal axes corresponding to the anatomic superior-inferior (axial), medial-lateral (sagittal), and anterior-posterior (coronal) directions. A subset of the specimens (n=67) was then destructively tested in the superior-inferior (axial) direction to measure the ultimate compressive strength. The MR images were segmented into bone and marrow phases and then analyzed in 3D. Ellipsoids were fitted to the mean intercept lengths, using single value decomposition and the primary orientation of the trabeculae and used to calculate the anisotropy of trabecular architecture. Stereological measures were derived using a previously developed model and measures such

  13. Trabecular bone scales allometrically in mammals and birds

    PubMed Central

    Doube, Michael; Kłosowski, Michał M.; Wiktorowicz-Conroy, Alexis M.; Hutchinson, John R.; Shefelbine, Sandra J.

    2011-01-01

    Many bones are supported internally by a latticework of trabeculae. Scaling of whole bone length and diameter has been extensively investigated, but scaling of the trabecular network is not well characterized. We analysed trabecular geometry in the femora of 90 terrestrial mammalian and avian species with body masses ranging from 3 g to 3400 kg. We found that bone volume fraction does not scale substantially with animal size, while trabeculae in larger animals' femora are thicker, further apart and fewer per unit volume than in smaller animals. Finite element modelling indicates that trabecular scaling does not alter the bulk stiffness of trabecular bone, but does alter strain within trabeculae under equal applied loads. Allometry of bone's trabecular tissue may contribute to the skeleton's ability to withstand load, without incurring the physiological or mechanical costs of increasing bone mass. PMID:21389033

  14. Modeling orthotropic elasticity, localized plasticity and fracture in trabecular bone

    NASA Astrophysics Data System (ADS)

    O'Connor, D. T.; Elkhodary, K. I.; Fouad, Y.; Greene, M. S.; Sabet, F. A.; Qian, J.; Zhang, Y.; Liu, W. K.; Jasiuk, I.

    2016-05-01

    This work develops a model for the mechanical response of trabecular bone including plasticity, damage and fracture. It features a resultant lamellar orientation that captures trabecular strut anisotropic elasticity, and introduces asymmetric J2 plasticity with isotropic hardening to capture evolving strut tensile and compressive dissipative properties. A continuum compatibility based damage and fracture criterion is also proposed to model fracture surface generation. We investigated fracture of a trabecular bone network under a compressive load, for which failure modes of both tension and compression were identified at the strut level. The predicted trabecular network response was found to fall within the range of experimental results reported in literature. We also investigated the response of idealized struts under compression, tension and bending using our model. Individual struts were found to exhibit micro-buckling under compression and micro-necking under tension. These instabilities are however masked by the multiplicity and complexity of strut orientations at the trabecular network level.

  15. Modeling orthotropic elasticity, localized plasticity and fracture in trabecular bone

    NASA Astrophysics Data System (ADS)

    O'Connor, D. T.; Elkhodary, K. I.; Fouad, Y.; Greene, M. S.; Sabet, F. A.; Qian, J.; Zhang, Y.; Liu, W. K.; Jasiuk, I.

    2016-09-01

    This work develops a model for the mechanical response of trabecular bone including plasticity, damage and fracture. It features a resultant lamellar orientation that captures trabecular strut anisotropic elasticity, and introduces asymmetric J2 plasticity with isotropic hardening to capture evolving strut tensile and compressive dissipative properties. A continuum compatibility based damage and fracture criterion is also proposed to model fracture surface generation. We investigated fracture of a trabecular bone network under a compressive load, for which failure modes of both tension and compression were identified at the strut level. The predicted trabecular network response was found to fall within the range of experimental results reported in literature. We also investigated the response of idealized struts under compression, tension and bending using our model. Individual struts were found to exhibit micro-buckling under compression and micro-necking under tension. These instabilities are however masked by the multiplicity and complexity of strut orientations at the trabecular network level.

  16. Simulation of trabecular mineralization measurements in micro-CT

    NASA Astrophysics Data System (ADS)

    Prevrhal, Sven

    2006-08-01

    Micro-CT for bone structural analysis has progressed from an in-vitro laboratory technique to devices for in-vivo assessment of small animals and the peripheral human skeleton. Currently, topological parameters of bone architecture are the primary goals of analysis. Additional measurement of the density or degree of mineralization (DMB) of trabecular and cortical bone at the microscopic level is desirable to study effects of disease and treatment progress. This information is not commonly extracted because of the challenges of accurate measurement and calibration at the tissue level. To assess the accuracy of micro-CT DMB measurements in a realistic but controlled situation, we prepared bone-mimicking watery solutions at concentrations of 100 to 600 mg/cm3 K2PO4H and scanned them with micro-CT, both in glass vials and microcapillary tubes with inner diameters of 50, 100 and 150 mm to simulate trabecular thickness. Values of the linear attenuation coefficients m in the reconstructed image are commonly affected by beam hardening effects for larger samples and by partial volume effects for small volumes. We implemented an iterative reconstruction technique to reduce beam hardening. Partial voluming was sought to be reduced by excluding voxels near the tube wall. With these two measures, improvement on the constancy of the reconstructed voxel values and linearity with solution concentration could be observed to over 90% accuracy. However, since the expected change in real bone is small more measurements are needed to confirm that micro-CT can indeed be adapted to assess bone mineralization at the tissue level.

  17. Trabecular bone strength at the knee.

    PubMed

    Hvid, I

    1988-02-01

    The axial strength of trabecular bone at the knee is critical for the maintenance of support and fixation of the prosthetic components after total surface knee arthroplasty. The resistance of trabecular bone to penetration was measured posteriorly, centrally, and anteriorly in each of the tibial and femoral condyles in 150 consecutive total knee arthroplasties. Forty-seven rheumatoid knees and 88 osteoarthritic knees were evaluated. The correlation of bone strength with selected clinical parameters was found to be too poor to predict bone strength. Tibial bone strength was lower in rheumatoid than in osteoarthritic knees. Steroid medication did not influence tibial bone strength in rheumatoid arthritis. The distribution of bone strength between the medial and lateral condyles was closely dependent on knee alignment, with high medial strength in varus knees. At the unloaded condyle, strength was reduced relative to the findings for normally aligned knees. At the tibia, strength decreased with depth from the resection surface, while at the femur the converse was true. Tibial bone strength, both condylar and overall average, was lower than values reported in studies of normal cadaver knees. Evaluation of the absolute bone strength at the tibial condyles suggested that the values too low to meet load-bearing requirements after well-aligned knee replacement were infrequent. PMID:3276421

  18. Chondroconductive potential of tantalum trabecular metal.

    PubMed

    Gordon, Wanda J; Conzemius, Michael G; Birdsall, Elizabeth; Wannemuehler, Yvonne; Mallapragada, Surya; Lewallen, David G; Yaszemski, Michael J; O'Driscoll, Shawn W D

    2005-11-01

    Mesenchymal stem cells or chondrocytes have been implanted into joints in biodegradable matrices in order to improve the quality of healing cartilage defects; however, insufficient biomechanical strength of the construct at implantation is a limiting factor for clinical application. Logically, a construct with better biomechanical characteristics would provide better results. Tantalum trabecular metal (TTM) is osteoconductive and mechanically similar to subchondral bone. The objective of this pilot study was to determine if TTM is also chondroconductive. Small sections of TTM were cultured with emu and canine chondrocytes in static and dynamic culture environments. The sections cultured in dynamic bioreactors were diffusely covered with a cartilaginous matrix. Sections cultured in static conditions had no growth. Histologic evaluation from emu and canine dynamic cultures showed tissue that was heavily populated with mesenchymal cells that resembled chondrocytes, and glycosaminoglycan staining that was distributed throughout the matrix. Type II collagen content in the canine dynamic culture was 84% by SDS-PAGE. Tantalum trabecular metal is chondroconductive in vitro in a dynamic environment when cultured with adult canine or emu chondrocytes. This technology could be expanded to determine if cartilaginous-metallic constructs may be used for joint resurfacing of osteoarthritic joints. PMID:16161110

  19. Trabecular bone as a hierarchical material

    NASA Astrophysics Data System (ADS)

    Jasiuk, Iwona

    2004-03-01

    Trabecular bone is studied as a hierarchical material. The analysis includes the experimental characterization of bone's structure, the measurement of its mechanical properties, and the mechanics modeling at several different length scales: nanoscale (under 1 micron, crystal/fiber level), sub-microscale (1-10 microns, single lamella level), microscale (10-500 microns, single trabecula level), and mesoscale (1 mm - 10 cm, trabecular structure, random network of struts or plates). Experiments include the characterization of bone's ultrastructure using SEM (scanning electron microscopy) and TEM (transmission electron microscopy) at nano and sub-microscale levels. In addition, we use the x-ray microtomography, a nondestructive technique, which can provide the three-dimensional details of bone at mesostructural level. Measurements of mechanical properties are done using the MTS machine and nanoindentation apparatus. We use the MTS testing machine to determine constitutive relations of bone at mesoscale and the nanoindentation technique to determine the properties at lower scales. The experimental observations of bone's hierarchical structure are used in the theoretical analysis of bone's mechanical properties. The calculated results are compared with the experimentally measured ones. The material properties are determined at each scale both analytically (using micromechanics theories) and numerically (using a finite element method, a spring network, and beam network approaches). The computational challenges include a complex irregular, random structure at each level, spatial heterogeneity of bone's structure, applicability of separation of scales law, size of the representative volume element, and in general the dependence of properties on specimen size and boundary conditions.

  20. R'2 measured in trabecular bone in vitro: relationship to trabecular separation.

    PubMed

    Kang, C; Paley, M; Ordidge, R; Speller, R

    1999-09-01

    Measurement of key parameters of the microstructure of trabecular bone is critical to the study of osteoporosis and bone strength. Density based methods cannot provide this information, and give only the total amount of bone present, and not its arrangement. Magnetic resonance imaging has shown the potential to provide information related to the microarchitecture of the trabecular bone matrix. Twelve samples (8 x 8 x 8 mm3 bone cubes) were cut from sheep vertebrae such that the trabeculae ran either parallel or perpendicular to each face. Detailed measurements of the structure of these bone cubes were made by histomorphometry, and compared to R'2 and R*2 measured with a spin and gradient-echo sequence, Partially Refocused Interleaved Multiple Echo, at 1.5 Tesla. The precision of the R'2 measurement (% coefficient of variation) was 8.7+/-5.1, and 7.7+/-4.3 for R*2. Uncorrected values of R'2 and R*2 were significantly correlated to density measured by quantitative computed tomography (r = 0.87, p = 0.0005, and r = 0.90, p = 0.0002, respectively), and trabecular bone area measured by histomorphometry (r = 0.80, p = 0.002, and r = 0.83, p = 0.0008, respectively). Density correction was effected by imaging the same slice of bone in two orientations (90 degrees and 0 degrees ) to the main magnetic field. For both R'2 and R*2 there was a significant difference between measurements in the 90 degrees and 0 degrees orientations (p < 0.01). The difference between the two values was used, and termed R'2net or R*2net. The net parameters were independent of bone mass. R'2net and R*2net were significantly correlated to trabecular separation (p < 0.05) with r = -0.58 and r = -0.62, respectively. These results demonstrate the ability of magnetic resonance imaging to characterize a key measure of the trabecular microstucture. An increase in trabecular separation has important biomechanical consequences in osteoporosis. This result also strengthens the hypothesis that the sensitivity

  1. Dependences of ultrasonic properties on the propagation angle with respect to the trabecular alignment in trabecular bone

    NASA Astrophysics Data System (ADS)

    Lee, Kang Il

    2014-06-01

    The present study aims to investigate the dependences of ultrasonic properties on the propagation angle with respect to the trabecular alignment in 12 bovine femoral trabecular bone samples. The phase velocity and the attenuation coefficient of the fast wave measured at 0.5 MHz were found to decrease significantly with increasing angle and had their maximum values at 0°, i.e., for wave propagation in a direction parallel to the predominant trabecular alignment. The present study applied the angle-dependent Biot model by introducing anisotropy into the Biot model through the angle-dependent Young's, bulk, and shear moduli of the skeletal frame for trabecular bone to predict the measurements. Good agreement between the measurements and the prediction of the fast wave velocity suggests that the anisotropic fast wave velocity as a function of the propagation angle is mainly due to the variation in the elastic moduli of the skeletal frame with respect to the trabecular alignment.

  2. Measurement of the normalized broadband ultrasound attenuation in trabecular bone by using a bidirectional transverse transmission technique

    NASA Astrophysics Data System (ADS)

    Lee, Kang Il

    2015-01-01

    A new method for measuring the normalized broadband ultrasound attenuation (nBUA) in trabecular bone by using a bidirectional transverse transmission technique was proposed and validated with measurements obtained by using the conventional transverse transmission technique. There was no significant difference between the nBUA measurements obtained for 14 bovine femoral trabecular bone samples by using the bidirectional and the conventional transverse transmission techniques. The nBUA measured by using the two transverse transmission techniques showed strong positive correlations of r = 0.87 to 0.88 with the apparent bone density, consistent with the behavior in human trabecular bone invitro. We expect that the new method can be usefully applied for improved accuracy and precision in clinical measurements.

  3. Trabecular bone anisotropy and orientation in an Early Pleistocene hominin talus from East Turkana, Kenya.

    PubMed

    Su, Anne; Wallace, Ian J; Nakatsukasa, Masato

    2013-06-01

    Among the structural properties of trabecular bone, the degree of anisotropy is most often found to separate taxa with different habitual locomotor modes. This study examined the degree of anisotropy, the elongation, and primary orientation of trabecular bone in the KNM-ER 1464 Early Pleistocene hominin talus as compared with extant hominoid taxa. Modern human tali were found to have a pattern of relatively anisotropic and elongated trabeculae on the lateral aspect, which was not found in Pan, Gorilla, Pongo, or KNM-ER 1464. Trabecular anisotropy in the fossil talus most closely resembled that of the African apes except for a region of high anisotropy in the posteromedial talus. The primary orientation of trabeculae in the anteromedial region of KNM-ER 1464 was strikingly different from that of the great apes and very similar to that of modern humans in being directed parallel to the talar neck. These results suggest that, relative to that of modern humans, the anteromedial region of the KNM-ER 1464 talus may have transmitted body weight to the midfoot in a similar manner while the lateral aspect may have been subjected to more variable loading conditions. PMID:23601236

  4. Heme compounds in dinosaur trabecular bone.

    PubMed

    Schweitzer, M H; Marshall, M; Carron, K; Bohle, D S; Busse, S C; Arnold, E V; Barnard, D; Horner, J R; Starkey, J R

    1997-06-10

    Six independent lines of evidence point to the existence of heme-containing compounds and/or hemoglobin breakdown products in extracts of trabecular tissues of the large theropod dinosaur Tyrannosaurus rex. These include signatures from nuclear magnetic resonance and electron spin resonance that indicate the presence of a paramagnetic compound consistent with heme. In addition, UV/visible spectroscopy and high performance liquid chromatography data are consistent with the Soret absorbance characteristic of this molecule. Resonance Raman profiles are also consistent with a modified heme structure. Finally, when dinosaurian tissues were extracted for protein fragments and were used to immunize rats, the resulting antisera reacted positively with purified avian and mammalian hemoglobins. The most parsimonious explanation of this evidence is the presence of blood-derived hemoglobin compounds preserved in the dinosaurian tissues. PMID:9177210

  5. In vivo volumetric imaging of the human corneo-scleral limbus with spectral domain OCT

    PubMed Central

    Bizheva, Kostadinka; Hutchings, Natalie; Sorbara, Luigina; Moayed, Alireza A.; Simpson, Trefford

    2011-01-01

    The limbus is the structurally rich transitional region of tissue between the cornea on one side, and the sclera and conjunctiva on the other. This zone, among other things, contains nerves passing to the cornea, blood and lymph vasculature for oxygen and nutrient delivery and for waste, CO2 removal and drainage of the aqueous humour. In addition, the limbus contains stem cells responsible for the existence and healing of the corneal epithelium. Here we present 3D images of the healthy human limbus, acquired in vivo with a spectral domain optical coherence tomography system operating at 1060nm. Cross-sectional and volumetric images were acquired from temporal and nasal locations in the human limbus with ~3µm x 18µm (axial x lateral) resolution in biological tissue at the rate of 92,000 A-scans/s. The imaging enabled detailed mapping of the corneo-scleral tissue morphology, and visualization of structural details such as the Vogt palisades, the blood and lymph vasculature including the Schlemm’s canal and the trabecular meshwork, as well as corneal nerve fiber bundles. Non-invasive, volumetric, high resolution imaging reveals fine details of the normal human limbal structure, and promises to provide invaluable information about its changes in health and disease as well as during and after corneal surgery. PMID:21750758

  6. Effects of different loading patterns on the trabecular bone morphology of the proximal femur using adaptive bone remodeling.

    PubMed

    Banijamali, S Mohammad Ali; Oftadeh, Ramin; Nazarian, Ara; Goebel, Ruben; Vaziri, Ashkan; Nayeb-Hashemi, Hamid

    2015-01-01

    In this study, the changes in the bone density of human femur model as a result of different loadings were investigated. The model initially consisted of a solid shell representing cortical bone encompassing a cubical network of interconnected rods representing trabecular bone. A computationally efficient program was developed that iteratively changed the structure of trabecular bone by keeping the local stress in the structure within a defined stress range. The stress was controlled by either enhancing existing beam elements or removing beams from the initial trabecular frame structure. Analyses were performed for two cases of homogenous isotropic and transversely isotropic beams.Trabecular bone structure was obtained for three load cases: walking, stair climbing and stumbling without falling. The results indicate that trabecular bone tissue material properties do not have a significant effect on the converged structure of trabecular bone. In addition, as the magnitude of the loads increase, the internal structure becomes denser in critical zones. Loading associated with the stumbling results in the highest density;whereas walking, considered as a routine daily activity, results in the least internal density in different regions. Furthermore, bone volume fraction at the critical regions of the converged structure is in good agreement with previously measured data obtained from combinations of dual X-ray absorptiometry (DXA) and computed tomography (CT). The results indicate that the converged bone architecture consisting of rods and plates are consistent with the natural bone morphology of the femur. The proposed model shows a promising means to understand the effects of different individual loading patterns on the bone density. PMID:25392856

  7. Particle migration and gap healing around trabecular metal implants

    PubMed Central

    Kold, S.; Zippor, B.; Overgaard, S.; Søballe, K.

    2005-01-01

    Bone on-growth and peri-implant migration of polyethylene particles were studied in an experimental setting using trabecular metal and solid metal implants. Cylindrical implants of trabecular tantalum metal and solid titanium alloy implants with a glass bead blasted surface were inserted either in an exact surgical fit or with a peri-implant gap into a canine knee joint. We used a randomised paired design. Polyethylene particles were injected into the knee joint. In both types of surgical fit we found that the trabecular metal implants had superior bone ongrowth in comparison with solid metal implants (exact fit: 23% vs. 7% [p=0.02], peri-implant gap: 13% vs. 0% [p=0.02]. The number of peri-implant polyethylene particles was significantly reduced around the trabecular metal implants with a peri-implant gap compared with solid implants. PMID:16132987

  8. Fluctuation spectrum of fluid membranes coupled to an elastic meshwork: jump of the effective surface tension at the mesh size.

    PubMed

    Fournier, Jean-Baptiste; Lacoste, David; Raphaël, Elie

    2004-01-01

    We identify a class of composite membranes: fluid bilayers coupled to an elastic meshwork that are such that the meshwork's energy is a function F(el)[A(xi)] not of the real microscopic membrane area A, but of a smoothed membrane's area A(xi), which corresponds to the area of the membrane coarse grained at the mesh size xi. We show that the meshwork modifies the membrane tension sigma both below and above the scale xi, inducing a steep crossover of amplitude deltasigma=dF(el)/dA(xi). The predictions of our model account for the fluctuation spectrum of red blood cell membranes coupled to their cytoskeleton. Our results indicate that the cytoskeleton might be under extensional stress, which would provide a means to regulate available membrane areas. We also predict an observable tension jump for membranes decorated with polymer "brushes." PMID:14754023

  9. An ontogenetic framework linking locomotion and trabecular bone architecture with applications for reconstructing hominin life history.

    PubMed

    Raichlen, David A; Gordon, Adam D; Foster, Adam D; Webber, James T; Sukhdeo, Simone M; Scott, Robert S; Gosman, James H; Ryan, Timothy M

    2015-04-01

    The ontogeny of bipedal walking is considered uniquely challenging, due in part to the balance requirements of single limb support. Thus, locomotor development in humans and our bipedal ancestors may track developmental milestones including the maturation of the neuromuscular control system. Here, we examined the ontogeny of locomotor mechanics in children aged 1-8, and bone growth and development in an age-matched skeletal sample to identify bony markers of locomotor development. We show that step-to-step variation in mediolateral tibia angle relative to the vertical decreases with age, an indication that older children increase stability. Analyses of trabecular bone architecture in the distal tibia of an age-matched skeletal sample (the Norris Farms #36 archaeological skeletal collection) show a bony signal of this shift in locomotor stability. Using a grid of eleven cubic volumes of interest (VOI) in the distal metaphysis of each tibia, we show that the degree of anisotropy (DA) of trabecular struts changes with age. Intra-individual variation in DA across these VOIs is generally high at young ages, likely reflecting variation in loading due to kinematic instability. With increasing age, mean DA converges on higher values and becomes less variable across the distal tibia. We believe the ontogeny of distal tibia trabecular architecture reflects the development of locomotor stability in bipeds. We suggest this novel bony marker of development may be used to assess the relationship between locomotor development and other life history milestones in fossil hominins. PMID:25743432

  10. Trabecular scaffolds created using micro CT guided fused deposition modeling

    PubMed Central

    Tellis, B.C.; Szivek, J.A.; Bliss, C.L.; Margolis, D.S.; Vaidyanathan, R.K.; Calvert, P.

    2009-01-01

    Free form fabrication and high resolution imaging techniques enable the creation of biomimetic tissue engineering scaffolds. A 3D CAD model of canine trabecular bone was produced via micro CT and exported to a fused deposition modeler, to produce polybutylene terephthalate (PBT) trabeculated scaffolds and four other scaffold groups of varying pore structures. The five scaffold groups were divided into subgroups (n=6) and compression tested at two load rates (49 N/s and 294 N/s). Two groups were soaked in a 25 °C saline solution for 7 days before compression testing. Micro CT was used to compare porosity, connectivity density, and trabecular separation of each scaffold type to a canine trabecular bone sample. At 49 N/s the dry trabecular scaffolds had a compressive stiffness of 4.94±1.19 MPa, similar to the simple linear small pore scaffolds and significantly more stiff (p<0.05) than either of the complex interconnected pore scaffolds. At 294 N/s, the compressive stiffness values for all five groups roughly doubled. Soaking in saline had an insignificant effect on stiffness. The trabecular scaffolds matched bone samples in porosity; however, achieving physiologic connectivity density and trabecular separation will require further refining of scaffold processing. PMID:21461176

  11. Role of Trabecular Microarchitecture in Whole-Vertebral Body Biomechanical Behavior

    PubMed Central

    Fields, Aaron J.; Eswaran, Senthil K.; Jekir, Michael G.; Keaveny, Tony M.

    2009-01-01

    The role of trabecular microarchitecture in whole-vertebral biomechanical behavior remains unclear, and its influence may be obscured by such factors as overall bone mass, bone geometry, and the presence of the cortical shell. To address this issue, 22 human T9 vertebral bodies (11 female; 11 male; age range: 53–97 yr, 81.5 ± 9.6 yr) were scanned with μCT and analyzed for measures of trabecular microarchitecture, BMC, cross-sectional area, and cortical thickness. Sixteen of the vertebrae were biomechanically tested to measure compressive strength. To estimate vertebral compressive stiffness with and without the cortical shell for all 22 vertebrae, two high-resolution finite element models per specimen—one intact model and one with the shell removed—were created from the μCT scans and virtually compressed. Results indicated that BMC and the structural model index (SMI) were the individual parameters most highly associated with strength (R 2 = 0.57 each). Adding microarchitecture variables to BMC in a stepwise multiple regression model improved this association (R 2 = 0.85). However, the microarchitecture variables in that regression model (degree of anisotropy, bone volume fraction) differed from those when BMC was not included in the model (SMI, mean trabecular thickness), and the association was slightly weaker for the latter (R 2 = 0.76). The finite element results indicated that the physical presence of the cortical shell did not alter the relationships between microarchitecture and vertebral stiffness. We conclude that trabecular microarchitecture is associated with whole-vertebral biomechanical behavior and that the role of microarchitecture is mediated by BMC but not by the cortical shell. PMID:19338454

  12. Aqueous humor outflow effects of partial thickness channel created by a femtosecond laser in ex-vivo human eyes

    NASA Astrophysics Data System (ADS)

    Chai, Dongyul; Chaudhary, Gautam; Kurtz, Ron; Juhasz, Tibor

    2007-02-01

    The reduced outflow rate caused by the increased resistance through trabecular meshwork (TM) has been thought to be the main reason for elevated intraocular pressure (IOP). It has been demonstrated that femtosecond laser pulses tuned to 1.7 μm wavelength can create the partial thickness channel in the sclera in ex vivo human eyes [1] and aqueous outflow can be increased by these channels in porcine eyes [2]. It was also shown that the outflow rate is reduced over time in ex vivo human eyes [3]. Therefore, the control experiment without laser treatment at the same condition was conducted and showed that outflow was reduced by 1.5 +/- 0.8 μl/min at 15mmHg and 1.8 +/- 1.0 μl/min at 25mmHg. However, the outflow rate increased by 0.26 μl/min at 15mmHg and 0.15 μl/min at 25mmHg after the partial thickness channel was created, meaning the amount of increased outflow rate might be more than measured considering the outflow reduction in control experiment. We suggest that the femtosecond laser created partial thickness channel can increase the outflow rate and delay the progression of glaucoma.

  13. Premenopausal Trabecular Bone Loss is Associated with a Family History of Fragility Fracture

    PubMed Central

    Prior, J. C.; Hitchcock, C. L.; Vigna, Y. M.; Seifert-Klauss, V.

    2016-01-01

    Introduction: Although a fragility fracture family history (FFFH+) has repeatedly been shown to be associated with lower bone mineral density (BMD), its relationship to human BMD change is unclear. Animal research, however, documented that different purebred strains within rodent species have wide ranges in rates of bone acquisition during growth as well as in change post-ovariectomy. Our objective was to compare the rate of premenopausal spinal trabecular BMD change between women with and without a general family history of fragility fracture. Participants and Methods: Healthy premenopausal community women participated in prospective observational studies at two academic medical research centres: Vancouver, Canada (n = 66) and Munich, Germany (n = 20). The primary outcome was annual spinal BMD change, measured by quantitative computed tomography (QCT). The two studies employed similar methodologies for assessing QCT and FFFH. Results: Volunteer community participants had a mean age of 36.0 (SD, 6.9) years, body mass index 22.5 (2.4) and baseline QCT of 150.2 (22.5) mg/cm3 trabecular bone. The rates of BMD change were similar in both cities: − 3.5 (5.1)/year Vancouver, − 2.0 (3.4)/year Munich (95 % CI of difference: − 3.9, 0.9). Over a third of the women (31 of the 86, 36 %) reported FFFH+. Those with and without a FFFH were similar in demographics, nutrition, exercise, menstrual cycle and luteal phase lengths and physiological measures (serum calcium, osteocalcin and estradiol). However, women with FFFH+ lost trabecular BMD more rapidly: FFFH+, − 4.9 (5.0), FFFH−, − 2.2 (4.4) mg/cm3/year (95 % CI diff − 0.7 to − 4.8, F1.83 = 7.88, p = 0.006). FFFH+ explained 7.7 % of the variance in QCT volumetric trabecular spinal bone change/year in these healthy premenopausal women. Conclusion: This study shows for the first time that having a history of a fragility fracture in a family member is associated with a greater

  14. Massive acetabular bone loss: Limits of trabecular metal cages

    PubMed Central

    Villanueva-Martínez, Manuel; Ríos-Luna, Antonio; Diaz-Mauriño, Juán

    2011-01-01

    Massive acetabular bone loss (more than 50% of the acetabular area) can result in insufficient native bone for stable fixation and long-term bone ingrowth of conventional porous cups. The development of trabecular metal cages with osteoconductive properties may allow a more biological and versatile approach that will help restore bone loss, thus reducing the frequency of implant failure in the short-to-medium term. We report a case of massive bone loss affecting the dome of the acetabulum and the ilium, which was treated with a trabecular metal cage and particulate allograft. Although the trabecular metal components had no intrinsic stability, they did enhance osseointegration and incorporation of a non-impacted particulate graft, thus preventing failure of the reconstruction. The minimum 50% contact area between the native bone and the cup required for osseointegration with the use of porous cups may not hold for new trabecular metal cups, thus reducing the need for antiprotrusio cages. The osteoconductive properties of trabecular metal enhanced allograft incorportation and iliac bone rebuilding without the need to fill the defect with multiple wedges nor protect the reconstruction with an antiprotrusio cage. PMID:21221229

  15. Ultrasonic Evaluation of Deeply Located Trabecular Bones - Preliminary Results

    NASA Astrophysics Data System (ADS)

    Cieślik, Lucyna; Litniewski, Jerzy

    The analysis of ultrasonic signals scattered by soft tissues have been successfully applied for their characterization. Similarly, the trabecular bone backscattered signal contains information about the properties of the bone structure. Therefore scattering-based ultrasonic technique potentially enables the assessment of microstructure characteristics of a bone. The femoral neck fracture often occurs in the course of osteoporosis and can lead to severe complications. Therefore assessment of femoral bone microstructure and condition is important and essential for the diagnosis and treatment monitoring. As far most of the trabecular bone investigations have been performed in vitro. The only in vivo measurements were carried out in transmission and mostly concerned estimation of the attenuation in heel bone. We have built the ultrasonic scanner that could be useful in acquiring the RF (Radio Frequency) echoes backscattered by the trabecular bone in vivo. Moreover, the bone scanner provides data not only from heel bone but from deeply located bones as well (e.g. femoral bone). It can be also used for easily accessible bones like heel bone or breastbone. In this case a gel-pad is applied to assure focusing of ultrasound in trabecular bone (approximately 10 mm beneath the cortical bone). This study presents preliminary results of the attenuating properties evaluation of trabecular bone from the ultrasonic echoes backscattered by heel bone and femoral neck.

  16. The correlation between the SOS in trabecular bone and stiffness and density studied by finite-element analysis.

    PubMed

    Goossens, Liesbet; Vanderoost, Jef; Jaecques, Siegfried; Boonen, Steven; D'hooge, Jan; Lauriks, Walter; Van der Perre, Georges

    2008-01-01

    For the clinical assessment of osteoporosis (i.e., a degenerative bone disease associated with increased fracture risk), ultrasound has been proposed as an alternative or supplement to the dual-energy X-ray absorptiometry (DEXA) technique. However, the interaction of ultrasound waves with (trabecular) bone remains relatively poorly understood. The present study aimed to improve this understanding by simulating ultrasound wave propagation in 15 trabecular bone samples from the human lumbar spine, using microcomputed tomography-based finite-element modeling. The model included only the solid bone, without the bone marrow. Two structural parameters were calculated: the bone volume fraction (BV/TV) and the structural (apparent) elastic modulus (E(s)), and the ultrasound propagation parameter speed of sound (SOS). Relations between BV/TV and E(s) were similar to published experimental relations. At 1 MHz, correlations between SOS and the structural parameters BV/TV and Es were rather weak, but the results can be explained from the specific features of the trabecular structure and the intrinsic material elastic modulus E(i). In particular, the systematic differences between the three main directions provide information on the trabecular structure. In addition, at 1 MHz the correlation found between the simulated SOS values and those calculated from the simple bar equation was poor when the three directions are considered separately. Hence, under these conditions, the homogenization approach-including the bar equation-is not valid. However, at lower frequencies (50-300 kHz) this correlation significantly improved. It is concluded that detailed analysis of ultrasound wave propagation through the solid structure in various directions and with various frequencies, can yield much information on the structural and mechanical properties of trabecular bone. PMID:18599411

  17. Study of trabecular bone microstructure using spatial autocorrelation analysis

    NASA Astrophysics Data System (ADS)

    Wald, Michael J.; Vasilic, Branimir; Saha, Punam K.; Wehrli, Felix W.

    2005-04-01

    The spatial autocorrelation analysis method represents a powerful, new approach to quantitative characterization of structurally quasi-periodic anisotropic materials such as trabecular bone (TB). The method is applicable to grayscale images and thus does not require any preprocessing, such as segmentation which is difficult to achieve in the limited resolution regime of in vivo imaging. The 3D autocorrelation function (ACF) can be efficiently calculated using the Fourier transform. The resulting trabecular thickness and spacing measurements are robust to the presence of noise and produce values within the expected range as determined by other methods from μCT and μMRI datasets. TB features found from the ACF are shown to correlate well with those determined by the Fuzzy Distance transform (FDT) in the transverse plane, i.e. the plane orthogonal to bone"s major axis. The method is further shown to be applicable to in-vivo μMRI data. Using the ACF, we examine data acquired in a previous study aimed at evaluating the structural implications of male hypogonadism characterized by testosterone deficiency and reduced bone mass. Specifically, we consider the hypothesis that eugonadal and hypogonadal men differ in the anisotropy of their trabecular networks. The analysis indicates a significant difference in trabecular bone thickness and longitudinal spacing between the control group and the testosterone deficient group. We conclude that spatial autocorrelation analysis is able to characterize the 3D structure and anisotropy of trabecular bone and provides new insight into the structural changes associated with osteoporotic trabecular bone loss.

  18. Effects of spaceflight on trabecular bone in rats

    NASA Technical Reports Server (NTRS)

    Jee, W. S. S.; Wronski, T. J.; Morey, E. R.; Kimmel, D. B.

    1983-01-01

    Alterations in trabecular bone were observed in growing male Wistar rats after 18.5 days of orbital flight on the COSMOS 1129 biosatellite. Spaceflight induced a decreased mass of mineralized tissue and an increased fat content of the bone marrow in the proximal tibial and humeral metaphyses. The osteoblast population appeared to decline immediately adjacent to the growth cartilage-metaphyseal junction, but osteoclast numbers were unchanged. These results suggested that bone formation may have been inhibited during spaceflight, but resorption remained constant. With the exception of trabecular bone mass in the proximal tibia, the observed skeletal changes returned to normal during a 29-day postflight period.

  19. Modeling the Mechanical Consequences of Age-Related Trabecular Bone Loss by XFEM Simulation

    PubMed Central

    Fan, Ruoxun; Zhang, Xianbin; Liu, Jun; Jia, Zhengbin; Zhu, Dong

    2016-01-01

    The elderly are more likely to suffer from fracture because of age-related trabecular bone loss. Different bone loss locations and patterns have different effects on bone mechanical properties. Extended finite element method (XFEM) can simulate fracture process and was suited to investigate the effects of bone loss on trabecular bone. Age-related bone loss is indicated by trabecular thinning and loss and may occur at low-strain locations or other random sites. Accordingly, several ideal normal and aged trabecular bone models were created based on different bone loss locations and patterns; then, fracture processes from crack initiation to complete failure of these models were observed by XFEM; finally, the effects of different locations and patterns on trabecular bone were compared. Results indicated that bone loss occurring at low-strain locations was more detrimental to trabecular bone than that occurring at other random sites; meanwhile, the decrease in bone strength caused by trabecular loss was higher than that caused by trabecular thinning, and the effects of vertical trabecular loss on mechanical properties were more severe than horizontal trabecular loss. This study provided a numerical method to simulate trabecular bone fracture and distinguished different effects of the possible occurrence of bone loss locations and patterns on trabecular bone. PMID:27403206

  20. Modeling the Mechanical Consequences of Age-Related Trabecular Bone Loss by XFEM Simulation.

    PubMed

    Fan, Ruoxun; Gong, He; Zhang, Xianbin; Liu, Jun; Jia, Zhengbin; Zhu, Dong

    2016-01-01

    The elderly are more likely to suffer from fracture because of age-related trabecular bone loss. Different bone loss locations and patterns have different effects on bone mechanical properties. Extended finite element method (XFEM) can simulate fracture process and was suited to investigate the effects of bone loss on trabecular bone. Age-related bone loss is indicated by trabecular thinning and loss and may occur at low-strain locations or other random sites. Accordingly, several ideal normal and aged trabecular bone models were created based on different bone loss locations and patterns; then, fracture processes from crack initiation to complete failure of these models were observed by XFEM; finally, the effects of different locations and patterns on trabecular bone were compared. Results indicated that bone loss occurring at low-strain locations was more detrimental to trabecular bone than that occurring at other random sites; meanwhile, the decrease in bone strength caused by trabecular loss was higher than that caused by trabecular thinning, and the effects of vertical trabecular loss on mechanical properties were more severe than horizontal trabecular loss. This study provided a numerical method to simulate trabecular bone fracture and distinguished different effects of the possible occurrence of bone loss locations and patterns on trabecular bone. PMID:27403206

  1. Cellular Basis for Bimatoprost Effects on Human Conventional Outflow

    PubMed Central

    Piwnica, David; Jolas, Thierry; Carling, Robert W.; Cornell, Clive L.; Fliri, Hans; Martos, Jose; Pettit, Simon N.; Wang, Jenny W.; Woodward, David F.

    2010-01-01

    Purpose. Bimatoprost is a widely used ocular hypotensive agent to treat glaucoma. It lowers intraocular pressure in humans by increasing both pressure-independent (uveoscleral) and pressure-dependent (conventional) aqueous humor outflow. The present study specifically examines bimatoprost effects on the cells that populate human outflow tissues. Methods. The authors tested for prostamide receptor activation in primary cultures of human trabecular meshwork (TM), Schlemm's canal (SC), and ciliary smooth muscle (CSM) cells using cellular dielectric spectroscopy (CDS). Results. The authors observed that bimatoprost produced an immediate and concentration-dependent increase in cell monolayer impedance for TM, SC, and CSM cells with EC50 values of 4.3, 1.2, and 1.7 nM, respectively; corresponding to decreased cell contractility. Notably, in TM, SC, and CSM cells, bimatoprost was approximately equipotent to the selective FP receptor agonists fluprostenol and 17-phenyl PGF2α. Bimatoprost effects were insensitive to cholera toxin and pertussis toxin but were abolished by phorbol 12-myristate 13-acetate pretreatment, suggesting Gq-involvement in cell signaling. The effects of bimatoprost on TM and SC cells were inhibited by the prostamide receptor antagonist AGN211334, with IC50 values of 1.2 and 3.3 μM, respectively. Interestingly, AGN211334 behaved as an apparent inverse agonist in CDS assays involving TM cells but as a neutral prostamide antagonist with SC cells. Conclusions. Taken together, results suggest that bimatoprost specifically activates receptors in both cell types of the human conventional outflow pathway to modify intraocular pressure. However, only TM cell monolayers appear to have autocrine, or agonist-independent, receptor signaling that is sensitive to a prostamide receptor antagonist. PMID:20435598

  2. Targeted Disruption of the Myocilin Gene (Myoc) Suggests that Human Glaucoma-Causing Mutations Are Gain of Function

    PubMed Central

    Kim, Byong Su; Savinova, Olga V.; Reedy, Mark V.; Martin, Janice; Lun, Yi; Gan, Lin; Smith, Richard S.; Tomarev, Stanislav I.; John, Simon W. M.; Johnson, Randy L.

    2001-01-01

    Glaucoma is a heterogeneous eye disease and a major cause of blindness worldwide. Recently, primary open angle glaucoma (POAG)-associated mutations have been found in the trabecular meshwork inducible glucocorticoid response gene (TIGR), also known as the myocilin gene (MYOC), at the GLC1A locus on chromosome 1q21-q31. These mutations occurred in a subset of patients with juvenile- and adult-onset POAG and exhibited autosomal dominant inheritance. Ocular expression and its involvement in POAG suggest that TIGR/MYOC may have a role(s) in regulating intraocular pressure (IOP). Here, we report the generation and analysis of mice heterozygous and homozygous for a targeted null mutation in Myoc. Our study shows that Myoc mutant mice are both viable and fertile. Our in vivo findings further demonstrate that Myoc is not required for normal IOP or normal ocular morphology. The lack of a discernable phenotype in both Myoc-heterozygous and Myoc-null mice suggests that haploinsufficiency is not a critical mechanism for POAG in individuals with mutations in MYOC. Instead, disease-causing mutations in humans likely act by gain of function. PMID:11604506

  3. Analysis of trabecular bone microstructure using contour tree connectivity.

    PubMed

    Aydogan, Dogu Baran; Moritz, Niko; Aro, Hannu T; Hyttinen, Jari

    2013-01-01

    Millions of people worldwide suffer from fragility fractures, which cause significant morbidity, financial costs and even mortality. The gold standard to quantify structural properties of trabecular bone is based on the morphometric parameters obtained from microCT images of clinical bone biopsy specimens. The currently used image processing approaches are not able to fully explain the variation in bone strength. In this study, we introduce the contour tree connectivity (CTC) as a novel morphometric parameter to study trabecular bone quality. With CTC, we calculate a new connectivity measure for trabecular bone by using contour tree representation of binary images and algebraic graph theory. To test our approach, we use trabecular bone biopsies obtained from 55 female patients. We study the correlation of CTC with biomechanical test results as well as other morphometric parameters obtained from microCT. The results based on our dataset show that CTC is the 3rd best predictive feature of ultimate bone strength after bone volume fraction and degree of anisotropy. PMID:24579169

  4. Trabecular bone score in healthy ageing

    PubMed Central

    Bazzocchi, A; Ponti, F; Diano, D; Amadori, M; Albisinni, U; Battista, G

    2015-01-01

    Objective: The main aim of this work was to report on trabecular bone score (TBS) by dual-energy X-ray absorptiometry (DXA) of healthy Italian subjects to be used as a reference standard for future study in clinical and research settings. The secondary aim was to investigate the link between TBS and conventional parameters of bone and body composition by DXA. Methods: 250 individuals of 5 age bands (spanning from 18 to 70 years of age, equally distributed for both age and sex) were prospectively recruited. A lumbar spine (LS) DXA scan (Lunar iDXA™; GE Healthcare, Madison, WI) was acquired for each subject and then analysed with the latest version of TBS iNsight v. 2.1 (Med-Imaps, Pessac, France) software. LS bone mineral density (LS BMD), Z-score, T-score and TBS values were collected. Pearson's test was used to investigate the correlations between TBS and LS BMD and the influence of age, body mass index (BMI) and body composition on these parameters. Results: A significant decrease of TBS and LS BMD was observed with ageing in both males (TBS mean values from 1.486 to 1.374; LS BMD mean values from 1.219 to 1.187) and females (TBS mean values from 1.464 to 1.306; LS BMD mean values from 1.154 to 1.116). No statistically significant difference was achieved among males and females of the same age group for both TBS and LS BMD, with the exception of the fifth age group. A significant correlation was found between LS BMD and TBS values in both sexes (r  = 0.555–0.655, p < 0.0001). BMI influenced LS BMD but not TBS. TBS values were inversely correlated with some fat mass parameters, in particular with visceral adipose tissue (in males: r = −0.332, p < 0.001; in females: r = −0.348, p < 0.0001). No significant correlation was found between TBS and total lean mass, opposite to LS BMD (in males: r = 0.418; p < 0.0001; in females: r = −0.235; p < 0.001). Conclusion: This report is an attempt to start building a database for

  5. One year of alendronate treatment lowers microstructural stresses associated with trabecular microdamage initiation.

    PubMed

    O'Neal, Jessica M; Diab, Tamim; Allen, Matthew R; Vidakovic, Brani; Burr, David B; Guldberg, Robert E

    2010-08-01

    Alendronate, an anti-remodeling agent, is commonly used to treat patients suffering from osteoporosis by increasing bone mineral density. Though fracture risk is lowered, an increase in microdamage accumulation has been documented in patients receiving alendronate, leading to questions about the potentially detrimental effects of remodeling suppression on the local tissue (material) properties. In this study, trabecular bone cores from the distal femur of beagle dogs treated for one year with alendronate, at doses scaled by weight to approximate osteoporotic and Paget's disease treatment doses in humans, were subjected to uniaxial compression to induce microdamage. Tissue level von Mises stresses were computed for alendronate-treated and non-treated controls using finite element analysis and correlated to microdamage morphology. Using a modified version of the Moore and Gibson classification for damage morphology, we determined that the von Mises stress for trabeculae exhibiting severe and linear microcrack patterns was decreased by approximately 25% in samples treated with alendronate compared with non-treated controls (p<0.01), whereas there was no reduction in the von Mises stress state for diffuse microdamage formation. Furthermore, an examination of the architectural and structural characteristics of damaged trabeculae demonstrated that severely damaged trabeculae were thinner, more aligned with the loading axis, and less mineralized than undamaged trabeculae in alendronate-treated samples (p<0.01). Similar relationships with damage morphology were found only with trabecular orientation in vehicle-treated control dogs. These results indicate that changes in bone's architecture and matrix properties associated with one year of alendronate administration reduce trabecular bone's ability to resist the formation of loading-induced severe and linear microcracks, both of which dissipate less energy prior to fracture than does diffuse damage. PMID:20483387

  6. Effect of swimming exercise on three-dimensional trabecular bone microarchitecture in ovariectomized rats.

    PubMed

    Ju, Yong-In; Sone, Teruki; Ohnaru, Kazuhiro; Tanaka, Kensuke; Fukunaga, Masao

    2015-11-01

    Swimming is generally considered ineffective for increasing bone mass in humans, at least compared with weight-bearing sports. However, swimming exercise has sometimes been shown to have a strong positive effect on bone mass in small animals. This study investigated the effects of swimming on bone mass, strength, and microarchitecture in ovariectomized (OVX) rats. OVX or sham operations were performed on 18-wk-old female Fisher 344 rats. Rats were randomly divided into four groups: sham sedentary (Sham-CON), sham swimming exercised (Sham-SWI), OVX sedentary (OVX-CON), and OVX swimming exercised (OVX-SWI). Rats in exercise groups performed swimming in a water bath for 60 min/day, 5 days/wk, for 12 wk. Bone mineral density (BMD) in right femurs was analyzed using dual-energy X-ray absorptiometry. Three-dimensional trabecular architecture at the distal femoral metaphysis was analyzed using microcomputed tomography (μCT). Geometrical properties of diaphyseal cortical bone were evaluated in the midfemoral region using μCT. The biomechanical properties of femurs were analyzed using three-point bending. Femoral BMD was significantly decreased following ovariectomy. This change was suppressed by swimming. Trabecular bone thickness, number, and connectivity were decreased by ovariectomy, whereas structure model index (i.e., ratio of rod-like to plate-like trabeculae) increased. These changes were also suppressed by swimming exercise. Femurs displayed greater cortical width and maximum load in SWI groups than in CON groups. Together, these results demonstrate that swimming exercise drastically alleviated both OVX-induced decreases in bone mass and mechanical strength and the deterioration of trabecular microarchitecture in rat models of osteoporosis. PMID:26338454

  7. Prediction of trabecular bone qualitative properties using scanning quantitative ultrasound

    NASA Astrophysics Data System (ADS)

    Qin, Yi-Xian; Lin, Wei; Mittra, Erik; Xia, Yi; Cheng, Jiqi; Judex, Stefan; Rubin, Clint; Müller, Ralph

    2013-11-01

    Microgravity induced bone loss represents a critical health problem in astronauts, particularly occurred in weight-supporting skeleton, which leads to osteopenia and increase of fracture risk. Lack of suitable evaluation modality makes it difficult for monitoring skeletal status in long term space mission and increases potential risk of complication. Such disuse osteopenia and osteoporosis compromise trabecular bone density, and architectural and mechanical properties. While X-ray based imaging would not be practical in space, quantitative ultrasound may provide advantages to characterize bone density and strength through wave propagation in complex trabecular structure. This study used a scanning confocal acoustic diagnostic and navigation system (SCAN) to evaluate trabecular bone quality in 60 cubic trabecular samples harvested from adult sheep. Ultrasound image based SCAN measurements in structural and strength properties were validated by μCT and compressive mechanical testing. This result indicated a moderately strong negative correlations observed between broadband ultrasonic attenuation (BUA) and μCT-determined bone volume fraction (BV/TV, R2=0.53). Strong correlations were observed between ultrasound velocity (UV) and bone's mechanical strength and structural parameters, i.e., bulk Young's modulus (R2=0.67) and BV/TV (R2=0.85). The predictions for bone density and mechanical strength were significantly improved by using a linear combination of both BUA and UV, yielding R2=0.92 for BV/TV and R2=0.71 for bulk Young's modulus. These results imply that quantitative ultrasound can characterize trabecular structural and mechanical properties through measurements of particular ultrasound parameters, and potentially provide an excellent estimation for bone's structural integrity.

  8. Prediction of trabecular bone qualitative properties using scanning quantitative ultrasound

    PubMed Central

    Qin, Yi-Xian; Lin, Wei; Mittra, Erik; Xia, Yi; Cheng, Jiqi; Judex, Stefan; Rubin, Clint; Müller, Ralph

    2012-01-01

    Microgravity induced bone loss represents a critical health problem in astronauts, particularly occurred in weight-supporting skeleton, which leads to osteopenia and increase of fracture risk. Lack of suitable evaluation modality makes it difficult for monitoring skeletal status in long term space mission and increases potential risk of complication. Such disuse osteopenia and osteoporosis compromise trabecular bone density, and architectural and mechanical properties. While X-ray based imaging would not be practical in space, quantitative ultrasound may provide advantages to characterize bone density and strength through wave propagation in complex trabecular structure. This study used a scanning confocal acoustic diagnostic and navigation system (SCAN) to evaluate trabecular bone quality in 60 cubic trabecular samples harvested from adult sheep. Ultrasound image based SCAN measurements in structural and strength properties were validated by μCT and compressive mechanical testing. This result indicated a moderately strong negative correlations observed between broadband ultrasonic attenuation (BUA) and μCT-determined bone volume fraction (BV/TV, R2=0.53). Strong correlations were observed between ultrasound velocity (UV) and bone’s mechanical strength and structural parameters, i.e., bulk Young’s modulus (R2=0.67) and BV/TV (R2=0.85). The predictions for bone density and mechanical strength were significantly improved by using a linear combination of both BUA and UV, yielding R2=0.92 for BV/TV and R2=0.71 for bulk Young’s modulus. These results imply that quantitative ultrasound can characterize trabecular structural and mechanical properties through measurements of particular ultrasound parameters, and potentially provide an excellent estimation for bone’s structural integrity. PMID:23976803

  9. Prediction of trabecular bone qualitative properties using scanning quantitative ultrasound.

    PubMed

    Qin, Yi-Xian; Lin, Wei; Mittra, Erik; Xia, Yi; Cheng, Jiqi; Judex, Stefan; Rubin, Clint; Müller, Ralph

    2013-11-01

    Microgravity induced bone loss represents a critical health problem in astronauts, particularly occurred in weight-supporting skeleton, which leads to osteopenia and increase of fracture risk. Lack of suitable evaluation modality makes it difficult for monitoring skeletal status in long term space mission and increases potential risk of complication. Such disuse osteopenia and osteoporosis compromise trabecular bone density, and architectural and mechanical properties. While X-ray based imaging would not be practical in space, quantitative ultrasound may provide advantages to characterize bone density and strength through wave propagation in complex trabecular structure. This study used a scanning confocal acoustic diagnostic and navigation system (SCAN) to evaluate trabecular bone quality in 60 cubic trabecular samples harvested from adult sheep. Ultrasound image based SCAN measurements in structural and strength properties were validated by μCT and compressive mechanical testing. This result indicated a moderately strong negative correlations observed between broadband ultrasonic attenuation (BUA) and μCT-determined bone volume fraction (BV/TV, R(2)=0.53). Strong correlations were observed between ultrasound velocity (UV) and bone's mechanical strength and structural parameters, i.e., bulk Young's modulus (R(2)=0.67) and BV/TV (R(2)=0.85). The predictions for bone density and mechanical strength were significantly improved by using a linear combination of both BUA and UV, yielding R(2)=0.92 for BV/TV and R(2)=0.71 for bulk Young's modulus. These results imply that quantitative ultrasound can characterize trabecular structural and mechanical properties through measurements of particular ultrasound parameters, and potentially provide an excellent estimation for bone's structural integrity. PMID:23976803

  10. Local plate/rod descriptors of 3D trabecular bone micro-CT images from medial axis topologic analysis

    SciTech Connect

    Peyrin, Francoise; Attali, Dominique; Chappard, Christine; Benhamou, Claude Laurent

    2010-08-15

    Purpose: Trabecular bone microarchitecture is made of a complex network of plate and rod structures evolving with age and disease. The purpose of this article is to propose a new 3D local analysis method for the quantitative assessment of parameters related to the geometry of trabecular bone microarchitecture. Methods: The method is based on the topologic classification of the medial axis of the 3D image into branches, rods, and plates. Thanks to the reversibility of the medial axis, the classification is next extended to the whole 3D image. Finally, the percentages of rods and plates as well as their mean thicknesses are calculated. The method was applied both to simulated test images and 3D micro-CT images of human trabecular bone. Results: The classification of simulated phantoms made of plates and rods shows that the maximum error in the quantitative percentages of plate and rods is less than 6% and smaller than with the structure model index (SMI). Micro-CT images of human femoral bone taken in osteoporosis and early or advanced osteoarthritis were analyzed. Despite the large physiological variability, the present method avoids the underestimation of rods observed with other local methods. The relative percentages of rods and plates were not significantly different between osteoarthritis and osteoporotic groups, whereas their absolute percentages were in relation to an increase of rod and plate thicknesses in advanced osteoarthritis with also higher relative and absolute number of nodes. Conclusions: The proposed method is model-independent, robust to surface irregularities, and enables geometrical characterization of not only skeletal structures but entire 3D images. Its application provided more accurate results than the standard SMI on simple simulated phantoms, but the discrepancy observed on the advanced osteoarthritis group raises questions that will require further investigations. The systematic use of such a local method in the characterization of

  11. Automated selection of trabecular bone regions in knee radiographs

    SciTech Connect

    Podsiadlo, P.; Wolski, M.; Stachowiak, G. W.

    2008-05-15

    Osteoarthritic (OA) changes in knee joints can be assessed by analyzing the structure of trabecular bone (TB) in the tibia. This analysis is performed on TB regions selected manually by a human operator on x-ray images. Manual selection is time-consuming, tedious, and expensive. Even if a radiologist expert or highly trained person is available to select regions, high inter- and intraobserver variabilities are still possible. A fully automated image segmentation method was, therefore, developed to select the bone regions for numerical analyses of changes in bone structures. The newly developed method consists of image preprocessing, delineation of cortical bone plates (active shape model), and location of regions of interest (ROI). The method was trained on an independent set of 40 x-ray images. Automatically selected regions were compared to the ''gold standard'' that contains ROIs selected manually by a radiologist expert on 132 x-ray images. All images were acquired from subjects locked in a standardized standing position using a radiography rig. The size of each ROI is 12.8x12.8 mm. The automated method results showed a good agreement with the gold standard [similarity index (SI)=0.83 (medial) and 0.81 (lateral) and the offset=[-1.78, 1.27]x[-0.65,0.26] mm (medial) and [-2.15, 1.59]x[-0.58, 0.52] mm (lateral)]. Bland and Altman plots were constructed for fractal signatures, and changes of fractal dimensions (FD) to region offsets calculated between the gold standard and automatically selected regions were calculated. The plots showed a random scatter and the 95% confidence intervals were (-0.006, 0.008) and (-0.001, 0.011). The changes of FDs to region offsets were less than 0.035. Previous studies showed that differences in FDs between non-OA and OA bone regions were greater than 0.05. ROIs were also selected by a second radiologist and then evaluated. Results indicated that the newly developed method could replace a human operator and produces bone regions

  12. Cortical and trabecular deterioration in mouse models of Roux-en-Y gastric bypass.

    PubMed

    Yu, Elaine W; Carmody, Jill S; Brooks, Daniel J; LaJoie, Scott; Kaplan, Lee M; Bouxsein, Mary L

    2016-04-01

    Roux-en-Y gastric bypass (RYGB) is a profoundly effective treatment for severe obesity, but results in significant bone loss in patients. Developing a murine model that recapitulates this skeletal phenotype will provide a robust tool with which to study the physiologic mechanisms of this bone loss. We studied adult male C57BL/6J mice who underwent either RYGB or sham operation. Twelve weeks after surgery, we characterized biochemical bone markers (parathyroid hormone, PTH; C-telopeptide, CTX; and type 1 procollagen, P1NP) and bone microarchitectural parameters as measured by microcomputed tomography. RYGB-treated mice had significant trabecular and cortical bone deficits compared with sham-operated controls. Although adjustment for final body weight eliminated observed cortical differences, the trabecular bone volume fraction remained significantly lower in RYGB mice even after weight adjustment. PTH levels were similar between groups, but RYGB mice had significantly higher indices of bone turnover than sham controls. These data demonstrate that murine models of RYGB recapitulate patterns of bone loss and turnover that have been observed in human clinical studies. Future studies that exploit this murine model will help delineate the alterations in bone metabolism and mechanisms of bone loss after RYGB. PMID:26806052

  13. On the relationship of ultrasonic properties to density and architecture in trabecular bone

    NASA Astrophysics Data System (ADS)

    Nicholson, Patrick; Bouxsein, Mary

    2002-05-01

    As previously reported elsewhere, we have made ultrasonic measurements in human trabecular bone and have explored relationships with microstructural properties, the latter derived from microcomputed tomography. However, multicollinearity in these data means that conventional regression analysis cannot reliably identify the underlying causal relationships. In an effort to move beyond such limitations, we used our experimental data to test some models of possible interactions between ultrasound and bone. In particular, we compared several models for predicting acoustic velocity in two-phase media as a function of the bone volume fraction. We found good agreement only with the theory of Kuster and Toksoz [Geophysics 39, 587 (1974)] based on scattering by an effective medium. Turning our attention to attenuation, we examined relationships with trabecular thickness (Tb.Th) and the number of trabeculae per unit volume (Tb.N). The exponent relating attenuation to Tb.Th was 3.2, lower than the value of 4 predicted for long wavelength inelastic scattering by cylinders. This may be due to multiple scattering, since restricting the analysis to specimens with relatively low Tb.N yielded an exponent of 3.9. The exponent relating attenuation to Tb.N was 1.3, higher than the expected value of unity, which may again reflect the influence of multiple scattering.

  14. Three-dimensional quantification of structures in trabecular bone using measures of complexity

    NASA Astrophysics Data System (ADS)

    Marwan, Norbert; Kurths, Jürgen; Thomsen, Jesper Skovhus; Felsenberg, Dieter; Saparin, Peter

    2009-02-01

    The study of pathological changes of bone is an important task in diagnostic procedures of patients with metabolic bone diseases such as osteoporosis as well as in monitoring the health state of astronauts during long-term space flights. The recent availability of high-resolution three-dimensional (3D) imaging of bone challenges the development of data analysis techniques able to assess changes of the 3D microarchitecture of trabecular bone. We introduce an approach based on spatial geometrical properties and define structural measures of complexity for 3D image analysis. These measures evaluate different aspects of organization and complexity of 3D structures, such as complexity of its surface or shape variability. We apply these measures to 3D data acquired by high-resolution microcomputed tomography (μCT) from human proximal tibiae and lumbar vertebrae at different stages of osteoporotic bone loss. The outcome is compared to the results of conventional static histomorphometry and exhibits clear relationships between the analyzed geometrical features of trabecular bone and loss of bone density, but also indicate that the measures reveal additional information about the structural composition of bone, which were not revealed by the static histomorphometry. Finally, we have studied the dependency of the developed measures of complexity on the spatial resolution of the μCT data sets.

  15. Experimental validation of a nonlinear μFE model based on cohesive-frictional plasticity for trabecular bone.

    PubMed

    Schwiedrzik, J; Gross, T; Bina, M; Pretterklieber, M; Zysset, P; Pahr, D

    2016-04-01

    Trabecular bone is a porous mineralized tissue playing a major load bearing role in the human body. Prediction of age-related and disease-related fractures and the behavior of bone implant systems needs a thorough understanding of its structure-mechanical property relationships, which can be obtained using microcomputed tomography-based finite element modeling. In this study, a nonlinear model for trabecular bone as a cohesive-frictional material was implemented in a large-scale computational framework and validated by comparison of μFE simulations with experimental tests in uniaxial tension and compression. A good correspondence of stiffness and yield points between simulations and experiments was found for a wide range of bone volume fraction and degree of anisotropy in both tension and compression using a non-calibrated, average set of material parameters. These results demonstrate the ability of the model to capture the effects leading to failure of bone for three anatomical sites and several donors, which may be used to determine the apparent behavior of trabecular bone and its evolution with age, disease, and treatment in the future. PMID:26224581

  16. Lattice strains and load partitioning in bovine trabecular bone.

    SciTech Connect

    Akhtar, R.; Daymond, M. R.; Almer, J. D.; Mummery, P. M.

    2012-02-01

    Microdamage and failure mechanisms have been well characterized in bovine trabecular bone. However, little is known about how elastic strains develop in the apatite crystals of the trabecular struts and their relationship with different deformation mechanisms. In this study, wide-angle high-energy synchrotron X-ray diffraction has been used to determine bulk elastic strains under in situ compression. Dehydrated bone is compared to hydrated bone in terms of their response to load. During compression, load is initially borne by trabeculae aligned parallel to loading direction with non-parallel trabeculae deforming by bending. Ineffective load partitioning is noted in dehydrated bone whereas hydrated bone behaves like a plastically yielding foam

  17. [Merkel cell carcinoma (trabecular carcinoma) of the skin].

    PubMed

    Zala, L; Armagni, C; Krebs, A

    1983-04-01

    The Merkel cell carcinoma was first designated some years ago by the descriptive term trabecular carcinoma. Both names refer to a skin tumor occurring in elderly patients. This is another example where ultrastructural differentiating criteria are necessary for a definite diagnosis i.e., identification of so-called neurosecretory-like granules by electron microscopy. We report clinical, histological, ultrastructural, and histogenetic aspects of such a disease in a woman suffering from a metastasizing Merkel cell carcinoma. PMID:6853165

  18. Estimating Trabecular Bone Mechanical Properties From Non-Invasive Imaging

    NASA Technical Reports Server (NTRS)

    Hogan, Harry A.; Webster, Laurie

    1997-01-01

    An important component in developing countermeasures for maintaining musculoskeletal integrity during long-term space flight is an effective and meaningful method of monitoring skeletal condition. Magnetic resonance imaging (MRI) is an attractive non-invasive approach because it avoids the exposure to radiation associated with X-ray based imaging and also provides measures related to bone microstructure rather than just density. The purpose of the research for the 1996 Summer Faculty Fellowship period was to extend the usefulness of the MRI data to estimate the mechanical properties of trabecular bone. The main mechanical properties of interest are the elastic modulus and ultimate strength. Correlations are being investigated between these and fractal analysis parameters, MRI relaxation times, apparent densities, and bone mineral densities. Bone specimens from both human and equine donors have been studied initially to ensure high-quality MR images. Specimens were prepared and scanned from human proximal tibia bones as well as the equine distal radius. The quality of the images from the human bone appeared compromised due to freezing artifact, so only equine bone was included in subsequent procedures since these specimens could be acquired and imaged fresh before being frozen. MRI scans were made spanning a 3.6 cm length on each of 5 equine distal radius specimens. The images were then sent to Dr. Raj Acharya of the State University of New York at Buffalo for fractal analysis. Each piece was cut into 3 slabs approximately 1.2 cm thick and high-resolution contact radiographs were made to provide images for comparing fractal analysis with MR images. Dual energy X-ray absorptiometry (DEXA) scans were also made of each slab for subsequent bone mineral density determination. Slabs were cut into cubes for mechanical using a slow-speed diamond blade wafering saw (Buehler Isomet). The dimensions and wet weights of each cube specimen were measured and recorded. Wet weights

  19. 3D visualization of aqueous humor outflow structures in-situ in humans.

    PubMed

    Kagemann, Larry; Wollstein, Gadi; Ishikawa, Hiroshi; Sigal, Ian A; Folio, Lindsey S; Xu, Juan; Gong, Haiyan; Schuman, Joel S

    2011-09-01

    Aqueous humor (AH) exiting the eye via the trabecular meshwork and Schlemm's canal (SC) passes through the deep and intrascleral venous plexus (ISVP) or directly through aqueous veins. The purpose of this study was to visualize the human AH outflow system 360° in three dimensions (3D) during active AH outflow in a virtual casting. The conventional AH outflow pathways of 7 donor eyes were imaged with a modified Bioptigen spectral-domain optical coherence tomography system (Bioptigen Inc, USA; SuperLum LTD, Ireland) at a perfusion pressure of 20 mmHg (N = 3), and 10 mmHg (N = 4). In all eyes, 36 scans (3 equally distributed in each clock hour), each covering a 2 × 3 × 2 mm volume (512 frames, each 512 × 1024 pixels), were obtained. All image data were black/white inverted, and the background subtracted (ImageJ 1.40 g, http://rsb.info.nih.gov/ij/). Contrast was adjusted to isolate the ISVP. SC, collector channels, the deep and ISVP, and episcleral veins were observed throughout the limbus. Aqueous veins could be observed extending into the episcleral veins. Individual scan ISVP castings were rendered and assembled in 3D space in Amira 4.1 (Visage Imaging Inc. USA). A 360-degree casting of the ISVP was obtained in all perfused eyes. The ISVP tended to be dense and overlapping in the superior and inferior quadrants, and thinner in the lateral quadrants. The human AH outflow pathway can be imaged using SD-OCT. The more superficial structures of the AH outflow pathway present with sufficient contrast as to be optically isolated and cast in-situ 360° in cadaver eye perfusion models. This approach may be useful as a model in future studies of human AH outflow. PMID:21514296

  20. Development of trabecular bone surrogates for kyphoplasty-balloon dilatation training.

    PubMed

    Hollensteiner, Marianne; Samrykit, Markus; Hess, Michael; Fuerst, David; Schrempf, Andreas

    2015-01-01

    Vertebral compression fractures can limit quality of life. Cement augmentation techniques show good results in attaining pain relief. Kyphoplasty enables a better restoration of vertebra height due to a dilatable balloon tamp, which is inflated in the fractured vertebra. Surgical training of vertebral cement augmentation techniques is currently performed on patients or specimens. To enable another training possibility for surgical residents, a new hybrid patient simulator was developed. Artificial vertebrae allocate a realistic haptic feedback during needle insertion. Based on these results, new polyurethane foam recipes were developed to either enable a realistic needle insertion as well as a balloon tamp dilatation. Needle insertion forces of the newly developed foams were compared against commercially available artificial trabecular bone material and balloon tamp dilatations were performed in manufactured materials. Based on the matching needle insertion forces, two suitable material compositions for needle insertion and balloon dilatation training were found. This investigation is considered as a prior study before evaluation on human specimen. PMID:26737440

  1. Morphogenetic role of F-actin meshwork in chamber formation: immunolabeling results from symbiont bearing benthic foraminifera

    NASA Astrophysics Data System (ADS)

    Tyszka, Jaroslaw; Raitzsch, Markus; Bijma, Jelle; Höher, Nicole; Bickmeyer, Ulf; Rivera-Ingraham, Georginia; Topa, Paweł; Kaczmarek, Karina; Mewes, Antje; Bowser, Samuel; Travis, Jeffrey

    2015-04-01

    Foraminifera are excellent tracers of palaeoceanographic conditions recorded in their shell (test) morphology and chemical composition. Understanding foraminiferal morphology controlled by chamberwise growth can be reduced to processes of chamber formation. However, little is known about how foraminifera control the shape of the chamber wall to be biosynthesized and precipitated. Searching for fundamental morphogenetic features involved in biomineralization, we focused on foraminifers, which belong to the class Globothalamea. The most critical condition to run experiments was to have convenient access to early stages of chamber formation in any species of cultured benthic foraminifers. We have tested small foraminifers collected from the tidal flats of the North Sea. All species, including Ammonia, Haynesina, and Elphidium, turned out to be unsuitable due to their reproduction seasonality and/or unpredictability. The problem was solved by using symbiont bearing Amphistegina lessonii cultured in small aquaria. In well treated cultures, such foraminifera often reproduce on a glass wall surface, serving as a continuous source of juveniles. They tend to regularly construct chambers. Another important point is that symbiont bearing foraminifers usually do not construct opaque protective cysts from detritus that disturb observations. All these features facilitate immunolabeling experiments observed under confocal microscopy. Therefore, for the first time, we managed to label cytoskeleton proteins during the chamber formation in Foraminifera. The results show that the shape of chamber is predefined by a meshwork of F-actin, which acts as a dynamic organic scaffold most likely responsible for distribution and docking of biomineralizing molecules (glycoproteins). The F-actin meshwork interacts with microtubules and all associated proteins, which are involved in the morphogenesis of biomineralized structures. Foraminifera, like other eukaryotic cells, can form active

  2. [Non perforating trabecular surgery with reticulated hyaluronic acid implant].

    PubMed

    Robe-Collignon, N J; Collignon-Brach, J D

    2000-01-01

    Non perforating trabecular surgery (NPTS) with reticulated hyaluronic acid implant (Skgel) allows aqueous humor to leave anterior chamber through a thin trabeculo-Descemet's membrane into a sclerocorneal space filled with Skgel implant and then via the outflow physiological channels. Good intraocular pressure results are obtained with less or without external filtration decreasing the incidence of per- and postoperative complications found after trabeculectomy. This surgery is actually only indicated for primary open angle glaucoma, the trabeculectomy still remaining the gold standard procedure for the other glaucoma cases. PMID:11262887

  3. Predicting Trabecular Bone Stiffness from Clinical Cone-Beam CT and HR-pQCT Data; an In Vitro Study Using Finite Element Analysis

    PubMed Central

    Moreno, Rodrigo; Brismar, Torkel B.; Pahr, Dieter H.; Smedby, Örjan

    2016-01-01

    Stiffness and shear moduli of human trabecular bone may be analyzed in vivo by finite element (FE) analysis from image data obtained by clinical imaging equipment such as high resolution peripheral quantitative computed tomography (HR-pQCT). In clinical practice today, this is done in the peripheral skeleton like the wrist and heel. In this cadaveric bone study, fourteen bone specimens from the wrist were imaged by two dental cone beam computed tomography (CBCT) devices and one HR-pQCT device as well as by dual energy X-ray absorptiometry (DXA). Histomorphometric measurements from micro-CT data were used as gold standard. The image processing was done with an in-house developed code based on the automated region growing (ARG) algorithm. Evaluation of how well stiffness (Young’s modulus E3) and minimum shear modulus from the 12, 13, or 23 could be predicted from the CBCT and HR-pQCT imaging data was studied and compared to FE analysis from the micro-CT imaging data. Strong correlations were found between the clinical machines and micro-CT regarding trabecular bone structure parameters, such as bone volume over total volume, trabecular thickness, trabecular number and trabecular nodes (varying from 0.79 to 0.96). The two CBCT devices as well as the HR-pQCT showed the ability to predict stiffness and shear, with adjusted R2-values between 0.78 and 0.92, based on data derived through our in-house developed code based on the ARG algorithm. These findings indicate that clinically used CBCT may be a feasible method for clinical studies of bone structure and mechanical properties in future osteoporosis research. PMID:27513664

  4. Trabecular bone fracture healing simulation with finite element analysis and fuzzy logic.

    PubMed

    Shefelbine, Sandra J; Augat, Peter; Claes, Lutz; Simon, Ulrich

    2005-12-01

    Trabecular bone fractures heal through intramembraneous ossification. This process differs from diaphyseal fracture healing in that the trabecular marrow provides a rich vascular supply to the healing bone, there is very little callus formation, woven bone forms directly without a cartilage intermediary, and the woven bone is remodelled to form trabecular bone. Previous studies have used numerical methods to simulate diaphyseal fracture healing or bone remodelling, however not trabecular fracture healing, which involves both tissue differentiation and trabecular formation. The objective of this study was to determine if intramembraneous bone formation and remodelling during trabecular bone fracture healing could be simulated using the same mechanobiological principles as those proposed for diaphyseal fracture healing. Using finite element analysis and the fuzzy logic for diaphyseal healing, the model simulated formation of woven bone in the fracture gap and subsequent remodelling of the bone to form trabecular bone. We also demonstrated that the trabecular structure is dependent on the applied loading conditions. A single model that can simulate bone healing and remodelling may prove to be a useful tool in predicting musculoskeletal tissue differentiation in different vascular and mechanical environments. PMID:16214492

  5. Iliac crest trabecular bone mass and structure in patients with non-steroid treated rheumatoid arthritis.

    PubMed Central

    Mellish, R W; O'Sullivan, M M; Garrahan, N J; Compston, J E

    1987-01-01

    Iliac crest trabecular bone volume and structure have been studied in bone biopsy specimens from 48 patients with classical or definite rheumatoid arthritis, none of whom had received steroids. Results were compared with those obtained from healthy controls matched for age and sex. The mean trabecular bone volume in female patients aged 34-50 years was significantly lower than in controls (p less than 0.01); in male patients aged 34-50 years values were also lower than those in controls (mean (SD) 17.8 (3.2) v 22.4 (5.6)% total medullary volume), though this difference was not statistically significant. Values in older patients were similar to those of controls. The mean trabecular plate thickness was significantly lower in female patients in all three age groups when compared with the controls (p less than 0.005, 0.05, and 0.005). Similar but non-significant changes were seen in male patients. The mean trabecular plate density, an index of trabecular number, and the mean trabecular plate separation showed no age related change in either male or female patients, in contrast with the female control group, in whom the mean trabecular plate density decreased and separation increased with age. These results suggest that non-steroid treated rheumatoid arthritis is associated with premature bone loss, the structural basis of which is trabecular thinning. PMID:3426289

  6. Assessment of global morphological and topological changes in trabecular structure under the bone resorption process

    NASA Astrophysics Data System (ADS)

    Sidorenko, Irina N.; Bauer, Jan; Monetti, Roberto; Baum, Thomas; Rummeny, Ernst J.; Eckstein, Felix; Matsuura, Maiko; Lochmueller, Eva-Maria; Zysset, Philippe K.; Raeth, Christoph W.

    2012-03-01

    Osteoporosis is a frequent skeletal disease characterised both by loss of bone mineral mass and deterioration of cancellous bone micro-architecture. It can be caused by mechanical disuse, estrogen deficiency or natural age-related resorption process. Numerical analysis of high-resolution images of the trabecular network is recognised as a powerful tool for assessment of structural characteristics. Using μCT images of 73 thoracic and 78 lumbar human vertebral specimens in vitro with isotropic resolution of 26μm we simulate bone atrophy as random resorption of bone surface voxels. Global morphological and topological characteristics provided by four Minkowski Functionals (MF) are calculated for two numerical resorption models with and without conservation of global topological connectivity of the trabecular network, which simulates different types of bone loss in osteoporosis, as it has been described in males and females. Diagnostic performance of morphological and topological characteristics as a function of relative bone loss is evaluated by a correlation analysis with respect to experimentally measured Maximum Compressive Strength (MCS). In both resorption models the second MF, which coincides with bone surface fraction BS/TV, demonstrates almost constant value of Pearson's correlation coefficient with respect to the relative bone loss ▵BV/TV. This morphological characteristic does not vary considerably under age-related random resorption and can be used for predicting bone strength in the elderly. The third and fourth MF demonstrate an increasing correlation coefficients with MCS after applying random bone surface thinning without preserving topological connectivity, what can be used for improvement of evaluation of the current state of the structure.

  7. Anabolic and antiresorptive drugs improve trabecular microarchitecture and reduce fracture risk following radiation therapy.

    PubMed

    Arrington, Sarah A; Fisher, Erica R; Willick, Gordon E; Mann, Kenneth A; Allen, Matthew J

    2010-09-01

    Many patients with symptomatic bone metastases receive radiation therapy, even though radiation is known to have potential adverse effects on bone. We hypothesized that the concurrent use of a bisphosphonate drug (zoledronic acid, ZA) or a combination of ZA plus an anabolic agent (parathyroid hormone, PTH) would lead to improvements in the microarchitecture and mechanical properties of irradiated bone. Human breast cancer cells were injected into the distal femur of 56 female nude mice, which were then divided into four groups: no treatment (0 Gy), radiation administered 4 weeks postinjection (20 Gy), radiation plus ZA (12.5 microg/kg weekly from weeks 4 to 12) (20 Gy + ZA), and radiation followed by ZA (25 microg/kg weekly from weeks 4 to 8) and PTH(1-34) (100 microg microg/kg daily from weeks 8 to 12) (20 Gy + ZA + PTH). Left limbs served as normal control bones. Bone loss over the 12-week study was tracked with serial radiography and bone densitometry. At the end of the study, micro-computed tomography and mechanical testing were used to quantify bone microarchitecture and bone strength. Radiation alone failed to prevent tumor-induced decreases in bone mineral density (BMD), trabecular bone volume, and bone strength. Treatment with 20 Gy + ZA or 20 Gy + ZA + PTH as adjuncts to radiation was effective at preserving trabecular bone architecture and bone strength at normal levels. ZA reduced the risk of mechanical fragility following irradiation of a lytic bone lesion. Supplemental use of PTH did not result in further increases in bone strength but was associated with significant increases in BMD and bone mass, suggesting that it may be beneficial in enhancing bone architecture following radiation therapy. PMID:20563797

  8. Cyclic cryopreservation affects the nanoscale material properties of trabecular bone.

    PubMed

    Landauer, Alexander K; Mondal, Sumona; Yuya, Philip A; Kuxhaus, Laurel

    2014-11-01

    Tissues such as bone are often stored via freezing, or cryopreservation. During an experimental protocol, bone may be frozen and thawed a number of times. For whole bone, the mechanical properties (strength and modulus) do not significantly change throughout five freeze-thaw cycles. Material properties at the trabecular and lamellar scales are distinct from whole bone properties, thus the impact of freeze-thaw cycling at this scale is unknown. To address this, the effect of repeated freezing on viscoelastic material properties of trabecular bone was quantified via dynamic nanoindentation. Vertebrae from five cervine spines (1.5-year-old, male) were semi-randomly assigned, three-to-a-cycle, to 0-10 freeze-thaw cycles. After freeze-thaw cycling, the vertebrae were dissected, prepared and tested. ANOVA (factors cycle, frequency, and donor) on storage modulus, loss modulus, and loss tangent, were conducted. Results revealed significant changes between cycles for all material properties for most cycles, no significant difference across most of the dynamic range, and significant differences between some donors. Regression analysis showed a moderate positive correlation between cycles and material property for loss modulus and loss tangent, and weak negative correlation for storage modulus, all correlations were significant. These results indicate that not only is elasticity unpredictably altered, but also that damping and viscoelasticity tend to increase with additional freeze-thaw cycling. PMID:25278046

  9. Skeletal dosimetry based on µCT images of trabecular bone: update and comparisons

    NASA Astrophysics Data System (ADS)

    Kramer, R.; Cassola, V. F.; Vieira, J. W.; Khoury, H. J.; de Oliveira Lira, C. A. B.; Robson Brown, K.

    2012-06-01

    Two skeletal dosimetry methods using µCT images of human bone have recently been developed: the paired-image radiation transport (PIRT) model introduced by researchers at the University of Florida (UF) in the US and the systematic-periodic cluster (SPC) method developed by researchers at the Federal University of Pernambuco in Brazil. Both methods use µCT images of trabecular bone (TB) to model spongiosa regions of human bones containing marrow cavities segmented into soft tissue volumes of active marrow (AM), trabecular inactive marrow and the bone endosteum (BE), which is a 50 µm thick layer of marrow on all TB surfaces and on cortical bone surfaces next to TB as well as inside the medullary cavities. With respect to the radiation absorbed dose, the AM and the BE are sensitive soft tissues for the induction of leukaemia and bone cancer, respectively. The two methods differ mainly with respect to the number of bone sites and the size of the µCT images used in Monte Carlo calculations and they apply different methods to simulate exposure from radiation sources located outside the skeleton. The PIRT method calculates dosimetric quantities in isolated human bones while the SPC method uses human bones embedded in the body of a phantom which contains all relevant organs and soft tissues. Consequently, the SPC method calculates absorbed dose to the AM and to the BE from particles emitted by radionuclides concentrated in organs or from radiation sources located outside the human body in one calculation step. In order to allow for similar calculations of AM and BE absorbed doses using the PIRT method, the so-called dose response functions (DRFs) have been developed based on absorbed fractions (AFs) of energy for electrons isotropically emitted in skeletal tissues. The DRFs can be used to transform the photon fluence in homogeneous spongiosa regions into absorbed dose to AM and BE. This paper will compare AM and BE AFs of energy from electrons emitted in skeletal

  10. Clinical Application of Solid Model Based on Trabecular Tibia Bone CT Images Created by 3D Printer

    PubMed Central

    Cho, Jaemo; Park, Chan-Soo; Kim, Yeoun-Jae

    2015-01-01

    Objectives The aim of this work is to use a 3D solid model to predict the mechanical loads of human bone fracture risk associated with bone disease conditions according to biomechanical engineering parameters. Methods We used special image processing tools for image segmentation and three-dimensional (3D) reconstruction to generate meshes, which are necessary for the production of a solid model with a 3D printer from computed tomography (CT) images of the human tibia's trabecular and cortical bones. We examined the defects of the mechanism for the tibia's trabecular bones. Results Image processing tools and segmentation techniques were used to analyze bone structures and produce a solid model with a 3D printer. Conclusions These days, bio-imaging (CT and magnetic resonance imaging) devices are able to display and reconstruct 3D anatomical details, and diagnostics are becoming increasingly vital to the quality of patient treatment planning and clinical treatment. Furthermore, radiographic images are being used to study biomechanical systems with several aims, namely, to describe and simulate the mechanical behavior of certain anatomical systems, to analyze pathological bone conditions, to study tissues structure and properties, and to create a solid model using a 3D printer to support surgical planning and reduce experimental costs. These days, research using image processing tools and segmentation techniques to analyze bone structures to produce a solid model with a 3D printer is rapidly becoming very important. PMID:26279958

  11. Prediction of trabecular bone principal structural orientation using quantitative ultrasound scanning

    PubMed Central

    Lin, Liangjun; Cheng, Jiqi; Lin, Wei; Qin, Yi-Xian

    2016-01-01

    Bone has the ability to adapt its structure in response to the mechanical environment as defined as Wolff’s Law. The alignment of trabecular structure is intended to adapt to the particular mechanical milieu applied to it. Due to the absence of normal mechanical loading, it will be extremely important to assess the anisotropic deterioration of bone during the extreme conditions, i.e., long term space mission and disease orientated disuse, to predict risk of fractures. The propagation of ultrasound wave in trabecular bone is substantially influenced by the anisotropy of the trabecular structure. Previous studies have shown that both ultrasound velocity and amplitude is dependent on the incident angle of the ultrasound signal into the bone sample. In this work, seven bovine trabecular bone balls were used for rotational ultrasound measurement around three anatomical axes to elucidate the ability of ultrasound to identify trabecular orientation. Both ultrasound attenuation (ATT) and fast wave velocity (UV) were used to calculate the principal orientation of the trabecular bone. By comparing to the mean intercept length (MIL) tensor obtained from μCT, the angle difference of the prediction by UV was 4.45°, while it resulted in 11.67° angle difference between direction predicted by μCT and the prediction by ATT. This result demonstrates the ability of ultrasound as a non-invasive measurement tool for the principal structural orientation of the trabecular bone. PMID:22560370

  12. Trabecular bone microstructure scales allometrically in the primate humerus and femur

    PubMed Central

    Ryan, Timothy M.; Shaw, Colin N.

    2013-01-01

    Most analyses of trabecular microarchitecture in mammals have focused on the functional significance of interspecific variation, but they have not effectively considered the influence of body size or phylogeny on bone architecture. The goals of this study were to determine the relationship between trabecular bone and body size in the humeral and femoral heads of extant primates, and to assess the influence of phylogeny on bone microstructure. Using a sample of 235 individuals from 34 primate species, ranging in body size from 0.06 to 130 kg, the relationships between trabecular bone structure and body size were assessed by using conventional and phylogenetic regression analyses. Bone volume fraction, trabecular thickness and trabecular spacing increase with body size, whereas bone surface-area-to-volume ratio decreases. Shape variables such as trabecular number, connectivity density and degree of anisotropy scale inversely with size. Most of these variables scale with significant negative allometry, except bone surface-area-to-volume ratio, which scales with slight positive allometry. Phylogenetic regressions indicate a relatively weak phylogenetic signal in some trabecular bone variables. These data demonstrate that, relative to body size, large primates have thinner and more tightly packed trabeculae than small primates. The relatively thin trabeculae in large primates and other mammals, coupled with constraints on trabecular thickness related to osteocyte function, suggest that increased skeletal loads in the postcranial joints of large mammals are probably mitigated not only through alterations in trabecular microarchitecture, but also through other mechanisms such as changes in cortical bone distribution, limb posture and gait speed. PMID:23486443

  13. Heritability of Lumbar Trabecular Bone Mechanical Properties in Baboons

    PubMed Central

    Havill, L.M.; Allen, M.R.; Bredbenner, T.L.; Burr, D.B.; Nicolella, D.P.; Turner, C.H.; Warren, D.M.; Mahaney, M.C.

    2010-01-01

    Genetic effects on mechanical properties have been demonstrated in rodents, but not confirmed in primates. Our aim was to quantify the proportion of variation in vertebral trabecular bone mechanical properties that is due to the effects of genes. L3 vertebrae were collected from 110 females and 46 male baboons (6–32 years old) from a single extended pedigree. Cranio-caudally oriented trabecular bone cores were scanned with microCT then tested in monotonic compression to determine apparent ultimate stress, modulus, and toughness. Age and sex effects and heritability (h2) were assessed using maximum likelihood-based variance components methods. Additive effects of genes on residual trait variance were significant for ultimate stress (h2=0.58), toughness (h2=0.64), and BV/TV (h2=0.55). When BV/TV was accounted for, the residual variance in ultimate stress accounted for by the additive effects of genes was no longer significant. Toughness, however, showed evidence of a non-BV/TV-related genetic effect. Overall, maximum stress and modulus show strong genetic effects that are nearly entirely due to bone volume. Toughness shows strong genetic effects related to bone volume and shows additional genetic effects (accounting for 10% of the total trait variance) that are independent of bone volume. These results support continued use of bone volume as a focal trait to identify genes related to skeletal fragility, but also show that other focal traits related to toughness and variation in the organic component of bone matrix will enhance our ability to find additional genes that are particularly relevant to fatigue-related fractures. PMID:19900599

  14. Removal of trabecular metal osteonecrosis intervention implant and conversion to primary total hip arthroplasty.

    PubMed

    Owens, Joshua B; Ely, Erin E; Guilliani, Nathania M Figueroa; Suarez, Juan C; Patel, Preetesh D

    2012-06-01

    Core decompression and placement of the Trabecular Metal Osteonecrosis Intervention Implant have shown to be initially successful in treating early osteonecrosis. When treatment fails, however, patients often undergo primary total hip arthroplasty (THA) requiring removal of a previously inserted trabecular metal implant. We describe a technical tip for removal of a well-ingrown trabecular metal screw. A metal-cutting trephine placed over the screw allows for removal in an efficient manner while minimizing additional dissection and bone loss during conversion to THA. PMID:22425306

  15. Effect of micro-computed tomography voxel size and segmentation method on trabecular bone microstructure measures in mice.

    PubMed

    Christiansen, Blaine A

    2016-12-01

    Micro-computed tomography (μCT) is currently the gold standard for determining trabecular bone microstructure in small animal models. Numerous parameters associated with scanning and evaluation of μCT scans can strongly affect morphologic results obtained from bone samples. However, the effect of these parameters on specific trabecular bone outcomes is not well understood. This study investigated the effect of μCT scanning with nominal voxel sizes between 6-30 μm on trabecular bone outcomes quantified in mouse vertebral body trabecular bone. Additionally, two methods for determining a global segmentation threshold were compared: based on qualitative assessment of 2D images, or based on quantitative assessment of image histograms. It was found that nominal voxel size had a strong effect on several commonly reported trabecular bone parameters, in particular connectivity density, trabecular thickness, and bone tissue mineral density. Additionally, the two segmentation methods provided similar trabecular bone outcomes for scans with small nominal voxel sizes, but considerably different outcomes for scans with larger voxel sizes. The Qualitatively Selected segmentation method more consistently estimated trabecular bone volume fraction (BV/TV) and trabecular thickness across different voxel sizes, but the Histogram segmentation method more consistently estimated trabecular number, trabecular separation, and structure model index. Altogether, these results suggest that high-resolution scans be used whenever possible to provide the most accurate estimation of trabecular bone microstructure, and that the limitations of accurately determining trabecular bone outcomes should be considered when selecting scan parameters and making conclusions about inter-group variance or between-group differences in studies of trabecular bone microstructure in small animals. PMID:27430011

  16. Multiobjective topology optimization of trabecular Bone Structure in the spine and the femur: Implications for biomimcry

    NASA Astrophysics Data System (ADS)

    Elbanna, Ahmed; Peetz, Darin

    Bone is classically considered to be a self-optimizing structure in accordance with Wolff's law. However, while the structure's ability to adapt to changing stress patterns has been well documented, whether it is fully optimal for compliance is less certain (Sigmund, 2002). Given the complexity of many biological systems, it is expected that this structure serves several purposes. We present a multi-objective topology optimization formulation for trabecular bone in the human body at two locations: the vertebrae and the femur. We account for the effect of different conflicting objectives such as maximization of stiffness, maximization of surface area, and minimization of buckling susceptibility. Our formulation enables us to determine the relative role of each of these objective in optimizing the structure. Moreover, it provides an opportunity to explore what structural features have to evolve to meet a certain objective requirements that may have been absent otherwise. For example, inclusion of stability considerations introduce numerous horizontal and diagonal members in the topology in the case of human vertebrae under vertical loading. However, the stability is found to play a lesser role in the case of the femur bone optimization. Our formulation enables investigation of bone adaptation at different locations of the body as well as under different loading and boundary conditions (e.g. healthy and diseased discs for the case of the spine). We discuss the implications of our findings on developing design rules for bio-inspired and bio-mimetic architectured materials. National Science Foundation: CMMI.

  17. Numerical investigation of ultrasonic attenuation through 2D trabecular bone structures reconstructed from CT scans and random realizations.

    PubMed

    Gilbert, Robert P; Guyenne, Philippe; Li, Jing

    2014-02-01

    In this paper, we compare ultrasound interrogations of actual CT-scanned images of trabecular bone with artificial randomly constructed bone. Even though it is known that actual bone does not have randomly distributed trabeculae, we find that the ultrasound attenuations are close enough to cast doubt on any microstructural information, such as trabeculae width and distance between trabeculae, being gleaned from such experiments. More precisely, we perform numerical simulations of ultrasound interrogation on cancellous bone to investigate the phenomenon of ultrasound attenuation as a function of excitation frequency and bone porosity. The theoretical model is based on acoustic propagation equations for a composite fluid-solid material and is solved by a staggered-grid finite-difference scheme in the time domain. Numerical experiments are performed on two-dimensional bone samples reconstructed from CT-scanned images of real human calcaneus and from random distributions of fluid-solid particles generated via the turning bands method. A detailed comparison is performed on various parameters such as the attenuation rate and speed of sound through the bone samples as well as the normalized broadband ultrasound attenuation coefficient. Comparing results from these two types of bone samples allows us to assess the role of bone microstructure in ultrasound attenuation. It is found that the random model provides suitable bone samples for ultrasound interrogation in the transverse direction of the trabecular network. PMID:24480174

  18. Single cell lineage tracing reveals that oriented cell division contributes to trabecular morphogenesis and regional specification

    PubMed Central

    Li, Jingjing; Miao, Lianjie; Shieh, David; Spiotto, Ernest; Li, Jian; Zhou, Bin; Paul, Antoni; Schwartz, Robert J.; Firulli, Anthony B.; Singer, Harold A.; Huang, Guoying; Wu, Mingfu

    2016-01-01

    Summary The cardiac trabeculae are sheet-like structures extending from the myocardium that function to increase surface area. A lack of trabeculation causes embryonic lethality due to compromised cardiac function. To understand the cellular and molecular mechanisms of trabecular formation, we genetically labeled individual cardiomyocytes prior to trabeculation via the brainbow multicolor system, and traced and analyzed the labeled cells during trabeculation by whole-embryo clearing and imaging. The clones derived from labeled single cells displayed four different geometric patterns that are derived from different patterns of oriented cell division (OCD) and migration. Of the four types of clones, the inner, transmural, and mixed clones contributed to trabecular cardiomyocytes. Further studies showed that perpendicular OCD is an extrinsic asymmetric cell division that putatively contributes to trabecular regional specification. Furthermore, N-Cadherin deletion in labeled clones disrupted the clonal patterns. In summary, our data demonstrate that OCD contributes to trabecular morphogenesis and specification. PMID:27052172

  19. Fractal analysis as a means for the quantification of intramandibular trabecular bone loss from dental radiographs

    NASA Astrophysics Data System (ADS)

    Doyle, Michael D.; Rabin, Harold; Suri, Jasjit S.

    1991-04-01

    Atechnique is proposed which uses fractal analysis for the non- traumatic and non-invasive quantification of trabecular bone density in the mandible using standard dental radiographs. Binary images of trabecular bone patterns are derived from digitized radiographic images. Fractal analysis is then used to calculate the Hausdorif dimension (D) of the binary image patterns. Variations in D calculated with this method can be correlated with known cases of systemic osteoporosis to establish normal and abnormal ranges for the value of D.

  20. Serial Multifocal Electroretinograms during Long-term Elevation and Reduction of Intraocular Pressure in Non-human Primates

    PubMed Central

    Nork, T. Michael; Kim, Charlene B. Y.; Heatley, Gregg A.; Kaufman, Paul L.; Lucarelli, Mark J.; Levin, Leonard A.; Ver Hoeve, James N.

    2010-01-01

    The purpose of this study was to evaluate the relationship between elevations of intraocular pressure (IOP) and the multifocal electroretinogram (mfERG) in non-human primates. Experimental glaucoma was induced in 4 rhesus and 4 cynomolgus monkeys by laser trabecular meshwork destruction (LTD) in one eye. To evaluate the contribution of ganglion cells to mfERG changes, one monkey of each species had previously underwent unilateral optic nerve transection (ONT). After ≥ 44 weeks of elevation, the IOP was reduced by trabeculectomy in 2 non-transected animals. In the intact (non-transected) animals there was an increase in the amplitude of the early mfERG waveforms (N1 and P1) of the first order kernel (K1) throughout the period of IOP elevation in all of the rhesus, but not all of the cynomolgus monkeys. A species difference was also present as a decrease of the second order kernel, first slice (K2.1) in all of the cynomolgus monkeys but only in 1 of the rhesus monkeys (the 1 with the ONT). Similar IOP effects on the mfERG were seen in the ONT animals. Surgical lowering of IOP resulted in a return of the elevated K1 amplitudes to baseline levels. However, the depressed K2.1 RMS in the cynomolgus monkeys did not recover. These results demonstrate species-specific changes in cone-driven retinal function during periods of elevated IOP. These IOP-related effects can occur in the absence of retinal ganglion cells and may be reversible. PMID:20422254

  1. Measuring apparent trabecular structure with pQCT: a comparison with HR-pQCT.

    PubMed

    Lala, Deena; Cheung, Angela M; Lynch, Cheryl L; Inglis, Dean; Gordon, Chris; Tomlinson, George; Giangregorio, Lora

    2014-01-01

    We evaluated how comparable peripheral quantitative computed tomography (pQCT) measurements of cortical thickness, density, and apparent trabecular structure at the ultradistal tibia were with those measured with high-resolution pQCT (HR-pQCT). We also examined whether the accuracy of the pQCT-based trabecular and cortical measurements improved with reductions in slice thickness from the standard 2.2mm to 1.1 and 0.6mm. We immersed 15 dry tibia specimens in saline in a sealed cylinder and scanned 22.5mm from the distal tibia plateau using pQCT and HR-pQCT. pQCT underestimated cortical thickness by Stratec (CThStratec) and trabecular spacing (Tb.Sp) by 21.4% and 72.9%, whereas bone volume to total volume (BV/TV) and cortical density (CDen) were overestimated by 265.8% and 13.1%, respectively. Measurements of trabecular volumetric bone mineral density, trabecular area, total area, cortical thickness by custom software were comparable, but for CThStratec, Tb.Sp, BV/TV, and CDen, the differences between imaging devices varied with magnitude of the estimate. We recommend that researchers or clinicians interested in using pQCT to measure apparent trabecular structure or cortical thickness at the epiphyses, or in comparing findings from different devices, be aware of the differences between HR-pQCT and pQCT. PMID:23567093

  2. Preliminary study of slow and fast ultrasonic waves using MR images of trabecular bone phantom

    NASA Astrophysics Data System (ADS)

    Solis-Najera, S. E.; Neria-Pérez, J. A.; Medina, L.; Garipov, R.; Rodríguez, A. O.

    2014-11-01

    Cancellous bone is a complex tissue that performs physiological and biomechanical functions in all vertebrates. It is made up of trabeculae that, from a simplified structural viewpoint, can be considered as plates and beams in a hyperstatic structure that change with time leading to osteoporosis. Several methods has been developed to study the trabecular bone microstructure among them is the Biot's model which predicts the existence of two longitudinal waves in porous media; the slow and the fast waves, that can be related to porosity of the media. This paper is focused on the experimental detection of the two Biot's waves of a trabecular bone phantom, consisting of a trabecular network of inorganic hydroxyapatite. Experimental measurements of both waves were performed using through transmission ultrasound. Results had shown clearly that the propagation of two waves propagation is transversal to the trabecular alignment. Otherwise the waves are overlapped and a single wave seems to be propagated. To validate these results, magnetic resonance images were acquired to assess the trabecular direction, and to assure that the pulses correspond to the slow and fast waves. This approach offers a methodology for non-invasive studies of trabecular bones.

  3. Alteration patterns of trabecular bone microarchitectural characteristics induced by osteoarthritis over time

    PubMed Central

    Lee, Joo Hyung; Chun, Keyoung Jin; Kim, Han Sung; Kim, Sang Ho; Han, Paul; Jun, Yongtae; Lim, Dohyung

    2012-01-01

    Information regarding the alteration of trabecular bone microarchitecture, which is one of the important criteria to estimate bone condition, induced by osteoarthritis (OA) is sparse. The current study therefore aimed to identify and quantify patterns of alterations in trabecular bone microarchitectural characteristics at tibial epiphysis induced by OA using in vivo microcomputed tomography. Fourteen 8-week-old female Sprague Dawley rats were randomly divided into control (n = 7) and OA (n = 7) groups. Rats in the OA group were administered monoiodoacetate into the knee-joint cavity. The tibial joints were scanned by in vivo microcomputed tomography at 0, 4, and 8 weeks after administration. Two-way analysis of variance with Tukey’s honestly significant difference post hoc test was carried out for statistical analyses. The results showed that patterns of alterations in the trabecular bone microarchitectural characteristics in the OA group were not different from those in the control group from 0 to 4 weeks (P > 0.05), but differed from 4 to 8 weeks (P < 0.05). In particular, both trabecular bone thickness and trabecular bone separation distributions over time (4–8 weeks) differed significantly (P < 0.05). These findings suggest that the patterns of bone microarchitecture changes brought about by OA should be periodically considered in the diagnosis and management of arthritic symptoms over time. Improved understanding of the alteration pattern on trabecular bone microarchitecture may assist in developing more targeted treatment interventions for OA. PMID:22956865

  4. Ultrasonic wave propagation in trabecular bone predicted by the stratified model

    NASA Technical Reports Server (NTRS)

    Lin, W.; Qin, Y. X.; Rubin, C.

    2001-01-01

    The objective of this study was to investigate ultrasound propagation in trabecular bone by considering the wave reflection and transmission in a multilayered medium. The use of ultrasound to identify those at risk of osteoporosis is a promising diagnostic method providing a measure of bone mineral density (BMD). A stratified model was proposed to study the effect of transmission and reflection of ultrasound wave within the trabecular architecture on the relationship between ultrasound and BMD. The results demonstrated that ultrasound velocity in trabecular bone was highly correlated with the bone apparent density (r=0.97). Moreover, a consistent pattern of the frequency dependence of ultrasound attenuation coefficient has been observed between simulation using this model and experimental measurement of trabecular bone. The normalized broadband ultrasound attenuation (nBUA) derived from the simulation results revealed that nBUA was nonlinear with respect to trabecular porosity and BMD. The curve of the relationship between nBUA and BMD was parabolic in shape, and the peak magnitude of nBUA was observed at approximately 60% of bone porosity. These results agreed with the published experimental data and demonstrated that according to the stratified model, reflection and transmission were important factors in the ultrasonic propagation through the trabecular bone.

  5. Preliminary study of slow and fast ultrasonic waves using MR images of trabecular bone phantom

    SciTech Connect

    Solis-Najera, S. E. E-mail: angel.perez@ciencias.unam.mx Neria-Pérez, J. A. E-mail: angel.perez@ciencias.unam.mx Medina, L. E-mail: angel.perez@ciencias.unam.mx; Garipov, R.; Rodríguez, A. O.

    2014-11-07

    Cancellous bone is a complex tissue that performs physiological and biomechanical functions in all vertebrates. It is made up of trabeculae that, from a simplified structural viewpoint, can be considered as plates and beams in a hyperstatic structure that change with time leading to osteoporosis. Several methods has been developed to study the trabecular bone microstructure among them is the Biot’s model which predicts the existence of two longitudinal waves in porous media; the slow and the fast waves, that can be related to porosity of the media. This paper is focused on the experimental detection of the two Biot’s waves of a trabecular bone phantom, consisting of a trabecular network of inorganic hydroxyapatite. Experimental measurements of both waves were performed using through transmission ultrasound. Results had shown clearly that the propagation of two waves propagation is transversal to the trabecular alignment. Otherwise the waves are overlapped and a single wave seems to be propagated. To validate these results, magnetic resonance images were acquired to assess the trabecular direction, and to assure that the pulses correspond to the slow and fast waves. This approach offers a methodology for non-invasive studies of trabecular bones.

  6. Evaluation of trabecular bone patterns on dental radiographic images: influence of cortical bone

    NASA Astrophysics Data System (ADS)

    Amouriq, Yves; Evenou, Pierre; Arlicot, Aurore; Normand, Nicolas; Layrolle, Pierre; Weiss, Pierre; Guédon, Jean-Pierre

    2010-03-01

    For some authors trabecular bone is highly visible in intraoral radiographs. For other authors, the observed intrabony trabecular pattern is a representation of only the endosteal surface of cortical bone, not of intermedullary striae. The purpose of this preliminary study was to investigate the true anatomical structures that are visible in routine dental radiographs and classically denoted trabecular bone. This is a major point for bone texture analysis on radiographs. Computed radiography (CR) images of dog mandible section in molar region were compared with simulations calculated from high-resolution micro-CT volumes. Calculated simulations were obtained using the Mojette Transform. By digitally editing the CT volume, the simulations were separated into trabecular and cortical components into a region of interest. Different images were compared and correlated, some bone micro-architecture parameters calculated. A high correlation was found between computed radiographs and calculated simulations from micro-CT. The Mojette transform was successful to obtain high quality images. Cortical bone did not contribute to change in a major way simulated images. These first results imply that intrabony trabecular pattern observed on radiographs can not only be a representation of the cortical bone endosteal surface and that trabecular bone is highly visible in intraoral radiographs.

  7. Changes of trabecular bone under control of biologically mechanical mechanism

    NASA Astrophysics Data System (ADS)

    Wang, C.; Zhang, C. Q.; Dong, X.; Wu, H.

    2008-10-01

    In this study, a biological process of bone remodeling was considered as a closed loop feedback control system, which enables bone to optimize and renew itself over a lifetime. A novel idea of combining strain-adaptive and damage-induced remodeling algorithms at Basic Multicellular Unit (BMU) level was introduced. In order to make the outcomes get closer to clinical observation, the stochastic occurrence of microdamage was involved and a hypothesis that remodeling activation probability is related to the value of damage rate was assumed. Integrated with Finite Element Analysis (FEA), the changes of trabecular bone in morphology and material properties were simulated in the course of five years. The results suggest that deterioration and anisotropy of trabecluar bone are inevitable with natural aging, and that compression rather than tension can be applied to strengthen the ability of resistance to fracture. This investigation helps to gain more insight the mechanism of bone loss and identify improved treatment and prevention for osteoporosis or stress fracture.

  8. Trabecular Bone Strength Predictions of HR-pQCT and Individual Trabeculae Segmentation (ITS)-Based Plate and Rod Finite Element Model Discriminate Postmenopausal Vertebral Fractures

    PubMed Central

    Liu, X. Sherry; Wang, Ji; Zhou, Bin; Stein, Emily; Shi, Xiutao; Adams, Mark; Shane, Elizabeth; Guo, X. Edward

    2013-01-01

    While high-resolution peripheral quantitative computed tomography (HR-pQCT) has advanced clinical assessment of trabecular bone microstructure, nonlinear microstructural finite element (μFE) prediction of yield strength by HR-pQCT voxel model is impractical for clinical use due to its prohibitively high computational costs. The goal of this study was to develop an efficient HR-pQCT-based plate and rod (PR) modeling technique to fill the unmet clinical need for fast bone strength estimation. By using individual trabecula segmentation (ITS) technique to segment the trabecular structure into individual plates and rods, a patient-specific PR model was implemented by modeling each trabecular plate with multiple shell elements and each rod with a beam element. To validate this modeling technique, predictions by HR-pQCT PR model were compared with those of the registered high resolution μCT voxel model of 19 trabecular sub-volumes from human cadaveric tibiae samples. Both Young’s modulus and yield strength of HR-pQCT PR models strongly correlated with those of μCT voxel models (r2=0.91 and 0.86). Notably, the HR-pQCT PR models achieved major reductions in element number (>40-fold) and CPU time (>1,200-fold). Then, we applied PR model μFE analysis to HR-pQCT images of 60 postmenopausal women with (n=30) and without (n=30) a history of vertebral fracture. HR-pQCT PR model revealed significantly lower Young’s modulus and yield strength at the radius and tibia in fracture subjects compared to controls. Moreover, these mechanical measurements remained significantly lower in fracture subjects at both sites after adjustment for aBMD T-score at the ultradistal radius or total hip. In conclusion, we validated a novel HR-pQCT PR model of human trabecular bone against μCT voxel models and demonstrated its ability to discriminate vertebral fracture status in postmenopausal women. This accurate nonlinear μFE prediction of HR-pQCT PR model, which requires only seconds of

  9. Monitoring trabecular bone microdamage using a dynamic acousto-elastic testing method.

    PubMed

    Moreschi, H; Callé, S; Guerard, S; Mitton, D; Renaud, G; Defontaine, M

    2011-03-01

    Dynamic acousto-elastic testing (DAET) is based on the coupling of a low-frequency (LF) acoustic wave and high-frequency ultrasound (US) pulses (probing wave). It was developed to measure US viscoelastic and dissipative non-linearity in trabecular bone. It is well known that this complex biphasic medium contains microdamage, even when tissues are healthy. The purpose of the present study was to assess the sensitivity of DAET to monitor microdamage in human calcanei. Three protocols were therefore performed to investigate the regional heterogeneity of the calcaneus, the correlation between DAET measurements and microdamage revealed by histology, and DAET sensitivity to mechanically induced fatigue microdamage. The non-linear elastic parameter beta was computed for all these protocols. The study demonstrated the presence of high viscoelastic and dissipative non-linearity only in the region of the calcaneus close to the anterior talocalcaneal articulation (region of high bone density). Protocols 1 and 2 also showed that most unsorted calcanei did not naturally exhibit high non-linearity, which is correlated with a low level of microcracks. Nevertheless, when microdamage was actually present, high levels of US non-linearity were always found, with characteristic non-linear signatures such as hysteresis and tension/compression asymmetry. Finally, protocol 3 demonstrated the high sensitivity of DAET measurement to fatigue-induced microdamage. PMID:21485329

  10. Trabecular bone histomorphometric measurements and contrast-to-noise ratio in CBCT

    PubMed Central

    Smedby, Ö; Brismar, T B; Moreno, R

    2014-01-01

    Objectives: The aim of this study was to evaluate how imaging parameters at clinical dental CBCT affect the accuracy in quantifying trabecular bone structures, contrast-to-noise ratio (CNR) and radiation dose. Methods: 15 radius samples were examined using CBCT (Accuitomo FPD; J. Morita Mfg., Kyoto, Japan). Nine imaging protocols were used, differing in current, voltage, rotation degree, voxel size, imaging area and rotation time. Radiation doses were measured using a kerma area product-meter. After segmentation, six bone structure parameters and CNRs were quantified. Micro-CT (μCT) images with an isotropic resolution of 20 μm were used as a gold standard. Results: Structure parameters obtained by CBCT were strongly correlated to those by μCT, with correlation coefficients >0.90 for all studied parameters. Bone volume and trabecular thickness were not affected by changes in imaging parameters. Increased tube current from 5 to 8 mA, decreased isotropic voxel size from 125 to 80 μm and decreased rotation angle from 360° to 180° affected correlations for trabecular termini negatively. Decreasing rotation degree also weakened correlations for trabecular separation and trabecular number at 80 μm voxel size. Changes in the rotation degree and tube current affected CNR significantly. The radiation dose varied between 269 and 1153 mGy cm2. Conclusions: Trabecular bone structure can be accurately quantified by clinical dental CBCT in vitro, and the obtained structure parameters are strongly related to those obtained by μCT. A fair CNR and strong correlations can be obtained with a low radiation dose, indicating the possibility for monitoring trabecular bone structure also in vivo. PMID:25168811

  11. Multiscale modeling of trabecular bone marrow: understanding the micromechanical environment of mesenchymal stem cells during osteoporosis.

    PubMed

    Vaughan, T J; Voisin, M; Niebur, G L; McNamara, L M

    2015-01-01

    Mechanical loading directs the differentiation of mesenchymal stem cells (MSCs) in vitro and it has been hypothesized that the mechanical environment plays a role in directing the cellular fate of MSCs in vivo. However, the complex multicellular composition of trabecular bone marrow means that the precise nature of mechanical stimulation that MSCs experience in their native environment is not fully understood. In this study, we developed a multiscale model that discretely represents the cellular constituents of trabecular bone marrow and applied this model to characterize mechanical stimulation of MCSs in vivo.We predicted that cell-level strains in certain locations of the trabecular marrow microenvironment were greater in magnitude (maximum e12¼24,000 le) than levels that have been found to result in osteogenic differentiation of MSCs in vitro (>8000 le),which may indicate that the native mechanical environment of MSCs could direct cellular fate in vivo. The results also showed that cell–cell adhesions could play an important role in mediating mechanical stimulation within the MSC population in vivo. The model was applied to investigate how changes that occur during osteoporosis affected mechanical stimulation in the cellular microenvironment of trabecular bone marrow. Specifically,a reduced bone volume (BV) resulted in an overall increase in bone deformation, leading to greater cell-level mechanical stimulation in trabecular bone marrow (maximume12¼48,000 le). An increased marrow adipocyte content resulted in slightly lower levels of stimulation within the adjacent cell population due to a shielding effect caused by the more compliant behavior of adipocytes (maximum e12¼41,000 le). Despite this reduction, stimulation levels in trabecular bone marrow during osteoporosis remained much higher than those predicted to occur under healthy conditions. It was found that compensatory mechanobiological responses that occur during osteoporosis, such as increased

  12. Survivorship of Trabecular Metal Anchored Glenoid Total Shoulder Arthroplasties.

    PubMed

    Styron, Joseph F; Marinello, Patrick G; Peers, Sebastian; Seitz, William H

    2016-09-01

    Trabecular metal anchored glenoids (TMAGs) were developed to counter the pervasive problem of component loosening at the bone-cement interface in total shoulder arthroplasty. Increased failure rates associated with the glenoid component have been previously reported due to increased rates of glenoid failures. Our hypothesis was that in our patients, the failure rate of TMAG implants is similar to or less than reported failure rates of traditional all polyethylene glenoid components. A medical chart review of 66 consecutive patients treated with a TMAG total shoulder replacement was conducted including clinical and radiographic follow-up. Paired t test analyses were used to compare the patients' preoperative and postoperative shoulder range of motion. Patients on average had 50.2 months of clinical follow-up available. Although the radiographs of several patients demonstrated focal areas of lucency, none of the patients demonstrated evidence of glenoid loosening. Glenoid component failure was a rare occurrence, happening only once in the 66 patients (1.5%). The patient with a glenoid fracture sustained that complication 6 years after her index total shoulder replacement. She was the only patient in the series who required revision surgery. Most patients experienced significant improvements in their shoulder range of motion, improving forward flexion from 73.7 to 144.2 degrees (P<0.0001), internal rotation from L5 to T8 (P<0.0001), and external rotation 12.8 to 48.9 degrees (P<0.0001). With improved implant design and meticulous surgical technique, recent iterations of TMAG components do not produce excessive failure rates but result in significant functional improvements. PMID:27328424

  13. Mechanical stimulation of bone marrow in situ induces bone formation in trabecular explants.

    PubMed

    Birmingham, E; Kreipke, T C; Dolan, E B; Coughlin, T R; Owens, P; McNamara, L M; Niebur, G L; McHugh, P E

    2015-04-01

    Low magnitude high frequency (LMHF) loading has been shown to have an anabolic effect on trabecular bone in vivo. However, the precise mechanical signal imposed on the bone marrow cells by LMHF loading, which induces a cellular response, remains unclear. This study investigates the influence of LMHF loading, applied using a custom designed bioreactor, on bone adaptation in an explanted trabecular bone model, which isolated the bone and marrow. Bone adaptation was investigated by performing micro CT scans pre and post experimental LMHF loading, using image registration techniques. Computational fluids dynamic models were generated using the pre-experiment scans to characterise the mechanical stimuli imposed by the loading regime prior to adaptation. Results here demonstrate a significant increase in bone formation in the LMHF loaded group compared to static controls and media flow groups. The calculated shear stress in the marrow was between 0.575 and 0.7 Pa, which is within the range of stimuli known to induce osteogenesis by bone marrow mesenchymal stem cells in vitro. Interestingly, a correlation was found between the bone formation balance (bone formation/resorption), trabecular number, trabecular spacing, mineral resorption rate, bone resorption rate and mean shear stresses. The results of this study suggest that the magnitude of the shear stresses generated due to LMHF loading in the explanted bone cores has a contributory role in the formation of trabecular bone and improvement in bone architecture parameters. PMID:25281407

  14. Experimentally-based multiscale model of the elastic moduli of bovine trabecular bone and its constituents.

    PubMed

    Hamed, Elham; Novitskaya, Ekaterina; Li, Jun; Jasiuk, Iwona; McKittrick, Joanna

    2015-09-01

    The elastic moduli of trabecular bone were modeled using an analytical multiscale approach. Trabecular bone was represented as a porous nanocomposite material with a hierarchical structure spanning from the collagen-mineral level to the trabecular architecture level. In parallel, compression testing was done on bovine femoral trabecular bone samples in two anatomical directions, parallel to the femoral neck axis and perpendicular to it, and the measured elastic moduli were compared with the corresponding theoretical results. To gain insights on the interaction of collagen and minerals at the nanoscale, bone samples were deproteinized or demineralized. After such processing, the treated samples remained as self-standing structures and were tested in compression. Micro-computed tomography was used to characterize the hierarchical structure of these three bone types and to quantify the amount of bone porosity. The obtained experimental data served as inputs to the multiscale model and guided us to represent bone as an interpenetrating composite material. Good agreement was found between the theory and experiments for the elastic moduli of the untreated, deproteinized, and demineralized trabecular bone. PMID:26046284

  15. Effect of Low-Dose MDCT and Iterative Reconstruction on Trabecular Bone Microstructure Assessment.

    PubMed

    Kopp, Felix K; Holzapfel, Konstantin; Baum, Thomas; Nasirudin, Radin A; Mei, Kai; Garcia, Eduardo G; Burgkart, Rainer; Rummeny, Ernst J; Kirschke, Jan S; Noël, Peter B

    2016-01-01

    We investigated the effects of low-dose multi detector computed tomography (MDCT) in combination with statistical iterative reconstruction algorithms on trabecular bone microstructure parameters. Twelve donated vertebrae were scanned with the routine radiation exposure used in our department (standard-dose) and a low-dose protocol. Reconstructions were performed with filtered backprojection (FBP) and maximum-likelihood based statistical iterative reconstruction (SIR). Trabecular bone microstructure parameters were assessed and statistically compared for each reconstruction. Moreover, fracture loads of the vertebrae were biomechanically determined and correlated to the assessed microstructure parameters. Trabecular bone microstructure parameters based on low-dose MDCT and SIR significantly correlated with vertebral bone strength. There was no significant difference between microstructure parameters calculated on low-dose SIR and standard-dose FBP images. However, the results revealed a strong dependency on the regularization strength applied during SIR. It was observed that stronger regularization might corrupt the microstructure analysis, because the trabecular structure is a very small detail that might get lost during the regularization process. As a consequence, the introduction of SIR for trabecular bone microstructure analysis requires a specific optimization of the regularization parameters. Moreover, in comparison to other approaches, superior noise-resolution trade-offs can be found with the proposed methods. PMID:27447827

  16. Trabecular bone structure in the mandibular condyles of gouging and nongouging platyrrhine primates.

    PubMed

    Ryan, Timothy M; Colbert, Matthew; Ketcham, Richard A; Vinyard, Christopher J

    2010-04-01

    The relationship between mandibular form and biomechanical function is a topic of significant interest to morphologists and paleontologists alike. Several previous studies have examined the morphology of the mandible in gouging and nongouging primates as a means of understanding the anatomical correlates of this feeding behavior. The goal of the current study was to quantify the trabecular bone structure of the mandibular condyle of gouging and nongouging primates to assess the functional morphology of the jaw in these animals. High-resolution computed tomography scan data were collected from the mandibles of five adult common marmosets (Callithrix jacchus), saddle-back tamarins (Saguinus fuscicollis), and squirrel monkeys (Saimiri sciureus), respectively, and various three-dimensional morphometric parameters were measured from the condylar trabecular bone. No significant differences were found among the taxa for most trabecular bone structural features. Importantly, no mechanically significant parameters, such as bone volume fraction and degree of anisotropy, were found to vary significantly between gouging and nongouging primates. The lack of significant differences in mechanically relevant structural parameters among these three platyrrhine taxa may suggest that gouging as a habitual dietary behavior does not involve significantly higher loads on the mandibular condyle than other masticatory behaviors. Alternatively, the similarities in trabecular architecture across these three taxa may indicate that trabecular bone is relatively unimportant mechanically in the condyle of these primates and therefore is functionally uninformative. PMID:19918988

  17. Trabecular mineral content of the spine in women with hip fracture: CT measurement

    SciTech Connect

    Firooznia, H.; Rafii, M.; Golimbu, C.; Schwartz, M.S.; Ort, P.

    1986-06-01

    The trabecular bone mineral content (BMC) of the spine was measured by computed tomography in 185 women aged 47-84 years with vertebral fracture (n = 74), hip fracture (n = 83), and both vertebral and hip fracture (n = 28). Eighty-seven percent of vertebral-fracture patients, 38% of hip-fracture patients, and 82% of vertebral- and hip-fracture patients had spinal BMC values below the fifth percentile for healthy premenopausal women and values 64%, 9%, and 68% below the fifth percentile for age-matched control subjects. No significant loss of spinal trabecular bone was seen in patients with hip fracture. If it is assumed that the rate of trabecular bone loss is the same in the spine and femoral neck, then hip fracture (unlike osteoporotic vertebral fracture) is not associated with disproportionate loss of trabecular bone. Hip fracture occurs secondary to weakening of bone and increased incidence of falls. Bone weakening may be due to disproportionate loss of trabecular or cortical bone, proportionate loss of both, or other as yet undetermined qualitative changes in bone.

  18. Effect of Low-Dose MDCT and Iterative Reconstruction on Trabecular Bone Microstructure Assessment

    PubMed Central

    Baum, Thomas; Nasirudin, Radin A.; Mei, Kai; Garcia, Eduardo G.; Burgkart, Rainer; Rummeny, Ernst J.; Kirschke, Jan S.; Noël, Peter B.

    2016-01-01

    We investigated the effects of low-dose multi detector computed tomography (MDCT) in combination with statistical iterative reconstruction algorithms on trabecular bone microstructure parameters. Twelve donated vertebrae were scanned with the routine radiation exposure used in our department (standard-dose) and a low-dose protocol. Reconstructions were performed with filtered backprojection (FBP) and maximum-likelihood based statistical iterative reconstruction (SIR). Trabecular bone microstructure parameters were assessed and statistically compared for each reconstruction. Moreover, fracture loads of the vertebrae were biomechanically determined and correlated to the assessed microstructure parameters. Trabecular bone microstructure parameters based on low-dose MDCT and SIR significantly correlated with vertebral bone strength. There was no significant difference between microstructure parameters calculated on low-dose SIR and standard-dose FBP images. However, the results revealed a strong dependency on the regularization strength applied during SIR. It was observed that stronger regularization might corrupt the microstructure analysis, because the trabecular structure is a very small detail that might get lost during the regularization process. As a consequence, the introduction of SIR for trabecular bone microstructure analysis requires a specific optimization of the regularization parameters. Moreover, in comparison to other approaches, superior noise-resolution trade-offs can be found with the proposed methods. PMID:27447827

  19. A resilient formin-derived cortical actin meshwork in the rear drives actomyosin-based motility in 2D confinement

    PubMed Central

    Ramalingam, Nagendran; Franke, Christof; Jaschinski, Evelin; Winterhoff, Moritz; Lu, Yao; Brühmann, Stefan; Junemann, Alexander; Meier, Helena; Noegel, Angelika A.; Weber, Igor; Zhao, Hongxia; Merkel, Rudolf; Schleicher, Michael; Faix, Jan

    2015-01-01

    Cell migration is driven by the establishment of disparity between the cortical properties of the softer front and the more rigid rear allowing front extension and actomyosin-based rear contraction. However, how the cortical actin meshwork in the rear is generated remains elusive. Here we identify the mDia1-like formin A (ForA) from Dictyostelium discoideum that generates a subset of filaments as the basis of a resilient cortical actin sheath in the rear. Mechanical resistance of this actin compartment is accomplished by actin crosslinkers and IQGAP-related proteins, and is mandatory to withstand the increased contractile forces in response to mechanical stress by impeding unproductive blebbing in the rear, allowing efficient cell migration in two-dimensional-confined environments. Consistently, ForA supresses the formation of lateral protrusions, rapidly relocalizes to new prospective ends in repolarizing cells and is required for cortical integrity. Finally, we show that ForA utilizes the phosphoinositide gradients in polarized cells for subcellular targeting. PMID:26415699

  20. A resilient formin-derived cortical actin meshwork in the rear drives actomyosin-based motility in 2D confinement.

    PubMed

    Ramalingam, Nagendran; Franke, Christof; Jaschinski, Evelin; Winterhoff, Moritz; Lu, Yao; Brühmann, Stefan; Junemann, Alexander; Meier, Helena; Noegel, Angelika A; Weber, Igor; Zhao, Hongxia; Merkel, Rudolf; Schleicher, Michael; Faix, Jan

    2015-01-01

    Cell migration is driven by the establishment of disparity between the cortical properties of the softer front and the more rigid rear allowing front extension and actomyosin-based rear contraction. However, how the cortical actin meshwork in the rear is generated remains elusive. Here we identify the mDia1-like formin A (ForA) from Dictyostelium discoideum that generates a subset of filaments as the basis of a resilient cortical actin sheath in the rear. Mechanical resistance of this actin compartment is accomplished by actin crosslinkers and IQGAP-related proteins, and is mandatory to withstand the increased contractile forces in response to mechanical stress by impeding unproductive blebbing in the rear, allowing efficient cell migration in two-dimensional-confined environments. Consistently, ForA supresses the formation of lateral protrusions, rapidly relocalizes to new prospective ends in repolarizing cells and is required for cortical integrity. Finally, we show that ForA utilizes the phosphoinositide gradients in polarized cells for subcellular targeting. PMID:26415699

  1. Strength through structure: visualization and local assessment of the trabecular bone structure

    NASA Astrophysics Data System (ADS)

    Räth, C.; Monetti, R.; Bauer, J.; Sidorenko, I.; Müller, D.; Matsuura, M.; Lochmüller, E.-M.; Zysset, P.; Eckstein, F.

    2008-12-01

    The visualization and subsequent assessment of the inner human bone structures play an important role for better understanding the disease- or drug-induced changes of bone in the context of osteoporosis giving prospect for better predictions of bone strength and thus of the fracture risk of osteoporotic patients. In this work, we show how the complex trabecular bone structure can be visualized using μCT imaging techniques at an isotropic resolution of 26 μm. We quantify these structures by calculating global and local topological and morphological measures, namely Minkowski functionals (MFs) and utilizing the (an-)isotropic scaling index method (SIM) and by deriving suitable texture measures based on MF and SIM. Using a sample of 151 specimens taken from human vertebrae in vitro, we correlate the texture measures with the mechanically measured maximum compressive strength (MCS), which quantifies the strength of the bone probe, by using Pearson's correlation coefficient. The structure parameters derived from the local measures yield good correlations with the bone strength as measured in mechanical tests. We investigate whether the performance of the texture measures depends on the MCS value by selecting different subsamples according to MCS. Considering the whole sample the results for the newly defined parameters are better than those obtained for the standard global histomorphometric parameters except for bone volume/total volume (BV/TV). If a subsample consisting only of weak bones is analysed, the local structural analysis leads to similar and even better correlations with MCS as compared to BV/TV. Thus, the MF and SIM yield additional information about the stability of the bone especially in the case of weak bones, which corroborates the hypothesis that the bone structure (and not only its mineral mass) constitutes an important component of bone stability.

  2. Experimental observation of ultrasound fast and slow waves through three-dimensional printed trabecular bone phantoms.

    PubMed

    Mézière, F; Juskova, P; Woittequand, J; Muller, M; Bossy, E; Boistel, Renaud; Malaquin, L; Derode, A

    2016-02-01

    In this paper, ultrasound measurements of 1:1 scale three-dimensional (3D) printed trabecular bone phantoms are reported. The micro-structure of a trabecular horse bone sample was obtained via synchrotron x-ray microtomography, converted to a 3D binary data set, and successfully 3D-printed at scale 1:1. Ultrasound through-transmission experiments were also performed through a highly anisotropic version of this structure, obtained by elongating the digitized structure prior to 3D printing. As in real anisotropic trabecular bone, both the fast and slow waves were observed. This illustrates the potential of stereolithography and the relevance of such bone phantoms for the study of ultrasound propagation in bone. PMID:26936578

  3. Inhibition of cortical and trabecular bone formation in the long bones of immobilized monkeys

    NASA Technical Reports Server (NTRS)

    Wronski, T. J.; Morey, E. R.

    1983-01-01

    Tetracycline derivatives are administered on three separate occasions to label the sites of bone formation. Determinations are made of the tetracycline-labeling frequency and mineral apposition rate of osteons and trabecular bone surfaces in the humerus and femur. The inhibition of bone formation induced by immobilization is found to be more pronounced in trabecular bone. The immobilized monkeys exhibit a moderate, but statistically nonsignificant, reduction in the percentage of osteons forming bone. Conversely, the dramatic decline in the percentage of trabecular surfaces undergoing bone formation in the monkeys is found to be highly significant. The diminished rate of mineral apposition in osteons is seen as suggesting that osteoblastic activity is impaired in cortical bone during immobilization.

  4. Ultrasound propagation in trabecular bone: a numerical study of the influence of microcracks.

    PubMed

    Callé, Samuel; Moreschi, Hélène; Renaud, Guillaume; Defontaine, Marielle

    2014-07-01

    The accumulation of microdamage in trabecular bone tissue is suspected of being a predictive indicator of osteoporosis diagnosis. To quantify this microdamage, the Dynamic AcoustoElastic Testing (DAET) method measures the Time Of Flight (TOF) and amplitude variations of transmitted ultrasound (US) pulses, while the bone sample is submitted to a low frequency sinusoidal hydrostatic pressure (opening/closing of microcracks). However, DAET is both sensitive to viscoelastic properties changes and microcracks density. To verify the microcracks density contribution on DAET results, a numerical approach is proposed. Multliple configurations of microdamaged trabecular bone-tissue-like mesh have been simulated. A 2D pseudo-spectral time domain numerical model was then developed to simulate linear wave propagation in heterogeneous solids. The influence of the microcracks number and orientation on the US TOF was particularly investigated. Results are discussed and compared with experimental data obtained from DAET measurements in trabecular bone samples. PMID:24041497

  5. Hierarchical analysis and multi-scale modelling of rat cortical and trabecular bone

    PubMed Central

    Oftadeh, Ramin; Entezari, Vahid; Spörri, Guy; Villa-Camacho, Juan C.; Krigbaum, Henry; Strawich, Elsa; Graham, Lila; Rey, Christian; Chiu, Hank; Müller, Ralph; Hashemi, Hamid Nayeb; Vaziri, Ashkan; Nazarian, Ara

    2015-01-01

    The aim of this study was to explore the hierarchical arrangement of structural properties in cortical and trabecular bone and to determine a mathematical model that accurately predicts the tissue's mechanical properties as a function of these indices. By using a variety of analytical techniques, we were able to characterize the structural and compositional properties of cortical and trabecular bones, as well as to determine the suitable mathematical model to predict the tissue's mechanical properties using a continuum micromechanics approach. Our hierarchical analysis demonstrated that the differences between cortical and trabecular bone reside mainly at the micro- and ultrastructural levels. By gaining a better appreciation of the similarities and differences between the two bone types, we would be able to provide a better assessment and understanding of their individual roles, as well as their contribution to bone health overall. PMID:25808343

  6. Morphological models of trabecular bone suitable for high-porosity regions and vertebrae.

    PubMed

    Rammohan, Abhishek Vishwanath; Tan, Vincent Beng Chye

    2016-10-01

    The complex microarchitecture of trabecular bone makes it difficult to perform computational analyses on the real structure. Researchers have often resorted to using morphological idealizations employing simplified geometries. One such idealized structure, based on the gyroid, was found to mimic trabecular bone well. However, structures generated using the basic gyroid equation manifested discontinuities at high porosities. Another disadvantage of the gyroid is that it cannot model vertebral trabecular bone, which generally resembles cubic cells. To address these two shortcomings, we describe: (i) a modified structure based on the skeletal gyroid, which remains connected even at extremely high porosities, (ii) a cubic grid-like structure, based on the primitive minimal surface, for studying vertebrae. PMID:26892403

  7. Distributional Variations in Trabecular Architecture of the Mandibular Bone: An In Vivo Micro-CT Analysis in Rats

    PubMed Central

    Liu, Zhongshuang; Yan, Chengwei; kang, Chen; Zhang, Bin; Li, Ying

    2015-01-01

    Purpose To evaluate the effect of trabecular thickness and trabecular separation on modulating the trabecular architecture of the mandibular bone in ovariectomized rats. Materials and Methods Fourteen 12-week-old adult female Wistar rats were divided into an ovariectomy group (OVX) and a sham-ovariectomy group (sham). Five months after the surgery, the mandibles from 14 rats (seven OVX and seven sham) were analyzed by micro-CT. Images of inter-radicular alveolar bone of the mandibular first molars underwent three-dimensional reconstruction and were analyzed. Results Compared to the sham group, trabecular thickness in OVX alveolar bone decreased by 27% (P = 0.012), but trabecular separation in OVX alveolar bone increased by 59% (P = 0.005). A thickness and separation map showed that trabeculae of less than 100μm increased by 46%, whereas trabeculae of more than 200μm decreased by more than 40% in the OVX group compared to those in the sham group. Furthermore, the OVX separation of those trabecular of more than 200μm was 65% higher compared to the sham group. Bone mineral density (P = 0.028) and bone volume fraction (p = 0.001) were also significantly decreased in the OVX group compared to the sham group. Conclusions Ovariectomy-induced bone loss in mandibular bone may be related to the distributional variations in trabecular thickness and separation which profoundly impact the modulation of the trabecular architecture. PMID:25625431

  8. Apparent- and Tissue-Level Yield Behaviors of L4 Vertebral Trabecular Bone and Their Associations with Microarchitectures.

    PubMed

    Gong, He; Wang, Lizhen; Fan, Yubo; Zhang, Ming; Qin, Ling

    2016-04-01

    The precise quantification of vertebral trabecular bone strength and the associations between the microarchitecture and nonlinear mechanics of trabecular bone under various loading conditions may provide insights into trabecular bone quality and trabecular strength prediction based on microarchitectures. In this research, 44 cubic L4 vertebral trabecular bone specimens (5 × 5 × 5 mm(3)) were selected from six male Chinese donors aged 62-70 years. For each vertebral trabecular cube, micro-computed tomography image-based nonlinear micro-finite element analyzes were conducted under compressive and tensile loadings along two orthogonal directions. A bilinear tissue constitutive model was used to describe the nonlinearity of bone tissue material. In each analysis, apparent Young's modulus and initial apparent yield point were determined; the average tissue von Mises stress at the apparent yield point was also calculated, and the amount of tissue elements yielded was obtained. Principal components (PCs) analysis revealed three independent components of the microarchitectural parameters of the vertebral trabecular bones; these three PCs can account for 80.744% of the total variability of trabecular microarchitectures; the first PC (PC1) included bone volume fraction, connectivity density and trabecular number; the second PC (PC2) comprised structure model index and degree of anisotropy; and the third PC (PC3) represented trabecular thickness and age. Multivariate linear regression analysis showed that the PCs were strongly predictive of the apparent- and tissue-level mechanical parameters of the vertebral trabecular bone. To gain further insights into the mechanical properties of trabecular bone, we divided the six vertebral bodies into two groups based on the microarchitectural parameters: high-quality group and low-quality group. We then compared the differences in the mechanical parameters between tension and compression, as well as along longitudinal and

  9. Computer modelling of the structure of the cortical and trabecular bone tissue

    NASA Astrophysics Data System (ADS)

    Kolmakova, Tatyana

    2015-10-01

    The paper presents computer models of the structure of cortical and trabecular bone tissue. The model fragment of the cortical bone tissue was built based on a real image of the natural bone microstructure. The osteons and Haversian canals were directly taken into consideration. The Volkmann's canals and the orientation of the collagenous mineral fibers in the osteons and the surrounding matrix were considered indirectly. The model fragment of the trabecular bone tissue was built based on the data of structure of the real bone fragments, taking into account the orientation of the trabecules of bones, their length and thickness.

  10. Osteoblast-specific Notch2 inactivation causes increased trabecular bone mass at specific sites of the appendicular skeleton.

    PubMed

    Yorgan, Timur; Vollersen, Nele; Riedel, Christoph; Jeschke, Anke; Peters, Stephanie; Busse, Bjoern; Amling, Michael; Schinke, Thorsten

    2016-06-01

    Notch signaling is a key pathway controlling various cell fate decisions during embryogenesis and adult life. It is activated by binding of specific ligands to four different Notch receptors that are subsequently cleaved by presenilins to release an intracellular domain that enters the nucleus and activates specific transcription factors. While the skeletal analysis of various mouse models with activated or inactivated Notch signaling has demonstrated a general impact of this pathway on bone remodeling, the more recent identification of NOTCH2 mutations in individuals with Hajdu-Cheney syndrome (HCS) has highlighted its human relevance. Since HCS is primarily characterized by skeletal defects, these latter findings led us to analyze the specific role of Notch2 in skeletal remodeling. After observing Notch2 expression in osteoblasts and osteoclasts, we utilized Runx2-Cre and Lyz2-Cre mice to inactivate Notch2 in cells of the osteoblast or osteoclast lineage, respectively. Whereas Notch2(fl/fl)/Lyz2-Cre mice did not display significant alterations of skeletal growth, bone mass or remodeling, Notch2(fl/fl)/Runx2-Cre mice progressively developed skeletal abnormalities in long bones. More specifically, these mice displayed a striking increase of trabecular bone mass in the proximal femur and the distal tibia at 6 and 12months of age. Whereas undecalcified sectioning of the respective regions did not reveal impaired osteocyte differentiation as a potential trigger for the observed phenotype, ex vivo experiments with bone marrow cells identified an increased osteogenic capacity of Notch2(fl/fl)/Runx2-Cre cultures. Collectively, our findings demonstrate that Notch2 physiologically regulates bone remodeling by inhibiting trabecular bone formation in the appendicular skeleton. Understanding the underlying mechanisms may help to improve diagnosis and therapy of HCS. PMID:27102824

  11. A new approach to quantify trabecular resorption adjacent to cemented knee arthroplasty.

    PubMed

    Mann, Kenneth A; Miller, Mark A; Pray, Caitlin L; Verdonschot, Nico; Janssen, Dennis

    2012-02-23

    A new micro-computed tomography (μCT) image processing approach to estimate the loss of cement-bone interlock was developed using the concept that PMMA cement flows and cures around trabeculae during the total knee arthroplasty procedure. The initial mold shape of PMMA cement was used to estimate the amount of interdigitated bone at the time of implantation and following in vivo service using enbloc human postmortem retrievals. Laboratory prepared specimens, where there would be no biological bone resorption, were used as controls to validate the approach and estimate errors. The image processing technique consisted of identifying bone and cement from the μCT scan set, dilation of the cement to identify the cement cavity space, and Boolean operations to identify the different components of the interdigitated cement-bone regions. For laboratory prepared specimens, there were small errors in the estimated resorbed bone volume fraction (reBVfr=0.11 ± 0.09) and loss in contact area fraction (CAfr=0.06 ± 0.15). These values would be zero if there were no error in the method. For the postmortem specimens, the resorbed volume fraction (reBVfr=0.85 ± 0.16) was large, meaning that only 15% of the cement mold shape was still filled with bone. The loss of contact area fraction (CAfr=0.84 ± 0.17) was similarly large. This new approach provides a convenient method to visualize and quantify trabecular bone loss from interdigitated regions from postmortem retrievals. The technique also illustrates for the first time that there are dramatic changes in how bone is fixed to cement following in vivo service. PMID:22227315

  12. Expanding the Description of Spaceflight Effects beyond Bone Mineral Density [BMD]: Trabecular Bone Score [TBS] in ISS Astronauts

    NASA Technical Reports Server (NTRS)

    Sibonga, J. D.; Spector, E. R.; King, L. J.; Evans, H. J.; Smith, S. A.

    2014-01-01

    Dual-energy x-ray absorptiometry [DXA] is the widely-applied bone densitometry method used to diagnose osteoporosis in a terrestrial population known to be at risk for age-related bone loss. This medical test, which measures areal bone mineral density [aBMD] of clinically-relevant skeletal sites (e.g., hip and spine), helps the clinician to identify which persons, among postmenopausal women and men older than 50 years, are at high risk for low trauma or fragility fractures and might require an intervention. The most recognized osteoporotic fragility fracture is the vertebral compression fracture which can lead to kyphosis or hunched backs typically seen in the elderly. DXA measurement of BMD however is recognized to be insufficient as a sole index for assessing fracture risk. DXA's limitation may be related to its inability to monitor changes in structural parameters, such as trabecular vs. cortical bone volumes, bone geometry or trabecular microarchitecture. Hence, in order to understand risks to human health and performance due to space exposure, NASA needs to expand its measurements of bone to include other contributors to skeletal integrity. To this aim, the Bone and Mineral Lab conducted a pilot study for a novel measurement of bone microarchitecture that can be obtained by retrospective analysis of DXA scans. Trabecular Bone Score (TBS) assesses changes to trabecular microarchitecture by measuring the grey color "texture" information extracted from DXA images of the lumbar spine. An analysis of TBS in 51 ISS astronauts was conducted to assess if TBS could detect 1) an effect of spaceflight and 2) a response to countermeasures independent of DXA BMD. In addition, changes in trunk body lean tissue mass and in trunk body fat tissue mass were also evaluated to explore an association between body composition, as impacted by ARED exercise, and bone microarchitecture. The pilot analysis of 51 astronaut scans of the lumbar spine suggests that, following an ISS

  13. Effect of trabecular bone loss on cortical strain rate during impact in an in vitro model of avian femur

    PubMed Central

    Reich, Tal; Gefen, Amit

    2006-01-01

    Background Osteoporotic hip fractures occur due to loss of cortical and trabecular bone mass and consequent degradation in whole bone strength. The direct cause of most fractures is a fall, and hence, characterizing the mechanical behavior of a whole osteopenic bone under impact is important. However, very little is known about the mechanical interactions between cortical and trabecular bone during impact, and it is specifically unclear to what extent epiphyseal trabecular bone contributes to impact resistance of whole bones. We hypothesized that trabecular bone serves as a structural support to the cortex during impact, and hence, loss of a critical mass of trabecular bone reduces internal constraining of the cortex, and, thereby, decreases the impact tolerance of the whole bone. Methods To test this hypothesis, we conducted cortical strain rate measurements in adult chicken's proximal femora subjected to a Charpy impact test, after removing different trabecular bone core masses to simulate different osteopenic severities. Results We found that removal of core trabecular bone decreased by ~10-fold the cortical strain rate at the side opposite to impact (p < 0.01), i.e. from 359,815 ± 1799 μm/m per second (mean ± standard error) for an intact (control) specimen down to 35,997 ± 180 μm/m per second where 67% of the total trabecular bone mass (~0.7 grams in adult chicken) were removed. After normalizing the strain rate by the initial weight of bone specimens, a sigmoid relation emerged between normalized strain rate and removed mass of trabecular bone, showing very little effect on the cortex strain rate if below 10% of the trabecular mass is removed, but most of the effect was already apparent for less than 30% trabecular bone loss. An analytical model of the experiments supported this behavior. Conclusion We conclude that in our in vitro avian model, loss of over 10% of core trabecular bone substantially altered the deformation response of whole bone to impact

  14. In vivo study on hydroxyapatite scaffolds with trabecular architecture for bone repair.

    PubMed

    Appleford, Mark R; Oh, Sunho; Oh, Namsik; Ong, Joo L

    2009-06-15

    The objective of this research was to investigate the bone formation and angio-conductive potential of hydroxyapatite (HA) scaffolds closely matched to trabecular bone in a canine segmental defect after 3 and 12 weeks post implantation. Histomorphometric comparisons were made between naturally forming trabecular bone (control) and defects implanted with scaffolds fabricated with micro-size (M-HA) and nano-size HA (N-HA) ceramic surfaces. Scaffold architecture was similar to trabecular bone formed in control defects at 3 weeks. No significant differences were identified between the two HA scaffolds; however, significant bone in-growth was observed by 12 weeks with 43.9 +/- 4.1% and 50.4 +/- 8.8% of the cross-sectional area filled with mineralized bone in M-HA and N-HA scaffolds, respectively. Partially organized, lamellar collagen fibrils were identified by birefringence under cross-polarized light at both 3 and 12 weeks post implantation. Substantial blood vessel infiltration was identified in the scaffolds and compared with the distribution and diameter of vessels in the surrounding cortical bone. Vessels were less numerous but significantly larger than native cortical Haversian and Volkmann canals reflecting the scaffold architecture where open spaces allowed interconnected channels of bone to form. This study demonstrated the potential of trabecular bone modeled, highly porous and interconnected, HA scaffolds for regenerative orthopedics. PMID:18478555

  15. Boron and Fish Oil Have Different Beneficial Effects on Strength and Trabecular Microarchitecture of Bone

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recent findings suggest that boron and long-chain omega-3 polyunsaturated fatty acids have similar beneficial effects on bone strength and trabecular microarchitecture. Thus, an experiment was performed to confirm the beneficial effects and to determine whether dietary fatty acid composition would a...

  16. Relationship of Circulating Total Homocysteine and C-Reactive Protein to Trabecular Bone in Postmenopausal Women

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Homocysteine (Hcy) and C-reactive protein (CRP) are novel risk factors for osteoporosis. The purpose of this analysis was to determine the relationship of Hcy and CRP to volumetric trabecular bone, but also to assess their relationship to areal composite bone in healthy postmenopausal women (N=184)....

  17. Can Deterministic Mechanical Size Effects Contribute to Fracture and Microdamage Accumulation in Trabecular Bone?

    PubMed Central

    Siegmund, Thomas; Allen, Matthew R.; Burr, David B.

    2010-01-01

    Failure of bone under monotonic and cyclic loading is related to the bone mineral density, the quality of the bone matrix and the evolution of microcracks. The theory of linear elastic fracture mechanics has commonly been applied to describe fracture in bone. Evidence is presented that bone failure can be described through a non-linear theory of fracture. Thereby, deterministic size effects are introduced. Concepts of a non-linear theory are applied to discern how the interaction among bone matrix constituents (collagen and mineral), microcrack characteristics, and trabecular architecture can create distinctively differences in the fracture resistance at the bone tissue level. The nonlinear model is applied to interpret pre-clinical data concerning the effects of anti-osteoporotic agents on bone properties. The results show that bisphosphonate (BP) treatments that suppress bone remodeling will change trabecular bone in ways such that the size of the failure process zone relative to the trabecular thickness is reduced. Selective estrogen receptor modulators (SERMs) that suppress bone remodeling will change trabecular bone in ways such that the size of the failure process zone relative to the trabecular thickness is increased. The consequences of these changes are reflected in bone mechanical response and predictions are consistent with experimental observations in the animal model which show that BP treatment is associated with more brittle fracture and microcracks without altering the average length of the cracks, whereas SERM treatments lead to a more ductile fracture and mainly increase crack length with a smaller increase in microcrack density. The model suggests that BPs may be more effective in cases in which bone mass is very low, whereas SERMS may be more effective when milder osteoporotic symptoms are present. PMID:20398678

  18. Deterioration of trabecular plate-rod and cortical microarchitecture and reduced bone stiffness at distal radius and tibia in postmenopausal women with vertebral fractures.

    PubMed

    Wang, Ji; Stein, Emily M; Zhou, Bin; Nishiyama, Kyle K; Yu, Y Eric; Shane, Elizabeth; Guo, X Edward

    2016-07-01

    Postmenopausal women with vertebral fractures have abnormal bone microarchitecture at the distal radius and tibia by HR-pQCT, independent of areal BMD. However, whether trabecular plate and rod microarchitecture is altered in women with vertebral fractures is unknown. This study aims to characterize the abnormalities of trabecular plate and rod microarchitecture, cortex, and bone stiffness in postmenopausal women with vertebral fractures. HR-pQCT images of distal radius and tibia were acquired from 45 women with vertebral fractures and 45 control subjects without fractures. Trabecular and cortical compartments were separated by an automatic segmentation algorithm and subjected to individual trabecula segmentation (ITS) analysis for measuring trabecular plate and rod morphology and cortical bone evaluation for measuring cortical thickness and porosity, respectively. Whole bone and trabecular bone stiffness were estimated by finite element analysis. Fracture and control subjects did not differ according to age, race, body mass index, osteoporosis risk factors, or medication use. Women with vertebral fractures had thinner cortices, and larger trabecular area compared to the control group. By ITS analysis, fracture subjects had fewer trabecular plates, less axially aligned trabeculae and less trabecular connectivity at both the radius and the tibia. Fewer trabecular rods were observed at the radius. Whole bone stiffness and trabecular bone stiffness were 18% and 22% lower in women with vertebral fractures at the radius, and 19% and 16% lower at the tibia, compared with controls. The estimated failure load of the radius and tibia were also reduced in the fracture subjects by 13% and 14%, respectively. In summary, postmenopausal women with vertebral fractures had both trabecular and cortical microstructural deterioration at the peripheral skeleton, with a preferential loss of trabecular plates and cortical thinning. These microstructural deficits translated into lower

  19. Trabecular and cortical bone deficits are present in children and adolescents with cystic fibrosis.

    PubMed

    Kelly, Andrea; Schall, Joan; Stallings, Virginia A; Zemel, Babette S

    2016-09-01

    Osteopenia and increased fracture rates are well-recognized in adults with CF, but neither the specific contributions of cortical and trabecular bone deficits to bone fragility nor their presence in youth with CF are well-characterized. This study sought to characterize cortical and trabecular volumetric bone mineral density (vBMD), geometry, and biomechanical competence in children with CF and determine their relationship to growth, body composition, and disease severity. Peripheral quantitative computerized tomography (pQCT) measures of total, cortical, and trabecular vBMD, cortical, muscle, and fat cross-sectional areas (CSA), periosteal and endosteal circumferences, and the polar unweighted section modulus (Zp) of the tibia were converted to age- and tibial length-adjusted Z-scores in 97 CF and 199 healthy children (aged 8-21y). Effects of body composition and pulmonary function (forced expiratory volume in 1s, FEV1) upon pQCT outcomes were determined using linear regression. Children with CF (FEV1%-predicted: 84.4+19.7) had lower weight-, height-, BMI-, and whole body lean mass (LBM)-Z and tibial length. Females with CF had lower (p<0.01) total and trabecular vBMD; cortical, muscle, and fat CSA; Zp and periosteal circumference than females in the healthy reference group. These bone differences persisted after adjustment for BMI-Z and to a great extent following adjustment for muscle CSA. Males with CF had lower (p<0.01) cortical, muscle, and fat CSA and their trabecular vBMD deficit approached significance (p=0.069). Deficits were attenuated by adjustment for BMI-Z and to a greater extent adjustment for muscle CSA-Z. The relationship between FEV1%-predicted and pQCT outcomes persisted only in males following adjustment for age and BMI-Z. The CF cohort had lower tibial muscle CSA than expected for their LBM. In this relatively healthy, young CF cohort, deficits in trabecular and multiple cortical bone parameters were present. In females, deficits were greater

  20. Structure Model Index Does Not Measure Rods and Plates in Trabecular Bone

    PubMed Central

    Salmon, Phil L.; Ohlsson, Claes; Shefelbine, Sandra J.; Doube, Michael

    2015-01-01

    Structure model index (SMI) is widely used to measure rods and plates in trabecular bone. It exploits the change in surface curvature that occurs as a structure varies from spherical (SMI = 4), to cylindrical (SMI = 3) to planar (SMI = 0). The most important assumption underlying SMI is that the entire bone surface is convex and that the curvature differential is positive at all points on the surface. The intricate connections within the trabecular continuum suggest that a high proportion of the surface could be concave, violating the assumption of convexity and producing regions of negative differential. We implemented SMI in the BoneJ plugin and included the ability to measure the amounts of surface that increased or decreased in area after surface mesh dilation, and the ability to visualize concave and convex regions. We measured SMI and its positive (SMI+) and negative (SMI−) components, bone volume fraction (BV/TV), the fraction of the surface that is concave (CF), and mean ellipsoid factor (EF) in trabecular bone using 38 X-ray microtomography (XMT) images from a rat ovariectomy model of sex steroid rescue of bone loss, and 169 XMT images from a broad selection of 87 species’ femora (mammals, birds, and a crocodile). We simulated bone resorption by eroding an image of elephant trabeculae and recording SMI and BV/TV at each erosion step. Up to 70%, and rarely <20%, of the trabecular surface is concave (CF 0.155–0.700). SMI is unavoidably influenced by aberrations induced by SMI−, which is strongly correlated with BV/TV and CF. The plate-to-rod transition in bone loss is an erroneous observation resulting from the close and artifactual relationship between SMI and BV/TV. SMI cannot discern between the distinctive trabecular geometries typical of mammalian and avian bone, whereas EF clearly detects birds’ more plate-like trabeculae. EF is free from confounding relationships with BV/TV and CF. SMI results reported in the literature should be

  1. Structure Model Index Does Not Measure Rods and Plates in Trabecular Bone.

    PubMed

    Salmon, Phil L; Ohlsson, Claes; Shefelbine, Sandra J; Doube, Michael

    2015-01-01

    Structure model index (SMI) is widely used to measure rods and plates in trabecular bone. It exploits the change in surface curvature that occurs as a structure varies from spherical (SMI = 4), to cylindrical (SMI = 3) to planar (SMI = 0). The most important assumption underlying SMI is that the entire bone surface is convex and that the curvature differential is positive at all points on the surface. The intricate connections within the trabecular continuum suggest that a high proportion of the surface could be concave, violating the assumption of convexity and producing regions of negative differential. We implemented SMI in the BoneJ plugin and included the ability to measure the amounts of surface that increased or decreased in area after surface mesh dilation, and the ability to visualize concave and convex regions. We measured SMI and its positive (SMI(+)) and negative (SMI(-)) components, bone volume fraction (BV/TV), the fraction of the surface that is concave (CF), and mean ellipsoid factor (EF) in trabecular bone using 38 X-ray microtomography (XMT) images from a rat ovariectomy model of sex steroid rescue of bone loss, and 169 XMT images from a broad selection of 87 species' femora (mammals, birds, and a crocodile). We simulated bone resorption by eroding an image of elephant trabecule and recording SMI and BV/TV at each erosion step. Up to 70%, and rarely <20%, of the trabecular surface is concave (CF 0.155-0.700). SMI is unavoidably influenced by aberrations induced by SMI(-), which is strongly correlated with BV/TV and CF. The plate-to-rod transition in bone loss is an erroneous observation resulting from the close and artifactual relationship between SMI and BV/TV. SMI cannot discern between the distinctive trabecular geometries typical of mammalian and avian bone, whereas EF clearly detects birds' more plate-like trabecule. EF is free from confounding relationships with BV/TV and CF. SMI results reported in the literature should be

  2. Development of a Model of Elevated Intraocular Pressure in Rats by Gene Transfer of Bone Morphogenetic Protein 2

    PubMed Central

    Buie, LaKisha K.; Karim, Md.Zahidul; Smith, Matthew H.; Borrás, Teresa

    2013-01-01

    Purpose. To determine whether inducing calcification in the trabecular meshwork results in elevated IOP in living rats. To use this property to create an elevated IOP animal model by gene transfer of bone morphogenetic protein 2 (BMP2). Methods. Calcification was assessed by alizarin red staining in primary human trabecular meshwork (HTM) cells and alkaline phosphatase (ALP) activity in the angle tissue. Brown Norway (BN) and Wistar rats were intracamerally injected with Ad5BMP2 (OS) and control Ad5.CMV-Null (OD). IOPs were taken twice a week and expressed as mean integral pressures. Morphology was assessed on fixed, paraffin-embedded anterior segments. Retinal ganglion cells (RGCs) were quantified on retrograde and Brn-3a–labeled flat mounts using MetaMorph software. Results. BMP2-treated cells displayed marked increase in calcification. Trabecular meshwork tissue showed moderate ALP activity at 13 days postinjection. Fifty-four of 55 BN and 15 of 19 Wistar rats displayed significantly elevated IOP. In a representative 29-day experiment, the integral IOP difference between treated and control eyes was 367.7 ± 83 mm Hg-days (P = 0.007). Morphological evaluation revealed a well-organized trabecular meshwork tissue, exhibiting denser matrix in the treated eyes. The Ad5BMP2-treated eye showed 34.4% ± 4.8% (P = 0.00002) loss of peripheral RGC over controls. Conclusions. Gene transfer of the calcification inducer BMP2 gene to the trabecular meshwork induces elevated IOP in living rats without altering the basic structure of the tissue. This strategy generates an elevated IOP model in rats that would be useful for evaluation of glaucoma drugs targeting the outflow pathway. PMID:23821199

  3. Total Water, Phosphorus Relaxation and Inter-Atomic Organic to Inorganic Interface Are New Determinants of Trabecular Bone Integrity

    PubMed Central

    Rai, Ratan Kumar; Barbhuyan, Tarun; Singh, Chandan; Mittal, Monika; Khan, Mohd. Parvez; Sinha, Neeraj; Chattopadhyay, Naibedya

    2013-01-01

    Bone is the living composite biomaterial having unique structural property. Presently, there is a considerable gap in our understanding of bone structure and composition in the native state, particularly with respect to the trabecular bone, which is metabolically more active than cortical bones, and is readily lost in post-menopausal osteoporosis. We used solid-state nuclear magnetic resonance (NMR) to compare trabecular bone structure and composition in the native state between normal, bone loss and bone restoration conditions in rat. Trabecular osteopenia was induced by lactation as well as prolonged estrogen deficiency (bilateral ovariectomy, Ovx). Ovx rats with established osteopenia were administered with PTH (parathyroid hormone, trabecular restoration group), and restoration was allowed to become comparable to sham Ovx (control) group using bone mineral density (BMD) and µCT determinants. We used a technique combining 1H NMR spectroscopy with 31P and 13C to measure various NMR parameters described below. Our results revealed that trabecular bones had diminished total water content, inorganic phosphorus NMR relaxation time (T1) and space between the collagen and inorganic phosphorus in the osteopenic groups compared to control, and these changes were significantly reversed in the bone restoration group. Remarkably, bound water was decreased in both osteopenic and bone restoration groups compared to control. Total water and T1 correlated strongly with trabecular bone density, volume, thickness, connectivity, spacing and resistance to compression. Bound water did not correlate with any of the microarchitectural and compression parameters. We conclude that total water, T1 and atomic space between the crystal and organic surface are altered in the trabecular bones of osteopenic rats, and PTH reverses these parameters. Furthermore, from these data, it appears that total water and T1 could serve as trabecular surrogates of micro-architecture and compression

  4. Case report: Trabecular juvenile ossifying fibroma presenting as a sellar mass.

    PubMed

    Neidert, Marian Christoph; Woernle, Christoph Michael; Burkhardt, Jan-Karl; Reimann, Regina; Hug, Eugen; Bernays, René-Ludwig

    2013-11-01

    A 15-year-old girl presented with left occulomotor nerve palsy and was found to have a space occupying lesion of the sellar region with invasion of the left cavernous sinus. A transsphenoidal approach lead to subtotal removal of a solid tumor with some remnants in the cavernous sinus and revealed the diagnosis of trabecular juvenile ossifying fibroma (JOF). A repeat magnetic resonance imaging was obtained within 1 month that showed intrasellar recurrence and growing tumor in the cavernous sinus. Therefore, a combined transsphenoidal and transcranial approach was performed to more aggressively remove the tumor. Subsequently, adjuvant proton radiotherapy was performed. JOF of the trabecular type is a rare fibro-osseous lesion of the craniofacial skeleton almost exclusively occurring in the maxilla or the mandible. To our knowledge, this is the first case of this tumor entity presenting as a sellar mass. PMID:22777925

  5. The relationship between ultrasonic backscatter and trabecular anisotropic microstructure in cancellous bone

    NASA Astrophysics Data System (ADS)

    Liu, Chengcheng; Ta, Dean; Fujita, Fuminori; Hachiken, Takuma; Matsukawa, Mami; Mizuno, Katsunori; Wang, Weiqi

    2014-02-01

    To investigate the relationship between ultrasonic backscatter and trabecular microstructure, ultrasonic backscatter measurements were performed on cylindrical bovine cancellous bone samples in vitro. The backscatter signals from different specimen angles were obtained by rotating the specimen at various central frequencies. The backscatter signal varied a lot as the specimen angle changed. The main trabecular alignment (MTA) orientation was estimated by the maximum of signal energy and integrated reflection coefficient, or the minor axis of fitted ellipse for apparent integrated backscatter and the backscattered spectrum centroid frequency versus specimen angle. The degree of anisotropy (DA) was estimated by the eccentricity of the fitted ellipse with highly significant correlations. The MTA orientation and DA value estimation method proposed in this study is useful for ultrasonic cancellous bone assessment.

  6. Diet-induced obesity alters bone remodeling leading to decreased femoral trabecular bone mass in mice.

    PubMed

    Cao, Jay J; Sun, Li; Gao, Hongwei

    2010-03-01

    Obesity-derived body mass may be detrimental to bone health through not well-defined mechanisms. In this study we determined changes in bone structure and serum cytokines related to bone metabolism in diet-induced obese mice. Mice fed a high-fat diet (HFD) had higher serum tartrate-resistant acid phosphatase (TRAP) and leptin but lower osteocalcin concentrations than those fed the normal-fat diet. The HFD increased multinucleated TRAP-positive osteoclasts in bone marrow compared to the control diet. Despite being much heavier, mice fed the HFD had lower femoral bone volume, trabecular number, and connectivity density and higher trabecular separation than mice on the control diet. These findings suggest that obesity induced by a HFD increases bone resorption that may blunt any positive effects of increased body weight on bone. PMID:20392249

  7. The Use of Trabecular Metal Cones in Complex Primary and Revision Total Knee Arthroplasty.

    PubMed

    Brown, Nicholas M; Bell, Joshua A; Jung, Edward K; Sporer, Scott M; Paprosky, Wayne G; Levine, Brett R

    2015-09-01

    Trabecular metal cones are one option for treating osseous defects during TKA. A total of 83 consecutive TKAs utilizing cones with an average of 40 months follow-up were reviewed. There were 24 males and 59 females, with an average age of 69 years old. Four were complex primary and 79 were revision procedures. Of 83 patients, 10 (12%) required repeat revision surgery (8 infections, one periprosthetic fracture, one aseptic loosening) and overall, 37 of 83 patients (45%) experienced at least one complication. Of 73 unrevised knees, 72 (99%) demonstrated radiographic evidence of osseointegration. Despite a high complication rate in this population, trabecular metal cones represent an attractive option for managing bone loss in complex primary and revision TKA with a high rate of osseointegration. PMID:26100475

  8. Trabecular bone class mapping across resolutions: translating methods from HR-pQCT to clinical CT

    NASA Astrophysics Data System (ADS)

    Valentinitsch, Alexander; Fischer, Lukas; Patsch, Janina M.; Bauer, Jan; Kainberger, Franz; Langs, Georg; DiFranco, Matthew

    2015-03-01

    Quantitative assessment of 3D bone microarchitecture in high-resolution peripheral quantitative computed tomography (HR-pQCT) has shown promise in fracture risk assessment and biomechanics, but is limited to the distal radius and tibia. Trabecular microarchitecture classes (TMACs), based on voxel-wise clustering texture and structure tensor features in HRpQCT, is extended in this paper to quantify trabecular bone classes in clinical multi-detector CT (MDCT) images. Our comparison of TMACs in 12 cadaver radii imaged using both HRpQCT and MDCT yields a mean Dice score of up to 0.717+/-0.40 and visually concordant bone quality maps. Further work to develop clinically viable bone quantitative imaging using HR-pQCT validation could have a significant impact on overall bone health assessment.

  9. Metrology applied to ultrasound characterization of trabecular bones using the AIB parameter

    NASA Astrophysics Data System (ADS)

    Braz, D. S.; Silva, C. E.; Alvarenga, A. V.; Junior, D. S.; Costa-Félix, R. P. B.

    2016-07-01

    Apparent Integrated Backscattering (AIB) presents correlation between Apparent Backscatter Transfer Function and the transducer bandwidth. Replicas of trabecular bones (cubes of 20 mm side length) created by 3D printing technique were characterized using AIB with a 2.25 MHz center frequency transducer. A mechanical scanning system was used to acquire multiple backscatter signals. An uncertainty model in measurement was proposed based on the Guide to the Expression of Uncertainty in Measurement. Initial AIB results are not metrologically reliable, presenting high measurement uncertainties (sample: 5_0.2032/AIB: -15.1 dB ± 13.9 dB). It is noteworthy that the uncertainty model proposed contributes as unprecedented way for metrological assessment of trabecular bone characterization using AIB.

  10. A signature dissimilarity measure for trabecular bone texture in knee radiographs

    SciTech Connect

    Woloszynski, T.; Podsiadlo, P.; Stachowiak, G. W.; Kurzynski, M.

    2010-05-15

    Purpose: The purpose of this study is to develop a dissimilarity measure for the classification of trabecular bone (TB) texture in knee radiographs. Problems associated with the traditional extraction and selection of texture features and with the invariance to imaging conditions such as image size, anisotropy, noise, blur, exposure, magnification, and projection angle were addressed. Methods: In the method developed, called a signature dissimilarity measure (SDM), a sum of earth mover's distances calculated for roughness and orientation signatures is used to quantify dissimilarities between textures. Scale-space theory was used to ensure scale and rotation invariance. The effects of image size, anisotropy, noise, and blur on the SDM developed were studied using computer generated fractal texture images. The invariance of the measure to image exposure, magnification, and projection angle was studied using x-ray images of human tibia head. For the studies, Mann-Whitney tests with significance level of 0.01 were used. A comparison study between the performances of a SDM based classification system and other two systems in the classification of Brodatz textures and the detection of knee osteoarthritis (OA) were conducted. The other systems are based on weighted neighbor distance using compound hierarchy of algorithms representing morphology (WND-CHARM) and local binary patterns (LBP). Results: Results obtained indicate that the SDM developed is invariant to image exposure (2.5-30 mA s), magnification (x1.00-x1.35), noise associated with film graininess and quantum mottle (<25%), blur generated by a sharp film screen, and image size (>64x64 pixels). However, the measure is sensitive to changes in projection angle (>5 deg.), image anisotropy (>30 deg.), and blur generated by a regular film screen. For the classification of Brodatz textures, the SDM based system produced comparable results to the LBP system. For the detection of knee OA, the SDM based system achieved 78

  11. Three-dimensional (3D) microarchitecture correlations with 2D projection image gray-level variations assessed by trabecular bone score using high-resolution computed tomographic acquisitions: effects of resolution and noise.

    PubMed

    Winzenrieth, Renaud; Michelet, Franck; Hans, Didier

    2013-01-01

    The aim of the present study is to determine the level of correlation between the 3-dimensional (3D) characteristics of trabecular bone microarchitecture, as evaluated using microcomputed tomography (μCT) reconstruction, and trabecular bone score (TBS), as evaluated using 2D projection images directly derived from 3D μCT reconstruction (TBSμCT). Moreover, we have evaluated the effects of image degradation (resolution and noise) and X-ray energy of projection on these correlations. Thirty human cadaveric vertebrae were acquired on a microscanner at an isotropic resolution of 93 μm. The 3D microarchitecture parameters were obtained using MicroView (GE Healthcare, Wauwatosa, MI). The 2D projections of these 3D models were generated using the Beer-Lambert law at different X-ray energies. Degradation of image resolution was simulated (from 93 to 1488 μm). Relationships between 3D microarchitecture parameters and TBSμCT at different resolutions were evaluated using linear regression analysis. Significant correlations were observed between TBSμCT and 3D microarchitecture parameters, regardless of the resolution. Correlations were detected that were strongly to intermediately positive for connectivity density (0.711 ≤ r² ≤ 0.752) and trabecular number (0.584 ≤ r² ≤ 0.648) and negative for trabecular space (-0.407 ≤ r² ≤ -0.491), up to a pixel size of 1023 μm. In addition, TBSμCT values were strongly correlated between each other (0.77 ≤ r² ≤ 0.96). Study results show that the correlations between TBSμCT at 93 μm and 3D microarchitecture parameters are weakly impacted by the degradation of image resolution and the presence of noise. PMID:22749406

  12. Trabecular homogeneity index derived from plain radiograph to evaluate bone quality.

    PubMed

    Thevenot, Jérôme; Hirvasniemi, Jukka; Finnilä, Mikko; Pulkkinen, Pasi; Kuhn, Volker; Link, Thomas; Eckstein, Felix; Jämsä, Timo; Saarakkala, Simo

    2013-12-01

    Radiographic texture analysis has been developed lately to improve the assessment of bone architecture as a determinant of bone quality. We validate here an algorithm for the evaluation of trabecular homogeneity index (HI) in the proximal femur from hip radiographs, with a focus on the impact of the principal compressive system of the trabecular bone, and evaluate its correlation with femoral strength, bone mineral density (BMD), and volumetric trabecular structure parameters. A semiautomatic custom-made algorithm was applied to calculate the HI in the femoral neck and trochanteric areas from radiographs of 178 femoral bone specimens (mean age 79.3 ± 10.4 years). Corresponding neck region was selected in CT scans to calculate volumetric parameters of trabecular structure. The site-specific BMDs were assessed from dual-energy X-ray absorptiometry (DXA), and the femoral strength was experimentally tested in side-impact configuration. Regression analysis was performed between the HI and biomechanical femoral strength, BMD, and volumetric parameters. The correlation between HI and failure load was R(2)  = 0.50; this result was improved to R(2)  = 0.58 for cervical fractures alone. The discrimination of bones with high risk of fractures (load <3000 N) was similar for HI and BMD (AUC = 0.87). Regression analysis between the HIs versus site-specific BMDs yielded R(2)  = 0.66 in neck area, R(2)  = 0.60 in trochanteric area, and an overall of R(2)  = 0.66 for the total hip. Neck HI and BMD correlated significantly with volumetric structure parameters. We present here a method to assess HI that can explain 50% of an experimental failure load and determines bones with high fracture risk with similar accuracy as BMD. The HI also had good correlation with DXA and computed tomography-derived data. PMID:23677814

  13. The in situ mechanics of trabecular bone marrow: the potential for mechanobiological response.

    PubMed

    Metzger, Thomas A; Kreipke, Tyler C; Vaughan, Ted J; McNamara, Laoise M; Niebur, Glen L

    2015-01-01

    Bone adapts to habitual loading through mechanobiological signaling. Osteocytes are the primary mechanical sensors in bone, upregulating osteogenic factors and downregulating osteoinhibitors, and recruiting osteoclasts to resorb bone in response to microdamage accumulation. However, most of the cell populations of the bone marrow niche,which are intimately involved with bone remodeling as the source of bone osteoblast and osteoclast progenitors, are also mechanosensitive. We hypothesized that the deformation of trabecular bone would impart mechanical stress within the entrapped bone marrow consistent with mechanostimulation of the constituent cells. Detailed fluid-structure interaction models of porcine femoral trabecular bone and bone marrow were created using tetrahedral finite element meshes. The marrow was allowed to flow freely within the bone pores, while the bone was compressed to 2000 or 3000 microstrain at the apparent level.Marrow properties were parametrically varied from a constant 400 mPas to a power law rule exceeding 85 Pas. Deformation generated almost no shear stress or pressure in the marrow for the low viscosity fluid, but exceeded 5 Pa when the higher viscosity models were used. The shear stress was higher when the strain rate increased and in higher volume fraction bone. The results demonstrate that cells within the trabecular bone marrow could be mechanically stimulated by bone deformation, depending on deformation rate, bone porosity, and bone marrow properties. Since the marrow contains many mechanosensitive cells, changes in the stimulatory levels may explain the alterations in bone marrow morphology with aging and disease, which may in turn affect the trabecular bone mechanobiology and adaptation. PMID:25363343

  14. Boron and fish oil have different beneficial effects on strength and trabecular microarchitecture of bone.

    PubMed

    Nielsen, Forrest H; Stoecker, Barbara J

    2009-01-01

    An experiment was performed to determine whether boron deprivation would adversely affect vertebra (trabecular) bone microarchitecture, and whether any adverse effect would be modified by dietary fatty acid composition. Female rats were fed diets containing 0.1mg (9 micromol) boron/kg in a factorial arrangement with variables of supplemental boron at 0 (boron-deprived) or 3 (boron-adequate) mg (278 micromol)/kg and fat sources of 75 g safflower oil/kg or 65 g fish (menhaden)oil/kg plus 10 g linoleic acid/kg. After 6 weeks, six females per treatment were bred. Dams and pups continued on their respective diets through gestation, lactation, and after weaning. At age 21 weeks, the microarchitecture of the fourth lumbar vertebrae from 12 randomly selected pups from each treatment was determined by microcomputed tomography. Boron deprivation decreased bone volume fraction and increased trabecular separation and structural model index. Boron deprivation decreased trabecular thickness when the dietary oil was safflower. A three-point bending test for bone strength found that boron deprivation decreased the maximum force needed to break the femur. Feeding fish oil instead of safflower oil decreased connectivity density in vertebrae of boron-deficient but not in boron-adequate rats. Fish oil instead of safflower oil increased the maximum force to break and the bending moment of the femur, especially in rats fed adequate boron. The findings confirm that boron and fish oil are beneficial to cortical bone strength, and show that nutritional intakes of boron are beneficial for trabecular bone microarchitecture and influence the beneficial effects of fish oil on bone. PMID:19486829

  15. Evaluating the macroscopic yield behaviour of trabecular bone using a nonlinear homogenisation approach.

    PubMed

    Levrero-Florencio, Francesc; Margetts, Lee; Sales, Erika; Xie, Shuqiao; Manda, Krishnagoud; Pankaj, Pankaj

    2016-08-01

    Computational homogenisation approaches using high resolution images and finite element (FE) modelling have been extensively employed to evaluate the anisotropic elastic properties of trabecular bone. The aim of this study was to extend its application to characterise the macroscopic yield behaviour of trabecular bone. Twenty trabecular bone samples were scanned using a micro-computed tomography device, converted to voxelised FE meshes and subjected to 160 load cases each (to define a homogenised multiaxial yield surface which represents several possible strain combinations). Simulations were carried out using a parallel code developed in-house. The nonlinear algorithms included both geometrical and material nonlinearities. The study found that for tension-tension and compression-compression regimes in normal strain space, the yield strains have an isotropic behaviour. However, in the tension-compression quadrants, pure shear and combined normal-shear planes, the macroscopic strain norms at yield have a relatively large variation. Also, our treatment of clockwise and counter-clockwise shears as separate loading cases showed that the differences in these two directions cannot be ignored. A quadric yield surface, used to evaluate the goodness of fit, showed that an isotropic criterion adequately represents yield in strain space though errors with orthotropic and anisotropic criteria are slightly smaller. Consequently, although the isotropic yield surface presents itself as the most suitable assumption, it may not work well for all load cases. This work provides a comprehensive assessment of material symmetries of trabecular bone at the macroscale and describes in detail its macroscopic yield and its underlying microscopic mechanics. PMID:27108348

  16. Assessment of cortical and trabecular bone distribution in the beagle skeleton by neutron activation analysis

    SciTech Connect

    Parks, N.J.; Jee, W.S.; Dell, R.B.; Miller, G.E.

    1986-07-01

    The distribution of bone calcium between morphologically identifiable cortical and trabecular bone obtained by dissection and quantitated by neutron activation analysis (NAA) is described. The skeleton of a female beagle dog was dissected into approximately 400 pieces and assayed for /sup 49/Ca produced in the University of California, Irvine TRIGA reactor. For each of the skeletal sections, we give the initial weight of the alcohol-fixed tissue, which includes cortical bone, trabecular bone, marrow, and cartilage, and a final tissue weight after the marrow and trabecular bone have been dissected away; total section and cortical section calcium weights are reported. The level of detail is represented, for example, by the vertebrae, which were divided into three parts (body, spine, and transverse processes) and by the long bones, which were divided into 10-12 parts such that characterization of the epiphysis, metaphysis, and diaphysis was accomplished. The median percentage cortical calcium values for cervical, thoracic, and lumbar vertebrae were 82%, 56%, and 66%, respectively; however, variation within these groups and among individual vertebral sections was about a factor of 2. For long bones, the median percentage cortical calcium varied from 90-100% in the midshaft to below 50% in the proximal and distal sections. The final calculated cortical tissue-to-calcium mass ratio (TCR) varied from about 4.5 for midshafts of the long bones to about 9 for thoracic vertebral bodies and indicated that the mineral fraction of cortical bone is not constant throughout the skeleton. The ratio of cortical to trabecular calcium in the skeleton was 79.6:20.4.

  17. iStent trabecular micro-bypass stent for open-angle glaucoma

    PubMed Central

    Le, Kim; Saheb, Hady

    2014-01-01

    Trabecular micro-bypass stents, commonly known as iStents, are micro-invasive glaucoma surgery (MIGS) devices used to treat open-angle glaucoma. Like other MIGS procedures that enhance trabecular outflow, the iStent lowers intraocular pressure (IOP) by creating a direct channel between the anterior chamber and Schlemm’s canal. iStents are typically implanted at the time of phacoemulsification for patients with open-angle glaucoma and visually significant cataracts. This review summarizes the published data regarding the efficacy, safety, and cost considerations of trabecular micro-bypass stents. Most studies found statistically significant reductions in mean IOP and ocular medication use after combined phacoemulsification with single or double iStent implantation. The devices were found to be very safe, with a safety profile similar to that of cataract surgery. Complications were infrequent, with the most common complications being temporary stent obstruction or malposition, which resolved with observation or secondary procedures. Future studies are needed to evaluate long-term outcomes, patient satisfaction, cost effectiveness, and expanded indications. PMID:25284980

  18. Bioactive glass-derived trabecular coating: a smart solution for enhancing osteointegration of prosthetic elements.

    PubMed

    Vitale-Brovarone, Chiara; Baino, Francesco; Tallia, Francesca; Gervasio, Cristina; Verné, Enrica

    2012-10-01

    In this work, the use of foam-like glass-ceramic scaffolds as trabecular coatings on ceramic prosthetic devices to enhance implant osteointegration is proposed. The feasibility of this innovative device was explored in a simplified, flat geometry: glass-ceramic scaffolds, prepared by polymeric sponge replication and mimicking the trabecular architecture of cancellous bone, were joined to alumina square substrates by a dense glass coating (interlayer). The role played by different formulations of starting glasses was examined, with particular care to the effect on the mechanical properties and bioactivity of the final coating. Microindentations at the coating/substrate interface and tensile tests were performed to evaluate the bonding strength between the sample's components. In vitro bioactive behaviour was assessed by soaking in simulated body fluid and evaluating the apatite formation on the surface and inside the pores of the trabecular coating. The concepts disclosed in the present study can have a significant impact in the field of implantable devices, suggesting a valuable alternative to traditional, often invasive bone-prosthesis fixation. PMID:22532097

  19. Generation of an Atlas of the Proximal Femur and Its Application to Trabecular Bone Analysis

    PubMed Central

    Carballido-Gamio, Julio; Folkesson, Jenny; Karampinos, Dimitrios C.; Baum, Thomas; Link, Thomas M.; Majumdar, Sharmila; Krug, Roland

    2013-01-01

    Automatic placement of anatomically corresponding volumes of interest and comparison of parameters against a standard of reference are essential components in studies of trabecular bone. Only recently, in vivo MR images of the proximal femur, an important fracture site, could be acquired with high-spatial resolution. The purpose of this MRI trabecular bone study was two-fold: (1) to generate an atlas of the proximal femur to automatically place anatomically corresponding volumes of interest in a population study and (2) to demonstrate how mean models of geodesic topological analysis parameters can be generated to be used as potential standard of reference. Ten females were used to generate the atlas and geodesic topological analysis models, and 10 females were used to demonstrate the atlas-based trabecular bone analysis. All alignments were based on three-dimensional (3D) multiresolution affine transformations followed by 3D multiresolution free-form deformations. Mean distances less than 1 mm between aligned femora, and sharp edges in the atlas and in fused gray-level images of registered femora indicated that the anatomical variability was well accommodated and explained by the free-form deformations. PMID:21432904

  20. Effect of low-dose CT and iterative reconstruction on trabecular bone microstructure assessment

    NASA Astrophysics Data System (ADS)

    Kopp, Felix K.; Baum, Thomas; Nasirudin, Radin A.; Mei, Kai; Garcia, Eduardo G.; Burgkart, Rainer; Rummeny, Ernst J.; Bauer, Jan S.; Noël, Peter B.

    2016-03-01

    The trabecular bone microstructure is an important factor in the development of osteoporosis. It is well known that its deterioration is one effect when osteoporosis occurs. Previous research showed that the analysis of trabecular bone microstructure enables more precise diagnoses of osteoporosis compared to a sole measurement of the mineral density. Microstructure parameters are assessed on volumetric images of the bone acquired either with high-resolution magnetic resonance imaging, high-resolution peripheral quantitative computed tomography or high-resolution computed tomography (CT), with only CT being applicable to the spine, which is one of clinically most relevant fracture sites. However, due to the high radiation exposure for imaging the whole spine these measurements are not applicable in current clinical routine. In this work, twelve vertebrae from three different donors were scanned with standard and low radiation dose. Trabecular bone microstructure parameters were assessed for CT images reconstructed with statistical iterative reconstruction (SIR) and analytical filtered backprojection (FBP). The resulting structure parameters were correlated to the biomechanically determined fracture load of each vertebra. Microstructure parameters assessed for low-dose data reconstructed with SIR significantly correlated with fracture loads as well as parameters assessed for standard-dose data reconstructed with FBP. Ideal results were achieved with low to zero regularization strength yielding microstructure parameters not significantly different from those assessed for standard-dose FPB data. Moreover, in comparison to other approaches, superior noise-resolution trade-offs can be found with the proposed methods.

  1. Does mechanical stimulation really protect the architecture of trabecular bone? A simulation study.

    PubMed

    Maurer, Manfred M; Weinkamer, Richard; Müller, Ralph; Ruffoni, Davide

    2015-08-01

    Although it is beyond doubt that mechanical stimulation is crucial to maintain bone mass, its role in preserving bone architecture is much less clear. Commonly, it is assumed that mechanics helps to conserve the trabecular network since an "accidental" thinning of a trabecula due to a resorption event would result in a local increase of load, thereby activating bone deposition there. However, considering that the thin trabecula is part of a network, it is not evident that load concentration happens locally on the weakened trabecula. The aim of this work was to clarify whether mechanical load has a protective role for preserving the trabecular network during remodeling. Trabecular bone is made dynamic by a remodeling algorithm, which results in a thickening/thinning of trabeculae with high/low strain energy density. Our simulations show that larger deviations from a regular cubic lattice result in a greater loss of trabeculae. Around lost trabeculae, the remaining trabeculae are on average thinner. More generally, thin trabeculae are more likely to have thin trabeculae in their neighborhood. The plausible consideration that a thin trabecula concentrates a higher amount of strain energy within itself is therefore only true when considering a single isolated trabecula. Mechano-regulated remodeling within a network-like architecture leads to local concentrations of thin trabeculae. PMID:25501464

  2. [Trabecular hyalinizing adenoma of the thyroid (HAT): A report of two cases].

    PubMed

    Román-González, Alejandro; Simón-Duque, Carlos; Camilo-Pérez, Juan; Vélez-Hoyo, Alejandro

    2016-01-01

    The hyalinizing trabecular adenoma is a rare lesion of the thyroid. There is controversy in the literature about the correct name for this disease. Dr. Carney defended the benign nature of this condition and therefore continues calling it adenoma, the World Health Organization calls for the potential of tumor malignancy, and others qualify it as a variant of papillary carcinoma based on the presence of rearranged in transformation/papillary thyroid carcinoma (RET/PTC) rearrangements. In Latin America there are few reported cases. Two cases of hyalinizing trabecular adenoma are reported. The first is a 40-year-old woman with a thyroid nodule of 3x3 cm. The immunohistochemistry was positive for thyroglobulin and calcitonin and negative for cytokeratin 19 and chromogranin. The second case is a 36-year-old patient with a thyroid nodule of 4x4 cm with an immunohistochemical pattern identical to the first case. Trabecular hyalinizing adenoma is a benign disease, easily confused with papillary or medullary thyroid carcinoma. Awareness of this entity will allow a better classification and management of thyroid conditions. PMID:26927651

  3. The relationship between dental implant stability and trabecular bone structure using cone-beam computed tomography

    PubMed Central

    2016-01-01

    Purpose The objective of this study was to investigate the relationships between primary implant stability as measured by impact response frequency and the structural parameters of trabecular bone using cone-beam computed tomography(CBCT), excluding the effect of cortical bone thickness. Methods We measured the impact response of a dental implant placed into swine bone specimens composed of only trabecular bone without the cortical bone layer using an inductive sensor. The peak frequency of the impact response spectrum was determined as an implant stability criterion (SPF). The 3D microstructural parameters were calculated from CT images of the bone specimens obtained using both micro-CT and CBCT. Results SPF had significant positive correlations with trabecular bone structural parameters (BV/TV, BV, BS, BSD, Tb.Th, Tb.N, FD, and BS/BV) (P<0.01) while SPF demonstrated significant negative correlations with other microstructural parameters (Tb.Sp, Tb.Pf, and SMI) using micro-CT and CBCT (P<0.01). Conclusions There was an increase in implant stability prediction by combining BV/TV and SMI in the stepwise forward regression analysis. Bone with high volume density and low surface density shows high implant stability. Well-connected thick bone with small marrow spaces also shows high implant stability. The combination of bone density and architectural parameters measured using CBCT can predict the implant stability more accurately than the density alone in clinical diagnoses. PMID:27127692

  4. The poro-viscoelastic properties of trabecular bone: a micro computed tomography-based finite element study.

    PubMed

    Sandino, Clara; McErlain, David D; Schipilow, John; Boyd, Steven K

    2015-04-01

    Bone is a porous structure with a solid phase that contains hydroxyapatite and collagen. Due to its composition, bone is often represented either as a poroelastic or as a viscoelastic material; however, the poro-viscoelastic formulation that allows integrating the effect of both the fluid flow and the collagen on the mechanical response of the tissue, has not been applied yet. The objective of this study was to develop a micro computed tomography (µCT)-based finite element (FE) model of trabecular bone that includes both the poroelastic and the viscoelastic nature of the tissue. Cubes of trabecular bone (N=25) from human distal tibia were scanned with µCT and stress relaxation experiments were conducted. The µCT images were the basis for sample specific FE models, and the stress relaxation experiments were simulated applying a poro-viscoelastic formulation. The model considers two scales of the tissue: the intertrabecular pore and the lacunar-canalicular pore scales. Independent viscoelastic and poroelastic models were also developed to determine their contribution to the poro-viscoelastic model. All the experiments exhibited a similar relaxation trend. The average reaction force before relaxation was 9.28 × 10(2)N (SD ± 5.11 × 10(2)N), and after relaxation was 4.69 × 10(2)N (SD ± 2.88 × 10(2)N). The slope of the regression line between the force before and after relaxation was 1.92 (R(2)=0.96). The poro-viscoelastic models captured 49% of the variability of the experimental data before relaxation and 33% after relaxation. The relaxation predicted with viscoelastic models was similar to the poro-viscoelastic ones; however, the poroelastic formulation underestimated the reaction force before relaxation. These data suggest that the contribution of viscoelasticity (fluid flow-independent mechanism) to the mechanical response of the tissue is significantly greater than the contribution of the poroelasticity (fluid flow-dependent mechanism). PMID:25591049

  5. Influence of Trabecular Bone on Peri-Implant Stress and Strain Based on Micro-CT Finite Element Modeling of Beagle Dog

    PubMed Central

    Liao, Sheng-hui; Zhu, Xing-hao; Xie, Jing; Sohodeb, Vikesh Kumar; Ding, Xi

    2016-01-01

    The objective of this investigation is to analyze the influence of trabecular microstructure modeling on the biomechanical distribution of the implant-bone interface. Two three-dimensional finite element mandible models, one with trabecular microstructure (a refined model) and one with macrostructure (a simplified model), were built. The values of equivalent stress at the implant-bone interface in the refined model increased compared with those of the simplified model and strain on the contrary. The distributions of stress and strain were more uniform in the refined model of trabecular microstructure, in which stress and strain were mainly concentrated in trabecular bone. It was concluded that simulation of trabecular bone microstructure had a significant effect on the distribution of stress and strain at the implant-bone interface. These results suggest that trabecular structures could disperse stress and strain and serve as load buffers. PMID:27403424

  6. Influence of Trabecular Bone on Peri-Implant Stress and Strain Based on Micro-CT Finite Element Modeling of Beagle Dog.

    PubMed

    Liao, Sheng-Hui; Zhu, Xing-Hao; Xie, Jing; Sohodeb, Vikesh Kumar; Ding, Xi

    2016-01-01

    The objective of this investigation is to analyze the influence of trabecular microstructure modeling on the biomechanical distribution of the implant-bone interface. Two three-dimensional finite element mandible models, one with trabecular microstructure (a refined model) and one with macrostructure (a simplified model), were built. The values of equivalent stress at the implant-bone interface in the refined model increased compared with those of the simplified model and strain on the contrary. The distributions of stress and strain were more uniform in the refined model of trabecular microstructure, in which stress and strain were mainly concentrated in trabecular bone. It was concluded that simulation of trabecular bone microstructure had a significant effect on the distribution of stress and strain at the implant-bone interface. These results suggest that trabecular structures could disperse stress and strain and serve as load buffers. PMID:27403424

  7. Orientation-weighted local Minkowski functionals in 3D for quantitative assessment of trabecular bone structure in the hip

    NASA Astrophysics Data System (ADS)

    Boehm, H. F.; Bitterling, H.; Weber, C.; Kuhn, V.; Eckstein, F.; Reiser, M.

    2007-03-01

    Fragility fractures or pathologic fractures of the hip, i.e. fractures with no apparent trauma, represent the worst complication in osteoporosis with a mortality close to 25% during the first post-traumatic year. Over 90% of hip fractures result from falls from standing height. A substantial number of femoral fractures are initiated in the femoral neck or the trochanteric regions which contain an internal architecture of trabeculae that are functionally highly specialized to withstand the complex pattern of external and internal forces associated with human gait. Prediction of the mechanical strength of bone tissue can be achieved by dedicated texture analysis of data obtained by high resolution imaging modalities, e.g. computed tomography (CT) or magnetic resonance tomography (MRI). Since in the case of the proximal femur, the connectivity, regional distribution and - most of all - the preferred orientation of individual trabeculae change considerably within narrow spatial limits, it seems most reasonable to evaluate the femoral bone structure on an orientation-weighted, local scale. In past studies, we could demonstrate the advantages of topological analysis of bone structure using the Minkowski Functionals in 3D on a global and on a local scale. The current study was designed to test the hypothesis that the prediction of the mechanical competence of the proximal femur by a new algorithm considering orientational changes of topological properties in the trabecular architecture is feasible and better suited than conventional methods based on the measurement of the mineral density of bone tissue (BMD).

  8. Ocular Hypotensive Effects of the ATP-Sensitive Potassium Channel Opener Cromakalim in Human and Murine Experimental Model Systems

    PubMed Central

    Roy Chowdhury, Uttio; Bahler, Cindy K.; Holman, Bradley H.; Dosa, Peter I.; Fautsch, Michael P.

    2015-01-01

    Elevated intraocular pressure (IOP) is the most prevalent and only treatable risk factor for glaucoma, a leading cause of irreversible blindness worldwide. Unfortunately, all current therapeutics used to treat elevated IOP and glaucoma have significant and sometimes irreversible side effects necessitating the development of novel compounds. We evaluated the IOP lowering ability of the broad spectrum KATP channel opener cromakalim. Cultured human anterior segments when treated with 2 μM cromakalim showed a decrease in pressure (19.33 ± 2.78 mmHg at 0 hours to 13.22 ± 2.64 mmHg at 24 hours; p<0.001) when compared to vehicle treated controls (15.89 ± 5.33 mmHg at 0 h to 15.56 ± 4.88 mmHg at 24 hours; p = 0.89). In wild-type C57BL/6 mice, cromakalim reduced IOP by 18.75 ± 2.22% compared to vehicle treated contralateral eyes (17.01 ± 0.32 mmHg at 0 hours to 13.82 ± 0.37 mmHg at 24 hours; n = 10, p = 0.002). Cromakalim demonstrated an additive effect when used in conjunction with latanoprost free acid, a common ocular hypotensive drug prescribed to patients with elevated IOP. To examine KATP channel subunit specificity, Kir6.2(-/-) mice were treated with cromakalim, but unlike wild-type animals, no change in IOP was noted. Histologic analysis of treated and control eyes in cultured human anterior segments and in mice showed similar cell numbers and extracellular matrix integrity within the trabecular meshwork, with no disruptions in the inner and outer walls of Schlemm’s canal. Together, these studies suggest that cromakalim is a potent ocular hypotensive agent that lowers IOP via activation of Kir6.2 containing KATP channels, its effect is additive when used in combination with the commonly used glaucoma drug latanoprost, and is not toxic to cells and tissues of the aqueous humor outflow pathway, making it a candidate for future therapeutic development. PMID:26535899

  9. Distribution of pseudoexfoliation material on anterior segment structures in human autopsy eyes after cataract surgery with intraocular lens implantation.

    PubMed

    Schmack, Ingo; Auffarth, Gerd Uwe

    2016-06-01

    The purpose of the study was to evaluate the distribution and amount of pseudoexfoliation material (PXM) on anterior segment structures in pseudophakic human autopsy eyes with pseudoexfoliation (PEX) syndrome and to study its impact on fixation and decentration of posterior chamber intraocular lenses (IOLs). Sixteen human autopsy eyes (donor age [mean ± SD] 77.5 ± 8.6 years; range, 70-90 years) with history of cataract surgery and PEX syndrome were analyzed for distribution and accumulation of PXM on structures of the anterior segment by light microscopy. Quantitative IOL decentration measurements were performed using the Miyake-Apple posterior view technique. All 16 eyes displayed IOLs which were either fixed symmetrically in the capsular bag (n = 8) or asymmetrically with one haptic in the sulcus and one in the bag (n = 7) or at the pars plicata of the ciliary body (n = 1). In the majority, PXM was found around the pars plicata (average grade: 1.6 ± 0.53 µm) and the lens capsule (average grade: 1.05 ± 0.46 µm). Minor amounts were detected at the pars plana and the trabecular meshwork. IOL decentration measurements ranged from 0.51 ± 0.35 (symmetrical-fixation) to 0.61 ± 0.43 mm (asymmetrical-fixation). There was only a weak statistically not significant correlation in regard to the amount of PXM and IOL decentration and between PXM distribution and the IOL fixation site. PXM contributes to weakening of the suspensory apparatus of the crystalline lens. Although PXM induced tissue alterations predispose for a broad spectrum of intra- and postoperative complications, the amount and distribution of PXM on different anterior segment structures showed only a weak correlation to IOL decentration or fixation location. PMID:26307751

  10. What Lies Behind NSF Astronomer Demographics? Subjectivities of Women, Minorities and Foreign-born Astronomers within Meshworks of Big Science Astronomy

    NASA Astrophysics Data System (ADS)

    Guillen, Reynal; Gu, D.; Holbrook, J.; Murillo, L. F.; Traweek, S.

    2011-01-01

    Our current research focuses on the trajectory of scientists working with large-scale databases in astronomy, following them as they strategically build their careers, digital infrastructures, and make their epistemological commitments. We look specifically at how gender, ethnicity, nationality intersect in the process of subject formation in astronomy, as well as in the process of enrolling partners for the construction of instruments, design and implementation of large-scale databases. Work once figured as merely technical support, such assembling data catalogs, or as graphic design, generating pleasing images for public support, has been repositioned at the core of the field. Some have argued that such databases enable a new kind of scientific inquiry based on data exploration, such as the "fourth paradigm" or "data-driven" science. Our preliminary findings based on oral history interviews and ethnography provide insights into meshworks of women, African-American, "Hispanic," Asian-American and foreign-born astronomers. Our preliminary data suggest African-American men are more successful in sustaining astronomy careers than Chicano and Asian-American men. A distinctive theme in our data is the glocal character of meshworks available to and created by foreign-born women astronomers working at US facilities. Other data show that the proportion of Asian to Asian American and foreign-born Latina/o to Chicana/o astronomers is approximately equal. Futhermore, Asians and Latinas/os are represented in significantly greater numbers than Asian Americans and Chicanas/os. Among professional astronomers in the US, each ethnic minority group is numbered on the order of tens, not hundreds. Project support is provided by the NSF EAGER program to University of California, Los Angeles under award 0956589.

  11. Ex vivo assessment of trabecular bone structure from three-dimensional projection reconstruction MR micro-images.

    PubMed

    Accardo, Agostino; Candido, Giulia; Jellús, Vladimír; Toffanin, Renato; Vittur, Franco

    2003-08-01

    Magnetic resonance (MR) imaging has recently been proposed for assessing osteoporosis and predicting fracture risks. However, accurate acquisition techniques and image analysis protocols for the determination of the trabecular bone structure are yet to be defined. The aim of this study was to assess the potential of projection reconstruction (PR) MR microscopy in the analysis of the three-dimensional (3-D) architecture of trabecular bone and in the prediction of its biomechanical properties. High-resolution 3-D PR images (41 x 41 x 82 microm3 voxels) of 15 porcine trabecular bone explants were analyzed to determine the trabecular bone volume fraction (Vv), the mean trabecular thickness (Tb.Th), and the mean trabecular separation (Tb.Sp) using the method of directed secants. These parameters were then compared with those derived from 3-D conventional spin-echo microimages. In both cases, segmentation of the high-resolution images into bone and bone marrow was obtained using a spatial adaptive threshold. The contemporary inclusion of Vv, Tb.Th and 1/Tb.Sp in a multiple regression analysis significantly improved the prediction of Young's modulus (YM). The parameters derived from the PR spin-echo images were found to be stronger predictors of YM (R2 = 0.94, p = 0.004) than those derived from conventional spin-echo images (R2 = 0.79, p = 0.051). Our study indicates that projection reconstruction MR microscopy appears to be more accurate than the conventional Fourier transform method in the quantification of trabecular bone structure and in the prediction of its bioimechanical properties. The proposed PR approach should be readily adaptable to the in vivo MRI studies of osteoporosis. PMID:12892324

  12. C-arm CT for histomorphometric evaluation of lumbar spine trabecular microarchitecture: a study on anorexia nervosa patients.

    PubMed

    Phan, C M; Khalilzadeh, O; Dinkel, J; Wang, I S; Bredella, M A; Misra, M; Miller, K K; Klibanski, A; Gupta, R

    2013-07-01

    Bone histomorphometry measurements require high spatial resolution that may not be feasible using multidetector CT (MDCT). This study evaluated the trabecular microarchitecture of lumbar spine using MDCT and C-arm CT in a series of young adult patients with anorexia nervosa (AN). 11 young females with AN underwent MDCT (anisotropic resolution with a slice thickness of ~626 μm) and C-arm CT (isotropic resolution of ~200 µm). Standard histomorphometric parameters the of L1 vertebral body, namely the apparent trabecular bone volume fraction (BV/TV), trabecular thickness (TbTh), trabecular number (TbN) and trabecular separation (TbSp), were analysed using MicroView software (GE Healthcare, Piscataway, NJ). Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry. Trabecular parameters derived from MDCT and C-arm CT were compared, and their association with BMD parameters was evaluated. Histomorphometric parameters derived from C-arm CT, namely TbTh, TbN and TbSp, were significantly different from the corresponding MDCT parameters. There were no significant correlations between C-arm CT-derived parameters and the corresponding MDCT-derived parameters. C-arm CT-derived parameters were significantly (p<0.001) correlated with anteroposterior L1 spine BMD and Z-scores: TbTh (r=0.723, r=0.744, respectively), TbN (r=-0.720, r=-0.712, respectively) and TbSp (r=0.656, r=0.648, respectively). BV/TV, derived from C-arm CT, was significantly associated with body mass index (r=0.636) and ideal body weight (r=0.730) (p<0.05). These associations were not present in MDCT-derived parameters. This study suggests that the spatial resolution offered by C-arm CT more accurately captures the histomorphometric parameters of trabecular morphology than MDCT in patients with AN. PMID:23640801

  13. Risedronate does not reduce mechanical loading-related increases in cortical and trabecular bone mass in mice

    PubMed Central

    Sugiyama, Toshihiro; Meakin, Lee B.; Galea, Gabriel L.; Jackson, Brendan F.; Lanyon, Lance E.; Ebetino, Frank H.; Russell, R. Graham G.; Price, Joanna S.

    2011-01-01

    To establish whether the combination of anti-resorptive therapy with mechanical loading has a negative, additive or synergistic effect on bone structure, we assessed the separate and combined effects of risedronate and non-invasive dynamic loading on trabecular and cortical bone. Seventeen-week-old female C57BL/6 mice were given daily subcutaneous injections of vehicle (n = 20) or risedronate at a dose of 0.15, 1.5, 15 or 150 μg/kg/day (n = 10 in each) for 17 days. From the fourth day of treatment, the right tibiae were subjected to a single period of axial loading (40 cycles/day) for three alternate days per week for two weeks. The left tibiae were used as internal controls. Trabecular and cortical sites in the tibiae were analyzed by high-resolution micro-computed tomography and imaging of fluorochrome labels. In the non-loaded tibiae, treatment with the higher doses of risedronate at 15 or 150 μg/kg/day resulted in higher trabecular bone volume and trabecular number than in vehicle-treated controls, whereas such treatment was associated with no differences in cortical bone volume at any dose. In the loaded tibiae, loading induced increases in trabecular and cortical bone volume compared with contra-lateral controls primarily through increased trabecular thickness and periosteal expansion, respectively, independently of risedronate treatment. In conclusion, the response to mechanical loading in both trabecular and cortical bone in mice is therefore not impaired by short-term treatment with risedronate, even over a 1000-fold dose range. In considering the optimization of treatments for osteoporosis, it is reassuring that anti-resorptive therapy and mechanical loading can exert independent beneficial effects. This article is part of a Special Issue entitled Bisphosphonates. PMID:21497678

  14. Wavelet based characterization of ex vivo vertebral trabecular bone structure with 3T MRI compared to microCT

    SciTech Connect

    Krug, R; Carballido-Gamio, J; Burghardt, A; Haase, S; Sedat, J W; Moss, W C; Majumdar, S

    2005-04-11

    Trabecular bone structure and bone density contribute to the strength of bone and are important in the study of osteoporosis. Wavelets are a powerful tool to characterize and quantify texture in an image. In this study the thickness of trabecular bone was analyzed in 8 cylindrical cores of the vertebral spine. Images were obtained from 3 Tesla (T) magnetic resonance imaging (MRI) and micro-computed tomography ({micro}CT). Results from the wavelet based analysis of trabecular bone were compared with standard two-dimensional structural parameters (analogous to bone histomorphometry) obtained using mean intercept length (MR images) and direct 3D distance transformation methods ({micro}CT images). Additionally, the bone volume fraction was determined from MR images. We conclude that the wavelet based analyses delivers comparable results to the established MR histomorphometric measurements. The average deviation in trabecular thickness was less than one pixel size between the wavelet and the standard approach for both MR and {micro}CT analysis. Since the wavelet based method is less sensitive to image noise, we see an advantage of wavelet analysis of trabecular bone for MR imaging when going to higher resolution.

  15. Relationships of the phase velocity with the microarchitectural parameters in bovine trabecular bone in vitro: Application of a stratified model

    NASA Astrophysics Data System (ADS)

    Lee, Kang Il

    2012-08-01

    The present study aims to provide insight into the relationships of the phase velocity with the microarchitectural parameters in bovine trabecular bone in vitro. The frequency-dependent phase velocity was measured in 22 bovine femoral trabecular bone samples by using a pair of transducers with a diameter of 25.4 mm and a center frequency of 0.5 MHz. The phase velocity exhibited positive correlation coefficients of 0.48 and 0.32 with the ratio of bone volume to total volume and the trabecular thickness, respectively, but a negative correlation coefficient of -0.62 with the trabecular separation. The best univariate predictor of the phase velocity was the trabecular separation, yielding an adjusted squared correlation coefficient of 0.36. The multivariate regression models yielded adjusted squared correlation coefficients of 0.21-0.36. The theoretical phase velocity predicted by using a stratified model for wave propagation in periodically stratified media consisting of alternating parallel solid-fluid layers showed reasonable agreements with the experimental measurements.

  16. Pressure and shear stress in trabecular bone marrow during whole bone loading.

    PubMed

    Metzger, Thomas A; Schwaner, Stephen A; LaNeve, Anthony J; Kreipke, Tyler C; Niebur, Glen L

    2015-09-18

    Skeletal adaptation to mechanical loading is controlled by mechanobiological signaling. Osteocytes are highly responsive to applied strains, and are the key mechanosensory cells in bone. However, many cells residing in the marrow also respond to mechanical cues such as hydrostatic pressure and shear stress, and hence could play a role in skeletal adaptation. Trabecular bone encapsulates marrow, forming a poroelastic solid. According to the mechanical theory, deformation of the pores induces motion in the fluid-like marrow, resulting in pressure and velocity gradients. The latter results in shear stress acting between the components of the marrow. To characterize the mechanical environment of trabecular bone marrow in situ, pore pressure within the trabecular compartment of whole porcine femurs was measured with miniature pressure transducers during stress-relaxation and cyclic loading. Pressure gradients ranging from 0.013 to 0.46 kPa/mm were measured during loading. This range was consistent with calculated pressure gradients from continuum scale poroelastic models with the same permeability. Micro-scale computational fluid dynamics models created from computed tomography images were used to calculate the micromechanical stress in the marrow using the measured pressure differentials as boundary conditions. The volume averaged shear stress in the marrow ranged from 1.67 to 24.55 Pa during cyclic loading, which exceeds the mechanostimulatory threshold for mesenchymal lineage cells. Thus, the loading of bone through activities of daily living may be an essential component of bone marrow health and mechanobiology. Additional studies of cell-level interactions during loading in healthy and disease conditions will provide further incite into marrow mechanobiology. PMID:26283413

  17. Type III collagen regulates osteoblastogenesis and the quantity of trabecular bone.

    PubMed

    Volk, Susan W; Shah, Shalin R; Cohen, Arthur J; Wang, Yanjian; Brisson, Becky K; Vogel, Laurie K; Hankenson, Kurt D; Adams, Sherrill L

    2014-06-01

    Type III collagen (Col3), a fibril-forming collagen, is a major extracellular matrix component in a variety of internal organs and skin. It is also expressed at high levels during embryonic skeletal development and is expressed by osteoblasts in mature bone. Loss of function mutations in the gene encoding Col3 (Col3a1) are associated with vascular Ehlers-Danlos syndrome (EDS). Although the most significant clinical consequences of this syndrome are associated with catastrophic failure and impaired healing of soft tissues, several studies have documented skeletal abnormalities in vascular EDS patients. However, there are no reports of the role of Col3 deficiency on the murine skeleton. We compared craniofacial and skeletal phenotypes in young (6-8 weeks) and middle-aged (>1 year) control (Col3(+/+)) and haploinsufficient (Col3(+/-)) mice, as well as young null (Col3(-/-)) mice by microcomputed tomography (μCT). Although Col3(+/-) mice did not have significant craniofacial abnormalities based upon cranial morphometrics, μCT analysis of distal femur trabecular bone demonstrated significant reductions in bone volume (BV), bone volume fraction (BV/TV), connectivity density, structure model index and trabecular thickness in young adult female Col3(+/-) mice relative to wild-type littermates. The reduction in BV/TV persisted in female mice at 1 year of age. Next, we evaluated the role of Col3 in vitro. Osteogenesis assays revealed that cultures of mesenchymal progenitors collected from Col3(-/-) embryos display decreased alkaline phosphatase activity and reduced capacity to undergo mineralization. Consistent with this data, a reduction in expression of osteogenic markers (type I collagen, osteocalcin and bone sialoprotein) correlates with reduced bone Col3 expression in Col3(+/-) mice and with age in vivo. A small but significant reduction in osteoclast numbers was found in Col3(+/-) compared to Col3(+/+) bones. Taken together, these findings indicate that Col3 plays a

  18. Characterizing trabecular bone structure for assessing vertebral fracture risk on volumetric quantitative computed tomography

    NASA Astrophysics Data System (ADS)

    Nagarajan, Mahesh B.; Checefsky, Walter A.; Abidin, Anas Z.; Tsai, Halley; Wang, Xixi; Hobbs, Susan K.; Bauer, Jan S.; Baum, Thomas; Wismüller, Axel

    2015-03-01

    While the proximal femur is preferred for measuring bone mineral density (BMD) in fracture risk estimation, the introduction of volumetric quantitative computed tomography has revealed stronger associations between BMD and spinal fracture status. In this study, we propose to capture properties of trabecular bone structure in spinal vertebrae with advanced second-order statistical features for purposes of fracture risk assessment. For this purpose, axial multi-detector CT (MDCT) images were acquired from 28 spinal vertebrae specimens using a whole-body 256-row CT scanner with a dedicated calibration phantom. A semi-automated method was used to annotate the trabecular compartment in the central vertebral slice with a circular region of interest (ROI) to exclude cortical bone; pixels within were converted to values indicative of BMD. Six second-order statistical features derived from gray-level co-occurrence matrices (GLCM) and the mean BMD within the ROI were then extracted and used in conjunction with a generalized radial basis functions (GRBF) neural network to predict the failure load of the specimens; true failure load was measured through biomechanical testing. Prediction performance was evaluated with a root-mean-square error (RMSE) metric. The best prediction performance was observed with GLCM feature `correlation' (RMSE = 1.02 ± 0.18), which significantly outperformed all other GLCM features (p < 0.01). GLCM feature correlation also significantly outperformed MDCTmeasured mean BMD (RMSE = 1.11 ± 0.17) (p< 10-4). These results suggest that biomechanical strength prediction in spinal vertebrae can be significantly improved through characterization of trabecular bone structure with GLCM-derived texture features.

  19. Mechanical properties, density and quantitative CT scan data of trabecular bone with and without metastases.

    PubMed

    Kaneko, Tadashi S; Bell, Jason S; Pejcic, Marina R; Tehranzadeh, Jamshid; Keyak, Joyce H

    2004-04-01

    Pathologic fracture of the hip due to metastatic lesions in bone is a serious problem. This study examined the effect of metastatic lesions on the material properties and quantitative computed tomography (QCT) data of trabecular bone. Twelve distal femora were obtained, four with lytic and/or blastic metastatic lesions (group L), four without lesions but from donors who died from breast, prostate, or lung cancer (group NL), and four from donors with no cancer (group NC). Each specimen was CT scanned, and 56, 15x15x15-mm cubes of trabecular bone were cut. QCT density (rho(QCT)), compressive elastic modulus (E), compressive yield and ultimate strengths (S(y) and S(u)), and ash density (rho(ash)) of each cube were determined. Regression analysis was performed between rho(ash) and E, S(y), S(u) and rho(QCT), and analysis of covariance was used to identify differences between groups. Power relationships that did not depend on group (p >/= 0.1) were found between E and rho(ash) (0.74 /= 0.94; p<0.001). rho(ash) was strongly related to rho(QCT) (r >/= 0.99; p<0.001). These results indicate that metastatic disease does not significantly impair the ability of QCT to provide an accurate and precise estimate of rho(ash) that can be used to estimate mechanical properties of trabecular bone with and without metastases. PMID:14996564

  20. Interleukin-6 gene knockout antagonizes high-fat-induced trabecular bone loss.

    PubMed

    Wang, Chunyu; Tian, Li; Zhang, Kun; Chen, Yaxi; Chen, Xiang; Xie, Ying; Zhao, Qian; Yu, Xijie

    2016-10-01

    The purpose of the study was to determine the roles of interleukin-6 (IL6) in fat and bone communication. Male wild-type (WT) mice and IL6 knockout (IL6(-/-)) mice were fed with either regular diet (RD) or high-fat diet (HFD) for 12 weeks. Bone mass and bone microstructure were evaluated by micro-computed tomography. Gene expression related to lipid and bone metabolisms was assayed with real-time quantitative polymerase chain reaction. Bone marrow cells from both genotypes were induced to differentiate into osteoblasts or osteoclasts, and treated with palmitic acid (PA). HFD increased the body weight and fat pad weight, and impaired lipid metabolism in both WT and IL6(-/-) mice. The dysregulation of lipid metabolism was more serious in IL6(-/-) mice. Trabecular bone volume fraction, trabecular bone number and trabecular bone thickness were significantly downregulated in WT mice after HFD than those in the RD (P < 0.05). However, these bone microstructural parameters were increased by 53%, 34% and 40%, respectively, in IL6(-/-) mice than those in WT mice on the HFD (P < 0.05). IL6(-/-) osteoblasts displayed higher alkaline phosphatase (ALP) activity and higher mRNA levels of Runx2 and Colla1 than those in WT osteoblasts both in the control and PA treatment group (P < 0.05). IL6(-/-) mice showed significantly lower mRNA levels of PPARγ and leptin and higher mRNA levels of adiponectin in comparison with WT mice on HFD. In conclusion, these findings suggested that IL6 gene deficiency antagonized HFD-induced bone loss. IL6 might bridge lipid and bone metabolisms and could be a new potential therapeutic target for lipid metabolism disturbance-related bone loss. PMID:27493246

  1. Trabecular Reorganization in Consecutive Iliac Crest Biopsies when Switching from Bisphosphonate to Strontium Ranelate Treatment

    PubMed Central

    Jobke, Björn; Burghardt, Andrew J.; Muche, Burkhard; Hahn, Michael; Semler, Jutta; Amling, Michael; Majumdar, Sharmila; Busse, Björn

    2011-01-01

    Background Several agents are available to treat osteoporosis while addressing patient-specific medical needs. Individuals' residual risk to severe fracture may require changes in treatment strategy. Data at osseous cellular and microstructural levels due to a therapy switch between agents with different modes of action are rare. Our study on a series of five consecutively taken bone biopsies from an osteoporotic individual over a six-year period analyzes changes in cellular characteristics, bone microstructure and mineralization caused by a therapy switch from an antiresorptive (bisphosphonate) to a dual action bone agent (strontium ranelate). Methodology/Principal Findings Biopsies were progressively taken from the iliac crest of a female patient. Four biopsies were taken during bisphosphonate therapy and one biopsy was taken after one year of strontium ranelate (SR) treatment. Furthermore, serum bone markers and dual x-ray absorptiometry measurements were acquired. Undecalcified histology was used to assess osteoid parameters and bone turnover. Structural indices and degree of mineralization were determined using microcomputed tomography, quantitative backscattered electron imaging, and combined energy dispersive x-ray/µ-x-ray-fluorescence microanalysis. Conclusions/Significance Microstructural data revealed a notable increase in bone volume fraction after one year of SR treatment compared to the bisphosphonate treatment period. Indices of connectivity density, structure model index and trabecular bone pattern factor were predominantly enhanced indicating that the architectural transformation from trabecular rods to plates was responsible for the bone volume increase and less due to changes in trabecular thickness and number. Administration of SR following bisphosphonates led to a maintained mineralization profile with an uptake of strontium on the bone surface level. Reactivated osteoclasts designed tunneling, hook-like intratrabecular resorption sites. The

  2. Electrical and dielectric properties of bovine trabecular bone - relationships with mechanical properties and mineral density

    NASA Astrophysics Data System (ADS)

    Sierpowska, J.; Töyräs, J.; Hakulinen, M. A.; Saarakkala, S.; Jurvelin, J. S.; Lappalainen, R.

    2003-03-01

    Interrelationships of trabecular bone electrical and dielectric properties with mechanical characteristics and density are poorly known. While electrical stimulation is used for healing fractures, better understanding of these relations has clinical importance. Furthermore, earlier studies have suggested that bone electrical and dielectric properties depend on the bone density and could, therefore, be used to predict bone strength. To clarify these issues, volumetric bone mineral density (BMDvol), electrical and dielectric as well as mechanical properties were determined from 40 cylindrical plugs of bovine trabecular bone. Phase angle, relative permittivity, loss factor and conductivity of wet bovine trabecular bone were correlated with Young's modulus, yield stress, ultimate strength, resilience and BMDvol. The reproducibility of in vitro electrical and dielectric measurements was excellent (standardized coefficient of variation less than 1%, for all parameters), especially at frequencies higher than 1 kHz. Correlations of electrical and dielectric parameters with the bone mechanical properties or density were frequency-dependent. The relative permittivity showed the strongest linear correlations with mechanical parameters (r > 0.547, p < 0.01, n = 40, at 50 kHz) and with BMDvol (r = 0.866, p < 0.01, n = 40, at 50 kHz). In general, linear correlations between relative permittivity and mechanical properties or BMDvol were highest at frequencies over 6 kHz. In addition, a significant site-dependent variation of electrical and dielectric characteristics, mechanical properties and BMDvol was revealed in bovine femur (p < 0.05, Kruskall-Wallis H-test). Based on the present results, we conclude that the measurement of electrical and dielectric properties provides quantitative information that is related to bone quantity and quality.

  3. Strain analysis of trabecular bone using time-resolved X-ray microtomography

    NASA Astrophysics Data System (ADS)

    Jiroušek, Ondřej; Zlámal, Petr; Kytýř, Daniel; Kroupa, Martin

    2011-05-01

    A micro-radiographic system composed of microfocus X-ray tube and a large flat panel detector has been adapted for imaging complicated internal microstructure of trabecular bone under applied deformation. To capture the deforming microstructure a load was applied in small increments while the sample was tomographically scanned. Reconstruction of the internal structure is provided using backprojection algorithm for equiangular cone-beam projection data. From the reconstructed cross-sections a finite element (FE) model of the microstructure was developed and loaded according to the experiment. Deformation behavior of the FE model was compared to the experimentally determined response of the sample.

  4. Differences of three-dimensional trabecular microstructure in osteopenic rat models caused by ovariectomy and neurectomy.

    PubMed

    Ito, M; Nishida, A; Nakamura, T; Uetani, M; Hayashi, K

    2002-04-01

    We investigated the differences in three-dimensional microstructure of bone in cases of osteopenia caused by two different procedures: ovariectomy (ovx) and sciatic neurectomy (nx). Thirty-nine 8-week-old female Lewis rats were divided into two groups: (1) ovx and sham operation; and (2) nx and sham operation. At 12 weeks of age these rats were killed to sample the right tibiae. The samples were scanned using microcomputed tomography to obtain metric parameters such as bone volume fraction (BV/TV), trabecular thickness (Tb.Th), and trabecular separation (Tb.Sp), and nonmetric parameters such as structure model index (SMI), trabecular bone pattern factor (TBPf), and degree of anisotropy (DA). The changes in all microstructural parameters were significant in both the ovx and nx groups, with those of BV/TV, Tb.Th, Tb.Sp, and SMI more significant in the ovx group than in the nx group, in comparison to their respective controls. The significantly higher coefficient of variance for Tb.Th across the entire analyzed area of the individual samples indicated that the trabecular thinning occurred heterogenously and that the microstructural deterioration induced by ovx and nx appeared to be locally accelerated, so as to induce perforation and disappearance of trabeculae. The DA increased significantly in the ovx rats, whereas it decreased in the nx rats. The appearance of microstructural deterioration differed between the two osteopenic models. The three-dimensional (3D) images from the nx rats showed flake-like trabeculae, whereas the ovx rats exhibited a diffuse disappearance of trabeculae, especially in the central part of the tibia, but with a preservation of shape for those trabeculae that were retained. The reduction in cortical area was more significant in the nx group. nx and ovx resulted in significant changes in bone microstructure, showing perforation and removal of trabeculae due to locally accelerated bone resorption. The 3D microcomputed tomography images

  5. Trabecular bone structural parameters evaluated using dental cone-beam computed tomography: cellular synthetic bones

    PubMed Central

    2013-01-01

    Objective This study compared the adequacy of dental cone beam computed tomography (CBCT) and micro computed tomography (micro-CT) in evaluating the structural parameters of trabecular bones. Methods The cellular synthetic bones in 4 density groups (Groups 1–4: 0.12, 0.16, 0.20, and 0.32 g/cm3) were used in this study. Each group comprised 8 experimental specimens that were approximately 1 cm3. Dental CBCT and micro-CT scans were conducted on each specimen to obtain independent measurements of the following 4 trabecular bone structural parameters: bone volume fraction (BV/TV), specific bone surface (BS/BV), trabecular thickness (Tb.Th.), and trabecular separation (Tb.Sp.). Wilcoxon signed ranks tests were used to compare the measurement variations between the dental CBCT and micro-CT scans. A Spearman analysis was conducted to calculate the correlation coefficients (r) of the dental CBCT and micro-CT measurements. Results and Conclusion Of the 4 groups, the BV/TV and Tb.Th. measured using dental CBCT were larger compared with those measured using micro-CT. By contrast, the BS/BV measured using dental CBCT was significantly less compared with those measured using micro-CT. Furthermore, in the low-density groups (Groups 1 and 2), the Tb.Sp. measured using dental CBCT was smaller compared with those measured using micro-CT. However, the Tb.Sp. measured using dental CBCT was slightly larger in the high-density groups (Groups 3 and 4) than it was in the low density groups. The correlation coefficients between the BV/TV, BS/BV, Tb.Th., and Tb.Sp. values measured using dental CBCT and micro-CT were 0.9296 (p < .001), 0.8061 (p < .001), 0.9390 (p < .001), and 0.9583 (p < .001), respectively. Although the dental CBCT and micro-CT approaches exhibited high correlations, the absolute values of BV/TV, BS/BV, Tb.Th., Tb.Sp. differed significantly between these measurements. Additional studies must be conducted to evaluate using dental CBCT in clinical practice. PMID

  6. Cortical Bone Morphological and Trabecular Bone Microarchitectural Changes in the Mandible and Femoral Neck of Ovariectomized Rats

    PubMed Central

    Hsu, Pei-Yu; Tsai, Ming-Tzu; Wang, Shun-Ping; Chen, Ying-Ju; Wu, Jay; Hsu, Jui-Ting

    2016-01-01

    Objective This study used microcomputed tomography (micro-CT) to evaluate the effects of ovariectomy on the trabecular bone microarchitecture and cortical bone morphology in the femoral neck and mandible of female rats. Materials and Methods Twelve female Wister rats were divided into two groups: the control and ovariectomized groups. The rats in the ovariectomized group received ovariectomy at 8 weeks of age; all the rats were sacrificed at 20 weeks of age, and their mandibles and femurs were removed and scanned using micro-CT. Four microstructural trabecular bone parameters were measured for the region below the first mandibular molar and the femoral neck region: bone volume fraction (BV/TV), trabecular thickness (TbTh), trabecular separation (TbSp), and trabecular number (TbN). In addition, four cortical bone parameters were measured for the femoral neck region: total cross-sectional area (TtAr), cortical area (CtAr), cortical bone area fraction (CtAr/TtAr), and cortical thickness (CtTh). The CtTh at the masseteric ridge was used to assess the cortical bone morphology in the mandible. The trabecular bone microarchitecture and cortical bone morphology in the femoral necks and mandibles of the control group were compared with those of the ovariectomized group. Furthermore, Spearman’s correlation (rs) was conducted to analyze the correlation between the osteoporosis conditions of the mandible and femoral neck. Results Regarding the trabecular bone microarchitectural parameters, the BV/TV of the trabecular bone microarchitecture in the femoral necks of the control group (61.199±11.288%, median ± interquartile range) was significantly greater than that of the ovariectomized group (40.329±5.153%). Similarly, the BV/TV of the trabecular bone microarchitecture in the mandibles of the control group (51.704±6.253%) was significantly greater than that of the ovariectomized group (38.486±9.111%). Furthermore, the TbSp of the femoral necks in the ovariectomized group

  7. The 3D-based scaling index algorithm to optimize structure analysis of trabecular bone in postmenopausal women with and without osteoporotic spine fractures

    NASA Astrophysics Data System (ADS)

    Muller, Dirk; Monetti, Roberto A.; Bohm, Holger F.; Bauer, Jan; Rummeny, Ernst J.; Link, Thomas M.; Rath, Christoph W.

    2004-05-01

    The scaling index method (SIM) is a recently proposed non-linear technique to extract texture measures for the quantitative characterisation of the trabecular bone structure in high resolution magnetic resonance imaging (HR-MRI). The three-dimensional tomographic images are interpreted as a point distribution in a state space where each point (voxel) is defined by its x, y, z coordinates and the grey value. The SIM estimates local scaling properties to describe the nonlinear morphological features in this four-dimensional point distribution. Thus, it can be used for differentiating between cluster-, rod-, sheet-like and unstructured (background) image components, which makes it suitable for quantifying the microstructure of human cancellous bone. The SIM was applied to high resolution magnetic resonance images of the distal radius in patients with and without osteoporotic spine fractures in order to quantify the deterioration of bone structure. Using the receiver operator characteristic (ROC) analysis the diagnostic performance of this texture measure in differentiating patients with and without fractures was compared with bone mineral density (BMD). The SIM demonstrated the best area under the curve (AUC) value for discriminating the two groups. The reliability of our new texture measure and the validity of our results were assessed by applying bootstrapping resampling methods. The results of this study show that trabecular structure measures derived from HR-MRI of the radius in a clinical setting using a recently proposed algorithm based on a local 3D scaling index method can significantly improve the diagnostic performance in differentiating postmenopausal women with and without osteoporotic spine fractures.

  8. Magnetic resonance imaging of the calcaneus: preliminary assessment of trabecular bone-dependent regional variations in marrow relaxation time compared with dual X-ray absorptiometry

    NASA Technical Reports Server (NTRS)

    Guglielmi, G.; Selby, K.; Blunt, B. A.; Jergas, M.; Newitt, D. C.; Genant, H. K.; Majumdar, S.

    1996-01-01

    RATIONALE AND OBJECTIVES: Marrow transverse relaxation time (T2*) in magnetic resonance (MR) imaging may be related to the density and structure of the surrounding trabecular network. We investigated regional variations of T2* in the human calcaneus and compared the findings with bone mineral density (BMD), as measured by dual X-ray absorpiometry (DXA). Short- and long-term precisions were evaluated first to determine whether MR imaging would be useful for the clinical assessment of disease status and progression in osteoporosis. METHODS: Gradient-recalled echo MR images of the calcaneus were acquired at 1.5 T from six volunteers. Measurements of T2* were compared with BMD and (for one volunteer) conventional radiography. RESULTS: T2* values showed significant regional variation; they typically were shortest in the superior region of the calcaneus. There was a linear correlation between MR and DXA measurements (r = .66 for 1/T2* versus BMD). Differences in T2* attributable to variations in analysis region-of-interest placement were not significant for five of the six volunteers. Sagittal MR images had short- and long-term precision errors of 4.2% and 3.3%, respectively. For DXA, the precision was 1.3% (coefficient of variation). CONCLUSION: MR imaging may be useful for trabecular bone assessment in the calcaneus. However, given the large regional variations in bone density and structure, the choice of an ROI is likely to play a major role in the accuracy, precision, and overall clinical efficacy of T2* measurements.

  9. Analyzing µCT images of bone specimen with wavelets and scaling indices: Which texture measure does better to depict the trabecular bone structure?

    NASA Astrophysics Data System (ADS)

    Raeth, Christoph W.; Bauer, Jan; Mueller, Dirk; Rummeny, Ernst J.; Link, Thomas M.; Majumdar, Sharmila; Eckstein, Felix; Monetti, Roberto

    2007-03-01

    The visualisation and subsequent quantification of the inner bone structure plays an important role for better understanding the disease- or drug-induced changes of the bone in the context of osteoporosis. Scaling indices (SIM) are well suited to quantify these structures on a local level, especially to discriminate between plate-like and rod-like structural elements. Local filters based on wavelets (WVL) are a standard technique in texture analysis. So far, they are mainly used for two-dimensional image data sets. Here we extend the formalism of the spherical Mexican hat wavelets to the analysis of three-dimensional tomographic images and evaluate its performance in comparison with scaling indices, histomorphometric measures and BMD. μCT images with isotropic resolution of 30 x 30 x 30 μm of a sample of 19 trabecular bone specimen of human thoracic vertebrae were acquired. In addition, the bone mineral density was measured by QCT. The maximum compressive strength (MCS) was determined in a biomechanical test. Some wavelet-based as well as all scaling index- based texture measures show a significantly higher correlation with MCS (WVL: ρ2=0.54, SIM: ρ2=0.53-0.56) than BMD (ρ2=0.46), where we find slightly better correlations for SIM than for WVL. The SIM and WVL results are comparable but not better to those obtained with histomorphometric measures (BV/TV: ρ2=0.45, Tr. N.: ρ2=0.67, Tr.Sp.: ρ2=0.67). In conclusion, WVL and SIM techniques can successfully be applied to μCT image data. Since the two measures characterize the image structures on a local scale, they offer the possibility to directly identify and discriminate rods and sheets of the trabecular structure. This property may give new insights about the bone constituents responsible for the mechanical strength.

  10. The Initial Slope of the Variogram, Foundation of the Trabecular Bone Score, Is Not or Is Poorly Associated With Vertebral Strength.

    PubMed

    Maquer, Ghislain; Lu, Yongtao; Dall'Ara, Enrico; Chevalier, Yan; Krause, Matthias; Yang, Lang; Eastell, Richard; Lippuner, Kurt; Zysset, Philippe K

    2016-02-01

    Trabecular bone score (TBS) rests on the textural analysis of dual-energy X-ray absorptiometry (DXA) to reflect the decay in trabecular structure characterizing osteoporosis. Yet, its discriminative power in fracture studies remains incomprehensible because prior biomechanical tests found no correlation with vertebral strength. To verify this result possibly owing to an unrealistic setup and to cover a wide range of loading scenarios, the data from three previous biomechanical studies using different experimental settings were used. They involved the compressive failure of 62 human lumbar vertebrae loaded 1) via intervertebral discs to mimic the in vivo situation ("full vertebra"); 2) via the classical endplate embedding ("vertebral body"); or 3) via a ball joint to induce anterior wedge failure ("vertebral section"). High-resolution peripheral quantitative computed tomography (HR-pQCT) scans acquired from prior testing were used to simulate anterior-posterior DXA from which areal bone mineral density (aBMD) and the initial slope of the variogram (ISV), the early definition of TBS, were evaluated. Finally, the relation of aBMD and ISV with failure load (F(exp)) and apparent failure stress (σexp) was assessed, and their relative contribution to a multilinear model was quantified via ANOVA. We found that, unlike aBMD, ISV did not significantly correlate with F(exp) and σexp , except for the "vertebral body" case (r(2) = 0.396, p = 0.028). Aside from the "vertebra section" setup where it explained only 6.4% of σexp (p = 0.037), it brought no significant improvement to aBMD. These results indicate that ISV, a replica of TBS, is a poor surrogate for vertebral strength no matter the testing setup, which supports the prior observations and raises a fortiori the question of the deterministic factors underlying the statistical relationship between TBS and vertebral fracture risk. PMID:26234619

  11. A NEW ALGORITHM FOR TRABECULAR BONE THICKNESS COMPUTATION AT LOW RESOLUTION ACHIEVED UNDER IN VIVO CONDITION

    PubMed Central

    Liu, Yinxiao; Jin, Dakai; Saha, Punam K.

    2015-01-01

    Adult bone diseases, especially osteoporosis, lead to increased risk of fracture associated with substantial morbidity, mortality, and financial costs. Clinically, osteoporosis is defined by low bone mineral density (BMD); however, increasing evidence suggests that the micro-architectural quality of trabecular bone (TB) is an important determinant of bone strength and fracture risk. Accurate measurement of trabecular thickness and marrow spacing is of significant interest for early diagnosis of osteoporosis or treatment effects. Here, we present a new robust algorithm for computing TB thickness and marrow spacing at a low resolution achievable in vivo. The method uses a star-line tracing technique that effectively deals with partial voluming effects of in vivo imaging where voxel size is comparable to TB thickness. Experimental results on cadaveric ankle specimens have demonstrated the algorithm’s robustness (ICC>0.98) under repeat scans of multi-row detector computed tomography (MD-CT) imaging. It has been observed in experimental results that TB thickness and marrow spacing measures as computed by the new algorithm have strong association (R2 ∈{0.85, 0.87}) with TB’s experimental mechanical strength measures. PMID:27330678

  12. Multi-Elemental Profiling of Tibial and Maxillary Trabecular Bone in Ovariectomised Rats

    PubMed Central

    Han, Pingping; Lu, Shifeier; Zhou, Yinghong; Moromizato, Karine; Du, Zhibin; Friis, Thor; Xiao, Yin

    2016-01-01

    Atomic minerals are the smallest components of bone and the content of Ca, being the most abundant mineral in bone, correlates strongly with the risk of osteoporosis. Postmenopausal women have a far greater risk of suffering from OP due to low Ca concentrations in their bones and this is associated with low bone mass and higher bone fracture rates. However, bone strength is determined not only by Ca level, but also a number of metallic and non-metallic elements in bone. Thus, in this study, the difference of metallic and non-metallic elements in ovariectomy-induced osteoporosis tibial and maxillary trabecular bone was investigated in comparison with sham operated normal bone by laser ablation inductively-coupled plasma mass spectrometry using a rat model. The results demonstrated that the average concentrations of 25Mg, 28Si, 39K, 47Ti, 56Fe, 59Co, 77Se, 88Sr, 137Ba, and 208Pb were generally higher in tibia than those in maxilla. Compared with the sham group, Ovariectomy induced more significant changes of these elements in tibia than maxilla, indicating tibial trabecular bones are more sensitive to changes of circulating estrogen. In addition, the concentrations of 28Si, 77Se, 208Pb, and Ca/P ratios were higher in tibia and maxilla in ovariectomised rats than those in normal bone at all time-points. The present study indicates that ovariectomy could significantly impact the element distribution and concentrations between tibia and maxilla. PMID:27338361

  13. Trabecular bone score (TBS) as a new complementary approach for osteoporosis evaluation in clinical practice

    PubMed Central

    Harvey, N.C.; Glüer, C.C.; Binkley, N.; McCloskey, E.V.; Brandi, M-L.; Cooper, C.; Kendler, D.; Lamy, O.; Laslop, A.; Camargos, B.M.; Reginster, J-Y.; Rizzoli, R.; Kanis, J.A.

    2015-01-01

    Trabecular bone score (TBS) is a recently-developed analytical tool that performs novel grey-level texture measurements on lumbar spine dual X-ray absorptiometry (DXA) images, and thereby captures information relating to trabecular microarchitecture. In order for TBS to usefully add to bone mineral density (BMD) and clinical risk factors in osteoporosis risk stratification, it must be independently associated with fracture risk, readily obtainable, and ideally, present a risk which is amenable to osteoporosis treatment. This paper summarizes a review of the scientific literature performed by a Working Group of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis. Low TBS is consistently associated with an increase in both prevalent and incident fractures that is partly independent of both clinical risk factors and areal BMD (aBMD) at the lumbar spine and proximal femur. More recently, TBS has been shown to have predictive value for fracture independent of fracture probabilities using the FRAX® algorithm. Although TBS changes with osteoporosis treatment, the magnitude is less than that of aBMD of the spine, and it is not clear how change in TBS relates to fracture risk reduction. TBS may also have a role in the assessment of fracture risk in some causes of secondary osteoporosis (e.g. diabetes, hyperparathyroidism and glucocorticoid-induced osteoporosis). In conclusion, there is a role for TBS in fracture risk assessment in combination with both aBMD and FRAX. PMID:25988660

  14. Bone marrow monocyte PECAM-1 deficiency elicits increased osteoclastogenesis resulting in trabecular bone loss.

    PubMed

    Wu, Yue; Tworkoski, Kathryn; Michaud, Michael; Madri, Joseph A

    2009-03-01

    In our investigations of the bone marrow (BM) of PECAM-1 null (knockout, KO) mice, we observed that the trabecular bone volume and number of trabeculae were significantly reduced in femoral and tibial long bones. Further studies in vitro revealed increased numbers and size of osteoclasts, enhanced bone resorption on dentin substrates, and hypersensitivity to macrophage CSF and receptor activator of NF-kappaB ligand in BM-derived osteoclast precursor cultures from KO mice. Associations among PECAM-1, Syk, and SHP-1 were found in wild-type BM monocyte derived osteoclast-like cells. The absence of PECAM-1 and SHP-1 interactions in the KO cells leads to the dysregulation of Syk kinases and/or phosphatases, possibly SHP-1. Indeed, KO derived osteoclast-like cells exhibited increased Syk tyrosine phosphorylation levels compared with WT cells. Lastly, WT mice engrafted with marrow from KO kindred showed loss of trabecular bone analogous to KO mice, consistent with increased osteoclastogenesis. PMID:19234161

  15. Trabecular bone of precocials at birth; Are they prepared to run for the wolf(f)?

    PubMed

    Gorissen, Ben M C; Wolschrijn, Claudia F; van Vilsteren, Anouk A M; van Rietbergen, Bert; van Weeren, P René

    2016-07-01

    Bone is a dynamic tissue adapting to loading according to "Wolff's law of bone adaptation." During very early life, however, such a mechanism may not be adequate enough to adapt to the dramatic change in environmental challenges in precocial species. Their neonates are required to stand and walk within hours after birth, in contrast to altricial animals that have much more time to adapt from the intrauterine environment to the outside world. In this study, trabecular bone parameters of the talus and sagittal ridge of the tibia from stillborn but full-term precocials (calves and foals) were analyzed by micro-CT imaging in order to identify possible anticipatory mechanisms to loading. Calculated average bone volume fraction in the Shetland pony (49-74%) was significantly higher compared to Warmblood foals (28-51%). Bovine trabecular bone was characterized by a low average bone volume fraction (22-28%), however, more directional anisotropy was found. It is concluded that anticipatory strategies in skeletal development exist in precocial species, which differ per species and are most likely related to anatomical differences in joint geometry and related loading patterns. The underlying regulatory mechanisms are still unknown, but they may be based on a genetic blueprint for the development of bone. More knowledge, both about a possible blueprint and its regulation, will be helpful in understanding developmental bone and joint diseases. J. Morphol. 277:948-956, 2016. © 2016 Wiley Periodicals, Inc. PMID:27098190

  16. Feasibility of bone assessment by using the nonlinear parameter in trabecular bone

    NASA Astrophysics Data System (ADS)

    Lee, Kang Il

    2013-04-01

    The purpose of the present study is to investigate the feasibility of assessing bone status and osteoporosis by using the nonlinear parameter B/A in bovine trabecular bone in vitro. The B/A values measured in 18 bovine femoral trabecular bone samples by using a finite-amplitude through-transmission method ranged from 63.3 to 122.6. The apparent bone density was highly correlated with the B/A and with the existing quantitative ultrasound parameters of the speed of sound (SOS) and the normalized broadband ultrasound attenuation (nBUA), with Pearson's correlation coefficients of r = 0.83 to 0.96. The best univariate predictor of the apparent bone density was the B/A, with an adjusted squared correlation coefficient of r 2 = 0.91. These results suggest that the B/A, in addition to the SOS and the nBUA, may have potential as an index for the assessment of bone status and osteoporosis.

  17. Influence of tool geometry on drilling performance of cortical and trabecular bone.

    PubMed

    Tuijthof, G J M; Frühwirt, C; Kment, C

    2013-08-01

    Minimally invasive surgery poses high demands on tool design. The goal was to measure the influence of drill bit geometry on maximum thrust forces required for drilling, and compare this relative to the known influence of feed rate and bone composition. Blind holes were drilled perpendicular to the iliac crest up to 10 mm depth in cadaveric pelvic bones of 20 pigs (adolescent) and 11 goats (full grown) with eight substantially different drill bits of ∅ 3-3.2 mm. Subsequently, boreholes were drilled perpendicular to the ilium with the same drill bits at three different feed rates (0.58 mm/s, 0.83 mm/s, 1.08 mm/s). The mean maximum thrust force ranges from 10 to 110 N for cortical bone, and from 3 to 65 N for trabecular bone. The results show that both drill bit geometry and feed rate have a significant influence on the maximum thrust forces, with a dominant influence of drill bit geometry in terms of shape of the flutes, sharpness of cutting edges and value of point angle. The differences in thrust forces between cortical and trabecular bone are substantial for all measured conditions. The measured values can be used for drill design. PMID:23298783

  18. Multi-Elemental Profiling of Tibial and Maxillary Trabecular Bone in Ovariectomised Rats.

    PubMed

    Han, Pingping; Lu, Shifeier; Zhou, Yinghong; Moromizato, Karine; Du, Zhibin; Friis, Thor; Xiao, Yin

    2016-01-01

    Atomic minerals are the smallest components of bone and the content of Ca, being the most abundant mineral in bone, correlates strongly with the risk of osteoporosis. Postmenopausal women have a far greater risk of suffering from OP due to low Ca concentrations in their bones and this is associated with low bone mass and higher bone fracture rates. However, bone strength is determined not only by Ca level, but also a number of metallic and non-metallic elements in bone. Thus, in this study, the difference of metallic and non-metallic elements in ovariectomy-induced osteoporosis tibial and maxillary trabecular bone was investigated in comparison with sham operated normal bone by laser ablation inductively-coupled plasma mass spectrometry using a rat model. The results demonstrated that the average concentrations of (25)Mg, (28)Si, (39)K, (47)Ti, (56)Fe, (59)Co, (77)Se, (88)Sr, (137)Ba, and (208)Pb were generally higher in tibia than those in maxilla. Compared with the sham group, Ovariectomy induced more significant changes of these elements in tibia than maxilla, indicating tibial trabecular bones are more sensitive to changes of circulating estrogen. In addition, the concentrations of (28)Si, (77)Se, (208)Pb, and Ca/P ratios were higher in tibia and maxilla in ovariectomised rats than those in normal bone at all time-points. The present study indicates that ovariectomy could significantly impact the element distribution and concentrations between tibia and maxilla. PMID:27338361

  19. Computational modelling of the mechanics of trabecular bone and marrow using fluid structure interaction techniques.

    PubMed

    Birmingham, E; Grogan, J A; Niebur, G L; McNamara, L M; McHugh, P E

    2013-04-01

    Bone marrow found within the porous structure of trabecular bone provides a specialized environment for numerous cell types, including mesenchymal stem cells (MSCs). Studies have sought to characterize the mechanical environment imposed on MSCs, however, a particular challenge is that marrow displays the characteristics of a fluid, while surrounded by bone that is subject to deformation, and previous experimental and computational studies have been unable to fully capture the resulting complex mechanical environment. The objective of this study was to develop a fluid structure interaction (FSI) model of trabecular bone and marrow to predict the mechanical environment of MSCs in vivo and to examine how this environment changes during osteoporosis. An idealized repeating unit was used to compare FSI techniques to a computational fluid dynamics only approach. These techniques were used to determine the effect of lower bone mass and different marrow viscosities, representative of osteoporosis, on the shear stress generated within bone marrow. Results report that shear stresses generated within bone marrow under physiological loading conditions are within the range known to stimulate a mechanobiological response in MSCs in vitro. Additionally, lower bone mass leads to an increase in the shear stress generated within the marrow, while a decrease in bone marrow viscosity reduces this generated shear stress. PMID:23519534

  20. Trabecular bone score (TBS) as a new complementary approach for osteoporosis evaluation in clinical practice.

    PubMed

    Harvey, N C; Glüer, C C; Binkley, N; McCloskey, E V; Brandi, M-L; Cooper, C; Kendler, D; Lamy, O; Laslop, A; Camargos, B M; Reginster, J-Y; Rizzoli, R; Kanis, J A

    2015-09-01

    Trabecular bone score (TBS) is a recently-developed analytical tool that performs novel grey-level texture measurements on lumbar spine dual X-ray absorptiometry (DXA) images, and thereby captures information relating to trabecular microarchitecture. In order for TBS to usefully add to bone mineral density (BMD) and clinical risk factors in osteoporosis risk stratification, it must be independently associated with fracture risk, readily obtainable, and ideally, present a risk which is amenable to osteoporosis treatment. This paper summarizes a review of the scientific literature performed by a Working Group of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis. Low TBS is consistently associated with an increase in both prevalent and incident fractures that is partly independent of both clinical risk factors and areal BMD (aBMD) at the lumbar spine and proximal femur. More recently, TBS has been shown to have predictive value for fracture independent of fracture probabilities using the FRAX® algorithm. Although TBS changes with osteoporosis treatment, the magnitude is less than that of aBMD of the spine, and it is not clear how change in TBS relates to fracture risk reduction. TBS may also have a role in the assessment of fracture risk in some causes of secondary osteoporosis (e.g., diabetes, hyperparathyroidism and glucocorticoid-induced osteoporosis). In conclusion, there is a role for TBS in fracture risk assessment in combination with both aBMD and FRAX. PMID:25988660

  1. Estimation of trabecular thickness in gray-scale images through granulometric analysis

    NASA Astrophysics Data System (ADS)

    Moreno, Rodrigo; Borga, Magnus; Smedby, Örjan

    2012-02-01

    This paper extends to gray-scale the method proposed by Hildebrand and Rüegsegger for estimating thickness of trabecular bone, which is the most used in trabecular bone research, where local thickness at a point is defined as the diameter of the maximum inscribed ball that includes that point. The proposed extension takes advantage of the equivalence between this method and the opening function computed for the granulometry generated by the opening operation of mathematical morphology with ball-shaped structuring elements of different diameter. The proposed extension (a) uses gray-scale instead of binary mathematical morphology, (b) uses all values of the pattern spectrum of the granulometry instead of the maximum peak as used for binary images, (c) corrects bias on local thickness estimations generated by partial volume effects, and (d) uses the gray-scale as a weighting function for global thickness estimation. The proposed extension becomes equivalent to the original method when it is applied to binary images. A new non-flat structuring element is also proposed in order to reduce the discretization errors generated by traditional flat structuring elements. Translation invariance can be attained by up-sampling the images through interpolation by a factor of two. Results for synthetic and real images show that the quality of the measurements obtained through the original method strongly depends on the binarization process, whereas the measurements obtained through the proposed extension do not. Consequently, the proposed extension is more appropriate for images with limited resolution where binarization is not trivial.

  2. Assessment of trabecular bone changes around endosseous implants using image analysis techniques: A preliminary study

    PubMed Central

    El Zuki, Mervet; Horner, Keith

    2014-01-01

    Purpose The objective of this study was to assess the trabecular bone changes that occurred around functional endosseous dental implants by means of radiographic image analysis techniques. Materials and Methods Immediate preoperative and postoperative periapical radiographs of de-identified implant patients at the University Dental Hospital of Manchester were retrieved, screened for specific inclusion criteria, digitized, and quantified for structural elements of the trabecular bone around the endosseous implants, by using image analysis techniques. Data were analyzed using SPSS version 11.5. P values of less than 0.05 were considered statistically significant. Results A total of 12 implants from 11 patients were selected for the study, and 26 regions of interest were obtained. There was a significant increase in the bone area in terms of the mean distance between nodes (p=0.006) and a significant decrease in the marrow area in terms of the bone area (p=0.006) and the length of marrow spaces (p=0.032). Conclusion It appeared that the bone around the implant underwent remodeling that resulted in a net increase in bone after implant placement. PMID:24944962

  3. Bonding strength of glass-ceramic trabecular-like coatings to ceramic substrates for prosthetic applications.

    PubMed

    Chen, Qiang; Baino, Francesco; Pugno, Nicola M; Vitale-Brovarone, Chiara

    2013-04-01

    A new approach based on the concepts of quantized fracture mechanics (QFM) is presented and discussed in this paper to estimate the bonding strength of trabecular-like coatings, i.e. glass-ceramic scaffolds mimicking the architecture of cancellous bone, to ceramic substrates. The innovative application of glass-derived scaffolds as trabecular-like coatings is proposed in order to enhance the osteointegration of prosthetic ceramic devices. The scaffolds, prepared by polymeric sponge replication, are joined to alumina substrates by a dense glass-ceramic coating (interlayer) and the so-obtained 3-layer constructs are investigated from micro-structural, morphological and mechanical viewpoints. In particular, the fracture strengths of three different crack propagation modes, i.e. glass-derived scaffold fracture, interface delamination or mixed fracture, are predicted in agreement with those of experimental mechanical tests. The approach proposed in this work could have interesting applications towards an ever more rational design of bone tissue engineering biomaterials and coatings, in view of the optimization of their mechanical properties for making them actually suitable for clinical applications. PMID:23827605

  4. Implant design and its effects on osseointegration over time within cortical and trabecular bone.

    PubMed

    Beutel, Bryan G; Danna, Natalie R; Granato, Rodrigo; Bonfante, Estevam A; Marin, Charles; Tovar, Nick; Suzuki, Marcelo; Coelho, Paulo G

    2016-08-01

    Healing chambers present at the interface between implant and bone have become a target for improving osseointegration. The objective of the present study was to compare osseointegration of several implant healing chamber configurations at early time points and regions of interest within bone using an in vivo animal femur model. Six implants, each with a different healing chamber configuration, were surgically implanted into each femur of six skeletally mature beagle dogs (n = 12 implants per dog, total n = 72). The implants were harvested at 3 and 5 weeks post-implantation, non-decalcified processed to slides, and underwent histomorphometry with measurement of bone-to-implant contact (BIC) and bone area fraction occupied (BAFO) within healing chambers at both cortical and trabecular bone sites. Microscopy demonstrated predominantly woven bone at 3 weeks and initial replacement of woven bone by lamellar bone by 5 weeks. BIC and BAFO were both significantly increased by 5 weeks (p < 0.001), and significantly higher in cortical than trabecular bone (p < 0.001). The trapezoidal healing chamber design demonstrated a higher BIC than other configurations. Overall, a strong temporal and region-specific dependence of implant osseointegration in femurs was noted. Moreover, the findings suggest that a trapezoidal healing chamber configuration may facilitate the best osseointegration. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1091-1097, 2016. PMID:26034012

  5. Grizzly bears (Ursus arctos horribilis) and black bears (Ursus americanus) prevent trabecular bone loss during disuse (hibernation).

    PubMed

    McGee-Lawrence, Meghan E; Wojda, Samantha J; Barlow, Lindsay N; Drummer, Thomas D; Castillo, Alesha B; Kennedy, Oran; Condon, Keith W; Auger, Janene; Black, Hal L; Nelson, O Lynne; Robbins, Charles T; Donahue, Seth W

    2009-12-01

    Disuse typically causes an imbalance in bone formation and bone resorption, leading to losses of cortical and trabecular bone. In contrast, bears maintain balanced intracortical remodeling and prevent cortical bone loss during disuse (hibernation). Trabecular bone, however, is more detrimentally affected than cortical bone in other animal models of disuse. Here we investigated the effects of hibernation on bone remodeling, architectural properties, and mineral density of grizzly bear (Ursus arctos horribilis) and black bear (Ursus americanus) trabecular bone in several skeletal locations. There were no differences in bone volume fraction or tissue mineral density between hibernating and active bears or between pre- and post-hibernation bears in the ilium, distal femur, or calcaneus. Though indices of cellular activity level (mineral apposition rate, osteoid thickness) decreased, trabecular bone resorption and formation indices remained balanced in hibernating grizzly bears. These data suggest that bears prevent bone loss during disuse by maintaining a balance between bone formation and bone resorption, which consequently preserves bone structure and strength. Further investigation of bone metabolism in hibernating bears may lead to the translation of mechanisms preventing disuse-induced bone loss in bears into novel treatments for osteoporosis. PMID:19703606

  6. Modeling and analysis of multiple scattering of acoustic waves in complex media: application to the trabecular bone.

    PubMed

    Wojcik, J; Litniewski, J; Nowicki, A

    2011-10-01

    The integral equations that describe scattering in the media with step-rise changing parameters have been numerically solved for the trabecular bone model. The model consists of several hundred discrete randomly distributed elements. The spectral distribution of scattering coefficients in subsequent orders of scattering has been presented. Calculations were carried on for the ultrasonic frequency ranging from 0.5 to 3 MHz. Evaluation of the contribution of the first, second, and higher scattering orders to total scattering of the ultrasounds in trabecular bone was done. Contrary to the approaches that use the μCT images of trabecular structure to modeling of the ultrasonic wave propagation condition, the 3D numerical model consisting of cylindrical elements mimicking the spatial matrix of trabeculae, was applied. The scattering, due to interconnections between thick trabeculae, usually neglected in trabecular bone models, has been included in calculations when the structure backscatter was evaluated. Influence of the absorption in subsequent orders of scattering is also addressed. Results show that up to 1.5 MHz, the influence of higher scattering orders on the total scattered field characteristic can be neglected while for the higher frequencies, the relatively high amplitude interference peaks in higher scattering orders clearly occur. PMID:21973345

  7. Adaptations of trabecular bone to low magnitude vibrations result in more uniform stress and strain under load.

    PubMed

    Judex, Stefan; Boyd, Steve; Qin, Yi-Xian; Turner, Simon; Ye, Kenny; Müller, Ralph; Rubin, Clinton

    2003-01-01

    Extremely low magnitude mechanical stimuli (<10 microstrain) induced at high frequencies are anabolic to trabecular bone. Here, we used finite element (FE) modeling to investigate the mechanical implications of a one year mechanical intervention. Adult female sheep stood with their hindlimbs either on a vibrating plate (30 Hz, 0.3 g) for 20 min/d, 5 d/wk or on an inactive plate. Microcomputed tomography data of 1 cm bone cubes extracted from the medial femoral condyles were transformed into FE meshes. Simulated compressive loads applied to the trabecular meshes in the three orthogonal directions indicated that the low level mechanical intervention significantly increased the apparent trabecular tissue stiffness of the femoral condyle in the longitudinal (+17%, p<0.02), anterior-posterior (+29%, p<0.01), and medial-lateral (+37%, p<0.01) direction, thus reducing apparent strain magnitudes for a given applied load. For a given apparent input strain (or stress), the resultant stresses and strains within trabeculae were more uniformly distributed in the off-axis loading directions in cubes of mechanically loaded sheep. These data suggest that trabecular bone responds to low level mechanical loads with intricate adaptations beyond a simple reduction in apparent strain magnitude, producing a structure that is stiffer and less prone to fracture for a given load. PMID:12572652

  8. Women with Anorexia Nervosa: Finite Element and Trabecular Structure Analysis by Using Flat-Panel Volume CT

    PubMed Central

    Phan, Catherine M.; Misra, Madhusmita; Bredella, Miriam A.; Miller, Karen K.; Fazeli, Pouneh K.; Bayraktar, Harun H.; Klibanski, Anne; Gupta, Rajiv

    2010-01-01

    Purpose: To use finite element modeling based on flat-panel volume computed tomography (CT) and bone mineral density (BMD) provided by dual-energy x-ray absorptiometry (DXA) to compare bone failure load, stiffness, and trabecular structure in women with anorexia nervosa (AN) and age-matched normal-weight control subjects. Materials and Methods: The study was approved by the institutional review board and complied with HIPAA guidelines. Informed consent was obtained. Fourteen women, eight with AN (mean age, 26.6 years) and six control subjects (mean age, 26.3 years), underwent flat-panel volume CT of the distal radius to determine apparent trabecular bone volume fraction (BV/TV), apparent trabecular number (TbN), apparent trabecular thickness (TbTh), and apparent trabecular separation (TbSp). Bone strength and stiffness were calculated from uniaxial compression tests by using finite element models created from flat-panel volume CT. DXA was used to determine BMD of the radius, lumbar spine, and hip. Means ± standard deviations of all variables were calculated for both groups and compared (Student t test). Univariate regression analysis and stepwise regression modeling were performed. Results: Patients with AN had lower values for stiffness (284.77 kN/mm ± 76.14 vs 389.97 kN/mm ± 84.90, P = .04), failure load (4.98 kN ± 1.23 vs 7.01 kN ± 1.52, P = .02), BV/TV (0.32% ± 0.09 vs 0.44% ± 0.02, P = .007), and TbN (1.15 mm−3 ± 0.20 vs 1.43 mm−3 ± 0.13, P = .008) and higher values for TbSp (0.62 mm ± 0.20 vs 0.40 mm ± 0.04, P = .02) compared with normal-weight control subjects. TbTh was lower in women with AN (P = .1). BMD measurements were significantly lower for the AN group. BMD measurements and trabecular parameters (except TbTh) correlated with stiffness and failure load (r = 0.58 to 0.83). Conclusion: Failure load and stiffness are abnormal in women with AN compared with those in normal-weight control subjects and correlate with BMD and trabecular

  9. Effect of trabecular orientation on mechanical resistance and ultrasound propagation in specimens of equine vertebrae.

    PubMed

    Cavani, Francesco; Fini, Milena; de Terlizzi, Francesca; Cadossi, Matteo; Ciminelli, Luca; Ortolani, Sergio; Cherubini, Roberto; De Aloysio, Domenico; Giavaresi, Gianluca; Cadossi, Ruggero; Canè, Valerio

    2003-12-01

    Osteoporosis involves alterations, not only in density, but also in the architectural organisation of the bone; in particular, trabecular orientation, following the skeletal load directions, lends a high degree of stiffness to the whole bone. We investigated the relationship between trabecular orientation, density, stiffness and ultrasound (US) propagation in two orthogonal directions (par. = parallel to, and ort. = orthogonal to the main orientation of the trabeculae) in cylindrical equine bone specimens (thoracic vertebrae) where a preferential orientation is present. A total of 15 cylinders were progressively decalcified with 0.2 mol/L ethylenediaminetetraacetic acid (EDTA). At different levels of decalcification, we measured the apparent density (g/cm(3)), bone mineral density or BMD (g/cm(2)), stiffness coefficient (MPa) and various US parameters. Before decalcification, stiffness values were the same in all directions. As the decalcification proceeded, the stiffness declined and, at low BMD values, it was significantly different in the two directions, being the highest in the par. one. Different behaviours of US parameters were observed in the two directions: SoS (speed of sound) was closely related to apparent density, BMD and stiffness in the par. direction (r = 0.88, 0.92 and 0.88, respectively, p < 0.0001). In the ort. direction, no significant association has been found between SoS and apparent density, BMD or stiffness. In the same experimental setup, US fast wave amplitude (FWA) was related to apparent density and BMD in the par. direction (r = 0.72 and 0.67, respectively, p < 0.0001) and in the ort. direction (r = 0.83 and r = 0.84 respectively, p < 0.0001). FWA was also correlated to stiffness in both directions (r = 0.61 par.; 0.81 ort., p < 0.0001). These results show that trabecular orientation strongly influences both mechanical properties of bone and US propagation. Furthermore, we found that US parameters can be predictors of mechanical

  10. Characterization of drug-release kinetics in trabecular bone from titania nanotube implants

    PubMed Central

    Aw, Moom Sinn; Khalid, Kamarul A; Gulati, Karan; Atkins, Gerald J; Pivonka, Peter; Findlay, David M; Losic, Dusan

    2012-01-01

    Purpose The aim of this study was to investigate the application of the three-dimensional bone bioreactor for studying drug-release kinetics and distribution of drugs in the ex vivo cancellous bone environment, and to demonstrate the application of nanoengineered titanium (Ti) wires generated with titania nanotube (TNT) arrays as drug-releasing implants for local drug delivery Methods Nanoengineered Ti wires covered with a layer of TNT arrays implanted in bone were used as a drug-releasing implant. Viable bovine trabecular bone was used as the ex vivo bone substrate embedded with the implants and placed in the bone reactor. A hydrophilic fluorescent dye (rhodamine B) was used as the model drug, loaded inside the TNT–Ti implants, to monitor drug release and transport in trabecular bone. The distribution of released model drug in the bone was monitored throughout the bone structure, and concentration profiles at different vertical (0–5 mm) and horizontal (0–10 mm) distances from the implant surface were obtained at a range of release times from 1 hour to 5 days. Results Scanning electron microscopy confirmed that well-ordered, vertically aligned nanotube arrays were formed on the surface of prepared TNT–Ti wires. Thermogravimetric analysis proved loading of the model drug and fluorescence spectroscopy was used to show drug-release characteristics in-vitro. The drug release from implants inserted into bone ex vivo showed a consistent gradual release of model drug from the TNT–Ti implants, with a characteristic three-dimensional distribution into the surrounding bone, over a period of 5 days. The parameters including the flow rate of bone culture medium, differences in trabecular microarchitecture between bone samples, and mechanical loading were found to have the most significant influence on drug distribution in the bone. Conclusion These results demonstrate the utility of the Zetos™ system for ex vivo drug-release studies in bone, which can be applied to

  11. Additively Manufactured 3D Porous Ti-6Al-4V Constructs Mimic Trabecular Bone Structure and Regulate Osteoblast Proliferation, Differentiation and Local Factor Production in a Porosity and Surface Roughness Dependent Manner

    PubMed Central

    Cheng, Alice; Humayun, Aiza; Cohen, David J.; Boyan, Barbara D.; Schwartz, Zvi

    2014-01-01

    Additive manufacturing by laser sintering is able to produce high resolution metal constructs for orthopaedic and dental implants. In this study, we used a human trabecular bone template to design and manufacture Ti-6Al-4V constructs with varying porosity via laser sintering. Characterization of constructs revealed interconnected porosities ranging from 15–70% with compressive moduli of 2063–2954 MPa. These constructs with macro porosity were further surface-treated to create a desirable multi-scale micro-/nano-roughness, which has been shown to enhance the osseointegration process. Osteoblasts (MG63 cells) exhibited high viability when grown on the constructs. Proliferation (DNA) and alkaline phosphatase specific activity (ALP), an early differentiation marker, decreased as porosity increased, while osteocalcin (OCN), a late differentiation marker, as well as osteoprotegerin (OPG), vascular endothelial growth factor (VEGF) and bone morphogenetic proteins 2 and 4 (BMP2, BMP4) increased with increasing porosity. 3D constructs with the highest porosity and surface modification supported the greatest osteoblast differentiation and local factor production. These results indicate that additively manufactured 3D porous constructs mimicking human trabecular bone and produced with additional surface treatment can be customized for increased osteoblast response. Increased factors for osteoblast maturation and differentiation on high porosity constructs suggest the enhanced performance of these surfaces for increasing osseointegration in vivo. PMID:25287305

  12. Numerical simulation on the adaptation of forms in trabecular bone to mechanical disuse and basic multi-cellular unit activation threshold at menopause

    NASA Astrophysics Data System (ADS)

    Gong, He; Fan, Yubo; Zhang, Ming

    2008-04-01

    The objective of this paper is to identify the effects of mechanical disuse and basic multi-cellular unit (BMU) activation threshold on the form of trabecular bone during menopause. A bone adaptation model with mechanical- biological factors at BMU level was integrated with finite element analysis to simulate the changes of trabecular bone structure during menopause. Mechanical disuse and changes in the BMU activation threshold were applied to the model for the period from 4 years before to 4 years after menopause. The changes in bone volume fraction, trabecular thickness and fractal dimension of the trabecular structures were used to quantify the changes of trabecular bone in three different cases associated with mechanical disuse and BMU activation threshold. It was found that the changes in the simulated bone volume fraction were highly correlated and consistent with clinical data, and that the trabecular thickness reduced significantly during menopause and was highly linearly correlated with the bone volume fraction, and that the change trend of fractal dimension of the simulated trabecular structure was in correspondence with clinical observations. The numerical simulation in this paper may help to better understand the relationship between the bone morphology and the mechanical, as well as biological environment; and can provide a quantitative computational model and methodology for the numerical simulation of the bone structural morphological changes caused by the mechanical environment, and/or the biological environment.

  13. Identification of couple-stress moduli of vertebral trabecular bone based on the 3D internal architectures.

    PubMed

    Goda, Ibrahim; Ganghoffer, Jean-François

    2015-11-01

    The purpose of this paper is to develop a homogeneous, orthotropic couple-stress continuum model as a substitute of the 3D periodic heterogeneous cellular solid model of vertebral trabecular bone. Vertebral trabecular bone is modeled as a porous material with an idealized periodic structure made of 3D open cubic cells, which is effectively orthotropic. The chosen architecture is based on studies of samples taken from the central part of vertebral bodies. The effective properties are obtained based on the response of the representative volume element under prescribed boundary conditions. Mixed boundary conditions comprising both traction and displacement boundary conditions are applied on the structure boundaries. In this contribution, the effective mechanical constants of the effective couple-stress continuum are deduced by an equivalent strain energy method. The characteristic lengths for bending and torsion are identified from the resulting homogenized orthotropic moduli. We conduct this study computationally using a finite element approach. Vertebral trabecular bone is modeled either as a cellular solid or as a two-phase material consisting of bone tissue (stiff phase) forming a trabecular network, and a surrounding soft tissue referring to the bone marrow present in the pores. Both the bone tissue forming the network and the pores are assumed to be homogeneous linear elastic, and isotropic media. The scale effects on the predicted couple stress moduli of these networks are investigated by varying the size of the bone specimens over which the boundary conditions are applied. The analysis using mixed boundary conditions gives results that are independent of unit cell size when computing the first couple stress tensor, while it is dependent on the cell size as to the second couple stress tensor moduli. This study provides overall guidance on how the size of the trabecular specimen influence couple stresses elastic moduli of cellular materials, with focus on bones

  14. Microdistribution and retention of injected /sup 239/Pu on trabecular bone surfaces of the beagle: implications for the induction of osteosarcoma

    SciTech Connect

    Wronski, T.J.; Smith, J.M.; Jee, W.S.S.

    1980-07-01

    A study was initiated to investigate the relationship between skeletal remodeling and the microdistribution and retention of /sup 239/Pu on trabecular bone surfaces of the beagle, and the contribution of these parameters to the nonuniform skeletal distribution of /sup 239/Pu-induced osteosarcomas. Young adult beagles were administered single iv injections of approx. 0.016 ..mu..Ci/kg monomeric /sup 239/Pu citrate and sacrificed at various times to 1 year after injection. The /sup 239/Pu concentration on trabecular bone surfaces was determined by counting fission fragment tracks in neutron-induced autoradiographs produced from thick (approx. 400 ..mu..m) bone sections. The rate of trabecular bone formation was calculated from an ultraviolet microscopic analysis of fluorescent tetracycline labels. The lumbar vertebra, pelvis, and proximal humerus, each of which exhibits a high incidence of /sup 239/Pu-induced osteosarcoma, were found to have a high intial concentration of /sup 239/Pu on their trabecular surfaces (approx. 7-8 pCi/cm/sup 2/) and a relatively high rate of trabecular bone formation. The /sup 239/Pu concentration at these sites decreased to approx. 2-3 pCi/cm/sup 2/ at the end of the first year. On the other hand, the proximal ulna and distal humerus, skeletal sites with a low tumor incidence, had a low intial concentration of /sup 239/Pu on their trabecular surfaces(approx. 1-2 pCi/cm/sup 2/) and a significantly lower rate of trabecular bone formation (P < 0.01). The /sup 239/Pu concentration at these sites remained nearly constant throughout the experimental period. These data suggest that the degree of the initial deposition of /sup 239/Pu on trabecular bone surfaces and the rate of trabecular bone turnover may play a role in the genesis of /sup 239/Pu-induced osteosarcomas.

  15. A review of the iStent® trabecular micro-bypass stent: safety and efficacy

    PubMed Central

    Wellik, Sarah R; Dale, Elizabeth A

    2015-01-01

    There is a significant demand for procedures that can effectively treat glaucoma with low risk and good visual outcomes. To fill this void, procedures termed “minimally invasive glaucoma surgery”, are gaining in popularity. This review will focus on the safety and efficacy of one such minimally invasive glaucoma surgery procedure, the trabecular micro-bypass stent. This stent is intended to lower intraocular pressure by directly cannulating Schlemm’s canal and thereby enhancing aqueous outflow. Recent randomized controlled trials and case series have demonstrated the micro-bypass stent to be a relatively safe procedure, with limited complications and no serious adverse sequelae. The most common complication across all studies was stent obstruction or malposition, which generally did not result in any adverse outcome in vision or pressure control. In addition, increased rates of hypotony, choroidal hemorrhage, or infection were not seen with the micro-bypass stent in comparison to cataract surgery alone. PMID:25931808

  16. The speed of sound through trabecular bone predicted by Biot theory.

    PubMed

    Yoon, Young June; Chung, Jae-Pil; Bae, Chul-Soo; Han, Seog-Young

    2012-02-23

    Cancellous bone is a highly porous material filled with fluid. The mechanical properties of cancellous bone determine whether the bone is normal or osteoporotic. Wave propagation can be used to measure the elastic constants of cancellous bone. Recently, poroelasticity theory has been used to predict the elastic constants of cancellous bone from the wave velocities. In this study, it is shown that the fast wave, predicted by the Biot theory, corresponds to the wave penetrating the trabeculae, while the slow wave is determined by the interaction between the trabeculae and the fluid. The trabecular shape does not affect the wave velocity significantly when using the variable, which is determined by the microstructure, and the slow wave velocity decreases after the porosity reaches 80%. PMID:22244093

  17. Improved Trabecular Bone Structure of 20-Month-Old Male Spontaneously Hypertensive Rats

    PubMed Central

    Lee, Tzu-Cheng; Burghardt, Andrew J.; Yao, Wei; Lane, Nancy E.; Majumdar, Sharmila; Gullberg, Grant T.; Seo, Youngho

    2014-01-01

    A few clinical studies have reported that elderly male participants with hypertensive disease frequently have higher BMD than the normotensive participants at several skeletal sites. The detailed mechanism is still unknown; therefore a study of bone structure and density using the hypertensive animal models could be informative. We used micro-computed tomography (μCT) to quantitatively evaluate the tibial and 3rd lumbar vertebral bones in the 20-month-old male spontaneous hypertensive rat (SHR). The BMD, volume fraction, and the microarchitecture changes of the SHR were compared to those of same-age normotensive controls (Wistar-Kyoto rat, WKY). We found that in the very old (20-month) male rats, the trabecular bone fraction and microstructure were higher than those in the same-age normotensive controls. The observation of the association of hypertension with BMD and bone strength in hypertensive rats warrants further investigations of bone mass and strength in elderly males with hypertension. PMID:25106873

  18. Novel Technique: Knee Arthrodesis Using Trabecular Metal Cones with Intramedullary Nailing and Intramedullary Autograft.

    PubMed

    Peterson, Blake E; Bal, Sonny; Aggarwal, Ajay; Crist, Brett D

    2016-08-01

    The failed total knee arthroplasty is a challenge to the surgeon and the patient. Infection, bone loss, and instability lead to a chronically painful and dysfunctional limb. Two-stage revision arthroplasty has been successful in clearing a majority of periprosthetic joint infections. However, there are many cases when the multiply revised and infected total knee arthroplasty cannot be salvaged. We report, a review of knee arthrodesis and a novel technique to manage significant bone loss. The use of trabecular metal cones and a long intramedullary nail can be used in concert with an autologous intramedullary bone graft to provide a stable, length restoring construct with sufficient biology to heal very large bone voids. With this technique we have successfully restored function and stability in the failed knee arthroplasty. PMID:26551067

  19. Fracture properties of growth plate cartilage compared to cortical and trabecular bone in ovine femora.

    PubMed

    Tschegg, E K; Celarek, A; Fischerauer, S F; Stanzl-Tschegg, S; Weinberg, A M

    2012-10-01

    Fracture mechanical parameters (notch tensile strength, specific fracture energy/crack resistance and specific crack initiation energy) of epiphyseal plate cartilage, trabecular bone (metaphysis) and cortical bone (diaphysis) were determined on ovine femur specimens. The fracture behaviour before and after crack initiation was recorded in force-displacement diagrams from wedge splitting tests. Crack propagation was stable both during and after the formation of a principal crack. This is the main advantage of the wedge-splitting method by Tschegg in comparison with tensile tests. Microscopy of the epiphyseal plate during fracture showed fibre elongation and tearing in the crack tip region. The results of this study can help to understand the mechanics of epiphyseal plate injuries and the obtained values can be used for computational simulations and models. PMID:23022566

  20. Pycnogenol® treatment inhibits bone mineral density loss and trabecular deterioration in ovariectomized rats

    PubMed Central

    Huang, Gangyong; Wu, Jianguo; Wang, Siqun; Wei, Yibing; Chen, Feiyan; Chen, Jie; Shi, Jingsheng; Xia, Jun

    2015-01-01

    Context: Pycnogenol® extracted from French maritime pine bark (Pinus pinaster Ait. subsp. atlantica) is functional for its antioxidant activity. Objective: To investigate the effects of Pycnogenol® on bone mineral density (BMD), trabecular microarchitecture and bone metabolism in ovariectomized (OVX) rats. Materials and methods: Thirty Sprague-Dawley rats were randomized into 3 groups: SHAM group (sham-operated rats), OVX group (OVX rats), and treatment group (OVX rats supplemented with 40 mg/kg Pycnogenol® by oral gavage). Serum levels of procollagen type I N-terminal propeptide (PINP), alkaline phosphatase (ALP) and minerals were detected at the end of 9 weeks of gavage. Deoxypyridinoline/creatinine (DPYD/Cr) and N-telopeptide of type I collagen/creatinine (NTX/Cr) rate in urine were also calculated. Left femora were collected for BMD determination, and the right distal femora were made into undecalcified specimens for histomorphometry analysis. Results: At the end of study, PINP level, DPYD/Cr and NTX/Cr rate were significantly increased, and femoral BMD were dramatically decreased in OVX group compared with SHAM group (P < 0.01) while serum minerals and ALP concentrations showed no significant difference. The treatment group had dramatically decreased biomarkers and increased BMD than OVX group (P < 0.01). Histomorphometry analysis showed worse bone microarchitecture parameters in the OVX group compared with the SHAM group which were significantly improved in the treatment group compared with the OVX group (P < 0.01). Discussion and conclusion: Pycnogenol® (40 mg/kg) can inhibit aggravated bone resorption, prevent BMD loss, and restore the impaired trabecular microarchitecture in OVX rats after 9-week-intervention. PMID:26379883

  1. Prediction of apparent trabecular bone stiffness through fourth-order fabric tensors.

    PubMed

    Moreno, Rodrigo; Smedby, Örjan; Pahr, Dieter H

    2016-08-01

    The apparent stiffness tensor is an important mechanical parameter for characterizing trabecular bone. Previous studies have modeled this parameter as a function of mechanical properties of the tissue, bone density, and a second-order fabric tensor, which encodes both anisotropy and orientation of trabecular bone. Although these models yield strong correlations between observed and predicted stiffness tensors, there is still space for reducing accuracy errors. In this paper, we propose a model that uses fourth-order instead of second-order fabric tensors. First, the totally symmetric part of the stiffness tensor is assumed proportional to the fourth-order fabric tensor in the logarithmic scale. Second, the asymmetric part of the stiffness tensor is derived from relationships among components of the harmonic tensor decomposition of the stiffness tensor. The mean intercept length (MIL), generalized MIL (GMIL), and fourth-order global structure tensor were computed from images acquired through microcomputed tomography of 264 specimens of the femur. The predicted tensors were compared to the stiffness tensors computed by using the micro-finite element method ([Formula: see text]FE), which was considered as the gold standard, yielding strong correlations ([Formula: see text] above 0.962). The GMIL tensor yielded the best results among the tested fabric tensors. The Frobenius error, geodesic error, and the error of the norm were reduced by applying the proposed model by 3.75, 0.07, and 3.16 %, respectively, compared to the model by Zysset and Curnier (Mech Mater 21(4):243-250, 1995) with the second-order MIL tensor. From the results, fourth-order fabric tensors are a good alternative to the more expensive [Formula: see text]FE stiffness predictions. PMID:26341838

  2. Effect of a novel load-bearing trabecular Nitinol scaffold on rabbit radius bone regeneration

    NASA Astrophysics Data System (ADS)

    Gotman, Irena; Zaretzky, Asaph; Psakhie, Sergey G.; Gutmanas, Elazar Y.

    2015-10-01

    The research aim was to evaluate the bone regeneration capability of novel load-bearing NiTi alloy (Nitinol) scaffolds in a critical-size defect (CSD) model. High strength "trabecular Nitinol" scaffolds were prepared by PIRAC (Powder Immersion Reaction Assisted Coating) annealing of the highly porous Ni foam in Ti powder at 900°C. This was followed by PIRAC nitriding to mitigate the release of potentially toxic Ni ions. Scaffolds phase composition and microstructure were characterized by X-ray diffraction and scanning electron microscopy (SEM/EDS), and their mechanical properties were tested in compression. New Zealand white rabbits received bone defect in right radius and were divided in four groups randomly. In the control group, nothing was placed in the defect. In other groups, NiTi scaffolds were implanted in the defect: (i) as produced, (ii) loaded with bone marrow aspirate (BMA), and (iii) biomimetically CaP-coated. The animals were sacrificed after 12 weeks. The forelimbs with scaffolds were resected, fixed, sectioned and examined in SEM. New bone formation inside the scaffold was studied by EDS analysis and by the processing of backscattered electron images. Bone ingrowth into the scaffold was observed in all implant groups, mostly next to the ulna. New bone formation was strongly enhanced by BMA loading and biomimeatic CaP coating, the bone penetrating as much as 1-1.5 mm into the scaffold. The results of this preliminary study demonstrate that the newly developed high strength trabecular Nitinol scaffolds can be successfully used for bone regeneration in critical size defects.

  3. Bovine viral diarrhea virus cyclically impairs long bone trabecular modeling in experimental persistently infected fetuses.

    PubMed

    Webb, B T; Norrdin, R W; Smirnova, N P; Van Campen, H; Weiner, C M; Antoniazzi, A Q; Bielefeldt-Ohmann, H; Hansen, T R

    2012-11-01

    Persistent infection (PI) with bovine viral diarrhea virus (BVDV) has been associated with osteopetrosis and other long bone lesions, most commonly characterized as transverse zones of unmodeled metaphyseal trabeculae in fetuses and calves. This study was undertaken to characterize the morphogenesis of fetal long bone lesions. Forty-six BVDV-naïve pregnant Hereford heifers of approximately 18 months of age were inoculated with noncytopathic BVDV type 2 containing media or media alone on day 75 of gestation to produce PI and control fetuses, respectively, which were collected via cesarean section on days 82, 89, 97, 192, and 245 of gestation. Radiographic and histomorphometric abnormalities were first detected on day 192, at which age PI fetal long bone metaphyses contained focal densities (4 of 7 fetuses) and multiple alternating transverse radiodense bands (3 of 7 fetuses). Day 245 fetuses were similarly affected. Histomorphometric analysis of proximal tibial metaphyses from day 192 fetuses revealed transverse zones with increased calcified cartilage core (Cg.V/BV, %) and trabecular bone (BV/TV, %) volumes in regions corresponding to radiodense bands (P < .05). Numbers of tartrate resistant acid phosphatase positive osteoclasts (N.Oc/BS, #/mm(2)) and bone perimeter occupied (Oc.S/BS, %) were both decreased (P < .05). Mineralizing surface (MS/BS, %), a measure of tissue level bone formation activity, was reduced in PI fetuses (P < .05). It is concluded that PI with BVDV induces cyclic abnormal trabecular modeling, which is secondary to reduced numbers of osteoclasts. The factors responsible for these temporal changes are unknown but may be related to the time required for osteoclast differentiation from precursor cells. PMID:22362966

  4. Effect of a novel load-bearing trabecular Nitinol scaffold on rabbit radius bone regeneration

    SciTech Connect

    Gotman, Irena Gutmanas, Elazar Y.; Zaretzky, Asaph; Psakhie, Sergey G.

    2015-10-27

    The research aim was to evaluate the bone regeneration capability of novel load-bearing NiTi alloy (Nitinol) scaffolds in a critical-size defect (CSD) model. High strength “trabecular Nitinol” scaffolds were prepared by PIRAC (Powder Immersion Reaction Assisted Coating) annealing of the highly porous Ni foam in Ti powder at 900°C. This was followed by PIRAC nitriding to mitigate the release of potentially toxic Ni ions. Scaffolds phase composition and microstructure were characterized by X-ray diffraction and scanning electron microscopy (SEM/EDS), and their mechanical properties were tested in compression. New Zealand white rabbits received bone defect in right radius and were divided in four groups randomly. In the control group, nothing was placed in the defect. In other groups, NiTi scaffolds were implanted in the defect: (i) as produced, (ii) loaded with bone marrow aspirate (BMA), and (iii) biomimetically CaP-coated. The animals were sacrificed after 12 weeks. The forelimbs with scaffolds were resected, fixed, sectioned and examined in SEM. New bone formation inside the scaffold was studied by EDS analysis and by the processing of backscattered electron images. Bone ingrowth into the scaffold was observed in all implant groups, mostly next to the ulna. New bone formation was strongly enhanced by BMA loading and biomimeatic CaP coating, the bone penetrating as much as 1–1.5 mm into the scaffold. The results of this preliminary study demonstrate that the newly developed high strength trabecular Nitinol scaffolds can be successfully used for bone regeneration in critical size defects.

  5. Trabecular domain factor and its influence on the strength of cancellous bone of the vertebral body.

    PubMed

    Tanaka, Y; Kokubun, S; Sato, T; Iwamoto, M; Sato

    2001-11-01

    The effects of architectural differences on the strength of cancellous bone of the vertebral body have not been clarified. This study was aimed at determining the influence of trabecular domain factor (TDF), a new histomorphometric parameter, on the maximum compressive strength (MCS) in vertebral cancellous bone. TDF is a variation coefficient representing the ratio dispersion of the area of each trabecula (Sd) to the area of its domain (D). A Voronoi diagram was used to determine trabecular domains. The materials comprised 35 lumbar vertebral bodies obtained at autopsy from 35 subjects aged 25-83 years. A mechanical test sample (12 x 12 x 16 mm) was cut out from each right half, and two large, undecalcified, horizontal sections from each left half. The fields (144 mm2 x 2) for image analyses were symmetrical with those for mechanical test samples in the other half of the same vertebral body. Bone volume (BV/TV), Sd, and D were semiautomatically measured. BV/TV correlated negatively with TDF (r = -0.73). Multiple regression analysis revealed the contributions of BV/TV (partial r = 0.75, p < 0.001) and TDF (partial r = -0.42, p < 0.02) to MCS. The model with BV/TV and TDF predicted MCS, 1.50 +0.15 BV/TV -0.03 TDF, more accurately (R2 = 0.83) than that with BV/TV alone (r2 = 0.79). We conclude that the bone volume primarily contributes to the MCS of vertebral cancellous bones but that the influence of TDF on the fragility becomes increasingly important as the bone volume decreases. PMID:11768199

  6. Ultrastructural and pharmacologic studies on laser-induced glaucoma in primates and rabbits

    SciTech Connect

    March, W.F.; Gherezghiher, T.; Koss, M.; Nordquist, R.

    1984-01-01

    Sustained high intraocular pressure resulting in optic nerve cupping and loss of ganglion cells was produced in five rhesus monkeys and eight pigmented rabbits by applying argon laser energy to the trabecular meshwork. In addition, the rabbits manifested buphthalmus. Flow of carbon particles subsequently injected into the anterior chamber was obstructed at the trabecular meshwork by a wound-healing response that closed the intratrabecular spaces. Besides this sustained high intraocular pressure as a result of late scarring, an acute hypertensive response was seen in all rabbits which may correspond to the acute hypertension seen after laser trabeculoplasty in humans. The acute hypertensive response could be only partially blocked by prostaglandin inhibitors and the authors believe that prostaglandins are not primarily responsible for this effect. Medications known to lower intraocular pressure were systematically tested in both glaucoma models.

  7. Megapinocytosis: a novel endocytic pathway.

    PubMed

    Bauer, Andrea; Subramanian, Narmadha; Villinger, Clarissa; Frascaroli, Giada; Mertens, Thomas; Walther, Paul

    2016-06-01

    M2 macrophages showed large endocytotic structures, very different from classical macropinosomes that we named megapinosomes. As observed in the scanning electron microscope, megapinosome formation started with a large (diameter of several micrometers) invagination of the plasma membrane. When the invagination was almost completed, the remaining opening was closed by an actinomorphous centripetal arrangement of many (about 50-100) microvilli-like structures. In transmission electron microscopy using high-pressure freezing, we observed that the megapinosome was filled with a trabecular meshwork that originated from the highly structured plasma membrane. The trabecular meshwork was topologically part of the cytosol and separated from the extracellular fluid by a lipid bilayer. According to ultrastructural features, we could define different phases of megapinosome formation and decay. Megapinosomes became more frequent when M2 macrophages were inoculated with human cytomegalovirus. We did not find megapinosome formation in M1 macrophages. PMID:26733077

  8. A Robust Algorithm for Thickness Computation at Low Resolution and Its Application to In Vivo Trabecular Bone CT Imaging

    PubMed Central

    Liu, Yinxiao; Jin, Dakai; Li, Cheng; Janz, Kathleen F.; Burns, Trudy L.; Torner, James C.; Levy, Steven M.; Saha, Punam K.

    2015-01-01

    Adult bone diseases, especially osteoporosis, lead to increased risk of fracture which in turn is associated with substantial morbidity, mortality, and financial costs. Clinically, osteoporosis is defined by low bone mineral density; however, increasing evidence suggests that the microarchitectural quality of trabecular bone (TB) is an important determinant of bone strength and fracture risk. Accurate measures of TB thickness and marrow spacing is of significant interest for early diagnosis of osteoporosis or treatment effects. Here, we present a new robust algorithm for computing TB thickness and marrow spacing at a low resolution achievable in vivo. The method uses a star-line tracing technique that effectively deals with partial voluming effects of in vivo imaging with voxel size comparable to TB thickness. Also, the method avoids the problem of digitization associated with conventional algorithms based on sampling distance transform along skeletons. Accuracy of the method was examined using computer-generated phantom images, while the robustness of the method was evaluated on human ankle specimens in terms of stability across a wide range of voxel sizes, repeat scan reproducibility under in vivo conditions, and correlation between thickness values computed at ex vivo and in vivo imaging resolutions. Also, the sensitivity of the method was examined by evaluating its ability to predict the bone strength of cadaveric specimens. Finally, the method was evaluated in a human study involving 40 healthy young-adult volunteers (age: 19–21 years; 20 males and 20 females) and ten athletes (age: 19–21 years; six males and four females). Across a wide range of voxel sizes, the new method is significantly more accurate and robust as compared to conventional methods. Both TB thickness and marrow spacing measures computed using the new method demonstrated strong associations (R2 ∈ [0.83, 0.87]) with bone strength. Also, the TB thickness and marrow spacing measures

  9. Evaluation of Trabecular Micro-Architecture in Non-Osteoporotic Post-Menopausal Women With and Without Fracture

    PubMed Central

    Kijowski, Richard; Tuite, Michael; Kruger, Diane; Del Rio, Alejandro Munoz; Kleerekoper, Michael; Binkley, Neil

    2012-01-01

    Purpose To compare microscopic magnetic resonance imaging (μMRI) parameters of trabecular micro-architecture between postmenopausal women with and without fracture who have normal or osteopenic bone mineral density (BMD) on dual-energy x-ray absorptiometry (DXA). Methods The study included 36 post-menopausal Caucasian women 50 years of age and older with normal or osteopenic BMD (T-scores better than −2.5 at the lumbar spine, proximal femur, and one-third radius on DXA). Eighteen women had a history of low-energy fracture, while 18 women had no history of fracture and served as an age, race, and ultra-distal radius BMD-matched control group. A three-dimensional fast large-angle spin-echo (FLASE) sequence with 137 μm × 137 μm × 400 μm resolution was performed through the non-dominant wrist of all 36 women using the same 1.5T scanner. The high resolution images were used to measure trabecular bone volume fraction, trabecular thickness, surface-to-curve ratio, and erosion index. Wilcoxon signed rank tests were used to compare differences in BMD and μMRI parameters between post-menopausal women with and without fracture. Results Post-menopausal women with fracture had significantly lower (p<0.05) trabecular bone volume fraction and surface-to-curve ratio and significantly higher (p<0.05) erosion index than post-menopausal women without fracture. There was no significant difference between post-menopausal women with and without fracture in trabecular thickness (p=0.80) and BMD of the spine (p=0.21), proximal femur (p=0.19), one-third radius (p=0.47), and ultra-distal radius (p=0.90). Conclusions Post-menopausal women with normal or osteopenic BMD who had a history of low energy fracture had significantly different (p<0.05) μMRI parameters than an age, race, and ultra-distal radius BMD-matched control group of postmenopausal women with no history of fracture. Our study suggests that μMRI can be used to identify individuals without a DXA-based diagnosis of

  10. Preclinical assessment of a new magnetic resonance-based technique for determining bone quality by characterization of trabecular microarchitecture.

    PubMed

    Evans, B A J; James, T W; James, K; Cox, A; Farr, L; Paisey, S J; Dempster, D W; Stone, M D; Griffiths, P A; Hugtenburg, R P; Brady, Sir M; Wells, T

    2014-12-01

    The utility of HR-CT to study longitudinal changes in bone microarchitecture is limited by subject radiation exposure. Although MR is not subject to this limitation, it is limited both by patient movement that occurs during prolonged scanning at distal sites, and by the signal-to-noise ratio that is achievable for high-resolution images in a reasonable scan time at proximal sites. Recently, a novel MR-based technique, fine structure analysis (FSA) (Chase et al. Localised one-dimensional magnetic resonance spatial frequency spectroscopy. PCT/US2012/068284 2012, James and Chase Magnetic field gradient structure characteristic assessment using one-dimensional (1D) spatial frequency distribution analysis. 7932720 B2, 2011) has been developed which provides both high-resolution and fast scan times, but which generates at a designated set of spatial positions (voxels) a one-dimensional signal of spatial frequencies. Appendix 1 provides a brief introduction to FSA. This article describes an initial exploration of FSA for the rapid, non-invasive characterization of trabecular microarchitecture in a preclinical setting. For L4 vertebrae of sham and ovariectomized (OVX) rats, we compared FSA-generated metrics with those from CT datasets and from CT-derived histomorphometry parameters, trabecular number (Tb.N), bone volume density (BV/TV), trabecular thickness (Tb.Th) and trabecular separation (Tb.Sp). OVX caused a reduction of the higher frequency structures that correspond to a denser trabecular lattice, while increasing the preponderance of lower frequency structures, which correspond to a more open lattice. As one example measure, the centroid of the FSA spectrum (which we refer to as fSAcB) showed strong correlation in the same region with CT-derived histomorphometry values: Tb.Sp: r -0.63, p < 0.001; Tb.N: r 0.71, p < 0.001; BV/TV: r 0.64, p < 0.001, Tb.Th: r 0.44, p < 0.05. Furthermore, we found a 17.5% reduction in fSAcB in OVX rats (p < 0.0001). In a longitudinal

  11. Nectin-1 spots as a novel adhesion apparatus that tethers mitral cell lateral dendrites in a dendritic meshwork structure of the developing mouse olfactory bulb.

    PubMed

    Inoue, Takahito; Fujiwara, Takeshi; Rikitake, Yoshiyuki; Maruo, Tomohiko; Mandai, Kenji; Kimura, Kazushi; Kayahara, Tetsuro; Wang, Shujie; Itoh, Yu; Sai, Kousyoku; Mori, Masahiro; Mori, Kensaku; Mizoguchi, Akira; Takai, Yoshimi

    2015-08-15

    Mitral cells project lateral dendrites that contact the lateral and primary dendrites of other mitral cells and granule cell dendrites in the external plexiform layer (EPL) of the olfactory bulb. These dendritic structures are critical for odor information processing, but it remains unknown how they are formed. In immunofluorescence microscopy, the immunofluorescence signal for the cell adhesion molecule nectin-1 was concentrated on mitral cell lateral dendrites in the EPL of the developing mouse olfactory bulb. In electron microscopy, the immunogold particles for nectin-1 were symmetrically localized on the plasma membranes at the contacts between mitral cell lateral dendrites, which showed bilateral darkening without dense cytoskeletal undercoats characteristic of puncta adherentia junctions. We named the contacts where the immunogold particles for nectin-1 were symmetrically accumulated "nectin-1 spots." The nectin-1 spots were 0.21 μm in length on average and the distance between the plasma membranes was 20.8 nm on average. In 3D reconstruction of serial sections, clusters of the nectin-1 spots formed a disc-like structure. In the mitral cell lateral dendrites of nectin-1-knockout mice, the immunogold particles for nectin-1 were undetectable and the plasma membrane darkening was electron-microscopically normalized, but the plasma membranes were partly separated from each other. The nectin-1 spots were further identified between mitral cell lateral and primary dendrites and between mitral cell lateral dendrites and granule cell dendritic spine necks. These results indicate that the nectin-1 spots constitute a novel adhesion apparatus that tethers mitral cell dendrites in a dendritic meshwork structure of the developing mouse olfactory bulb. PMID:25967681

  12. High resolution magnetic resonance imaging of the calcaneus: age-related changes in trabecular structure and comparison with dual X-ray absorptiometry measurements

    NASA Technical Reports Server (NTRS)

    Ouyang, X.; Selby, K.; Lang, P.; Engelke, K.; Klifa, C.; Fan, B.; Zucconi, F.; Hottya, G.; Chen, M.; Majumdar, S.; Genant, H. K.

    1997-01-01

    A high-resolution magnetic resonance imaging (MRI) protocol, together with specialized image processing techniques, was applied to the quantitative measurement of age-related changes in calcaneal trabecular structure. The reproducibility of the technique was assessed and the annual rates of change for several trabecular structure parameters were measured. The MR-derived trabecular parameters were compared with calcaneal bone mineral density (BMD), measured by dual X-ray absorptiometry (DXA) in the same subjects. Sagittal MR images were acquired at 1.5 T in 23 healthy women (mean age: 49.3 +/- 16.6 [SD]), using a three-dimensional gradient echo sequence. Image analysis procedures included internal gray-scale calibration, bone and marrow segmentation, and run-length methods. Three trabecular structure parameters, apparent bone volume (ABV/TV), intercept thickness (I.Th), and intercept separation (I.Sp) were calculated from the MR images. The short- and long-term precision errors (mean %CV) of these measured parameters were in the ranges 1-2% and 3-6%, respectively. Linear regression of the trabecular structure parameters vs. age showed significant correlation: ABV/TV (r2 = 33.7%, P < 0.0037), I.Th (r2 = 26.6%, P < 0.0118), I.Sp (r2 = 28.9%, P < 0.0081). These trends with age were also expressed as annual rates of change: ABV/TV (-0.52%/year), I.Th (-0.33%/year), and I.Sp (0.59%/year). Linear regression analysis also showed significant correlation between the MR-derived trabecular structure parameters and calcaneal BMD values. Although a larger group of subjects is needed to better define the age-related changes in trabecular structure parameters and their relation to BMD, these preliminary results demonstrate that high-resolution MRI may potentially be useful for the quantitative assessment of trabecular structure.

  13. Hyalinizing trabecular adenoma--a case report with FNAC histologic, MIB-1 proliferative index and immunohistochemical findings.

    PubMed

    Karak, A K; Sahoo, M; Bhatnagar, D

    1998-10-01

    Hyalinizing trabecular adenoma is a recently described benign thyroid tumor, almost exclusively occurring in females. The morphological features of this entity overlap with both papillary and medullary carcinoma to varying extent. This, in turn, creates a situation of serious diagnostic pitfall particularly for a false positive diagnosis of papillary carcinoma in fine needle aspiration (FNA) cytology. False consideration of medullary carcinoma is also possible by the unwary especially if staining for Congo red and/or immunostaining for calcitonin is not resorted to. At histologic level, the distinctive architectural pattern is however of great help and thus poses a much lesser danger of misdiagnosis. We relate here our experience in a recently encountered case of hyalinizing trabecular adenoma and describe detailed FNA cytologic and histologic findings along with immunohistochemical profile using a panel of eight monoclonal antibodies. The tumor proliferative potential has also been assessed using MIB-1 (Ki-67) immunostaining. The various pros and cons of diagnostic pitfalls are discussed. PMID:9866913

  14. Influence of the pore fluid on the phase velocity in bovine trabecular bone In Vitro: Prediction of the biot model

    NASA Astrophysics Data System (ADS)

    Lee, Kang Il

    2013-01-01

    The present study aims to investigate the influence of the pore fluid on the phase velocity in bovine trabecular bone in vitro. The frequency-dependent phase velocity was measured in 20 marrow-filled and water-filled bovine femoral trabecular bone samples. The mean phase velocities at frequencies between 0.6 and 1.2 MHz exhibited significant negative dispersions for both the marrow-filled and the water-filled samples. The magnitudes of the dispersions showed no significant differences between the marrow-filled and the water-filled samples. In contrast, replacement of marrow by water led to a mean increase in the phase velocity of 27 m/s at frequencies from 0.6 to 1.2 MHz. The theoretical phase velocities of the fast wave predicted by using the Biot model for elastic wave propagation in fluid-saturated porous media showed good agreements with the measurements.

  15. Trabecular Micro-Bypass Shunt (iStent®: Basic Science, Clinical, and Future)

    PubMed Central

    Craven, E. Randy

    2015-01-01

    The trabecular bypass stent offers an alternative to filtration surgery. Patients who may be ideal candidates for considering this procedure are those with prior conjunctival surgery; for example, those who had a 360° peritomy from a scleral buckle might not do well with a trabeculectomy and there is no space for a tube. Highly myopic patients do not tolerate hypotony well, and the iSTB may be an option for some of these patients. I have used the iSTB in patients on anticoagulants who could not stop them, and they needed something beyond medications and laser to lower the IOP in subjects with open-angle glaucoma. Young patients, especially those with one eye, who need rapid visual recovery (for instance to return to work) may be good candidates to consider the iSTB as well. Because of the position used for clear corneal cataract surgery, the temporal approach is best for doing these. Therefore, if you are doing cataract surgery on someone who needs a lower IOP, you already are in the correct position to implant the devices. Patients may need some medications after the procedure to lower the IOP to the level desired. The results from Armenia are encouraging, given an IOP of 11.8 mmHg after 2 iSTB stents and taking daily travoprost. These results are difficult to reach even with a trabeculectomy. When selecting your fist patients, avoid those with the congested episcleral veins, look for patients with wide open angles, and if you can see aqueous veins at the slit-lamp it may indicate a viable outflow system. Probably avoid patients with IOPs over 35 mmHg. The micro-invasive trabecular bypass stents offer an alternative surgical intervention for select patients with open-angle glaucoma. Recent studies show that combining these micro-stents with medications can lead to as low of an intraocular pressure (IOP) as is achieved by many more invasive incisional surgeries. The technique is quite precise and learning the procedure is similar to clear corneal

  16. Trabecular micro-bypass shunt (iStent®): basic science, clinical, and future).

    PubMed

    Craven, E Randy

    2015-01-01

    The trabecular bypass stent offers an alternative to filtration surgery. Patients who may be ideal candidates for considering this procedure are those with prior conjunctival surgery; for example, those who had a 360° peritomy from a scleral buckle might not do well with a trabeculectomy and there is no space for a tube. Highly myopic patients do not tolerate hypotony well, and the iSTB may be an option for some of these patients. I have used the iSTB in patients on anticoagulants who could not stop them, and they needed something beyond medications and laser to lower the IOP in subjects with open-angle glaucoma. Young patients, especially those with one eye, who need rapid visual recovery (for instance to return to work) may be good candidates to consider the iSTB as well. Because of the position used for clear corneal cataract surgery, the temporal approach is best for doing these. Therefore, if you are doing cataract surgery on someone who needs a lower IOP, you already are in the correct position to implant the devices. Patients may need some medications after the procedure to lower the IOP to the level desired. The results from Armenia are encouraging, given an IOP of 11.8 mmHg after 2 iSTB stents and taking daily travoprost. These results are difficult to reach even with a trabeculectomy. When selecting your fist patients, avoid those with the congested episcleral veins, look for patients with wide open angles, and if you can see aqueous veins at the slit-lamp it may indicate a viable outflow system. Probably avoid patients with IOPs over 35 mmHg. The micro-invasive trabecular bypass stents offer an alternative surgical intervention for select patients with open-angle glaucoma. Recent studies show that combining these micro-stents with medications can lead to as low of an intraocular pressure (IOP) as is achieved by many more invasive incisional surgeries. The technique is quite precise and learning the procedure is similar to clear corneal

  17. Prediction of biomechanical properties of trabecular bone in MR images with geometric features and support vector regression.

    PubMed

    Huber, Markus B; Lancianese, Sarah L; Nagarajan, Mahesh B; Ikpot, Imoh Z; Lerner, Amy L; Wismuller, Axel

    2011-06-01

    Whole knee joint MR image datasets were used to compare the performance of geometric trabecular bone features and advanced machine learning techniques in predicting biomechanical strength properties measured on the corresponding ex vivo specimens. Changes of trabecular bone structure throughout the proximal tibia are indicative of several musculoskeletal disorders involving changes in the bone quality and the surrounding soft tissue. Recent studies have shown that MR imaging also allows non-invasive 3-D characterization of bone microstructure. Sophisticated features like the scaling index method (SIM) can estimate local structural and geometric properties of the trabecular bone and may improve the ability of MR imaging to determine local bone quality in vivo. A set of 67 bone cubes was extracted from knee specimens and their biomechanical strength estimated by the yield stress (YS) [in MPa] was determined through mechanical testing. The regional apparent bone volume fraction (BVF) and SIM derived features were calculated for each bone cube. A linear multiregression analysis (MultiReg) and a optimized support vector regression (SVR) algorithm were used to predict the YS from the image features. The prediction accuracy was measured by the root mean square error (RMSE) for each image feature on independent test sets. The best prediction result with the lowest prediction error of RMSE = 1.021 MPa was obtained with a combination of BVF and SIM features and by using SVR. The prediction accuracy with only SIM features and SVR (RMSE = 1.023 MPa) was still significantly better than BVF alone and MultiReg (RMSE = 1.073 MPa). The current study demonstrates that the combination of sophisticated bone structure features and supervised learning techniques can improve MR-based determination of trabecular bone quality. PMID:21356612

  18. Cervical Vertebral Trabecular Bone Mineral Density in Great Danes With and Without Osseous-Associated Cervical Spondylomyelopathy

    PubMed Central

    Armstrong, J.; da Costa, R.C.; Martin-Vaquero, P.

    2015-01-01

    Background Great Danes (GDs) with osseous-associated cervical spondylomyelopathy (CSM) have osteoarthritis (OA) of the cervical vertebrae. OA is often associated with increases in bone mineral density (BMD) in people and dogs. Hypothesis/Objectives To compare the trabecular BMD of the cervical vertebrae between clinically normal (control) GDs and GDs with osseous-associated CSM by using computed tomography (CT). We hypothesized that the vertebral trabecular BMD of CSM-affected GDs would be higher than that of control GDs. Animals Client-owned GDs: 12 controls, 10 CSM affected. Methods Prospective study. CT of the cervical vertebral column was obtained alongside a calibration phantom. By placing a circular region of interest at the articular process joints, vertebral body, pedicles, and within each rod of the calibration phantom, trabecular BMD was measured in Hounsfield units, which were converted to diphosphate equivalent densities. Trabecular BMD measurements were compared between CSM-affected and control dogs, and between males and females within the control group. Results Differences between CSM-affected and control dogs were not significant for the articular processes (mean = −39; P = .37; 95% CI: −102 to 24), vertebral bodies (mean = −62; P = .08; 95% CI: −129 to 6), or pedicles (mean = −36; P = .51; 95% CI: −105 to 33). Differences between female and male were not significant. Conclusions and Clinical Importance This study revealed no difference in BMD between control and CSM-affected GDs. Based on our findings no association was detected between cervical OA and BMD in GDs with CSM. PMID:25312453

  19. Relationship between trabecular texture features of CT images and an amount of bone cement volume injection in percutaneous vertebroplasty

    NASA Astrophysics Data System (ADS)

    Tack, Gye Rae; Choi, Hyung Guen; Shin, Kyu-Chul; Lee, Sung J.

    2001-06-01

    Percutaneous vertebroplasty is a surgical procedure that was introduced for the treatment of compression fracture of the vertebrae. This procedure includes puncturing vertebrae and filling with polymethylmethacrylate (PMMA). Recent studies have shown that the procedure could provide structural reinforcement for the osteoporotic vertebrae while being minimally invasive and safe with immediate pain relief. However, treatment failures due to disproportionate PMMA volume injection have been reported as one of complications in vertebroplasty. It is believed that control of PMMA volume is one of the most critical factors that can reduce the incidence of complications. In this study, appropriate amount of PMMA volume was assessed based on the imaging data of a given patient under the following hypotheses: (1) a relationship can be drawn between the volume of PMMA injection and textural features of the trabecular bone in preoperative CT images and (2) the volume of PMMA injection can be estimated based on 3D reconstruction of postoperative CT images. Gray-level run length analysis was used to determine the textural features of the trabecular bone. The width of trabecular (T-texture) and the width of intertrabecular spaces (I-texture) were calculated. The correlation between PMMA volume and textural features of patient's CT images was also examined to evaluate the appropriate PMMA amount. Results indicated that there was a strong correlation between the actual PMMA injection volume and the area of the intertrabecular space and that of trabecular bone calculated from the CT image (correlation coefficient, requals0.96 and requals-0.95, respectively). T- texture (requals-0.93) did correlate better with the actual PMMA volume more than the I-texture (requals0.57). Therefore, it was demonstrated that appropriate PMMA injection volume could be predicted based on the textural analysis for better clinical management of the osteoporotic spine.

  20. Subchondral Bone Plate Changes More Rapidly than Trabecular Bone in Osteoarthritis.

    PubMed

    Zamli, Zaitunnatakhin; Robson Brown, Kate; Sharif, Mohammed

    2016-01-01

    Osteoarthritis (OA) is the most common joint disorder, characterised by focal loss of cartilage and increased subchondral bone remodelling at early OA stages of the disease. We have investigated the temporal and the spatial relationship between bone remodelling in subchondral bone plate (Sbp) and trabecular bone (Tb) in Dunkin Hartley (DH, develop OA early) and the Bristol Strain 2 (BS2, control which develop OA late) guinea pigs. Right tibias were dissected from six male animals of each strain, at 10, 16, 24 and 30 weeks of age. Micro-computed tomography was used to quantify the growth plate thickness (GpTh), subchondral bone plate thickness (SbpTh) and trabecular bone thickness (TbTh), and bone mineral density (BMD) in both Sbp and Tb. The rate of change was calculated for 10-16 weeks, 16-24 weeks and 24-30 weeks. The rate of changes in Sbp and Tb thickness at the earliest time interval (10-16 weeks) were significantly greater in DH guinea pigs than in the growth-matched control strain (BS2). The magnitude of these differences was greater in the medial side than the lateral side (DH: 22.7 and 14.75 µm/week, BS2: 5.63 and 6.67 µm/week, respectively). Similarly, changes in the BMD at the earliest time interval was greater in the DH strain than the BS2, again more pronounced in the disease prone medial compartment (DH: 0.0698 and 0.0372 g/cm³/week, BS2: 0.00457 and 0.00772 g/cm³/week, respectively). These changes observed preceded microscopic and cellular signs of disease as previously reported. The rapid early changes in SbpTh, TbTh, Sbp BMD and Tb BMD in the disease prone DH guinea pigs compared with the BS2 control strain suggest a link to early OA pathology. This is corroborated by the greater relative changes in subchondral bone in the medial compared with the lateral compartment. PMID:27618009

  1. Risedronate slows or partly reverses cortical and trabecular microarchitectural deterioration in postmenopausal women.

    PubMed

    Bala, Yohann; Chapurlat, Roland; Cheung, Angela M; Felsenberg, Dieter; LaRoche, Michel; Morris, Edward; Reeve, Jonathan; Thomas, Thierry; Zanchetta, Jose; Bock, Oliver; Ghasem-Zadeh, Ali; Djoumessi, Roger Martin Zebaze; Seeman, Ego; Rizzoli, René

    2014-02-01

    During early menopause, steady-state bone remodeling is perturbed; the number of basic multicellular units (BMUs) excavating cavities upon the endosteal surface exceeds the number (generated before menopause) concurrently refilling. Later in menopause, steady-state is restored; the many BMUs generated in early menopause refill as similarly large numbers of BMUs concurrently excavate new cavities. We hypothesized that risedronate reduces the number of cavities excavated. However, in younger postmenopausal women, the fewer cavities excavated will still exceed the fewer BMUs now refilling, so net porosity increases, but less than in controls. In older postmenopausal women, the fewer cavities excavated during treatment will be less than the many (generated during early menopause) now refilling, so net porosity decreases and trabecular volumetric bone mineral density (vBMD) increases. We recruited 324 postmenopausal women in two similarly designed double-blind placebo-controlled studies that included 161 younger (Group 1, ≤ 55 years) and 163 older (Group 2, ≥ 55 years) women randomized 2:1 to risedronate 35 mg/week or placebo. High-resolution peripheral computed tomography was used to image the distal radius and tibia. Cortical porosity was quantified using the StrAx1.0 software. Risedronate reduced serum carboxyterminal cross-linking telopeptide of type 1 bone collagen (CTX-1) and serum amino-terminal propeptide of type 1 procollagen (P1NP) by ∼50%. In the younger group, distal radius compact-appearing cortex porosity increased by 4.2% ± 1.6% (p = 0.01) in controls. This was prevented by risedronate. Trabecular vBMD decreased by 3.6% ± 1.4% (p = 0.02) in controls and decreased by 1.6% ± 0.6% (p = 0.005) in the risedronate-treated group. In the older group, changes did not achieve significance apart from a reduction in compact-appearing cortex porosity in the risedronate-treated group (0.9% ± 0.4%, p = 0.047). No between

  2. Improving the textural characterization of trabecular bone structure to quantify its changes: the locally adapted scaling vector method

    NASA Astrophysics Data System (ADS)

    Raeth, Christoph W.; Mueller, Dirk; Boehm, Holger F.; Rummeny, Ernst J.; Link, Thomas M.; Monetti, Roberto

    2005-04-01

    We extend the recently introduced scaling vector method (SVM) to improve the textural characterization of oriented trabecular bone structures in the context of osteoporosis. Using the concept of scaling vectors one obtains non-linear structural information from data sets, which can account for global anisotropies. In this work we present a method which allows us to determine the local directionalities in images by using scaling vectors. Thus it becomes possible to better account for local anisotropies and to implement this knowledge in the calculation of the scaling properties of the image. By applying this adaptive technique, a refined quantification of the image structure is possible: we test and evaluate our new method using realistic two-dimensional simulations of bone structures, which model the effect of osteoblasts and osteoclasts on the local change of relative bone density. The partial differential equations involved in the model are solved numerically using cellular automata (CA). Different realizations with slightly varying control parameters are considered. Our results show that even small changes in the trabecular structures, which are induced by variation of a control parameters of the system, become discernible by applying the locally adapted scaling vector method. The results are superior to those obtained by isotropic and/or bulk measures. These findings may be especially important for monitoring the treatment of patients, where the early recognition of (drug-induced) changes in the trabecular structure is crucial.

  3. Micro-computed tomography assisted distal femur metaphyseal blunt punch compression for determining trabecular bone strength in mice.

    PubMed

    Sankar, Uma; Pritchard, Zachary J; Voor, Michael J

    2016-05-01

    Shorter generation time and the power of genetic manipulation make mice an ideal model system to study bone biology as well as bone diseases. However their small size presents a challenge to perform strength measurements, particularly of the weight-bearing cancellous bone in the murine long bones. We recently developed an improved method to measure the axial compressive strength of the cancellous bone in the distal femur metaphysis in mice. Transverse micro-computed tomography image slices that are 7µm thick were used to locate the position where the epiphysis-metaphysis transition occurs. This enabled the removal of the distal femur epiphysis at the exact transition point exposing the full extent of metaphyseal trabecular bone, allowing more accurate and consistent measurement of its strength. When applied to a murine model system consisting of five month old male wild-type (WT) and Ca(2+)/calmodulin dependent protein kinase kinase 2 (CaMKK2) knockout (KO) Camkk2(-/-) mice that possess recorded differences in trabecular bone volume, data collected using this method showed good correlation between bone volume fraction and strength of trabecular bone. In combination with micro-computed tomography and histology, this method will provide a comprehensive and consistent assessment of the microarchitecture and tissue strength of the cancellous bone in murine mouse models. PMID:26947030

  4. NMR relaxation times of trabecular bone—reproducibility, relationships to tissue structure and effects of sample freezing

    NASA Astrophysics Data System (ADS)

    Prantner, Viktória; Isaksson, Hanna; Närväinen, Johanna; Lammentausta, Eveliina; Nissi, Mikko J.; Avela, Janne; Gröhn, Olli H. J.; Jurvelin, Jukka S.

    2010-12-01

    Nuclear magnetic resonance (NMR) spectroscopy provides a potential tool for non-invasive evaluation of the trabecular bone structure. The objective of this study was to determine the reproducibility of the NMR relaxation parameters (T2, Carr-Purcel-T2, T1ρ) for fat and water and relate those to the structural parameters obtained by micro-computed tomography (μCT). Especially, we aimed to evaluate the effect of freezing on the relaxation parameters. For storing bone samples, freezing is the standard procedure during which the biochemical and cellular organization of the bone marrow may be affected. Bovine trabecular bone samples were stored at -20 °C for 7 days and measured by NMR spectroscopy before and after freezing. The reproducibility of NMR relaxation parameters, as expressed by the coefficient of variation, ranged from 3.1% to 27.9%. In fresh samples, some correlations between NMR and structural parameters (Tb.N, Tb.Sp) were significant (e.g. the relaxation rate for T2 of fat versus Tb.Sp: r = -0.716, p < 0.01). Freezing did not significantly change the NMR relaxation times but the correlations between relaxation parameters and the μCT structural parameters were not statistically significant after freezing, suggesting some nonsystematic alterations of the marrow structure. Therefore, the use of frozen bone samples for NMR relaxation studies may provide inferior information about the trabecular bone structure.

  5. Assessment of Fat distribution and Bone quality with Trabecular Bone Score (TBS) in Healthy Chinese Men.

    PubMed

    Lv, Shan; Zhang, Aisen; Di, Wenjuan; Sheng, Yunlu; Cheng, Peng; Qi, Hanmei; Liu, Juan; Yu, Jing; Ding, Guoxian; Cai, Jinmei; Lai, Bin

    2016-01-01

    Whether fat is beneficial or detrimental to bones is still controversial, which may be due to inequivalence of the fat mass. Our objective is to define the effect of body fat and its distribution on bone quality in healthy Chinese men. A total of 228 men, aged from 38 to 89 years, were recruited. BMD, trabecular bone score (TBS), and body fat distribution were measured by dual-energy X-ray absorptiometry. Subcutaneous and visceral fat were assessed by MRI. In the Pearson correlation analysis, lumbar spine BMD exhibited positive associations with total and all regional fat depots, regardless of the fat distribution. However, the correlation disappeared with adjusted covariables of age, BMI, HDL-C, and HbA1c%. TBS was negatively correlated with fat mass. In multiple linear regression models, android fat (and not gynoid, trunk, or limbs fat) showed significant inverse association with TBS (β = -0.611, P < 0.001). Furthermore, visceral fat was described as a pathogenic fat harmful to TBS, even after adjusting for age and BMI (β = -0.280, P = 0.017). Our findings suggested that body fat mass, especially android fat and visceral fat, may have negative effects on bone microstructure; whereas body fat mass contributes to BMD through mechanical loading. PMID:27112305

  6. Assessment of Fat distribution and Bone quality with Trabecular Bone Score (TBS) in Healthy Chinese Men

    PubMed Central

    Lv, Shan; Zhang, Aisen; Di, Wenjuan; Sheng, Yunlu; Cheng, Peng; Qi, Hanmei; Liu, Juan; Yu, Jing; Ding, Guoxian; Cai, Jinmei; Lai, Bin

    2016-01-01

    Whether fat is beneficial or detrimental to bones is still controversial, which may be due to inequivalence of the fat mass. Our objective is to define the effect of body fat and its distribution on bone quality in healthy Chinese men. A total of 228 men, aged from 38 to 89 years, were recruited. BMD, trabecular bone score (TBS), and body fat distribution were measured by dual-energy X-ray absorptiometry. Subcutaneous and visceral fat were assessed by MRI. In the Pearson correlation analysis, lumbar spine BMD exhibited positive associations with total and all regional fat depots, regardless of the fat distribution. However, the correlation disappeared with adjusted covariables of age, BMI, HDL-C, and HbA1c%. TBS was negatively correlated with fat mass. In multiple linear regression models, android fat (and not gynoid, trunk, or limbs fat) showed significant inverse association with TBS (β = −0.611, P < 0.001). Furthermore, visceral fat was described as a pathogenic fat harmful to TBS, even after adjusting for age and BMI (β = −0.280, P = 0.017). Our findings suggested that body fat mass, especially android fat and visceral fat, may have negative effects on bone microstructure; whereas body fat mass contributes to BMD through mechanical loading. PMID:27112305

  7. Micro/Nanostructures and Mechanical Properties of Trabecular Bone in Ovariectomized Rats

    PubMed Central

    Hu, Shidi; Li, Jin; Liu, Lu; Dai, Ruchun; Sheng, Zhifeng; Wu, Xianping; Feng, Xiqiao; Yao, Xuefeng; Liao, Eryuan; Keller, Evan; Jiang, Yebin

    2015-01-01

    Bone mechanical properties encompass both geometric and material factors, while the effects of estrogen deficiency on the material and structural characteristics of bone at micro- to nanoscales are still obscure. We performed a series of combined methodological experiments, including nanoindentation assessment of intrinsic material properties, atomic force microscopy (AFM) characterization of trabecular (Tb) nanostructure, and Tb microarchitecture and 2D BMD. At 15 weeks after surgery, we found significantly less Tb bone mineral density (BMD) at organ (−27%) and at tissue level (−12%), Tb bone volume fraction (−29%), Tb thickness (−14%), and Tb number (−17%) in ovariectomy (OVX) rats than in sham operated (SHAM) rats, while the structure model index (+91%) and Tb separation (+19%) became significantly greater. AFM images showed lower roughness Tb surfaces with loosely packed large nodular structures and less compacted interfibrillar space in OVX than in SHAM. However, no statistically significant changes were in the Tb intrinsic material properties—nanoindentation hardness, elastic modulus, and plastic deformation—nanoindentation depths, and residual areas. Therefore, estrogen deprivation results in a dramatic deterioration in Tb micro/nanoarchitectures, 3D volumetric BMD at both organ and tissue levels, and 2D BMD, but not in the nanomechanical properties of the trabeculae per se. PMID:26273294

  8. Production of New Trabecular Bone in Osteopenic Ovariectomized Rats by Prostaglandin E2

    NASA Technical Reports Server (NTRS)

    Mori, S.; Jee, W. S. S.; Li, X. J.

    1992-01-01

    Serum chemistry and bone morphometry of the proximal tibial metaphysis were performed in 3 month-old double fluorescent-labeled, female Sprague-Dawley rats subjected to bilateral ovariectomy or sham surgery for 4 months prior to treatment with 0, 0.3, 1,3, or 6 mg of prostaglandin E2 (PGE2)/kg/day subcutaneously for 30 days. The 4 month postovariectomized rats possessed an osteopenic proximal tibial metaphysis with 7% trabecular area compared with controls (19%). PGE2 treatment elevated osteocalcin levels and augmented proximal tibial metaphyseal bone area in ovariectomized and sham-operated rats. Osteopenic, ovariectomized rats treated with 6 mg (PGE2)/kg/day for 30 days restored bone area to levels of agematched sham-operated rats. Morphometric analyses showed increased woven and lamellar bone area, fluorescent-labeled perimeter (osteoblastic recruitment), mineral apposition rate (osteoblastic activity), bone formation rate (BFR/BV), and longitudinal bone growth. These dramatic bone changes were all significantly increased at the doseresponse manner. This study showed that in vivo PGE2 is a powerful activator of bone remodeling, it increases both bone resorption and bone formation, and produces an anabolic effect by shifting bone balance to the positive direction. Furthermore, PGE2-induced augmentation of metaphyseal bone area in ovariectomized rats was at least two times greater than in sham-operated rats.

  9. Novel techniques for high-resolution functional imaging of trabecular bone

    NASA Astrophysics Data System (ADS)

    Thurner, Philipp J.; Muller, Ralph; Kindt, Johannes H.; Schitter, Georg; Fantner, Georg E.; Wyss, Peter; Sennhauser, Urs; Hansma, Paul K.

    2005-04-01

    In current biological and biomedical research, quantitative endpoints have become an important factor of success. Classically, such endpoints were investigated with 2D imaging, which is usually destructive and the 3D character of tissue gets lost. 3D imaging has gained in importance as a tool for both, qualitative and quantitative assessment of biological systems. In this context synchrotron radiation based tomography has become a very effective tool for opaque 3D tissue systems. Results from a new device are presented enabling the 3D investigation of trabecular bone under mechanical load in a time-lapsed fashion. Using the highly brilliant X-rays from a synchrotron radiation source, bone microcracks and an indication for un-cracked ligament bridging are uncovered. 3D microcrack analysis proves that the classification of microcracks from 2D images is ambiguous. Fatigued bone was found to fail in burst-like fashion, whereas non-fatigued bone exhibited a distinct failure band. Additionally, a higher increase in microcrack volume was detected in fatigued in comparison to non-fatigued bone. Below the spatial resolution accessible with synchrotron radiation tomography we investigated native and fractured bone surfaces on the molecular scale with atomic force microscopy. The mineralized fibrils detected on fracture surfaces give rise to the assumption that the mineral-mineral interface is the weakest link in bone. The presented results show the power of functional micro-imaging, as well as the possibilities for AFM imaging (functional nano-imaging) in this context.

  10. In vivo measurement of the trabecular bone mineral density by coherent and Compton. gamma. -ray scattering

    SciTech Connect

    Karellas, A.

    1984-01-01

    A photon scattering method for measuring the mineral density of trabecular bone (BMD) is described. By computing the ratio of the coherent to Compton scattered photons, the BMD can be measured accurately and without any significant interference by the surrounding tissue. This study shows theoretically and experimentally that an increase in the scatter angle, when using 60 keV photons from Am-241, results in a stronger power dependence on Z. This implies that by increasing the scatter angle, smaller changes in BMD can be detected, thus improving the sensitivity of the measurement. The dependence of the sensitivity on the energy of the incident photons was also investigated. A collimated beam of photons from 1200 mCi of Am-241 (60 keV) was used and the scattered photons were detected at a scatter angle of 71/sup 0/. The system was calibrated by using a new standard which contains bone mineral mixed homogeneously with a marrow simulating substance. This method was applied for the measurement of the calcaneal BMD in 21 normal volunteers and seven paraplegic patients. The BMD values for the normal group ranged from 170-300 mg/cm/sup 3/. The BMD for the paraplegics with injuries older than one year ranged from 90-150 mg/cm/sup 3/. This measurement has potential application in the diagnosis of early osteopenia and in monitoring the effect of various treatment regimens.

  11. Development and Applications of Porous Tantalum Trabecular Metal Enhanced Titanium Dental Implants

    PubMed Central

    Bencharit, Sompop; Byrd, Warren C.; Altarawneh, Sandra; Hosseini, Bashir; Leong, Austin; Reside, Glenn; Morelli, Thiago; Offenbacher, Steven

    2013-01-01

    Statement of Problem Porous tantalum trabecular metal has recently been incorporated in titanium dental implants as a new form of implant surface enhancement. However, there is little information on the applications of this material in implant dentistry. Methods We, therefore review the current literature on the basic science and clinical uses of this material. Results Porous tantalum metal is used to improve the contact between osseous structure and dental implants; and therefore presumably facilitate osseointegration. Success of porous tantalum metal in orthopedic implants led to the incorporation of porous tantalum metal in the design of root-from endosseous titanium implants. The porous tantalum three-dimensional enhancement of titanium dental implant surface allows for combining bone ongrowth together with bone ingrowth, or osseoincorporation. While little is known about the biological aspect of the porous tantalum in the oral cavity, there seems to be several possible advantages of this implant design. This article reviews the biological aspects of porous tantalum enhanced titanium dental implants, in particular the effects of anatomical consideration and oral environment to implant designs. Conclusions We propose here possible clinical situations and applications for this type of dental implant. Advantages and disadvantages of the implants as well as needed future clinical studies are discussed. PMID:23527899

  12. Alterations in Trabecular Bone Microarchitecture in the Ovine Spine and Distal Femur Following Ovariectomy

    PubMed Central

    Kreipke, Tyler C.; Rivera, Nicole C.; Garrison, Jacqueline G.; Easley, Jeremiah T.; Turner, A. Simon; Niebur, Glen L.

    2014-01-01

    Osteoporosis is a bone disease resulting in increased fracture risk as a result of alterations in both the quantity and quality of bone. Bone quality is a combination of metabolic and microarchitectural properties of bone that can help to explain the increased susceptibility to fracture. Translational animal models are essential to understanding the pathology and evaluating potential treatments of this disease. Large animal models, such as the ovariectomized sheep, have been used as a model for post-menopausal osteoporosis. However, long-term studies have not been carried out to observe the effects of ovariectomy after more than one year. This study employed micro-computed tomography to quantify changes in microarchitectural and mechanical parameters in the femoral condyles and vertebral bodies of sheep that were sacrificed one or two years following ovariectomy. In the vertebral body, microarchitectural characteristics were significantly degraded following one year of ovariectomy in comparison to controls. The mechanical anisotropy, determined from micro-scale finite element models, was also greater in the ovariectomized groups, although the fabric tensor anisotropy was similar. There was no greater architectural degradation following two years of ovariectomy compared to one. Ovariectomy had minimal effects on the trabecular architecture of the distal femur even after two years. These results indicate that the vertebral body is the preferred anatomic site for studying bone from the ovariectomized sheep model, and that the architectural changes stabilize after the first year. PMID:24720887

  13. Trabecular bone loss after administration of the second-generation antipsychotic risperidone is independent of weight gain

    PubMed Central

    Motyl, Katherine J.; Dick-de-Paula, Ingrid; Maloney, Ann E.; Lotinun, Sutada; Bornstein, Sheila; de Paula, Francisco J. A.; Baron, Roland; Houseknecht, Karen L.; Rosen, Clifford J.

    2011-01-01

    Second generation antipsychotics (SGAs) have been linked to metabolic and bone disorders in clinical studies, but the mechanisms of these side effects remain unclear. Additionally, no studies have examined whether SGAs cause bone loss in mice. Using in vivo and in vitro modeling we examined the effects of risperidone, the most commonly prescribed SGA, on bone in C57BL6/J (B6) mice. Mice were treated with risperidone orally by food supplementation at a dose of 1.25 mg/kg daily for 5 and 8 weeks, starting at 3.5 weeks of age. Risperidone reduced trabecular BV/TV, trabecular number and percent cortical area. Trabecular histomorphometry demonstrated increased resorption parameters, with no change in osteoblast number or function. Risperidone also altered adipose tissue distribution such that white adipose tissue mass was reduced and liver had significantly higher lipid infiltration. Next, in order to tightly control risperidone exposure, we administered risperidone by chronic subcutaneous infusion with osmotic minipumps (0.5 mg/kg daily for 4 weeks) in 7 week old female B6 mice. Similar trabecular and cortical bone differences were observed compared to the orally treated groups (reduced trabecular BV/TV, and connectivity density, and reduced percent cortical area) with no change in body mass, percent body fat, glucose tolerance or insulin sensitivity. Unlike in orally treated mice, risperidone infusion reduced bone formation parameters (serum P1NP, MAR and BFR/BV). Resorption parameters were elevated, but this increase did not reach statistical significance. To determine if risperidone could directly affect bone cells, primary bone marrow cells were cultured with osteoclast or osteoblast differentiation media. Risperidone was added to culture medium in clinically relevant doses of 0, 2.5 or 25 ng/ml. The number of osteoclasts was significantly increased by addition in vitro of risperidone while osteoblast differentiation was not altered. These studies indicate that

  14. Trabecular bone loss after administration of the second-generation antipsychotic risperidone is independent of weight gain.

    PubMed

    Motyl, Katherine J; Dick-de-Paula, Ingrid; Maloney, Ann E; Lotinun, Sutada; Bornstein, Sheila; de Paula, Francisco J A; Baron, Roland; Houseknecht, Karen L; Rosen, Clifford J

    2012-02-01

    Second generation antipsychotics (SGAs) have been linked to metabolic and bone disorders in clinical studies, but the mechanisms of these side effects remain unclear. Additionally, no studies have examined whether SGAs cause bone loss in mice. Using in vivo and in vitro modeling we examined the effects of risperidone, the most commonly prescribed SGA, on bone in C57BL6/J (B6) mice. Mice were treated with risperidone orally by food supplementation at a dose of 1.25 mg/kg daily for 5 and 8 weeks, starting at 3.5 weeks of age. Risperidone reduced trabecular BV/TV, trabecular number and percent cortical area. Trabecular histomorphometry demonstrated increased resorption parameters, with no change in osteoblast number or function. Risperidone also altered adipose tissue distribution such that white adipose tissue mass was reduced and liver had significantly higher lipid infiltration. Next, in order to tightly control risperidone exposure, we administered risperidone by chronic subcutaneous infusion with osmotic minipumps (0.5 mg/kg daily for 4 weeks) in 7 week old female B6 mice. Similar trabecular and cortical bone differences were observed compared to the orally treated groups (reduced trabecular BV/TV, and connectivity density, and reduced percent cortical area) with no change in body mass, percent body fat, glucose tolerance or insulin sensitivity. Unlike in orally treated mice, risperidone infusion reduced bone formation parameters (serum P1NP, MAR and BFR/BV). Resorption parameters were elevated, but this increase did not reach statistical significance. To determine if risperidone could directly affect bone cells, primary bone marrow cells were cultured with osteoclast or osteoblast differentiation media. Risperidone was added to culture medium in clinically relevant doses of 0, 2.5 or 25 ng/ml. The number of osteoclasts was significantly increased by addition in vitro of risperidone while osteoblast differentiation was not altered. These studies indicate that

  15. Acute hypothalamic suppression significantly affects trabecular bone but not cortical bone following recovery and ovariectomy surgery in a rat model

    PubMed Central

    Mitchell, Kathryn A.; Lunny, Megan

    2016-01-01

    Background. Osteoporosis is “a pediatric disease with geriatric consequences.” Bone morphology and tissue quality co-adapt during ontogeny for sufficient bone stiffness. Altered bone morphology from hypothalamic amenorrhea, a risk factor for low bone mass in women, may affect bone strength later in life. Our purpose was to determine if altered morphology following hypothalamic suppression during development affects cortical bone strength and trabecular bone volume (BV/TV) at maturity. Methods. Female rats (25 days old) were assigned to a control (C) group (n = 45) that received saline injections (.2 cc) or an experimental group (GnRH-a) (n = 45) that received gonadotropin releasing hormone antagonist injections (.24 mg per dose) for 25 days. Fifteen animals from each group were sacrificed immediately after the injection protocol at Day 50 (C, GnRH-a). The remaining animals recovered for 135 days and a subset of each group was sacrificed at Day 185 ((C-R) (n = 15) and (G-R) (n = 15)). The remaining animals had an ovariectomy surgery (OVX) at 185 days of age and were sacrificed 40 days later (C-OVX) (n = 15) and (G-OVX) (n = 15). After sacrifice femurs were mechanically tested and scanned using micro CT. Serum C-terminal telopeptides (CTX) and insulin-like growth factor 1 (IGF-1) were measured. Two-way ANOVA (2 groups (GnRH-a and Control) X 3 time points (Injection Protocol, Recovery, post-OVX)) was computed. Results. GnRH-a injections suppressed uterine weights (72%) and increased CTX levels by 59%. Bone stiffness was greater in the GnRH-a groups compared to C. Ash content and cortical bone area were similar between groups at all time points. Polar moment of inertia, a measure of bone architecture, was 15% larger in the GnRH-a group and remained larger than C (19%) following recovery. Both the polar moment of inertia and cortical area increased linearly with the increases in body weight. Following the injection protocol, trabecular BV/TV was 31% lower in the Gn

  16. Acute hypothalamic suppression significantly affects trabecular bone but not cortical bone following recovery and ovariectomy surgery in a rat model.

    PubMed

    Yingling, Vanessa R; Mitchell, Kathryn A; Lunny, Megan

    2016-01-01

    Background. Osteoporosis is "a pediatric disease with geriatric consequences." Bone morphology and tissue quality co-adapt during ontogeny for sufficient bone stiffness. Altered bone morphology from hypothalamic amenorrhea, a risk factor for low bone mass in women, may affect bone strength later in life. Our purpose was to determine if altered morphology following hypothalamic suppression during development affects cortical bone strength and trabecular bone volume (BV/TV) at maturity. Methods. Female rats (25 days old) were assigned to a control (C) group (n = 45) that received saline injections (.2 cc) or an experimental group (GnRH-a) (n = 45) that received gonadotropin releasing hormone antagonist injections (.24 mg per dose) for 25 days. Fifteen animals from each group were sacrificed immediately after the injection protocol at Day 50 (C, GnRH-a). The remaining animals recovered for 135 days and a subset of each group was sacrificed at Day 185 ((C-R) (n = 15) and (G-R) (n = 15)). The remaining animals had an ovariectomy surgery (OVX) at 185 days of age and were sacrificed 40 days later (C-OVX) (n = 15) and (G-OVX) (n = 15). After sacrifice femurs were mechanically tested and scanned using micro CT. Serum C-terminal telopeptides (CTX) and insulin-like growth factor 1 (IGF-1) were measured. Two-way ANOVA (2 groups (GnRH-a and Control) X 3 time points (Injection Protocol, Recovery, post-OVX)) was computed. Results. GnRH-a injections suppressed uterine weights (72%) and increased CTX levels by 59%. Bone stiffness was greater in the GnRH-a groups compared to C. Ash content and cortical bone area were similar between groups at all time points. Polar moment of inertia, a measure of bone architecture, was 15% larger in the GnRH-a group and remained larger than C (19%) following recovery. Both the polar moment of inertia and cortical area increased linearly with the increases in body weight. Following the injection protocol, trabecular BV/TV was 31% lower in the Gn

  17. ATP-Sensitive Potassium (KATP) Channel Activation Decreases Intraocular Pressure in the Anterior Chamber of the Eye

    PubMed Central

    Chowdhury, Uttio Roy; Bahler, Cindy K.; Hann, Cheryl R.; Chang, Minhwang; Resch, Zachary T.; Romero, Michael F.

    2011-01-01

    Purpose. ATP-sensitive potassium channel (KATP) openers target key cellular events, many of which have been implicated in glaucoma. The authors sought to determine whether KATP channel openers influence outflow facility in human anterior segment culture and intraocular pressure (IOP) in vivo. Methods. Anterior segments from human eyes were placed in perfusion organ culture and treated with the KATP channel openers diazoxide, nicorandil, and P1075 or the KATP channel closer glyburide (glibenclamide). The presence, functionality, and specificity of KATP channels were determined by RT-PCR, immunohistochemistry, and inside-out patch clamp in human trabecular meshwork (TM) tissue or primary cultures of normal human trabecular meshwork (NTM) cells. The effect of diazoxide on IOP in anesthetized Brown Norway rats was measured with a rebound tonometer. Results. KATP channel openers increased outflow facility in human anterior segments (0.14 ± 0.02 to 0.26 ± 0.09 μL/min/mm Hg; P < 0.001) compared with fellow control eyes (0.22 ± 0.11 to 0.21 ± 0.11 μL/min/mm Hg; P > 0.5). The effect was reversible, with outflow facility returning to baseline after drug removal. The addition of glyburide inhibited diazoxide from increasing outflow facility. Electrophysiology confirmed the presence and specificity of functional KATP channels. KATP channel subunits Kir6.1, Kir6.2, SUR2A, and SUR2B were expressed in TM and NTM cells. In vivo, diazoxide significantly lowered IOP in Brown Norway rats. Conclusions. Functional KATP channels are present in the trabecular meshwork. When activated by KATP channel openers, these channels increase outflow facility through the trabecular outflow pathway in human anterior segment organ culture and decrease IOP in Brown Norway rat eyes. PMID:21743021

  18. Directional fractal signature methods for trabecular bone texture in hand radiographs: Data from the Osteoarthritis Initiative

    SciTech Connect

    Wolski, M. Podsiadlo, P.; Stachowiak, G. W.

    2014-08-15

    Purpose: To develop directional fractal signature methods for the analysis of trabecular bone (TB) texture in hand radiographs. Problems associated with the small size of hand bones and the orientation of fingers were addressed. Methods: An augmented variance orientation transform (AVOT) and a quadrant rotating grid (QRG) methods were developed. The methods calculate fractal signatures (FSs) in different directions. Unlike other methods they have the search region adjusted according to the size of bone region of interest (ROI) to be analyzed and they produce FSs defined with respect to any chosen reference direction, i.e., they work for arbitrary orientation of fingers. Five parameters at scales ranging from 2 to 14 pixels (depending on image size and method) were derived from rose plots of Hurst coefficients, i.e., FS in dominating roughness (FS{sub Sta}), vertical (FS{sub V}) and horizontal (FS{sub H}) directions, aspect ratio (StrS), and direction signatures (StdS), respectively. The accuracy in measuring surface roughness and isotropy/anisotropy was evaluated using 3600 isotropic and 800 anisotropic fractal surface images of sizes between 20 × 20 and 64 × 64 pixels. The isotropic surfaces had FDs ranging from 2.1 to 2.9 in steps of 0.1, and the anisotropic surfaces had two dominating directions of 30° and 120°. The methods were used to find differences in hand TB textures between 20 matched pairs of subjects with (cases: approximate Kellgren-Lawrence (KL) grade ≥2) and without (controls: approximate KL grade <2) radiographic hand osteoarthritis (OA). The OA Initiative public database was used and 20 × 20 pixel bone ROIs were selected on 5th distal and middle phalanges. The performance of the AVOT and QRG methods was compared against a variance orientation transform (VOT) method developed earlier [M. Wolski, P. Podsiadlo, and G. W. Stachowiak, “Directional fractal signature analysis of trabecular bone: evaluation of different methods to detect early

  19. Magnetic resonance imaging artifact following anterior cervical discectomy and fusion with a trabecular metal cage.

    PubMed

    Elliott, Cameron A; Fox, Richard; Ashforth, Robert; Gourishankar, Sita; Nataraj, Andrew

    2016-03-01

    OBJECT This study was undertaken to evaluate the impact of postoperative MRI artifact on the assessment of ongoing spinal cord or nerve root compression after anterior cervical discectomy and fusion (ACDF) using a trabecular tantalum cage or bone autograft or allograft. METHODS The authors conducted a retrospective review of postoperative MRI studies of patients treated surgically for cervical disc degenerative disease or cervical instability secondary to trauma. Standard ACDF with either a trabecular tantalum cage or interbody bone graft had been performed. Postoperative MR images were shown twice in random order to each of 3 assessors (2 spine surgeons, 1 neuroradiologist) to determine whether the presence of a tantalum interbody cage and/or anterior cervical fixation plate or screws imparted MRI artifact significant enough to prevent reliable postoperative assessment of ongoing spinal cord or nerve root compression. RESULTS A total of 63 patients were identified. One group of 29 patients received a tantalum interbody cage, with 13 patients (45%) undergoing anterior plate fixation. A second group of 34 patients received bone auto- or allograft, with 23 (68%) undergoing anterior plate fixation. The paramagnetic implant construct artifact had minimal impact on visualization of postoperative surgical level spinal cord compression. In the cage group, 98% (171/174) of the cases were rated as assessable versus 99% in the bone graft group (201/204), with high intraobserver reliability. In contrast, for the assessment of ongoing surgical level nerve root compression, the presence of a tantalum cage significantly decreased visualization of nerve roots to 70% (121/174) in comparison with 85% (173/204) in the bone graft group (p < 0.001). When sequences using turbo spin echo (TSE), a T2-weighted axial sequence, were acquired, nerve roots were rated as assessable in 88% (69/78) of cases; when only axial T2-weighted sequences were available, the nerve roots were rated as

  20. Predicting mechanical competence of trabecular bone using 3D tensor-scale-based parameters

    NASA Astrophysics Data System (ADS)

    Saha, Punam K.; Wald, Michael J.; Radin, Alex; Wehrli, Felix W.

    2005-04-01

    Trabecular bone (TB) consists of a network of interconnected struts and plates occurring near the joints of long bones and in the axial skeleton. In response to mechanical stresses it remodels such that trabeculae are aligned with the major stress lines, thus leading to a highly anisotropic network. Beside bone volume fraction, anisotropy and topological indices are known to be strong predictor of the TB mechanical competence. In osteoporosis, the most common bone disorder, the remodeling balance is perturbed due to increased resorption, resulting in net bone loss accompanied by architectural deterioration, leading to fragile bone and increased fracture risk. In vertebral osteoporosis, preferential loss of transverse trabeculae leads to increased anisotropy and change in topology, hence exact measurements of these parameters are of paramount interest. Current in vivo imaging yields voxel size comparable to TB thickness, thus resulting in inherently fuzzy representations. The commonly used methods for anisotropy require binarization which is difficult to achieve in the limited spatial resolution regime where the intensity histogram is mono-modal. Here, we present a new tensor scale (t-scale) based TB architectural measures that (1) obviates binarization, and (2) yields localized measures. We evaluate the performance of this method on micro-CT images of vertebral bone and test the hypothesis that the method, along with BMD and other structural parameters, allows prediction of TB"s mechanical competence. Toward this goal, we estimate Young"s modulus (YM) of (13mm)3 vertebral TB samples under uniaxial loading and examine linear correlation of different t-scale parameters computed via micro-CT imaging .

  1. Superior fixation of pegged trabecular metal over screw-fixed pegged porous titanium fiber mesh

    PubMed Central

    2011-01-01

    Background and purpose Lasting stability of cementless implants depends on osseointegration into the implant surface, and long-term implant fixation can be predicted using radiostereometric analysis (RSA) with short-term follow-up. We hypothesized that there would be improved fixation of high-porosity trabecular metal (TM) tibial components compared to low-porosity titanium pegged porous fiber-metal (Ti) polyethylene metal backings. Methods In a prospective, parallel-group, randomized unblinded clinical trial, we compared cementless tibial components in patients aged 70 years and younger with osteoarthritis. The pre-study sample size calculation was 22 patients per group. 25 TM tibial components were fixed press-fit by 2 hexagonal pegs (TM group) and 25 Ti tibial components were fixed press-fit and by 4 supplemental screws (Ti group). Stereo radiographs for evaluation of absolute component migration (primary effect size) and single-direction absolute component migration (secondary effect size) were obtained within the first postoperative week and at 6 weeks, 6 months, 1 year, and 2 years. American Knee Society score was used for clinical assessment preoperatively, and at 1 and 2 years. Results There were no intraoperative complications, and no postoperative infections or revisions. All patients had improved function and regained full extension. All tibial components migrated initially. Most migration of the TM components (n = 24) occurred within the first 3 months after surgery whereas migration of the Ti components (n = 22) appeared to stabilize first after 1 year. The TM components migrated less than the Ti components at 1 year (p = 0.01) and 2 years (p = 0.004). Interpretation We conclude that the mechanical fixation of TM tibial components is superior to that of screw-fixed Ti tibial components. We expect long-term implant survival to be better with the TM tibial component. PMID:21434781

  2. Precision of nanoindentation protocols for measurement of viscoelasticity in cortical and trabecular bone.

    PubMed

    Isaksson, Hanna; Nagao, Shijo; Małkiewicz, Marta; Julkunen, Petro; Nowak, Roman; Jurvelin, Jukka S

    2010-08-26

    Nanoindentation has recently gained attention as a characterization technique for mechanical properties of biological tissues, such as bone, on the sub-micron level. However, optimal methods to characterize viscoelastic properties of bones are yet to be established. This study aimed to compare the time-dependent viscoelastic properties of bone tissue obtained with different nanoindentation methods. Bovine cortical and trabecular bone samples (n=8) from the distal femur and proximal tibia were dehydrated, embedded and polished. The material properties determined using nanoindentation were hardness and reduced modulus, as well as time-dependent parameters based on creep, loading-rate, dissipated energy and semi-dynamic testing under load control. Each loading protocol was repeated 160 times and the reproducibility was assessed based on the coefficient of variation (CV). Additionally, three well-characterized polymers were tested and CV values were calculated for reference. The employed methods were able to characterize time-dependent viscoelastic properties of bone. However, their reproducibility varied highly (CV 9-40%). The creep constant increased with increasing dwell time. The reproducibility was best with a 30s creep period (CV 18%). The dissipated energy was stable after three repeated load cycles, and the reproducibility improved with each cycle (CV 23%). The viscoelastic properties determined with semi-dynamic test increased with increase in frequency. These measurements were most reproducible at high frequencies (CV 9-10%). Our results indicate that several methods are feasible for the determination of viscoelastic properties of bone material. The high frequency semi-dynamic test showed the highest precision within the tested nanoindentation protocols. PMID:20478559

  3. Trabecular Bone Adaptation to Low-Magnitude High-Frequency Loading in Microgravity

    PubMed Central

    Torcasio, Antonia; Jähn, Katharina; Van Guyse, Maarten; Spaepen, Pieter; Tami, Andrea E.; Vander Sloten, Jos; Stoddart, Martin J.; van Lenthe, G. Harry

    2014-01-01

    Exposure to microgravity causes loss of lower body bone mass in some astronauts. Low-magnitude high-frequency loading can stimulate bone formation on earth. Here we hypothesized that low-magnitude high-frequency loading will also stimulate bone formation under microgravity conditions. Two groups of six bovine cancellous bone explants were cultured at microgravity on a Russian Foton-M3 spacecraft and were either loaded dynamically using a sinusoidal curve or experienced only a static load. Comparable reference groups were investigated at normal gravity. Bone structure was assessed by histology, and mechanical competence was quantified using μCT and FE modelling; bone remodelling was assessed by fluorescent labelling and secreted bone turnover markers. Statistical analyses on morphometric parameters and apparent stiffness did not reveal significant differences between the treatment groups. The release of bone formation marker from the groups cultured at normal gravity increased significantly from the first to the second week of the experiment by 90.4% and 82.5% in response to static and dynamic loading, respectively. Bone resorption markers decreased significantly for the groups cultured at microgravity by 7.5% and 8.0% in response to static and dynamic loading, respectively. We found low strain magnitudes to drive bone turnover when applied at high frequency, and this to be valid at normal as well as at microgravity. In conclusion, we found the effect of mechanical loading on trabecular bone to be regulated mainly by an increase of bone formation at normal gravity and by a decrease in bone resorption at microgravity. Additional studies with extended experimental time and increased samples number appear necessary for a further understanding of the anabolic potential of dynamic loading on bone quality and mechanical competence. PMID:24787094

  4. Scaling VOI size in 3D μCT studies of trabecular bone: a test of the over-sampling hypothesis.

    PubMed

    Lazenby, Richard A; Skinner, Matthew M; Kivell, Tracy L; Hublin, Jean-Jacques

    2011-02-01

    For comparative 3D microCT studies of trabecular bone, the use of a volume of interest (VOI) scaled to body size may avoid over-sampling the trabecular mass in smaller versus larger-bodied taxa and comparison of regions that are not functionally homologous (Fajardo and Müller: Am J Phys Anthropol 115 (2001) 327-336), though the influence on quantitative analyses using scaled versus nonscaled VOIs remains poorly characterized. We compare trabecular architectural properties reflecting mass, organization, and orientation from three volumes of interest (large, scaled, and small) obtained from the distal first metacarpal in a sample of Homo (n = 10) and Pan (n = 12). We test the null hypotheses that neither absolute VOI size, nor scaling of the VOI to metacarpal size as a proxy for body size, biases intraspecific analyses nor impacts the detection of interspecific differences. These hypotheses were only partially supported. While certain properties (e.g., bone volume fraction or trabecular thickness) were not affected by varying VOI size within taxa, others were significantly impacted (e.g., intersection surface, connectivity, and structure). In comparing large versus scaled VOIs, we found that the large VOI inflated the number and/or magnitude of significant differences between Homo and Pan. In summary, our results support the use of scaled VOIs in studies of trabecular architecture. PMID:20979207

  5. Comparison of radiograph-based texture analysis and bone mineral density with three-dimensional microarchitecture of trabecular bone

    SciTech Connect

    Ranjanomennahary, P.; Ghalila, S. Sevestre; Malouche, D; Marchadier, A.; Rachidi, M.; Benhamou, Cl.; Chappard, C.

    2011-01-15

    Purpose: Hip fracture is a serious health problem and textural methods are being developed to assess bone quality. The authors aimed to perform textural analysis at femur on high-resolution digital radiographs compared to three-dimensional (3D) microarchitecture comparatively to bone mineral density. Methods: Sixteen cadaveric femurs were imaged with an x-ray device using a C-MOS sensor. One 17 mm square region of interest (ROI) was selected in the femoral head (FH) and one in the great trochanter (GT). Two-dimensional (2D) textural features from the co-occurrence matrices were extracted. Site-matched measurements of bone mineral density were performed. Inside each ROI, a 16 mm diameter core was extracted. Apparent density (D{sub app}) and bone volume proportion (BV/TV{sub Arch}) were measured from a defatted bone core using Archimedes' principle. Microcomputed tomography images of the entire length of the core were obtained (Skyscan 1072) at 19.8 {mu}m of resolution and usual 3D morphometric parameters were computed on the binary volume after calibration from BV/TV{sub Arch}. Then, bone surface/bone volume, trabecular thickness, trabecular separation, and trabecular number were obtained by direct methods without model assumption and the structure model index was calculated. Results: In univariate analysis, the correlation coefficients between 2D textural features and 3D morphological parameters reached 0.83 at the FH and 0.79 at the GT. In multivariate canonical correlation analysis, coefficients of the first component reached 0.95 at the FH and 0.88 at the GT. Conclusions: Digital radiographs, widely available and economically viable, are an alternative method for evaluating bone microarchitectural structure.

  6. Trabecular bone response to mechanical loading in ovariectomized Sprague-Dawley rats depends on baseline bone quantity.

    PubMed

    Ko, Chang-Yong; Jung, Young Jin; Park, Ji Hyung; Seo, Donghyun; Han, Paul; Bae, Kiho; Schreiber, Jürgen; Kim, Han Sung

    2012-07-26

    Mechanical loading is one of the determining factors for bone modulation, and is therefore frequently used to treat or prevent bone loss; however, there appears to be no data on the effects of baseline bone quantity on this response. This study aimed to verify whether baseline bone quantity affects osteoporotic trabecular bone adaptive response to mechanical stimulation. Twenty-four female Sprague-Dawley (SD) rats were ovariectomized (OVX). After 3 weeks of OVX, rats were divided into a high bone quantity and a low bone quantity group, and rats in each group were then subdivided into 4 groups that were exposed to different loading strategies. In the loading groups, tibiae were stimulated through axial loading at 2000με of strain, for 1500 cycles each of 75s, 150s, or 250s. The sham treatment groups received no loading. Changes in BV/TV for trabecular bone in the tibia were measured at the baseline (before loading), and at 3 weeks and 6 weeks after loading. BV/TVs in loading groups of the low baseline bone quantity group were significantly increased at 6 weeks, compared with those in the no-loading groups (p<0.05), while those in the high quantity groups were not increased (p>0.05). A significant negative correlation was observed between baseline BV/TV and its relative variations at 3 weeks or 6 weeks (p<0.05). These results indicate that adaptive responses of osteoporotic trabecular bone to mechanical loading depend on baseline bone quantity. PMID:22663762

  7. Bone marrow capacity for bone cells and trabecular bone turnover in immobilized tibia after sciatic neurectomy in mice.

    PubMed

    Sakai, A; Nakamura, T; Tsurukami, H; Okazaki, R; Nishida, S; Tanaka, Y; Norimura, T; Suzuki, K

    1996-05-01

    Trabecular bone turnover and bone marrow capacity for the development of bone cells in the tibia were assessed after sciatic neurectomy (NX) in mice. The right hindlimbs of 6-week-old DDY mice were neurectomized and left hindlimbs were sham-operated and served as NX controls. Histomorphometrical analyses of the trabecular bone of the proximal tibia demonstrated the initial decrease in bone formation rate for the first 14 days and the subsequent increase in osteoclast surface for the next 14 days. The number of adherent stromal cells per tibia obtained for the NX limbs was reduced on days 7 and 10 postsurgically, and then recovered on day 12. However, the alkaline phosphatase activity of the cells was persistently depressed. The formation of osteoclast-like multinucleated cells in the marrow cultures obtained from NX limbs at days 10, 12, and 14 showed a significant increase in the medium containing parathyroid hormone (PTH). The number of colonies cultured for colony forming units-fibroblastic (CFU-f) that developed from the marrow cells did not differ in the NX and the contralateral limbs at any time during the period. On the other hand, the number of colonies cultured of colony forming units for granulocytes and macrophages (CFU-GM) was markedly increased for both the NX and the contralateral tibiae at days 12 and 14. This study clearly demonstrates that there are two stages in the development of osteopenia after NX. During the first 14 days, trabecular bone formation and number of marrow stromal cells are reduced. In the second 14 day period, the trabecular osteoclast number is increased and osteoclast formation from the bone marrow cells is enhanced in the presence of PTH. However, neither the CFU-f nor the CFU-GM assay could identify the changes in osteogenic or osteoclastogenic potential of the bone marrow. These in vitro assays provide limited information on the shifts in bone marrow cell lineages and the local environment producing osteopenia in the

  8. Trabecular and Cortical Bone of Growing C3H Mice Is Highly Responsive to the Removal of Weightbearing.

    PubMed

    Li, Bing; Sankaran, Jeyantt Srinivas; Judex, Stefan

    2016-01-01

    Genetic make-up strongly influences the skeleton's susceptibility to the loss of weight bearing with some inbred mouse strains experiencing great amounts of bone loss while others lose bone at much smaller rates. At young adulthood, female inbred C3H/HeJ (C3H) mice are largely resistant to catabolic pressure induced by unloading. Here, we tested whether the depressed responsivity to unloading is inherent to the C3H genetic make-up or whether a younger age facilitates a robust skeletal response to unloading. Nine-week-old, skeletally immature, female C3H mice were subjected to 3wk of hindlimb unloading (HLU, n = 12) or served as normal baseline controls (BC, n = 10) or age-matched controls (AC, n = 12). In all mice, cortical and trabecular architecture of the femur, as well as levels of bone formation and resorption, were assessed with μCT, histomorphometry, and histology. Changes in bone marrow progenitor cell populations were determined with flow cytometry. Following 21d of unloading, HLU mice had 52% less trabecular bone in the distal femur than normal age-matched controls. Reflecting a loss of trabecular tissue compared to baseline controls, trabecular bone formation rates (BFR/BS) in HLU mice were 40% lower than in age-matched controls. Surfaces undergoing osteoclastic resorption were not significantly different between groups. In the mid-diaphysis, HLU inhibited cortical bone growth leading to 14% less bone area compared to age-matched controls. Compared to AC, BFR/BS of HLU mice were 53% lower at the endo-cortical surface and 49% lower at the periosteal surface of the mid-diaphysis. The enriched osteoprogenitor cell population (OPC) comprised 2% of the bone marrow stem cells in HLU mice, significantly different from 3% OPC in the AC group. These data show that bone tissue in actively growing C3H mice is lost rapidly, or fails to grow, during the removal of functional weight bearing-in contrast to the insignificant response previously demonstrated in female

  9. Jagged1 expression by osteoblast-lineage cells regulates trabecular bone mass and periosteal expansion in mice.

    PubMed

    Youngstrom, D W; Dishowitz, M I; Bales, C B; Carr, E; Mutyaba, P L; Kozloff, K M; Shitaye, H; Hankenson, K D; Loomes, K M

    2016-10-01

    Loss-of-function mutations in the Notch ligand, Jagged1 (Jag1), result in multi-system developmental pathologies associated with Alagille syndrome (ALGS). ALGS patients present with skeletal manifestations including hemi-vertebrae, reduced bone mass, increased fracture incidence and poor bone healing. However, it is not known whether the increased fracture risk is due to altered bone homeostasis (primary) or nutritional malabsorption due to chronic liver disease (secondary). To determine the significance of Jag1 loss in bone, we characterized the skeletal phenotype of two Jag1-floxed conditional knockout mouse models: Prx1-Cre;Jag1(f/f) to target osteoprogenitor cells and their progeny, and Col2.3-Cre;Jag1(f/f) to target mid-stage osteoblasts and their progeny. Knockout phenotypes were compared to wild-type (WT) controls using quantitative micro-computed tomography, gene expression profiling and mechanical testing. Expression of Jag1 and the Notch target genes Hes1 and Hey1 was downregulated in all Jag1 knockout mice. Osteoblast differentiation genes were downregulated in whole bone of both groups, but unchanged in Prx1-Cre;Jag1(f/f) cortical bone. Both knockout lines exhibited changes in femoral trabecular morphology including decreased bone volume fraction and increased trabecular spacing, with males presenting a more severe trabecular osteopenic phenotype. Prx1-Cre;Jag1(f/f) mice showed an increase in marrow mesenchymal progenitor cell number and, counterintuitively, developed increased cortical thickness resulting from periosteal expansion, translating to greater mechanical stiffness and strength. Similar alterations in femoral morphology were observed in mice with canonical Notch signaling disrupted using Prx1-Cre-regulatable dominant-negative mastermind like-protein (dnMAML). Taken together, we report that 1) Jag1 negatively regulates the marrow osteochondral progenitor pool, 2) Jag1 is required for normal trabecular bone formation and 3) Notch signaling

  10. Trabecular and Cortical Bone of Growing C3H Mice Is Highly Responsive to the Removal of Weightbearing

    PubMed Central

    Judex, Stefan

    2016-01-01

    Genetic make-up strongly influences the skeleton’s susceptibility to the loss of weight bearing with some inbred mouse strains experiencing great amounts of bone loss while others lose bone at much smaller rates. At young adulthood, female inbred C3H/HeJ (C3H) mice are largely resistant to catabolic pressure induced by unloading. Here, we tested whether the depressed responsivity to unloading is inherent to the C3H genetic make-up or whether a younger age facilitates a robust skeletal response to unloading. Nine-week-old, skeletally immature, female C3H mice were subjected to 3wk of hindlimb unloading (HLU, n = 12) or served as normal baseline controls (BC, n = 10) or age-matched controls (AC, n = 12). In all mice, cortical and trabecular architecture of the femur, as well as levels of bone formation and resorption, were assessed with μCT, histomorphometry, and histology. Changes in bone marrow progenitor cell populations were determined with flow cytometry. Following 21d of unloading, HLU mice had 52% less trabecular bone in the distal femur than normal age-matched controls. Reflecting a loss of trabecular tissue compared to baseline controls, trabecular bone formation rates (BFR/BS) in HLU mice were 40% lower than in age-matched controls. Surfaces undergoing osteoclastic resorption were not significantly different between groups. In the mid-diaphysis, HLU inhibited cortical bone growth leading to 14% less bone area compared to age-matched controls. Compared to AC, BFR/BS of HLU mice were 53% lower at the endo-cortical surface and 49% lower at the periosteal surface of the mid-diaphysis. The enriched osteoprogenitor cell population (OPC) comprised 2% of the bone marrow stem cells in HLU mice, significantly different from 3% OPC in the AC group. These data show that bone tissue in actively growing C3H mice is lost rapidly, or fails to grow, during the removal of functional weight bearing—in contrast to the insignificant response previously demonstrated in

  11. Human evolution. Comment on "Human-like hand use in Australopithecus africanus".

    PubMed

    Almécija, Sergio; Wallace, Ian J; Judex, Stefan; Alba, David M; Moyà-Solà, Salvador

    2015-06-01

    Skinner and colleagues (Research Article, 23 January 2015, p. 395), based on metacarpal trabecular bone structure, argue that Australopithecus africanus employed human-like dexterity for stone tool making and use 3 million years ago. However, their evolutionary and biological assumptions are misinformed, failing to refute the previously existing hypothesis that human-like manipulation preceded systematized stone tool manufacture, as indicated by the fossil record. PMID:26045428

  12. Guidelines for Dual Energy X-Ray Absorptiometry Analysis of Trabecular Bone-Rich Regions in Mice: Improved Precision, Accuracy, and Sensitivity for Assessing Longitudinal Bone Changes.

    PubMed

    Shi, Jiayu; Lee, Soonchul; Uyeda, Michael; Tanjaya, Justine; Kim, Jong Kil; Pan, Hsin Chuan; Reese, Patricia; Stodieck, Louis; Lin, Andy; Ting, Kang; Kwak, Jin Hee; Soo, Chia

    2016-05-01

    Trabecular bone is frequently studied in osteoporosis research because changes in trabecular bone are the most common cause of osteoporotic fractures. Dual energy X-ray absorptiometry (DXA) analysis specific to trabecular bone-rich regions is crucial to longitudinal osteoporosis research. The purpose of this study is to define a novel method for accurately analyzing trabecular bone-rich regions in mice via DXA. This method will be utilized to analyze scans obtained from the International Space Station in an upcoming study of microgravity-induced bone loss. Thirty 12-week-old BALB/c mice were studied. The novel method was developed by preanalyzing trabecular bone-rich sites in the distal femur, proximal tibia, and lumbar vertebrae via high-resolution X-ray imaging followed by DXA and micro-computed tomography (micro-CT) analyses. The key DXA steps described by the novel method were (1) proper mouse positioning, (2) region of interest (ROI) sizing, and (3) ROI positioning. The precision of the new method was assessed by reliability tests and a 14-week longitudinal study. The bone mineral content (BMC) data from DXA was then compared to the BMC data from micro-CT to assess accuracy. Bone mineral density (BMD) intra-class correlation coefficients of the new method ranging from 0.743 to 0.945 and Levene's test showing that there was significantly lower variances of data generated by new method both verified its consistency. By new method, a Bland-Altman plot displayed good agreement between DXA BMC and micro-CT BMC for all sites and they were strongly correlated at the distal femur and proximal tibia (r=0.846, p<0.01; r=0.879, p<0.01, respectively). The results suggest that the novel method for site-specific analysis of trabecular bone-rich regions in mice via DXA yields more precise, accurate, and repeatable BMD measurements than the conventional method. PMID:26956416

  13. Cystatin A, a Potential Common Link for Mutant Myocilin Causative Glaucoma

    PubMed Central

    Kennedy, K. David; AnithaChristy, S. A.; Buie, LaKisha K.; Borrás, Teresa

    2012-01-01

    Myocilin (MYOC) is a 504 aa secreted glycoprotein induced by stress factors in the trabecular meshwork tissue of the eye, where it was discovered. Mutations in MYOC are linked to glaucoma. The glaucoma phenotype of each of the different MYOC mutation varies, but all of them cause elevated intraocular pressure (IOP). In cells, forty percent of wild-type MYOC is cleaved by calpain II, a cysteine protease. This proteolytic process is inhibited by MYOC mutants. In this study, we investigated the molecular mechanisms by which MYOC mutants cause glaucoma. We constructed adenoviral vectors with variants Q368X, R342K, D380N, K423E, and overexpressed them in human trabecular meshwork cells. We analyzed expression profiles with Affymetrix U133Plus2 GeneChips using wild-type and null viruses as controls. Analysis of trabecular meshwork relevant mechanisms showed that the unfolded protein response (UPR) was the most affected. Search for individual candidate genes revealed that genes that have been historically connected to trabecular meshwork physiology and pathology were altered by the MYOC mutants. Some of those had known MYOC associations (MMP1, PDIA4, CALR, SFPR1) while others did not (EDN1, MGP, IGF1, TAC1). Some, were top-changed in only one mutant (LOXL1, CYP1B1, FBN1), others followed a mutant group pattern. Some of the genes were new (RAB39B, STC1, CXCL12, CSTA). In particular, one selected gene, the cysteine protease inhibitor cystatin A (CSTA), was commonly induced by all mutants and not by the wild-type. Subsequent functional analysis of the selected gene showed that CSTA was able to reduce wild-type MYOC cleavage in primary trabecular meshwork cells while an inactive mutated CSTA was not. These findings provide a new molecular understanding of the mechanisms of MYOC-causative glaucoma and reveal CSTA, a serum biomarker for cancer, as a potential biomarker and drug for the treatment of MYOC-induced glaucoma. PMID:22615763

  14. Fractal lacunarity of trabecular bone and magnetic resonance imaging: New perspectives for osteoporotic fracture risk assessment

    PubMed Central

    Zaia, Annamaria

    2015-01-01

    Osteoporosis represents one major health condition for our growing elderly population. It accounts for severe morbidity and increased mortality in postmenopausal women and it is becoming an emerging health concern even in aging men. Screening of the population at risk for bone degeneration and treatment assessment of osteoporotic patients to prevent bone fragility fractures represent useful tools to improve quality of life in the elderly and to lighten the related socio-economic impact. Bone mineral density (BMD) estimate by means of dual-energy X-ray absorptiometry is normally used in clinical practice for osteoporosis diagnosis. Nevertheless, BMD alone does not represent a good predictor of fracture risk. From a clinical point of view, bone microarchitecture seems to be an intriguing aspect to characterize bone alteration patterns in aging and pathology. The widening into clinical practice of medical imaging techniques and the impressive advances in information technologies together with enhanced capacity of power calculation have promoted proliferation of new methods to assess changes of trabecular bone architecture (TBA) during aging and osteoporosis. Magnetic resonance imaging (MRI) has recently arisen as a useful tool to measure bone structure in vivo. In particular, high-resolution MRI techniques have introduced new perspectives for TBA characterization by non-invasive non-ionizing methods. However, texture analysis methods have not found favor with clinicians as they produce quite a few parameters whose interpretation is difficult. The introduction in biomedical field of paradigms, such as theory of complexity, chaos, and fractals, suggests new approaches and provides innovative tools to develop computerized methods that, by producing a limited number of parameters sensitive to pathology onset and progression, would speed up their application into clinical practice. Complexity of living beings and fractality of several physio-anatomic structures suggest

  15. Development and testing of texture discriminators for the analysis of trabecular bone in proximal femur radiographs

    SciTech Connect

    Huber, M. B.; Carballido-Gamio, J.; Fritscher, K.; Schubert, R.; Haenni, M.; Hengg, C.; Majumdar, S.; Link, T. M.

    2009-11-15

    }=0.61 (MF and MG features, p<0.01) and were partially independent of BMD. The correlations were dependent on the choice of the ROI and the texture measure. The best predictive multiregression model for failure load R{sub adj}{sup 2}=0.86 (p<0.001) included a set of recently developed texture methods (MF and SIM) but excluded bone mineral density and commonly used texture measures. Conclusions: The results suggest that texture information contained in trabecular bone structure visualized on radiographs may predict whether an implant anchorage can be used and may determine the local bone quality from preoperative radiographs.

  16. Trabecular-Iris Circumference Volume in Open Angle Eyes Using Swept-Source Fourier Domain Anterior Segment Optical Coherence Tomography

    PubMed Central

    Rigi, Mohammed; Blieden, Lauren S.; Nguyen, Donna; Chuang, Alice Z.; Baker, Laura A.; Bell, Nicholas P.; Lee, David A.; Mankiewicz, Kimberly A.; Feldman, Robert M.

    2014-01-01

    Purpose. To introduce a new anterior segment optical coherence tomography parameter, trabecular-iris circumference volume (TICV), which measures the integrated volume of the peripheral angle, and establish a reference range in normal, open angle eyes. Methods. One eye of each participant with open angles and a normal anterior segment was imaged using 3D mode by the CASIA SS-1000 (Tomey, Nagoya, Japan). Trabecular-iris space area (TISA) and TICV at 500 and 750 µm were calculated. Analysis of covariance was performed to examine the effect of age and its interaction with spherical equivalent. Results. The study included 100 participants with a mean age of 50 (±15) years (range 20–79). TICV showed a normal distribution with a mean (±SD) value of 4.75 µL (±2.30) for TICV500 and a mean (±SD) value of 8.90 µL (±3.88) for TICV750. Overall, TICV showed an age-related reduction (P = 0.035). In addition, angle volume increased with increased myopia for all age groups, except for those older than 65 years. Conclusions. This study introduces a new parameter to measure peripheral angle volume, TICV, with age-adjusted normal ranges for open angle eyes. Further investigation is warranted to determine the clinical utility of this new parameter. PMID:25210623

  17. Trabecular-iris circumference volume in open angle eyes using swept-source fourier domain anterior segment optical coherence tomography.

    PubMed

    Rigi, Mohammed; Blieden, Lauren S; Nguyen, Donna; Chuang, Alice Z; Baker, Laura A; Bell, Nicholas P; Lee, David A; Mankiewicz, Kimberly A; Feldman, Robert M

    2014-01-01

    Purpose. To introduce a new anterior segment optical coherence tomography parameter, trabecular-iris circumference volume (TICV), which measures the integrated volume of the peripheral angle, and establish a reference range in normal, open angle eyes. Methods. One eye of each participant with open angles and a normal anterior segment was imaged using 3D mode by the CASIA SS-1000 (Tomey, Nagoya, Japan). Trabecular-iris space area (TISA) and TICV at 500 and 750 µm were calculated. Analysis of covariance was performed to examine the effect of age and its interaction with spherical equivalent. Results. The study included 100 participants with a mean age of 50 (±15) years (range 20-79). TICV showed a normal distribution with a mean (±SD) value of 4.75 µL (±2.30) for TICV500 and a mean (±SD) value of 8.90 µL (±3.88) for TICV750. Overall, TICV showed an age-related reduction (P = 0.035). In addition, angle volume increased with increased myopia for all age groups, except for those older than 65 years. Conclusions. This study introduces a new parameter to measure peripheral angle volume, TICV, with age-adjusted normal ranges for open angle eyes. Further investigation is warranted to determine the clinical utility of this new parameter. PMID:25210623

  18. Trabecular bone strength is not an independent predictive factor for dynamic hip screw migration--A pr