A Comparison of Bone Mineral Density and Its Predictors in HIV-Infected and HIV-Uninfected Older Men

ObjectiveBone health in older individuals with HIV infection has not been well studied. This study aimed to compare bone mineral density (BMD), trabecular bone score (TBS), and bone markers between HIV-infected men and age- and body mass index (BMI)-matched HIV-uninfected men aged ≥60 years. We investigated the associations of risk factors related to fracture with BMD, TBS, and bone markers in HIV-infected men.MethodsThis cross-sectional study included 45 HIV-infected men receiving antiretroviral therapy and 42 HIV-uninfected men. Medical history, BMD and TBS measurements, and laboratory tests related to bone health were assessed in all the participants. HIV-related factors known to be associated with bone loss were assessed in the HIV-infected men.ResultsThe mean BMD, TBS, and osteopenia or osteoporosis prevalence were similar among the cases and controls. The HIV-infected men had significantly higher mean N-terminal propeptide of type 1 procollagen and C-terminal cross-linking telopeptide of type I collagen levels. Stepwise multiple linear regression analysis demonstrated that low BMI (lumbar spine, P = .015; femoral neck, P = .018; and total hip, P = .005), high C-terminal cross-linking telopeptide of type I collagen concentration (total hip, P = .042; and TBS, P = .010), and low vitamin D supplementation (TBS, P = .035) were independently associated with low BMD and TBS.ConclusionIn older HIV-infected men with a low fracture risk, the mean BMD and TBS were similar to those of the age- and BMI-matched controls. The mean bone marker levels were higher in the HIV group. Traditional risk factors for fracture, including low BMI, high C-terminal cross-linking telopeptide of type I collagen level, and low vitamin D supplementation, were significant predictors of low BMD and TBS.     

Conservation of placentation during the tertiary radiation of mammals in South America

The eutherian placenta is considered to possess great plasticity, but it is not clear how this variation reflects adaptation to different ecological niches. Because South America was isolated for most of the Tertiary, it represents a natural laboratory to examine this question. We here describe placentation in three South American groups: Xenarthra have been part of the fauna from at least the mid‐Paleocene whereas caviomorph rodents and Neotropical primates are each derived from a single founder that reached South America in the Eocene and Oligocene, respectively. The common ancestor of Xenarthra had a villous, haemochorial placenta, from which the labyrinthine, endotheliochorial placenta of sloths later evolved. Placentation in Caviomorpha follows an extraordinary stable pattern, characterized by a haemomonochorial, labyrinthine and highly lobed structure with specialized growing areas. This pattern was present before arrival of these rodents in South America and enabled a successful radiation especially during the spread of grasslands. Neotropical primates have haemochorial, trabecular placentas with a specialized maternal blood supply; a pattern that contrasts with that of Old World monkeys and may have been present in the founder generation on arrival in South America. In conclusion, there is a dichotomy within Xenarthra but otherwise the ancient South American mammals do not show much variation in principal placental characters. Thus, the successful radiation of these three groups, and their adaptation to diverse ecological niches, did not require substantial alterations in placentation. J. Morphol., 2013. © 2013 Wiley Periodicals, Inc.     

Extracellular vesicle‐mediated crosstalk between NPCE cells and TM cells result in modulation of Wnt signalling pathway and ECM remodelling

Primary open‐angle glaucoma is a leading cause of irreversible blindness, often associated with increased intraocular pressure. Extracellular vesicles (EVs) carry a specific composition of proteins, lipids and nucleotides have been considered as essential mediators of cell‐cell communication. Their potential impact for crosstalk between tissues responsible for aqueous humour production and out‐flow is largely unknown. The study objective was to investigate the effects of EVs derived from non‐pigmented ciliary epithelium (NPCE) primary cells on the expression of Wnt proteins in a human primary trabecular meshwork (TM) cells and define the mechanism underlying exosome‐mediated regulation that signalling pathway. Consistent with the results in TM cell line, EVs released by both primary NPCE cells and NPCE cell line showed diminished pGSK3β phosphorylation and decreased cytosolic levels of β‐catenin in primary TM cells. At the molecular level, we showed that NPCE exosome treatment downregulated the expression of positive GSKβ regulator‐AKT protein but increased the levels of GSKβ negative regulator‐PP2A protein in TM cells. NPCE exosome protein analysis revealed 584 miRNAs and 182 proteins involved in the regulation of TM cellular processes, including WNT/β‐catenin signalling pathway, cell adhesion and extracellular matrix deposition. We found that negative modulator of Wnt signalling miR‐29b was abundant in NPCE exosomal samples and treatment of TM cells with NPCE EVs significantly decreased COL3A1 expression. Suggesting that miR‐29b can be responsible for decreased levels of WNT/β‐catenin pathway. Overall, this study highlights a potential role of EVs derived from NPCE cells in modulating ECM proteins and TM canonical Wnt signalling.     

Endogenous ocular lipids as potential modulators of intraocular pressure

Elevated intraocular pressure (IOP) is a risk factor in glaucoma, a group of irreversible blinding diseases. Endogenous lipids may be involved in regulation of IOP homeostasis. We present comparative fold analysis of phospholipids and sphingolipids of aqueous humour and trabecular meshwork from human control vs primary open-angle glaucoma and mouse control (normotensive) vs ocular hypertensive state. The fold analysis in control vs disease state was based on ratiometric mass spectrometric data for above classes of lipids. We standardized in vitro assays for rapid characterization of lipids undergoing significant diminishment in disease state. Evaluation of lipids using in vitro assays helped select a finite number of lipids that may potentially expand cellular interstitial space embedded in an artificial matrix or increase fluid flow across a layer of cells. These assays reduced a number of lipids for initial evaluation using a mouse model, DBA/2J with spontaneous IOP elevation. These lipids were then used in other mouse models for confirmation of IOP lowering potential of a few lipids that were found promising in previous assessments. Our results provide selected lipid molecules that can be pursued for further evaluation and studies that may provide insight into their function.     

Stochastic multi-scale prediction on the apparent elastic moduli of trabecular bone considering uncertainties of biological apatite (BAp) crystallite orientation and image-based modelling

An assessment of the mechanical properties of trabecular bone is important in determining the fracture risk of human bones. Many uncertainty factors contribute to the dispersion of the estimated mechanical properties of trabecular bone. This study was undertaken in order to propose a computational scheme that will be able to predict the effective apparent elastic moduli of trabecular bone considering the uncertainties that are primarily caused by image-based modelling and trabecular stiffness orientation. The effect of image-based modelling which focused on the connectivity was also investigated. A stochastic multi-scale method using a first-order perturbation-based and asymptotic homogenisation theory was applied to formulate the stochastically apparent elastic properties of trabecular bone. The effective apparent elastic modulus was predicted with the introduction of a coefficient factor to represent the variation of bone characteristics due to inter-individual differences. The mean value of the predicted effective apparent Young's modulus in principal axis was found at approximately 460 MPa for respective 15.24% of bone volume fraction, and this is in good agreement with other experimental results. The proposed method may provide a reference for the reliable evaluation of the prediction of the apparent elastic properties of trabecular bone.     

Micro-finite element simulation of trabecular-bone post-yield behaviour – effects of material model,element size and type

Micro-finite element (micro-FE) analysis became a standard tool for the evaluation of trabecular bone mechanical properties. The accuracy of micro-FE models for linear analyses is well established. However, the accuracy of recently developed nonlinear micro-FE models for simulations of trabecular bone failure is not known. In this study, a trabecular bone specimen was compressed beyond the apparent yield point. The experiment was simulated using different micro-FE meshes with different element sizes and types, and material models based on cortical bone. The results from the simulations were compared with experimental results to study the effects of the different element and material models. It was found that a decrease in element size from 80 to 40 μm had little effect on predicted post-yield behaviour. Element type and material model had significant effects. Nevertheless, none of the established material models for cortical bone were able to predict the typical descent in the load-displacement curve seen during compression of trabecular bone.     

The sensitivity of nonlinear computational models of trabecular bone to tissue level constitutive model

Microarchitectural finite element models have become a key tool in the analysis of trabecular bone. Robust, accurate, and validated constitutive models would enhance confidence in predictive applications of these models and in their usefulness as accurate assays of tissue properties. Human trabecular bone specimens from the femoral neck (n = 3), greater trochanter (n = 6), and lumbar vertebra (n = 1) of eight different donors were scanned by μ-CT and converted to voxel-based finite element models. Unconfined uniaxial compression and shear loading were simulated for each of three different constitutive models: a principal strain-based model, Drucker–Lode, and Drucker–Prager. The latter was applied with both infinitesimal and finite kinematics. Apparent yield strains exhibited minimal dependence on the constitutive model, differing by at most 16.1%, with the kinematic formulation being influential in compression loading. At the tissue level, the quantities and locations of yielded tissue were insensitive to the constitutive model, with the exception of the Drucker–Lode model, suggesting that correlation of microdamage with computational models does not improve the ability to discriminate between constitutive laws. Taken together, it is unlikely that a tissue constitutive model can be fully validated from apparent-level experiments alone, as the calculations are too insensitive to identify differences in the outcomes. Rather, any asymmetric criterion with a valid yield surface will likely be suitable for most trabecular bone models.