Combined shear/compression structural testing of asymmetric sandwich structures

Asymmetric sandwich technology can be applied in the design of lightweight, non-pressurized aeronautical structures such as those of helicopters. A test rig of asymmetric sandwich structures subjected to compression/shear loads was designed, validated, and set up. It conforms to the standard certification procedure for composite aeronautical structures set out in the “test pyramid”, a multiscale approach. The static tests until failure showed asymmetric sandwich structures to be extremely resistant, which, in the case of the tested specimen shape, were characterized by the absence of buckling and failure compressive strains up to 10,000 μ strains. Specimens impacted with perforation damage were also tested, enabling the original phenomenon of crack propagation to be observed step-by-step. The results of the completed tests thus enable the concept to be validated, and justify the possibility of creating a much larger machine to overcome the drawbacks linked to the use of small specimens

Mineral maturity and crystallinity index are distinct characteristics of bone mineral

The purpose of this study was to test the hypothesis that mineral maturity and crystallinity index are two different characteristics of bone mineral. To this end, Fourier transform infrared microspectroscopy (FTIRM) was used. To test our hypothesis, synthetic apatites and human bone samples were used for the validation of the two parameters using FTIRM. Iliac crest samples from seven human controls and two with skeletal fluorosis were analyzed at the bone structural unit (BSU) level by FTIRM on sections 2–4 lm thick. Mineral maturity and crystallinity index were highly correlated in synthetic apatites but poorly correlated in normal human bone. In skeletal fluorosis, crystallinity index was increased and maturity decreased, supporting the fact of separate measurement of these two parameters. Moreover, results obtained in fluorosis suggested that mineral characteristics can be modified independently of bone remodeling. In conclusion, mineral maturity and crystallinity index are two different parameters measured separately by FTIRM and offering new perspectives to assess bone mineral traits in osteoporosis

The Ratio 1660/1690 cm−1 Measured by Infrared Microspectroscopy Is Not Specific of Enzymatic Collagen Cross-Links in Bone Tissue

In postmenopausal osteoporosis, an impairment in enzymatic cross-links (ECL) occurs, leading in part to a decline in bone biomechanical properties. Biochemical methods by high performance liquid chromatography (HPLC) are currently used to measure ECL. Another method has been proposed, by Fourier Transform InfraRed Imaging (FTIRI), to measure a mature PYD/immature DHLNL cross-links ratio, using the 1660/1690 cm−1 area ratio in the amide I band. However, in bone, the amide I band composition is complex (collagens, non-collagenous proteins, water vibrations) and the 1660/1690 cm−1 by FTIRI has never been directly correlated with the PYD/DHLNL by HPLC. A study design using lathyritic rats, characterized by a decrease in the formation of ECL due to the inhibition of lysyl oxidase, was used in order to determine the evolution of 1660/1690 cm−1 by FTIR Microspectroscopy in bone tissue and compare to the ECL quantified by HPLC. The actual amount of ECL was quantified by HPLC on cortical bone from control and lathyritic rats. The lathyritic group exhibited a decrease of 78% of pyridinoline content compared to the control group. The 1660/1690 cm−1 area ratio was increased within center bone compared to inner bone, and this was also correlated with an increase in both mineral maturity and mineralization index. However, no difference in the 1660/1690 cm−1 ratio was found between control and lathyritic rats. Those results were confirmed by principal component analysis performed on multispectral infrared images. In bovine bone, in which PYD was physically destructed by UV-photolysis, the PYD/DHLNL (measured by HPLC) was strongly decreased, whereas the 1660/1690 cm−1 was unmodified. In conclusion, the 1660/1690 cm−1 is not related to the PYD/DHLNL ratio, but increased with age of bone mineral, suggesting that a modification of this ratio could be mainly due to a modification of the collagen secondary structure related to the mineralization process

Vertebral anti-fracture efficacy of strontium ranelate according to pre-treatment bone turnover

Osteoporotic post-menopausal women patients in two randomised trials comparing the anti-fracture efficacy of strontium ranelate with placebo were separated into tertiles according to their baseline levels of biochemical markers of bone formation and resorption. The vertebral anti-fracture efficacy of strontium ranelate was shown to be independent of baseline bone turnover levels. INTRODUCTION: Bone turnover (BTO) levels vary among women at risk of osteoporotic fracture. Strontium ranelate is an anti-osteoporotic treatment increasing bone formation and reducing bone resorption. It was hypothesised that its anti-fracture efficacy would be independent of baseline BTO levels. METHODS: Post-menopausal women with osteoporosis from two pooled studies were stratified in tertiles according to baseline levels of two BTO markers: bone-specific alkaline phosphatase (b-ALP, n = 4995) and serum C-telopeptide cross-links (sCTX, n = 4891). Vertebral fracture risk was assessed over 3 years with strontium ranelate 2 g/day or placebo. RESULTS: In the placebo group, relative risk of vertebral fractures increased with BTO tertiles by 32% and 24% for patients in the highest tertile for b-ALP and CTX, respectively, compared to those in the lowest tertile. In the strontium ranelate group, incidences of vertebral fracture did not differ significantly across BTO tertiles. Significant reductions in vertebral fractures with strontium ranelate were seen in all tertiles of both markers, with relative risk reductions of 31% to 47% relative to placebo. Risk reduction did not differ among tertiles (b-ALP: p = 0.513; sCTX: p = 0.290). CONCLUSION: The vertebral anti-fracture efficacy of strontium ranelate was independent of baseline BTO levels. Strontium ranelate offers clinical benefits to women across a wide range of metabolic states

Towards new material biomarkers for fracture risk

Osteoporosis is a prevalent bone condition, characterised by low bone mass and increased fracture risk. Currently, the gold standard for identifying osteoporosis and increased fracture risk is through quantification of bone mineral density (BMD) using dual energy X-ray absorption (DEXA). However, the risk of osteoporotic fracture is determined collectively by bone mass, architecture and physicochemistry of the mineral composite building blocks. Thus DEXA scans alone inevitably fail to fully discriminate individuals who will suffer a fragility fracture. This study examines trabecular bone at both ultrastructure and microarchitectural levels to provide a detailed material view of bone, and therefore provides a more comprehensive explanation of osteoporotic fracture risk. Physicochemical characterisation obtained through X-ray diffraction and infrared analysis indicated significant differences in apatite crystal chemistry and nanostructure between fracture and non-fracture groups. Further, this study, through considering the potential correlations between the chemical biomarkers and microarchitectural properties of trabecular bone, has investigated the relationship between bone mechanical properties (e.g. fragility) and physicochemical material features

A new murine model of osteoblastic/osteolytic lesions from human androgen-resistant prostate cancer

BACKGROUND: Up to 80% of patients dying from prostate carcinoma have developed bone metastases that are incurable. Castration is commonly used to treat prostate cancer. Although the disease initially responds to androgen blockade strategies, it often becomes castration-resistant (CRPC for Castration Resistant Prostate Cancer). Most of the murine models of mixed lesions derived from prostate cancer cells are androgen sensitive. Thus, we established a new model of CRPC (androgen receptor (AR) negative) that causes mixed lesions in bone. METHODS: PC3 and its derived new cell clone PC3c cells were directly injected into the tibiae of SCID male mice. Tumor growth was analyzed by radiography and histology. Direct effects of conditioned medium of both cell lines were tested on osteoclasts, osteoblasts and osteocytes. RESULTS: We found that PC3c cells induced mixed lesions 10 weeks after intratibial injection. In vitro, PC3c conditioned medium was able to stimulate tartrate resistant acid phosphatase (TRAP)-positive osteoclasts. Osteoprotegerin (OPG) and endothelin-1 (ET1) were highly expressed by PC3c while dikkopf-1 (DKK1) expression was decreased. Finally, PC3c highly expressed bone associated markers osteopontin (OPN), Runx2, alkaline phosphatase (ALP), bone sialoprotein (BSP) and produced mineralized matrix in vitro in osteogenic conditions. CONCLUSIONS: We have established a new CRPC cell line as a useful system for modeling human metastatic prostate cancer which presents the mixed phenotype of bone metastases that is commonly observed in prostate cancer patients with advanced disease. This model will help to understand androgen-independent mechanisms involved in the progression of prostate cancer in bone and provides a preclinical model for testing the effects of new treatments for bone metastases

Cellular dosimetry of strontium-90 using the Monte Carlo code MCNPX, detection and X-ray microanalysis

The aim of this study is to provide data that increase knowledge about the possible health effects of exposure to 90Sr contaminant in drinking water. 90Sr detection in the mouse bone model plays an important complementary role with computational dosimetry in these investigations. S-value (absorbed dose per unit cumulated activity) calculations using Monte Carlo (MC) simulations, 90Sr detection by liquid scintillation β counting in the femur bone and X-ray microanalysis were carried out. The present work is focused on using MCNPX and its validation at a cellular level. The cytoplasm (Cy), nucleus (N) and 90Sr radiation source were simulated with the MC code MCNPX. Cells are assumed to be spherical, with the radii of the cell and cell nucleus ranging from 2 to 10 μm. The S-value (in Gy/Bq.s) calculations were provided for a 90Sr source distributed uniformly in the cell nucleus or cytoplasm and for two source-target combinations (t←s). A comparison between the calculated MC results and the MIRD values agreed very well since the relative deviations are less than 4%. The earliest results of X-ray microanalysis indicated that the 90Sr was below the detection limit (<0.1%) in the bone tissue. However, the measurements by liquid scintillation showed the presence of 90Sr in the femur bone