Burn Pit Smoke Condensate-Mediated Toxicity in Human Airway Epithelial Cells.

Burn pits are a method of open-air waste management that was common during military operations in Iraq, Afghanistan, and other regions in Southwest Asia. Veterans returning from deployment have reported respiratory symptoms, potentially from exposure to burn pit smoke, yet comprehensive assessment of such exposure on pulmonary health is lacking. We have previously shown that exposure to condensates from burn pit smoke emissions causes inflammation and cytotoxicity in mice. In this study, we explored the effects of burn pit smoke condensates on human airway epithelial cells (HAECs) to understand their impact on cellular targets in the human lung. HAECs were cultured at the air-liquid interface (ALI) and exposed to burn pit waste smoke condensates (plywood, cardboard, plastic, mixed, and mixed with diesel) generated under smoldering and flaming conditions. Cytotoxicity was evaluated by measuring transepithelial electrical resistance (TEER) and lactate dehydrogenase (LDH) release; toxicity scores (TSs) were quantified for each exposure. Pro-inflammatory cytokine release and modulation of gene expression were examined for cardboard and plastic condensate exposures. Burn pit smoke condensates generated under flaming conditions affected cell viability, with flaming mixed waste and plywood exhibiting the highest toxicity scores. Cardboard and plastic smoke condensates modulated cytokine secretion, with GM-CSF and IL-1ß altered in more than one exposure group. Gene expression of detoxifying enzymes (ALDH1A3, ALDH3A1, CYP1A1, CYP1B1, NQO1, etc.), mucins (MUC5AC, MUC5B), and cytokines was affected by several smoke condensates. Particularly, expression of IL6 was elevated following exposure to all burn pit smoke condensates, and polycyclic aromatic hydrocarbon acenaphthene was positively associated with the IL-6 level in the basolateral media of HAECs. These observations demonstrate that exposure to smoke condensates of materials present in burn pits adversely affects HAECs and that aberrant cytokine secretion and altered gene expression profiles following burn pit material smoke exposure could contribute to the development of airway disease.

Translating microcalcification biomarker information into the laboratory: A preliminary assessment utilizing core biopsies obtained from sites of mammographic calcification.

Rationale and objectives: The potential of breast microcalcification chemistry to provide clinically valuable intelligence is being increasingly studied. However, acquisition of crystallographic details has, to date, been limited to high brightness, synchrotron radiation sources. This study, for the first time, evaluates a laboratory-based system that interrogates histological sections containing microcalcifications. The principal objective was to determine the measurement precision of the laboratory system and assess whether this was sufficient to provide potentially clinical valuable information. Materials and methods: Sections from 5 histological specimens from breast core biopsies obtained to evaluate mammographic calcification were examined using a synchrotron source and a laboratory-based instrument. The samples were chosen to represent a significant proportion of the known breast tissue, mineralogical landscape. Data were subsequently analysed using conventional methods and microcalcification characteristics such as crystallographic phase, chemical deviation from ideal stoichiometry and microstructure were determined. Results: The crystallographic phase of each microcalcification (e.g., hydroxyapatite, whitlockite) was easily determined from the laboratory derived data even when a mixed phase was apparent. Lattice parameter values from the laboratory experiments agreed well with the corresponding synchrotron values and, critically, were determined to precisions that were significantly greater than required for potential clinical exploitation. Conclusion: It has been shown that crystallographic characteristics of microcalcifications can be determined in the laboratory with sufficient precision to have potential clinical value. The work will thus enable exploitation acceleration of these latent microcalcification features as current dependence upon access to limited synchrotron resources is minimized.

Emissions from plastic incineration induce inflammation, oxidative stress, and impaired bioenergetics in primary human respiratory epithelial cells.

Inhalation exposure to plastic incineration emissions (PIEs) is a problem of increasing human relevance, as plastic production and waste creation have drastically increased since mainstream integration during the 20th century. We investigated the effects of PIEs on human nasal epithelial cells (HNECs) to understand if such exposures cause damage and dysfunction to respiratory epithelia. Primary HNECs from male and female donors were cultured at air-liquid interface (ALI), and 16HBE cells were cultured on coverslips. Smoke condensates were generated from incineration of plastic at flaming (640°C) and smoldering (500°C) temperatures, and cells were subsequently exposed to these materials at 5-50 µg/cm2 concentrations. HNECs were assessed for mitochondrial dysfunction and 16HBE cells for glutathione oxidation in real-time analyses. HNEC culture supernatants and total RNA were collected at 4-h postexposure for cytokine and gene expression analysis, and results show that PIEs can acutely induce inflammation, oxidative stress, and mitochondrial dysfunction in HNECs, and that incineration temperature modifies biological responses. Specifically, condensates from flaming and smoldering PIEs significantly increased HNEC secretion of cytokines IL-8, IL-1ß, and IL-13, as well as expression of xenobiotic metabolism pathways and genes such as CYP1A1 and CYP1B1 at 5 and 20 µg/cm2 concentrations. Only 50 µg/cm2 flaming PIEs significantly increased glutathione oxidation in 16HBEs, and decreased respiration and ATP production in HNEC mitochondria. Impact Statement: Our data reveal the impact of incineration temperatures on biological outcomes associated with PIE exposures, emphasizing the importance of temperature as a factor when evaluating respiratory disease associated with PIEs exposure.

Conical shell X-ray beam tomosynthesis and micro-computed tomography for microarchitectural characterisation.

Bone quality is commonly used to diagnose bone diseases such as osteoporosis, with many studies focusing on microarchitecture for fracture prediction. In this study a bovine distal femur was imaged using both micro-computed tomography (µCT) and tomosynthesis using focal construct geometry (FCG) for comparison of microarchitectural parameters. Six regions of interest (ROIs) were compared between the two imaging modalities, with both global and adaptive methods used to binarize the images. FCG images were downsampled to the same pixel size as the µCT images. Bone morphometrics were determined using BoneJ, for each imaging modality, binarization technique and ROI. Bone area/total area was found to have few significant differences between FCG and µCT (p < 0.05 for two of six ROIs). Fractal Dimension had only one significant difference (p < 0.05 for one of six ROIs) between µCT and downsampled FCG (where pixel size was equalized). Trabecular thickness and trabecular spacing were observed to follow trends as observed for the corresponding µCT images, although many absolute values were significantly different (p < 0.05 for between one and six ROIs depending on image types used). This study demonstrates the utility of tomosynthesis for measurement of microarchitectural morphometrics.

A pilot study: effect of irisin on trabecular bone in a streptozotocin-induced animal model of type 1 diabetic osteopathy utilizing a micro-CT.

Background: Osteoporosis is a significant co-morbidity of type 1 diabetes mellitus (DM1) leading to increased fracture risk. Exercise-induced hormone 'irisin' in low dosage has been shown to have a beneficial effect on bone metabolism by increasing osteoblast differentiation and reducing osteoclast maturation, and inhibiting apoptosis and inflammation. We investigated the role of irisin in treating diabetic osteopathy by observing its effect on trabecular bone. Methods: DM1 was induced by intraperitoneal injection of streptozotocin 60 mg/kg body weight. Irisin in low dosage (5 µg twice a week for 6 weeks I/P) was injected into half of the control and 4-week diabetic male Wistar rats. Animals were sacrificed six months after induction of diabetes. The trabecular bone in the femoral head and neck was analyzed using a micro-CT technique. Bone turnover markers were measured using ELISA, Western blot, and RT-PCR techniques. Results: It was found that DM1 deteriorates the trabecular bone microstructure by increasing trabecular separation (Tb-Sp) and decreasing trabecular thickness (Tb-Th), bone volume fraction (BV/TV), and bone mineral density (BMD). Irisin treatment positively affects bone quality by increasing trabecular number p < 0.05 and improves the BMD, Tb-Sp, and BV/TV by 21-28%. The deterioration in bone microarchitecture is mainly attributed to decreased bone formation observed as low osteocalcin and high sclerostin levels in diabetic bone samples p < 0.001. The irisin treatment significantly suppressed the serum and bone sclerostin levels p < 0.001, increased the serum CTX1 levels p < 0.05, and also showed non-significant improvement in osteocalcin levels. Conclusions: This is the first pilot study to our knowledge that shows that a low dose of irisin marginally improves the trabecular bone in DM1 and is an effective peptide in reducing sclerostin levels.

Microcalcification crystallography as a potential marker of DCIS recurrence.

Ductal carcinoma in-situ (DCIS) accounts for 20-25% of all new breast cancer diagnoses. DCIS has an uncertain risk of progression to invasive breast cancer and a lack of predictive biomarkers may result in relatively high levels (~ 75%) of overtreatment. To identify unique prognostic biomarkers of invasive progression, crystallographic and chemical features of DCIS microcalcifications have been explored. Samples from patients with at least 5-years of follow up and no known recurrence (174 calcifications in 67 patients) or ipsilateral invasive breast cancer recurrence (179 microcalcifications in 57 patients) were studied. Significant differences were noted between the two groups including whitlockite relative mass, hydroxyapatite and whitlockite crystal maturity and, elementally, sodium to calcium ion ratio. A preliminary predictive model for DCIS to invasive cancer progression was developed from these parameters with an AUC of 0.797. These results provide insights into the differing DCIS tissue microenvironments, and how these impact microcalcification formation.

Exploration of utility of combined optical photothermal infrared and Raman imaging for investigating the chemical composition of microcalcifications in breast cancer.

Microcalcifications play an important role in cancer detection. They are evaluated by their radiological and histological characteristics but it is challenging to find a link between their morphology, their composition and the nature of a specific type of breast lesion. Whilst there are some mammographic features that are either typically benign or typically malignant often the appearances are indeterminate. Here, we explore a large range of vibrational spectroscopic and multiphoton imaging techniques in order to gain more information about the composition of the microcalcifications. For the first time, we validated the presence of carbonate ions in the microcalcifications by O-PTIR and Raman spectroscopy at the same time, the same location and the same high resolution (0.5 µm). Furthermore, the use of multiphoton imaging allowed us to create stimulated Raman histology (SRH) images which mimic histological images with all chemical information. In conclusion, we established a protocol for efficiently analysing the microcalcifications by iteratively refining the area of interest.

Conical shell illumination incorporating a moving aperture for depth-resolved high-energy X-ray diffraction.

In many applications, the main limitation of X-ray absorption methods is that the signals measured are a function of the attenuation coefficient, which tells us almost nothing about the chemical or crystallographic nature of objects under inspection. To calculate fundamental crystallographic parameters requires the measurement of diffracted photons from a sample. Standard laboratory diffraction methods have been refined for well over a century and provide 'gold standard' structural models for well-prepared samples and single crystals but have little applicability for thick heterogeneous samples as demanded by many screening applications. We present a new high-energy X-ray diffraction probe, which in comparison with previous depth-resolving hollow beam techniques, requires a single beam, point detector and a simple swept aperture to resolve sample signatures at unknown locations within an inspection space. We perform Monte Carlo simulations to support experiments on both single- and multiple-material localisation and identification. The new probe is configured and tested using low-cost commercial components to provide a rapid and cost-effective solution for applications including explosives detection, process control and diagnostics.

Breast calcification micromorphology classification.

OBJECTIVES: The importance of consistent terminology in describing the appearance of breast calcifications in mammography is well recognised. Imaging of calcifications using electron microscopy is a globally growing field of research. We therefore suggest that the time is ripe to develop a lexicon of terms for classifying the micromorphology of breast calcifications. METHODS: Calcifications within a wide range of histological sections of breast tissue, both benign and malignant, were imaged by Scanning Electron Microscopy (SEM). These images were examined, and the micromorphology of calcifications present was grouped to create a classification system. RESULTS: Based on the appearance of the calcifications observed, we propose five main categories for classification of the micromorphology of breast calcifications, namely, Dense Homogenous, Punctulate, Banded, Spongy and Aggregate. CONCLUSIONS: Use of the descriptive categories outlined here will help to ensure consistency and comparability of published observations on the micromorphology of breast calcifications. ADVANCES IN KNOWLEDGE: This is the first time a lexicon and classification system has been proposed for the micromorphology of breast calcifications, as observed by scanning electron microscopy of histological sections. This will facilitate comparability of observed relationships between micromorphology, mammographic appearance, chemistry and pathology.

Investigating pair distribution function use in analysis of nanocrystalline hydroxyapatite and carbonate-substituted hydroxyapatite.

Hydroxyapatite (HA) is a complex material, which is often nanocrystalline when found within a biological setting. This work has directly compared the structural characteristics derived from data collected using a conventional laboratory-based X-ray diffractometer with those collected from a dedicated pair distribution function (PDF) beamline at Diamond Light Source. In particular, the application of PDF analysis methods to carbonated HA is evaluated. 20 synthetic samples were measured using both X-ray diffraction (XRD) and PDFs. Both Rietveld refinement (of laboratory XRD data) and real-space refinement (of PDF data) were used to analyse all samples. The results of Rietveld and real-space refinements were compared to evaluate their application to crystalline and nanocrystalline hydroxyapatite. Significant relationships were observed between real-space refinement parameters and increasing carbonate substitution. Understanding the local order of synthetic hydroxyapatite can benefit several fields, including both biomedical and clinical settings.

A multi-modal exploration of heterogeneous physico-chemical properties of DCIS breast microcalcifications.

Ductal carcinoma in situ (DCIS) is frequently associated with breast calcification. This study combines multiple analytical techniques to investigate the heterogeneity of these calcifications at the micrometre scale. X-ray diffraction, scanning electron microscopy and Raman and Fourier-transform infrared spectroscopy were used to determine the physicochemical and crystallographic properties of type II breast calcifications located in formalin fixed paraffin embedded DCIS breast tissue samples. Multiple calcium phosphate phases were identified across the calcifications, distributed in different patterns. Hydroxyapatite was the dominant mineral, with magnesium whitlockite found at the calcification edge. Amorphous calcium phosphate and octacalcium phosphate were also identified close to the calcification edge at the apparent mineral/matrix barrier. Crystallographic features of hydroxyapatite also varied across the calcifications, with higher crystallinity centrally, and highest carbonate substitution at the calcification edge. Protein was also differentially distributed across the calcification and the surrounding soft tissue, with collagen and ß-pleated protein features present to differing extents. Combination of analytical techniques in this study was essential to understand the heterogeneity of breast calcifications and how this may link crystallographic and physicochemical properties of calcifications to the surrounding tissue microenvironment.

Prediction of Upstaging in Ductal Carcinoma in Situ Based on Mammographic Radiomic Features.

Background Improving diagnosis of ductal carcinoma in situ (DCIS) before surgery is important in choosing optimal patient management strategies. However, patients may harbor occult invasive disease not detected until definitive surgery. Purpose To assess the performance and clinical utility of mammographic radiomic features in the prediction of occult invasive cancer among women diagnosed with DCIS on the basis of core biopsy findings. Materials and Methods In this Health Insurance Portability and Accountability Act-compliant retrospective study, digital magnification mammographic images were collected from women who underwent breast core-needle biopsy for calcifications that was performed at a single institution between September 2008 and April 2017 and yielded a diagnosis of DCIS. The database query was directed at asymptomatic women with calcifications without a mass, architectural distortion, asymmetric density, or palpable disease. Logistic regression with regularization was used. Differences across training and internal test set by upstaging rate, age, lesion size, and estrogen and progesterone receptor status were assessed by using the Kruskal-Wallis or χ2 test. Results The study consisted of 700 women with DCIS (age range, 40-89 years; mean age, 59 years ± 10 [standard deviation]), including 114 with lesions (16.3%) upstaged to invasive cancer at subsequent surgery. The sample was split randomly into 400 women for the training set and 300 for the testing set (mean ages: training set, 59 years ± 10; test set, 59 years ± 10; P = .85). A total of 109 radiomic and four clinical features were extracted. The best model on the test set by using all radiomic and clinical features helped predict upstaging with an area under the receiver operating characteristic curve of 0.71 (95% CI: 0.62, 0.79). For a fixed high sensitivity (90%), the model yielded a specificity of 22%, a negative predictive value of 92%, and an odds ratio of 2.4 (95% CI: 1.8, 3.2). High specificity (90%) corresponded to a sensitivity of 37%, positive predictive value of 41%, and odds ratio of 5.0 (95% CI: 2.8, 9.0). Conclusion Machine learning models that use radiomic features applied to mammographic calcifications may help predict upstaging of ductal carcinoma in situ, which can refine clinical decision making and treatment planning. © RSNA, 2022.

Transposon mutagenesis identifies cooperating genetic drivers during keratinocyte transformation and cutaneous squamous cell carcinoma progression.

The systematic identification of genetic events driving cellular transformation and tumor progression in the absence of a highly recurrent oncogenic driver mutation is a challenge in cutaneous oncology. In cutaneous squamous cell carcinoma (cuSCC), the high UV-induced mutational burden poses a hurdle to achieve a complete molecular landscape of this disease. Here, we utilized the Sleeping Beauty transposon mutagenesis system to statistically define drivers of keratinocyte transformation and cuSCC progression in vivo in the absence of UV-IR, and identified both known tumor suppressor genes and novel oncogenic drivers of cuSCC. Functional analysis confirms an oncogenic role for the ZMIZ genes, and tumor suppressive roles for KMT2C, CREBBP and NCOA2, in the initiation or progression of human cuSCC. Taken together, our in vivo screen demonstrates an extremely heterogeneous genetic landscape of cuSCC initiation and progression, which can be harnessed to better understand skin oncogenic etiology and prioritize therapeutic candidates.

A time-course Raman spectroscopic analysis of spontaneous in vitro microcalcifications in a breast cancer cell line.

Microcalcifications are early markers of breast cancer and can provide valuable prognostic information to support clinical decision-making. Current detection of calcifications in breast tissue is based on X-ray mammography, which involves the use of ionizing radiation with potentially detrimental effects, or MRI scans, which have limited spatial resolution. Additionally, these techniques are not capable of discriminating between microcalcifications from benign and malignant lesions. Several studies show that vibrational spectroscopic techniques are capable of discriminating and classifying breast lesions, with a pathology grade based on the chemical composition of the microcalcifications. However, the occurrence of microcalcifications in the breast and the underlying mineralization process are still not fully understood. Using a previously established model of in vitro mineralization, the MDA-MB-231 human breast cancer cell line was induced using two osteogenic agents, inorganic phosphate (Pi) and ß-glycerophosphate (ßG), and direct monitoring of the mineralization process was conducted using Raman micro-spectroscopy. MDA-MB-231 cells cultured in a medium supplemented with Pi presented more rapid mineralization (by day 3) than cells exposed to ßG (by day 11). A redshift of the phosphate stretching peak for cells supplemented with ßG revealed the presence of different precursor phases (octacalcium phosphate) during apatite crystal formation. These results demonstrate that Raman micro-spectroscopy is a powerful tool for nondestructive analysis of mineral species and can provide valuable information for evaluating mineralization dynamics and any associated breast cancer progression, if utilized in pathological samples.

Age related changes of rib cortical bone matrix and the application to forensic age-at-death estimation.

Forensic anthropology includes, amongst other applications, the positive identification of unknown human skeletal remains. The first step in this process is an assessment of the biological profile, that is: sex, age, stature and ancestry. In forensic contexts, age estimation is one of the main challenges in the process of identification. Recently established admissibility criteria are driving researchers towards standardisation of methodological procedures. Despite these changes, experience still plays a central role in anthropological examinations. In order to avoid this issue, age estimation procedures (i) must be presented to the scientific community and published in peer reviewed journals, (ii) accurately explained in terms of procedure and (iii) present clear information about the accuracy of the estimation and possible error rates. In order to fulfil all these requirements, a number of methods based on physiological processes which result in biochemical changes in various tissue structures at the molecular level, such as modifications in DNA-methylation and telomere shortening, racemization of proteins and stable isotopes analysis, have been developed. The current work proposes a new systematic approach in age estimation based on tracing physicochemical and mechanical degeneration of the rib cortical bone matrix. This study used autopsy material from 113 rib specimens. A set of 33 parameters were measured by standard bio-mechanical (nanoindentation and microindentation), physical (TGA/DSC, XRD and FTIR) and histomorphometry (porosity-ImageJ) methods. Stepwise regressions were used to create equations that would produce the best 'estimates of age at death' vs real age of the cadavers. Five equations were produced; in the best of cases an equation counting 7 parameters had an R2 = 0.863 and mean absolute error of 4.64 years. The present method meets all the admissibility criteria previously described. Furthermore, the method is experience-independent and as such can be performed without previous expert knowledge of forensic anthropology and human anatomy.

New insights into the application of pair distribution function studies to biogenic and synthetic hydroxyapatites.

Biogenic and synthetic hydroxyapatites are confounding materials whose properties remain uncertain, even after years of study. Pair distribution function (PDF) analysis was applied to hydroxyapatites in the 1970's and 1980's, but this area of research has not taken full advantage of the relatively recent advances in synchrotron facilities. Here, synchrotron X-ray PDF analysis is compared to techniques commonly used to characterise hydroxyapatite (such as wide angle X-ray scattering, Fourier-transform infrared spectroscopy and thermogravimetric analysis) for a range of biogenic and synthetic hydroxyapatites with a wide range of carbonate substitution. Contributions to the pair distribution function from collagen, carbonate and finite crystallite size were examined through principal component analysis and comparison of PDFs. Noticeable contributions from collagen were observed in biogenic PDFs when compared to synthetic PDFs (namely r < 15 Å), consistent with simulated PDFs of collagen structures. Additionally, changes in local structure were observed for PDFs of synthetic hydroxyapatites with differing carbonate content, notably in features near 4 Å, 8 Å and 19 Å. Regression models were generated to predict carbonate substitution from peak position within the PDFs.

A new parafocusing paradigm for X-ray diffraction.

A new approach to parafocusing X-ray diffraction implemented with an annular incident beam is demonstrated for the first time. The method exploits an elliptical specimen path on a flat sample to produce relatively high intensity maxima that can be measured with a point detector. It is shown that the flat-specimen approximation tolerated by conventional Bragg-Brentano geometries is not required. A theoretical framework, simulations and experimental results for both angular- and energy-dispersive measurement modes are presented and the scattering signatures compared with data obtained with a conventional pencil-beam arrangement.

The use of µCT and fractal dimension for fracture prediction in osteoporotic individuals.

Osteoporosis (OP) is a widespread condition with commonly associated fracture sites at the hip, vertebra and wrist. This study examines the effects of age and osteoporosis on bone quality by comparing the efficacy of using parameters which indicate bone quality (both traditional clinical parameters such as bone mineral density (BMD), as well as apparent Young's modulus determined by finite element analysis, among others) to predict fracture. Non-fracture samples were collected from the femoral heads of 83 donors (44 males, 39 females), and fracture samples were obtained from the femoral heads of 17 donors (female). Microarchitectural parameters (Bone Volume/Total Volume [BV/TV], Bone Surface/Bone Volume [BS/BV], Tissue Mineral Density [TMD, etc.]) were measured from µCT of each sample as well as 2D and 3D fractal dimension (D2D and D3D respectively). A cube was cropped from µCT images and an isotropic hexahedral element was assigned to each voxel. Finite element analysis was used to calculate the Young's modulus for each sample. Overall, values for microarchitectural characteristics, fractal dimension measurements and Young's Modulus were consistent with values within literature. Significant correlations are observed between age and BV/TV for non-fracture males and females, as well as between age and volumetric BMD (vBMD) for the same groups. Significant differences are present between age-matched non-fracture and fracture females for BV/TV, BS/BV, vBMD, TMD, D2D, D3D, (p < 0.01 for all). Properties which are not age dependent are significantly different between age-matched non-fracture and fracture specimens, indicating OP is a disease, and not just an accelerated aging process.

Calcification Microstructure Reflects Breast Tissue Microenvironment.

Microcalcifications are important diagnostic indicators of disease in breast tissue. Tissue microenvironments differ in many aspects between normal and cancerous cells, notably extracellular pH and glycolytic respiration. Hydroxyapatite microcalcification microstructure is also found to differ between tissue pathologies, including differential ion substitutions and the presence of additional crystallographic phases. Distinguishing between tissue pathologies at an early stage is essential to improve patient experience and diagnostic accuracy, leading to better disease outcome. This study explores the hypothesis that microenvironment features may become immortalised within calcification crystallite characteristics thus becoming indicators of tissue pathology. In total, 55 breast calcifications incorporating 3 tissue pathologies (benign - B2, ductal carcinoma in-situ - B5a and invasive malignancy - B5b) from archive formalin-fixed paraffin-embedded core needle breast biopsies were analysed using X-ray diffraction. Crystallite size and strain were determined from 548 diffractograms using Williamson-Hall analysis. There was an increased crystallinity of hydroxyapatite with tissue malignancy compared to benign tissue. Coherence length was significantly correlated with pathology grade in all basis crystallographic directions (P < 0.01), with a greater difference between benign and in situ disease compared to in-situ disease and invasive malignancy. Crystallite size and non-uniform strain contributed to peak broadening in all three pathologies. Furthermore, crystallite size and non-uniform strain normal to the basal planes increased significantly with malignancy (P < 0.05). Our findings support the view that tissue microenvironments can influence differing formation mechanisms of hydroxyapatite through acidic precursors, leading to differential substitution of carbonate into the hydroxide and phosphate sites, causing significant changes in crystallite size and non-uniform strain.

Age-Related Changes in Femoral Head Trabecular Microarchitecture.

Osteoporosis is a prevalent bone condition, characterised by low bone mineral density and increased fracture risk. Currently, the gold standard for identifying osteoporosis and increased fracture risk is through quantification of bone mineral density using dual energy X-ray absorption. However, many studies have shown that bone strength, and consequently the probability of fracture, is a combination of both bone mass and bone 'quality' (architecture and material chemistry). Although the microarchitecture of both non-fracture and osteoporotic bone has been previously investigated, many of the osteoporotic studies are constrained by factors such as limited sample number, use of ovariectomised animal models, and lack of male and female discrimination. This study reports significant differences in bone quality with respect to the microarchitecture between fractured and non-fractured human femur specimens. Micro-computed tomography was utilised to investigate the microarchitecture of femoral head trabecular bone from a relatively large cohort of non-fracture and fracture human donors. Various microarchitectural parameters have been determined for both groups, providing an understanding of the differences between fracture and non -fracture material. The microarchitecture of non-fracture and fracture bone tissue is shown to be significantly different for many parameters. Differences between sexes also exist, suggesting differences in remodelling between males and females in the fracture group. The results from this study will, in the future, be applied to develop a fracture model which encompasses bone density, architecture and material chemical properties for both female and male tissues.