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The vertebral centra of sharks consist of cartilage, and many species' centra contain a bioapatite related to that in bone. Centra microarchitectures at the 0.5-50 µm scale do not appear to have been described previously. This study examines centrum microarchitecture in lamniform and carcharhiniform sharks with synchrotron microComputed Tomography (microCT), scanning electron microscopy and spectroscopy and light microscopy. The analysis centers on the blue shark (carcharhiniform) and shortfin mako (lamniform), species studied with all three modalities. Synchrotron microCT results from seven other species complete the report. The main centrum structures, the corpus calcareum and intermedialia, consist of fine, closely-spaced, mineralized trabeculae whose mean thicknesses and spacings range from 4.5 to 11.2 µm and 4.5 to 15.6 µm, respectively. A significant (p = 0.00001) positive linear relationship between and exists for multiple positions within one mako centrum. Carcharhiniform species' and exhibit an inverse linear relationship (p = 0.005) while in lamniforms these variables tend toward a positive relationship which does not reach statistical significance (p = 0.099). In all species, the trabeculae form an uninterrupted, interconnected network, and the unmineralized volumes are similarly interconnected. Small differences in mineralization level are observed in trabeculae. Centrum growth band pairs are found to consist of locally higher /lower mineral volume fraction. Within the intermedialia, radial canals and radial microrods were characterized, and compacted trabeculae are prominent in the mako intermedialia. The centra's mineralized central zones were non-trabecular and are also described. This study's novel result is the demonstration that the mineralized cartilage of sharks' vertebral bodies (centra) consists of a fine 3D array of interconnected plates (trabeculae) and an interpenetrating network of unmineralized tissue. This microstructure is radically different from that in tesserae or in teeth, the other main mineralized shark tissues. Using volumetric synchrotron microComputed Tomography, numerical values of mean trabecular thickness and spacing and their relationship were measured for nine species. Scanning electron microscopy added a higher resolution view of the microstructures, and histology provided complementary information on cartilage and cells. The present results suggest centra microstructure helps accommodate the very large in vivo strains and may prevent damage accumulation during millions of cycles of swimming-induced loading. [Display omitted] [ABSTRACT FROM AUTHOR]

The effect of milk on bone health is controversial. In this study, the effects of yak milk in mice with retinoic acid-induced osteoporosis (OP) were evaluated. Yak milk was provided to OP mice as a nutrition supplement for 6 wk. The results showed that yak milk significantly reduced bone turnover markers (tartrate acid phosphatase and alkaline phosphatase). The yak milk treatment was also associated with remarkably increased bone mineral density, bone volume, trabecular thickness, and trabecular number, as well as improved biomechanical properties (maximum load and stress) of the tibia. Furthermore, yak milk mitigated the deterioration of the network and thickness of trabecular bone in treated OP mice compared with the OP model group. The results indicated that yak milk could improve bone mass and microarchitecture through the inhibition of bone resorption in OP mice. [ABSTRACT FROM AUTHOR]

U.S. Army Basic Combat Training (BCT) improves tibial volumetric bone mineral density (BMD) and structure in most, but not all soldiers. Few studies have investigated whether changes in serum bone biomarkers during BCT are associated with changes in tibial BMD and bone structure following BCT. To characterize bone biomarker changes during BCT and to investigate the relationship between changes in bone biomarkers and changes in tibial BMD and bone structure. We enrolled 235 trainees entering BCT in this ten-week prospective observational study. Trainees provided fasted blood samples and questionnaires weekly throughout BCT. Procollagen type 1 N-terminal propeptide (PINP) and C-terminal telopeptide of type 1 collagen (CTX) were measured by enzyme-linked immunoabsorbent assays every two weeks during BCT. We evaluated body composition and mass via dual-energy X-ray absorptiometry and bone structure, microarchitecture, and mineral density at the distal tibia via high-resolution peripheral quantitative computed tomography at baseline and post-BCT. Both male (n = 110) and female trainees (n = 125) were young (20.9 ± 3.7 and 20.7 ± 4.3 years, respectively), with normal to overweight BMIs (25.2 ± 4.1 and 24.2 ± 3.6 kg/m2, respectively). In female trainees, PINP increased during and post-BCT compared to baseline, with the greatest increase in PINP at week four (45.4 % ± 49.6, p < 0.0001), whereas there were no changes in CTX. PINP also increased in male trainees, but only at weeks two and four (21.9 % ± 24.5, p = 0.0027 and 35.9 % ± 35.8, p < 0.0001, respectively). Unlike female trainees, in males, CTX was lower than baseline at weeks four, eight, and post-BCT. The change in PINP from baseline to week four of BCT was positively associated with changes in tibial BMD, Tb.BMD, Tb.Th, Tb.BV/TV, Ct.Th, Ct.Ar, and Ct.Po from the baseline to post-BCT. The bone formation marker PINP increases during U.S. Army BCT, especially during the first four weeks. Increases in PINP, but not CTX, were correlated with improved BMD and bone structure in the distal tibia. • U.S. Army Basic Combat Training (BCT) improves tibial vBMD and structure in most, but not all soldiers. • In females, PINP increased during and post-BCT compared to baseline: with the greatest increase in PINP at week 4, no changes in CTX. • Unlike female trainees, in males, CTX was lower than baseline at weeks 4, 8, and post-BCT. • The change in PINP from baseline to week 4was associated with changes in Tb.BMD, Tb.Th, Tb.BV/TV, Ct.Th, Ct.Ar, and Ct.Po. • Increases in PINP, but not CTX, were correlated with improved BMD and bone structure in the distal tibia. [ABSTRACT FROM AUTHOR]

Osteoporotic fractures, prevalent in the elderly, pose a significant health and economic burden. Current methods for predicting fracture risk, primarily relying on bone mineral density, provide only modest accuracy. If better spatial resolution of trabecular bone in a clinical scan were available, a more complete assessment of fracture risk would be obtained using microarchitectural measures of bone (i.e. trabecular thickness, trabecular spacing, bone volume fraction, etc.). However, increased resolution comes at the cost of increased radiation or can only be applied at small volumes of distal skeletal locations. This study explores super-resolution (SR) technology to enhance clinical CT scans of proximal femurs and better reveal the trabecular microarchitecture of bone. Using a deep-learning-based (i.e. subset of artificial intelligence) SR approach, low-resolution clinical CT images were upscaled to higher resolution and compared to corresponding MicroCT-derived images. SR-derived 2-dimensional microarchitectural measurements, such as degree of anisotropy, bone volume fraction, trabecular spacing, and trabecular thickness were within 16 % error compared to MicroCT data, whereas connectivity density exhibited larger error (as high as 1094 %). SR-derived 3-dimensional microarchitectural metrics exhibited errors <18 %. This work showcases the potential of SR technology to enhance clinical bone imaging and holds promise for improving fracture risk assessments and osteoporosis detection. Further research, including larger datasets and refined techniques, can advance SR's clinical utility, enabling comprehensive microstructural assessment across whole bones, thereby improving fracture risk predictions and patient-specific treatment strategies. [ABSTRACT FROM AUTHOR]

Objectives: In elite figure skaters, to determine if there was a difference in volumetric bone mineral density and bone strength between 1) figure skaters and population-based normative data, 2) single or pair skaters and ice dancers, and 3) the landing and takeoff legs.Design: Cross-sectional.Methods: Figure skaters had their non-dominant distal radius and bilateral tibia scanned using high-resolution peripheral quantitative computed tomography. Volumetric bone mineral density was determined at the total, cortical and trabecular compartments, and finite element analysis estimated bone strength. Normative data was used to compare the total bone mineral density of figure skaters to a population-based cohort. Independent t-tests compared differences between skating discipline, and paired t-tests compared skeletal parameters for the landing and takeoff leg.Results: Twenty elite skaters (mean age 22 ± 6.2; female = 11, male = 9) completed scans. Compared with the general population, the mean percentile rank for skaters' total volumetric bone mineral density was below normal at the radius (27th percentile) and normal at the tibia (54th percentile). Single or pair skaters had more robust bone in the landing compared with their takeoff leg. Specifically, the landing leg had higher total bone mineral density (2.8%) and trabecular bone mineral density (6.5%), and superior bone strength (8.5%) than the takeoff leg (p < 0.05).Conclusions: Volumetric bone mineral density and strength differences in figure skaters were discipline dependent. Side-to-side differences were observed in single and pair skaters where the landing leg is denser, larger and stronger than the takeoff leg. [ABSTRACT FROM AUTHOR]

High resolution peripheral quantitative computed tomography (HR-pQCT) was designed to study bone mineral density (BMD) and microarchitecture in peripheral sites at the distal radius and tibia. With the introduction of the second generation HR-pQCT scanner (XtremeCT II, Scanco Medical) that has a larger, longer gantry it is now possible to study the human knee in vivo using HR-pQCT. Previous validation of HR-pQCT measurements at the distal radius and tibia against micro-CT is not representative of the knee because the increased cross-sectional area, greater amount of soft tissue surrounding the scan region, and different imaging protocol result in potentially increased beam hardening effects and photon scatter and different signal-to-noise ratio. The objective of this study is to determine the accuracy of density and microarchitecture measurements in the human knee measured by HR-pQCT using an in vivo protocol. Twelve fresh-frozen cadaver knees were imaged using in vivo HR-pQCT (60.7 µm) protocol. Subsequentially, distal femurs were extracted and imaged using a higher resolution (30.3 µm) ex vivo protocol, replicating micro-CT imaging. Scans were registered so that agreement of density and bone microarchitecture measurements could be determined using linear regression and Bland-Altman plots. All density and microarchitecture outcomes were highly correlated between the 2 protocols (R2 > 0.89) albeit with statistically significant differences between absolute measures based on paired t tests. All parameters showed accuracy between 4.5% and 8.7%, and errors were highly systematic, particularly for trabecular BMD and trabecular thickness (R2 > 0.93). We found that BMD and microarchitecture measurements in the distal femur obtained using an in vivo HR-pQCT knee protocol contained systematic errors, and accurately represented measurements obtained using a micro-CT equivalent imaging protocol. This work establishes the validity and limitations of using HR-pQCT to study the BMD and microarchitecture of human knees in future clinical studies. [ABSTRACT FROM AUTHOR]

Medication-related osteonecrosis of the jaw (MRONJ) is a severe side effect of antiresorptive (AR) drugs such as bisphosphonates (BP) and denosumab (Dmab). Although several risk factors are described, the etiology of MRONJ is still not fully elucidated. Bone-strengthening is the primary aim of antiresorptive therapy; however, overly increased bone mass and microcrack accumulation are also discussed in MRONJ etiologies. The aim of this study is to evaluate the microarchitecture of jaw bones with micro−computed tomography (micro-CT) in AR-treated patients with or without MRONJ. Human jaw bone samples of AR-treated patients were separated into 11 groups by AR treatment bisphosphonate (BP), denosumab (Dmab), both (M) and control groups. Subgroups were divided according to the clinical localization as AR-exposed vital jaw bone (BP exp , Dmab exp , M exp), osteonecrosis–margin of a sequestrum (BPO mar , DmabO mar , MO mar) and osteonecrosis–sequestrum (BPO seq , DmabO seq , MO seq). Healthy jaw bone (C HB) and osteoporotic jaw bone (C OP) represent control groups. Samples underwent retrospective micro-CT and morphometric analysis in representative units by bone volume fraction (BV/TV), bone surface density (BS/BV), trabecular thickness (Tr.Th.), trabecular number (Tr.N.), trabecular space (Tr.Sp.), Euler characteristic for bone connectivity, bone mineral density (BMD) and tissue mineral density (TMD). A total of 141 samples from 78 patients were analyzed. BV/TV of M exp group (mean: 0.46 ± 0.27) was significantly higher than in the C OP group (mean: 0.14 ± 0.05; p = 0.0053). Tr.Th. differed significantly between the BP exp group (mean: 0.32 ± 0.15) and the M exp group (mean: 0.57 ± 0.20; p = 0.0452) as well as between the BPO seq group (mean: 0.25 ± 0.10) and the MO seq group (mean: 0.39 ± 0.18; p = 0.0417). Signs of trabecular thickening and unorganized trabecular microarchitecture from AR-exposed- to sequestrum groups, were analyzed in 3D reconstructions. However, BS/BV, Tr.N., and Tr.Sp. showed no significant differences. Euler characteristic of the BPO seq group (median: 7.46) doubled compared to that of the BP exp group (median: 14.97; p = 0.0064). Mineralization parameters BMD and TMD were similar in all groups. Findings show evidence of enhanced bone mass and suspect microarchitecture in some AR-treated jaw bone compared to osteoporotic jaw bone. Despite increased bone mass, some MRONJ samples showed decreased trabecular connectivity by Euler characteristic compared to AR-treated jaw bone. These samples may indicate extensive ossification and ineffective bone mass with superficially higher bone mass without existing or even reduced mechanical stability, indicated by connectivity loss. This result might also suggest a high risk to microcrack accumulation. At some point, possibly some kind of over-ossification could lead to under-nourishment and microarchitectural weakness, creating instability, subsequently increasing vulnerability to MRONJ. [ABSTRACT FROM AUTHOR]

When bio-grafts are used in bone healing, interstitial fluid flow (IFF) plays a critical role in both, enhancing bone remodeling and promoting scaffold degradation. Through this enhancement, the fluid will be spread within the network through cells lacuna in equilibrium way promoting osteocytes efficiency, growth factor, and paracrine signaling. The complete adaptation of both microarchitecture bone and scaffold in the transition zone is not possible (No technology of micro-manufacturing is available). However, in our model, the initial bone architecture was extracted from micro-CT. We determine then the dominant flow characteristics (flow magnitude, pressure, orientation, and the carried electrical potential) at the transition zone between native tissue and scaffold. We identify the area where we may have many governing flows escaping from bone not matching with scaffold opening pores. We identify as well, the locations of scaffold pores which do not coincide with enough open lacuna in native tissue, compromising the adequate fluid exchange during osteointegration. By identifying regions of low osteogenesis, we provide a customized pores architecture enhancing flow permeability, driving to spread the fluid energy and the streaming generated potential (SGP) to be in adequate locations. The model may be applied also to evaluate the support for cells migration, cells efficiency, proliferation, differentiation, and growth factors spread. We may promote the exchange of nano particles (NP) as well for carrying anti-microbial properties. However, the scaffold can be designed to promote osteogenesis through the transition region. Results, permit a customized bio-graft design, increasing the options of scaffold architectures with customized pores (position, concentration, and size). The proposed idea, prevent also compromising assembly mechanical stability. [Display omitted] [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • The blood glucose in STZ plus HFD-induced diabetic rats could be partially reversed by berberine. • Berberine was significantly associated with improvement in the trabecular bone mass loss and amelioration of the microarchitecture deterioration in diabetic rats. • Berberine has a protective effect on bone histomorphometry. • Oxidation, one of the important contributors for diabetic osteopathy, also was controlled by berberine. Abstract Diabetic osteoporosis is a complication of diabetes mellitus, and can result in an increased incidence of bone fractures and a delay in fracture healing. Berberine is one of the most widely distributed isoquinoline alkaloid in plants and possesses antioxidant properties. These properties can reduce the high glucose mediated in the dysfunction of human bone marrow stem cells. Therefore, the present study was designed to investigate the apparent beneficial effect of berberine on bone characteristics in streptozotocin plus HFD-induced diabetic rats. Rats were selected at random and divided into four groups: (A) control group (CG) (n = 10); (B) diabetic group (DG) (n = 10); (C) diabetic group with 50 mg kg−1day−1 of berberine (Brb-50) (n = 10); and (D) diabetic group with 100 mg kg−1day−1 of berberine (Brb-100) (n = 10). After 12 weeks of being treated with berberine, the femora from all rats were assessed and other blood biochemistries evaluated. Berberine at 50 mg/kg showed little effect and significance on diabetic osteopenia, while berberine at 100 mg/kg was significantly increased in diabetic rats. The same group also displayed a significantly decreased serum osteocalcin and serum alkaline phosphatase activity in diabetic rats. The impaired micro-architecture of the femurs in diabetic rats could partially be prevented by berberine with 100 mg/kg. In addition, berberine could to an extent restore the decreased bone formation and reabsorption of the femurs in diabetic rats through the histomorphometric analysis. Berberine could not only significantly lower the oxidative level of DNA damage, but also up-regulate the activity of serum antioxidants. According to our investigations and discoveries, we have found, that berberine may be a potential drug for controlling bone loss in diabetic osteoporosis. [ABSTRACT FROM AUTHOR]

Abstract Context Bone fragility in cerebral palsy (CP) is secondary to a complex interplay of functional, hormonal, and nutritional factors that affect bone remodelling. A greater understanding of bone microarchitectural changes seen in CP should assist therapeutic decision making. Objective To examine the relationship between trabecular bone score (TBS), BMD and fractures in adults with CP; the influence of clinical factors and body composition on bone microarchitecture were explored. Design Retrospective cross-sectional study. Setting and Participants 43 adults (25 male) with CP of median age 25 years (interquartile range 21.4–33.9) who had evaluable dual-energy X-ray absorptiometry imaging of the lumbar spine from a single tertiary hospital between 2005-March 2018. Results 24/43 (55.8%) of patients had TBS values indicating intermediate or high risk of fracture (<1.31). TBS correlated with areal BMD at the lumbar spine, femoral neck and total body. TBS was significantly associated with arm and leg lean mass, with adjustment for age, gender and height (adjusted R2 = 0.18, p = 0.042 for arm lean mass; adjusted R2 = 0.19, p = 0.036 for leg lean mass). There was no difference in TBS when patients were grouped by fracture status, anticonvulsant use, gonadal status or use of PEG feeding. TBS was lower in non-ambulatory patients compared with ambulatory patients (1.28 vs 1.37, p = 0.019). Conclusions Abnormal bone microarchitecture, as measured by TBS, was seen in >50% of young adults with CP. TBS correlated with both areal BMD and appendicular lean mass. Maintaining muscle function is likely to be important for bone health in young adults with CP and needs to be confirmed in further studies. Highlights • Low trabecular bone score is common in young adults with cerebral palsy • Trabecular bone score is higher in ambulatory adults than non-ambulatory adults • Trabecular bone score is associated with bone mineral density, body mass index and appendicular lean mass • These relationships provide insight into bone fragility in cerebral palsy and muscle-bone interactions [ABSTRACT FROM AUTHOR]

Abstract Marrow adipose tissue (MAT) in humans is distributed differentially across age and skeletal site. We have shown impaired microarchitecture and reduced bone strength at appendicular sites in conditions associated with high MAT of the axial skeleton in adults (including conditions of over- and undernutrition). Data are lacking regarding differences in MAT content of the appendicular versus the axial skeleton, and its relationship with bone microarchitecture and strength. Furthermore, data are conspicuously lacking in adolescents, a time when hematopoietic marrow is progressively converted to fatty marrow. The purpose of our study was to examine differential associations between appendicular (distal tibia) and axial (lumbar spine) MAT and bone microarchitecture and strength estimates of the distal tibia in adolescents with obesity. We hypothesized that compared to MAT of the axial skeleton (lumbar spine), MAT of the appendicular skeleton (distal tibia) would show stronger associations with bone microarchitecture and strength estimates of the appendicular skeleton (distal tibia). We evaluated 32 adolescents and young adults (27 females) with obesity; with a mean age of 17.8 ± 2.1 years and median body mass index (BMI) of 41.34 kg/m2, who underwent dual energy X-ray absorptiometry (DXA) for total fat mass, proton MR spectroscopy (1H-MRS) of the distal tibia and 4th lumbar vertebra for MAT, high resolution peripheral quantitative computed tomography (HR-pQCT) of the distal tibia for volumetric bone mineral density (vBMD) and microarchitecture, and micro finite element analysis (FEA) for distal tibial strength estimates. Linear correlations between bone parameters and MAT were determined using the Spearman or Pearson methods, depending on data distribution. Lumbar spine MAT was inversely associated with age (r = −0.36; p = 0.037). Total and trabecular vBMD and trabecular number at the distal tibia were inversely associated with MAT at the distal tibia (r = −0.39, p = 0.025; r = −0.51, p = 0.003; r = −0.42, p = 0.015 respectively) but not with lumbar spine MAT (r = −0.19, p = 0.27; r = −0.18, p = 0.3; r = 0.005, p = 0.97 respectively). In adolescents and young adults with obesity, the associations between MAT and appendicular bone parameters differ depending on the site of MAT assessment i.e. axial vs. appendicular. Studies evaluating these endpoints in adolescents and young adults with obesity should take the site of MAT assessment into consideration. Highlights • Marrow Adipose Tissue (MAT) content varies by age and skeletal site. • Associations differ between axial vs appendicular MAT and appendicular bone parameters. • BMD and microarchitecture at distal tibia have stronger associations with MAT content at distal tibia than lumbar spine MAT. [ABSTRACT FROM AUTHOR]

Skeletal fragility is a major complication of type 2 diabetes mellitus (T2D), but there is a poor understanding of mechanisms underlying T2D skeletal fragility. The increased fracture risk has been suggested to result from deteriorated bone microarchitecture or poor bone quality due to accumulation of advanced glycation end-products (AGEs). We conducted a clinical study to determine whether: 1) bone microarchitecture, AGEs, and bone biomechanical properties are altered in T2D bone, 2) bone AGEs are related to bone biomechanical properties, and 3) serum AGE levels reflect those in bone. To do so, we collected serum and proximal femur specimens from T2D ( n  = 20) and non-diabetic ( n  = 33) subjects undergoing total hip replacement surgery. A section from the femoral neck was imaged by microcomputed tomography (microCT), tested by cyclic reference point indentation, and quantified for AGE content. A trabecular core taken from the femoral head was imaged by microCT and subjected to uniaxial unconfined compression tests. T2D subjects had greater HbA 1 c (+23%, p  ≤ 0.0001), but no difference in cortical tissue mineral density, cortical porosity, or trabecular microarchitecture compared to non-diabetics. Cyclic reference point indentation revealed that creep indentation distance (+18%, p  ≤ 0.05) and indentation distance increase (+20%, p  ≤ 0.05) were greater in cortical bone from T2D than in non-diabetics, but no other indentation variables differed. Trabecular bone mechanical properties were similar in both groups, except for yield stress, which tended to be lower in T2D than in non-diabetics. Neither serum pentosidine nor serum total AGEs were different between groups. Cortical, but not trabecular, bone AGEs tended to be higher in T2D subjects (21%, p  = 0.09). Serum AGEs and pentosidine were positively correlated with cortical and trabecular bone AGEs. Our study presents new data on biomechanical properties and AGEs in adults with T2D, which are needed to better understand mechanisms contributing to diabetic skeletal fragility. [ABSTRACT FROM AUTHOR]

Background Context: The basivertebral foramen (BF), located in the middle posterior wall of the vertebral body, may induce local weakness and contribute to the formation of a retropulsed bone fragment (RBF) in thoracolumbar burst fracture (TLBF). We hypothesize that the mechanism of TLBF is related to the BF.Purpose: This study aimed to clarify the relationship between RBFs and the BF in TLBFs, and to explain the results using biomechanical experiments and micro-computed tomography (micro-CT).Study Design: A comprehensive research involving clinical radiology, micro-CT, and biomechanical experiments on cadaveric spines was carried out.Patient Sample: A total of 162 consecutive patients diagnosed with TLBF with RBFs, drawn from 256 patients who had reported accidents or injuries to their thoracolumbar spine, comprised the patient sample.Outcome Measures: Dimensions and location of the RBFs in relation to the BF were the outcome measures.Materials and Methods: Computed tomography reconstruction imaging was used to measure the dimensions and location of RBFs in 162 patients (length, height, width of RBF and vertebral body). Furthermore, micro-CT scans were obtained of 10 cadaveric spines. Each vertebral body was divided into three layers (superior, middle, and inferior), and each layer was divided further into nine regions (R1-R9). Microarchitecture parameters were calculated from micro-CT scans, including bone volume fraction (BV/TV), connectivity (Conn.D), trabecular number (Tb.N), trabecular thickness (Tb.Th), and bone mineral density (BMD). Differences were analyzed between regions and layers. Burst fractures were simulated on cadaveric spines to explore the fracture line location and test the relationship between RBFs and BF.Results: Retropulsed bone fragment width was usually one-third of the width of the vertebral body, whereas RBF length and height were approximately half of the corresponding vertebral body dimensions. Measures of trabecular bone quality were generally lowest in those central and superior regions of the vertebral body which are adjacent to the BF and which are most affected by burst fracture. In simulated TLBFs, the fracture line went across the vertex or upper surface of the BF.Conclusions: The most vulnerable regions in the vertebral body lie within or just superior to the BF. The central MR2 region in particular is at risk of fracture and RBF formation. [ABSTRACT FROM AUTHOR]

Background Altered bone microarchitecture and higher marrow adipose tissue (MAT) may reduce bone strength. High resolution pQCT (HRpQCT) allows assessment of volumetric BMD (vBMD), and size and microarchitecture parameters of bone, while 1H–magnetic resonance spectroscopy (1H–MRS) allows MAT evaluation. We have reported impaired microarchitecture at the non-weight bearing radius in adolescents with anorexia nervosa (AN) and that these changes may precede aBMD deficits. Data are lacking regarding effects of AN on microarchitecture and strength at the weight-bearing tibia in adolescents and young adults, and the impact of changes in microarchitecture and MAT on strength estimates. Objective To compare strength estimates at the distal tibia in adolescents/young adults with AN and controls in relation to vBMD, bone size and microarchitecture, and spine MAT. Design and methods This was a cross-sectional study of 47 adolescents/young adults with AN and 55 controls 14–24 years old that assessed aBMD and body composition using DXA, and distal tibia vBMD, size, microarchitecture and strength estimates using HRpQCT, extended cortical analysis, individual trabecular segmentation, and finite element analysis. Lumbar spine MAT (1H–MRS) was assessed in a subset of 19 AN and 22 controls. Results Areal BMD Z -scores were lower in AN than controls. At the tibia, AN had greater cortical porosity, lower total and cortical vBMD, cortical area and thickness, trabecular number, and strength estimates than controls. Within AN, strength estimates were positively associated with lean mass, aBMD, vBMD, bone size and microarchitectural parameters. MAT was higher in AN, and associated inversely with strength estimates. Conclusions Adolescents/young adults with AN have impaired microarchitecture at the weight-bearing tibia and higher spine MAT, associated with reduced bone strength. [ABSTRACT FROM AUTHOR]

Diabetic osteoporosis (DO) is a complication of diabetes mellitus. Our previous study showed that silibinin can attenuate high glucose mediated human bone marrow stem cells dysfunction through antioxidant effect. However, no study has yet investigated the effect of silibinin in diabetic rats. Therefore, we assessed the effects of silibinin on bone characteristics in streptozotocin-induced diabetic rats. The aim of our study was to determine whether providing silibinin in the different supplementation could prevent bone loss in diabetic rats or not. Rats were randomly divided into four groups: (1) control group (CG) (n = 10); (2) diabetic group (DG) (n = 10); (3) diabetic group with 50 mg kg −1 day −1 of silibinin orally (DG-50) (n = 10); and (4) diabetic group with 100 mg kg −1 day −1 of silibinin orally (DG-100) (n = 10). 12 weeks after streptozotocin (STZ) injection, the femora from all rats were assessed and oxidative stress was evaluated. Bone mineral density was significantly decreased in diabetic rats; these effects were prevented by treatment with silibinin (100 mg kg −1 day −1 orally). Similarly, in the DG and DG-50 groups, changes in microarchitecture of femoral metaphysis assessed by microcomputed tomography demonstrated simultaneous existence of diabetic osteoporosis; these impairments were prevented by silibinin (100 mg kg −1 day −1 orally). In conclusion, silibinin supplementation may have potential use as a possible therapy for maintaining skeletal health and these results can enhance the understanding of diabetic osteoporosis induced by diabetes. [ABSTRACT FROM AUTHOR]

Reinforcing potential of fibers is limited for a number of thermoplastic polymers due to the inherently weak interfacial bonding between the non-polar/non-reactive polymer matrix and fiber surface. To this end, the concept of enhancing the interfacial strength in thermoplastic composites via controlled mechanical interlocking between fiber surface and polymer matrix is explored. Specifically, infiltration of the thermoplastic polymer into the anchoring sites around the microstructures located on the fiber surface provided an efficient mechanical interlocking. A computational study has been performed for several different surface morphologies for a glass/polyethylene material system. The strength calculations addressed both material failure and detachment of the matrix material from the anchoring sites. The results obtained, which focused on shear loading, indicated that the surface morphology has a significant effect on the interfacial bonding strength. The computational analysis results showed that even without any interfacial friction or adhesion, the interface strength could achieve 50% of the theoretical strength of perfect matrix-fiber bonding for a plane interface. An optimal geometry and density of the microarchitectured features on the surface was identified for many cases in a parametric study. Friction at the interface between polymer matrix and fiber surface was shown to provide a significant increase in interfacial strength for cases where the frictionless case detached, but not for cases of material failure, which shows the promise of anchoring when friction and adhesion cannot be relied on. It was therefore demonstrated that the precise surface morphology modification is an effective approach to improve the interfacial bonding in fiber reinforced thermoplastic composites. [ABSTRACT FROM AUTHOR]

Multicore processors are customary within current generation computing systems. The overall concept of general purpose processing however remains a challenge as architects must provide increased performance for each advancing generation without solely relying on transistor scaling and additional cache levels. Although architects have steered towards heterogeneity to increase the performance and efficiency for a variety of workloads, the fundamental issue of how a single core's architecture may be improved and applied to the multiprocessor domain remains. This work builds upon the concept of Configurable Computing Units (CCU) - a nuanced approach to processor architectures and microarchitectures, employing reconfigurable datapaths and task-based execution. This work improves upon the efficiency of CCUs by applying various new design techniques including branch prediction, variable configuration, an OpenMP programming model, and Berkeley Dwarf testing. Experimental results using Gem5 demonstrate that a single CCU core can achieve dual-core performance, with a 1.29x decrease in area overhead and 55% of the power consumption required by a conventional CPU . [ABSTRACT FROM AUTHOR]

Valvular heart diseases are the third leading cause of cardiovascular disease, resulting in more than 25,000 deaths annually in the United States. Heart valve tissue engineering (HVTE) has emerged as a putative treatment strategy such that the designed construct would ideally withstand native dynamic mechanical environment, guide regeneration of the diseased tissue and more importantly, have the ability to grow with the patient. These desired functions could be achieved by biomimetic design of tissue-engineered constructs that recapitulate in vivo heart valve microenvironment with biomimetic architecture, optimal mechanical properties and possess suitable biodegradability and biocompatibility. Synthetic biodegradable elastomers have gained interest in HVTE due to their excellent mechanical compliance, controllable chemical structure and tunable degradability. This review focuses on the state-of-art strategies to engineer biomimetic elastomeric scaffolds for HVTE. We first discuss the various types of biodegradable synthetic elastomers and their key properties. We then highlight tissue engineering approaches to recreate some of the features in the heart valve microenvironment such as anisotropic and hierarchical tri-layered architecture, mechanical anisotropy and biocompatibility. Statement of Significance Heart valve tissue engineering (HVTE) is of special significance to overcome the drawbacks of current valve replacements. Although biodegradable synthetic elastomers have emerged as promising materials for HVTE, a mature HVTE construct made from synthetic elastomers for clinical use remains to be developed. Hence, this review summarized various types of biodegradable synthetic elastomers and their key properties. The major focus that distinguishes this review from the current literature is the thorough discussion on the key features of native valve microenvironments and various up-and-coming approaches to engineer synthetic elastomers to recreate these features such as anisotropic tri-layered architecture, mechanical anisotropy, biodegradability and biocompatibility. This review is envisioned to inspire and instruct the design of functional HVTE constructs and facilitate their clinical translation. [ABSTRACT FROM AUTHOR]

Knowledge of the histomorphometric structure of the vertebral body and factors influencing the structure is essential for a fundamental understanding of osteoporosis and osteoporotic fractures. The present study is focused on osteocyte density - a parameter seldom investigated so far – and trabecular width as well as bone area over tissue area in human vertebral bodies. Ninety-two vertebral body specimens (C5, C6, Th8, Th12, L1, L2) from 12 males and seven females were studied (Ethics Application Number A 2017–0072). The prepared vertebral specimens were extracted from the ventral aspect with a Jamshidi needle®. The punches were decalcified and subsequently H&E stained. Using the Fiji/Image J program (version 1.53 f, Wayne Resband, National Institute of Mental Health, USA), osteocyte numbers were counted per calcified bone surface, and the trabecular width and bone area of trabecular bone were measured. The collected data were analyzed using the statistical software package SPSS, version 23.0 (SPSS Inc., Chicago, USA). Pearson's correlation coefficient was used for correlation analyses. Multiple linear regression analyses were also performed. Osteocyte density did not differ significantly in comparisons based on gender and age (≤65 years; ≥66 years). Men had wider trabeculae (p < 0.001) and a higher bone area over tissue area (BA/TA, %) (p = 0.025) than women. Individuals over 65 years of age had thinner trabeculae (p < 0.001) and a smaller BA/TA (%) (p < 0.001) than younger individuals. Multiple linear regression analyses were performed to determine the influence of 'gender' and 'age' on trabecular width and bone area over tissue area. The R² was 0.388 for trabecular width and 0.227 for BA/TA (%). Per year of life, trabecular width decreases by 0.368 µm (β < 0.001) and BA/TA (%) by 0.001% (β = 0.001). Men have on average 8.2 µm wider trabeculae than women (β = 0.035). A negative correlation (r = −0.275) was observed between trabecular width and osteocyte density. The wider the trabeculae, the fewer osteocytes per mm² (p = 0.008). Surprisingly, we found no difference in osteocyte density with reference to age or gender. However, we did register significant age- and gender-related differences in bone area over tissue area and trabecular thickness. The age-related differences were more pronounced, implying that age-dependent loss of bone structure may be more important than differences between genders. [ABSTRACT FROM AUTHOR]

Fault injection attacks are considered one of the major threats to cyber–physical systems. The increasing complexity of embedded microprocessors involves complicated behaviours in presence of such attacks. Realistic fault models are required to study code vulnerabilities and be able to protect digital systems from these attacks. However, inferring fault models using only limited observations of faulty microprocessors is difficult. In this article, we present experiments that show the difficulty of characterizing and modeling the fault injection effects. From there, we propose a complete approach for fault analysis to build proper fault models at different abstraction levels, which will help in designing suitable countermeasures at reasonable cost. We also present a suite of experiments that works as a proof of concept to validate the proposed methodology. • Cross-layer fault analysis methodology to infer realistic fault models. • Holistic approach considering software, RTL and hardware abstraction levels. • Fault injection experiments on 3 different microcontrollers and 2 target programs. • RTL simulation validating the inferred fault models. • Reproducibility of state-of-the-art software fault models. [ABSTRACT FROM AUTHOR]

The really nontrivial goal of tissue engineering is combining all scaffold micro-architectural features, affecting both fluid-dynamical and mechanical performance, to obtain a fully functional implant. In this work we identified an optimal geometrical pattern for bone tissue engineering applications, best balancing several graft needs which correspond to competing design goals. In particular, we investigated the occurred changes in graft behavior by varying pore size (300 μm, 600 μm, 900 μm), interpore distance (equal to pore size or 300 μm fixed) and pores interconnection (absent, 45°-oriented, 90°-oriented). Mathematical considerations and Computational Fluid Dynamics (CFD) tools, here combined in a complete theoretical model, were carried out to this aim. Poly-lactic acid (PLA) based samples were realized by 3D printing, basing on the modeled architectures. A collagen (COL) coating was also realized on grafts surface and the interaction between PLA and COL, besides the protein contribution to graft bioactivity, was evaluated. Scaffolds were extensively characterized; human articular cells were used to test their biocompatibility and to evaluate the theoretical model predictions. Grafts fulfilled both the chemical and physical requirements. Finally, a good agreement was found between the theoretical model predictions and the experimental data, making these prototypes good candidates for bone graft replacements. [ABSTRACT FROM AUTHOR]

Type 1 Gaucher disease (GD) is an autosomal recessive lysosomal storage disease, affecting bone metabolism, structure and strength. Current bone assessment methods are not ideal. Semi-quantitative MRI scoring is unreliable, not standardized, and only evaluates bone marrow. DXA BMD is also used but is a limited predictor of bone fragility/fracture risk. Our purpose was to measure trabecular bone microarchitecture, as a biomarker of bone disease severity, in type 1 GD individuals with different GD genotypes and to apply machine learning based analytics to discriminate between GD patients and healthy individuals. Micro-MR imaging of the distal radius was performed on 20 type 1 GD patients and 10 healthy controls (HC). Fifteen stereological and textural measures (STM) were calculated from the MR images. General linear models demonstrated significant differences between GD and HC, and GD genotypes. Stereological measures, main contributors to the first two principal components (PCs), explained ~50% of data variation and were significantly different between males and females. Subsequent PCs textural measures were significantly different between GD patients and HC individuals. Textural measures also significantly differed between GD genotypes, and distinguished between GD patients with normal and pathologic DXA scores. PCA and SVM predictive analyses discriminated between GD and HC with maximum accuracy of 73% and area under ROC curve of 0.79. Trabecular STM differences can be quantified between GD patients and HC, and GD sub-types using micro-MRI and machine learning based analytics. Work is underway to expand this approach to evaluate GD disease burden and treatment efficacy. [ABSTRACT FROM AUTHOR]

Functional columns of primary auditory cortex (AI) are arranged in layers, each composed of highly connected fine-scale networks. The basic response properties and interactions within these local subnetworks have only begun to be assessed. We examined the functional diversity of neurons within the laminar microarchitecture of cat AI to determine the relationship of spectrotemporal processing between neighboring neurons. Neuronal activity was recorded across the cortical layers while presenting a dynamically modulated broadband noise. Spectrotemporal receptive fields (STRFs) and their nonlinear input/output functions (nonlinearities) were constructed for each neuron and compared for pairs of neurons simultaneously recorded at the same contact site. Properties of these local neuron pairs showed greater similarity than non-paired neurons within the same column for all considered parameters including firing rate, envelope-phase precision, preferred spectral and temporal modulation frequency, as well as for the threshold and transition of the response nonlinearity. This higher functional similarity of paired versus non-paired neurons was most apparent in infragranular neuron pairs, and less for local supragranular and granular pairs. The functional similarity of local paired neurons for firing rate, best temporal modulation frequency and two nonlinearity aspects was laminar dependent, with infragranular local pair-wise differences larger than for granular or supragranular layers. Synchronous spiking events between pairs of neurons revealed that simultaneous ‘Bicellular’ spikes, in addition to carrying higher stimulus information than non-synchronized spikes, encoded faster modulation frequencies. Bicellular functional differences to the best matched of the paired neurons could be substantial. Bicellular nonlinearities showed that synchronous spikes act to transmit stimulus information with higher fidelity and precision than non-synchronous spikes of the individual neurons, thus, likely enhancing stimulus feature selectivity in their target neurons. Overall, the well-correlated and temporally precise processing within local subnetworks of cat AI showed laminar-dependent functional diversity in spectrotemporal processing, despite high intra-columnar congruity in frequency preference. [ABSTRACT FROM AUTHOR]

The high resolution peripheral computed tomography (HR-pQCT) technique has seen recent developments with regard to the assessment of cortical porosity. In this study, we investigated the role of cortical porosity on bone strength in a large cohort of women. The distal radius and distal tibia were scanned by HR-pQCT. We assessed bone strength by estimating the failure load by microfinite element analysis (μFEA), with isotropic and homogeneous material properties. We built a multivariate model to predict it, using a few microarchitecture variables including cortical porosity. Among 857 Caucasian women analyzed with μFEA, we found that cortical and trabecular properties, along with the failure load, impaired slightly with advancing age in premenopausal women, the correlations with age being modest, with | r age | ranging from 0.14 to 0.38. After the onset of the menopause, those relationships with age were stronger for most parameters at both sites, with | r age | ranging from 0.10 to 0.64, notably for cortical porosity and failure load, which were markedly deteriorated with increasing age. Our multivariate model using microarchitecture parameters revealed that cortical porosity played a significant role in bone strength prediction, with semipartial r 2 = 0.22 only at the tibia in postmenopausal women. In conclusion, in our large cohort of women, we observed a small decline of bone strength at the tibia before the onset of menopause. We also found an age-related increase of cortical porosity at both scanned sites in premenopausal women. In postmenopausal women, the relatively high increase of cortical porosity accounted for the decline in bone strength only at the tibia. [ABSTRACT FROM AUTHOR]

Persons with type 1 and type 2 diabetes have increased fracture risk, attributed to deficits in the microarchitecture and strength of diabetic bone, thought to be mediated, in part, by the consequences of chronic hyperglycemia. Therefore, to examine the effects of a glucose-lowering SGLT2 inhibitor on blood glucose (BG) and bone homeostasis in a model of diabetic bone disease, male DBA/2J mice with or without streptozotocin (STZ)-induced hyperglycemia were fed chow containing the SGLT2 inhibitor, canagliflozin (CANA), or chow without drug, for 10 weeks of therapy. Thereafter, serum bone biomarkers were measured, fracture resistance of cortical bone was assessed by μCT analysis and a three-point bending test of the femur, and vertebral bone strength was determined by compression testing. In the femur metaphysis and L6 vertebra, long-term diabetes (DM) induced deficits in trabecular bone microarchitecture. In the femur diaphysis, a decrease in cortical bone area, cortical thickness and minimal moment of inertia occurred in DM (p < 0.0001, for all) while cortical porosity was increased (p < 0.0001). These DM changes were associated with reduced fracture resistance (decreased material strength and toughness; decreased structural strength and rigidity; p < 0.001 for all). Significant increases in PTH (p < 0.0001), RatLAPs (p = 0.0002), and urine calcium concentration (p < 0.0001) were also seen in DM. Canagliflozin treatment improved BG in DM mice by ~ 35%, but did not improve microarchitectural parameters. Instead, in canagliflozin-treated diabetic mice, a further increase in RatLAPs was evident, possibly suggesting a drug-related intensification of bone resorption. Additionally, detrimental metaphyseal changes were noted in canagliflozin-treated control mice. Hence, diabetic bone disease was not favorably affected by canagliflozin treatment, perhaps due to insufficient glycemic improvement. Instead, in control mice, long-term exposure to SGLT2 inhibition was associated with adverse effects on the trabecular compartment of bone. [ABSTRACT FROM AUTHOR]

Glucocorticoids have a beneficial anti-inflammatory and immunosuppressive effect, but their use is associated with decreased bone formation, bone mass and bone quality, resulting in an elevated fracture risk. Exercise and sclerostin antibody (Scl-Ab) administration have both been shown to increase bone formation and bone mass, therefore the ability of these treatments to inhibit glucocorticoid-induced osteopenia alone or in combination were assessed in a rodent model. Adult (4 months-old) male Wistar rats were allocated to a control group (C) or one of 4 groups injected subcutaneously with methylprednisolone (5 mg/kg/day, 5 days/week). Methylprednisolone treated rats were injected subcutaneously 2 days/week with vehicle (M) or Scl-Ab-VI (M + S: 25 mg/kg/day) and were submitted or not to treadmill interval training exercise (1 h/day, 5 days/week) for 9 weeks (M + E, M + E + S). Methylprednisolone treatment increased % fat mass and % apoptotic osteocytes, reduced whole body and femoral bone mineral content (BMC), reduced femoral bone mineral density (BMD) and osteocyte lacunae occupancy. This effect was associated with lower trabecular bone volume (BV/TV) at the distal femur. Exercise increased BV/TV, osteocyte lacunae occupancy, while reducing fat mass, the bone resorption marker NTx, and osteocyte apoptosis. Exercise did not affect BMC or cortical microarchitectural parameters. Scl-Ab increased the bone formation marker osteocalcin and prevented the deleterious effects of M on bone mass, further increasing BMC, BMD and BV/TV to levels above the C group. Scl-Ab increased femoral cortical bone parameters at distal part and midshaft. Scl-Ab prevented the decrease in osteocyte lacunae occupancy and the increase in osteocyte apoptosis induced by M. The addition of exercise to Scl-Ab treatment did not result in additional improvements in bone mass or bone strength parameters. These data suggest that although our exercise regimen did prevent some of the bone deleterious effects of glucocorticoid treatment, particularly in trabecular bone volume and osteocyte apoptosis, Scl-Ab treatment resulted in marked improvements in bone mass across the skeleton and in osteocyte viability, resulting in decreased bone fragility. [ABSTRACT FROM AUTHOR]

Context Young amenorrheic athletes (AA) have lower bone mineral density (BMD) and an increased prevalence of fracture compared with eumenorrheic athletes (EA) and non-athletes. Trabecular morphology is a determinant of skeletal strength and may contribute to fracture risk. Objectives To determine the variation in trabecular morphology among AA, EA, and non-athletes and to determine the association of trabecular morphology with fracture among AA. Design and setting A cross-sectional study performed at an academic clinical research center. Participants 161 girls and young women aged 14–26 years (97 AA, 32 EA, and 32 non-athletes). Main outcome measure We measured volumetric BMD (vBMD) and skeletal microarchitecture using high-resolution peripheral quantitative computed tomography. We evaluated trabecular morphology (plate-like vs. rod-like), orientation, and connectivity by individual trabecula segmentation. Results At the non-weight-bearing distal radius, the groups did not differ for trabecular vBMD. However, plate-like trabecular bone volume fraction (pBV/TV) was lower in AA vs. EA (p = 0.03), as were plate number (p = 0.03) and connectivity (p = 0.03). At the weight-bearing distal tibia, trabecular vBMD was higher in athletes vs. non-athletes (p = 0.05 for AA and p = 0.009 for EA vs. non-athletes, respectively). pBV/TV was higher in athletes vs. non-athletes (p = 0.04 AA and p = 0.005 EA vs. non-athletes), as were axially-aligned trabeculae, plate number, and connectivity. Among AA, those with a history of recurrent stress fracture had lower pBV/TV, axially-aligned trabeculae, plate number, plate thickness, and connectivity at the distal radius. Conclusions Trabecular morphology and alignment differ among AA, EA, and non-athletes. These differences may be associated with increased fracture risk. [ABSTRACT FROM AUTHOR]

Upper extremity fractures, including those at the humerus, are common among women with postmenopausal osteoporosis. Denosumab was shown to reduce humeral fractures in this population; however, no clinical or preclinical studies have quantified the effects of denosumab on humerus bone mineral density or bone microarchitecture changes. This study used micro-computed tomography (μCT) and computed tomography (CT), alongside image-based finite element (FE) models derived from both modalities, to quantify the effects of denosomab (DMAb) and alendronate (ALN) on humeral bone from acutely ovariectomized (OVX) cynomolgus monkeys. Animals were treated with 12 monthly injections of s.c. vehicle (VEH; n = 10), s.c. denosumab (DMAb; 25 mg/kg, n = 9), or i.v. alendronate (ALN; 50 μg/kg, n = 10). Two more groups received 6 months of VEH followed by 6 months of DMAb (VEH-DMAb; n = 7) or 6 months of ALN followed by 6 months of DMAb (ALN-DMAb; n = 9). After treatment, humeri were harvested and μCT was used to quantify tissue mineral density, trabecular morphology, and cortical porosity at the humeral head. Clinical CT imaging was also used to quantify trabecular and cortical bone mineral density (BMD) at the ultra-proximal, proximal, 1/5 proximal and midshaft of the bone. Finally, μCT-based FE models in compression, and CT-based FE models in compression, torsion, and bending, were developed to estimate differences in strength. Compared to VEH, groups that received DMAb at any time demonstrated lower cortical porosity and/or higher tissue mineral density via μCT; no effects on trabecular morphology were observed. FE estimated strength based on μCT was higher after 12-months DMAb (p = 0.020) and ALN-DMAb (p = 0.024) vs. VEH; respectively, FE predicted mean (SD) strength was 4649.88 (710.58) N, and 4621.10 (1050.16) N vs. 3309.4 (876.09) N. All antiresorptive treatments were associated with higher cortical BMD via CT at the 1/5 proximal and midshaft of the humerus; however, no differences in CT-based FE predicted strength were observed. Overall, these results help to explain the observed reductions in humeral fracture rate following DMAb treatment in women with postmenopausal osteoporosis. • OVX cynomolgus monkeys treated for 12 months with alendronate (ALN), denosomab (DMAb), DMAb after vehicle, or DMAb after ALN. • Antiresorptive treatment was associated with lower cortical porosity and greater density at the proximal humerus vs. vehicle. • Treatment was associated with greater stiffness and strength, as predicted using high-resolution finite element models. • Clinical computed tomography demonstrated treatment was associated with greater cortical bone density throughout the humerus. [ABSTRACT FROM AUTHOR]

Part I of this study presented a computational model-based approach for enhancing the performance of solid oxide fuel cells (SOFCs) with designed microarchitecture. The performance of such SOFCs was predicted to greatly improve through a systematic computational design and optimization approach. Part II here proves through experimental fabrication and characterization that microarchitectured SOFC performance can be improved as predicted by the model. A real and specific SOFC is chosen, fabricated and characterized to demonstrate the proof-of-concept. Fabrication techniques using sintering and laser ablation are demonstrated. Pore size and geometry are characterized by interferometry-based surface profilometry and scanning electron microscopy. SOFC button cell performance testing including power output performance and electrochemical impedance spectroscopy are performed. The results show that SOFC performance in a microarchitectured cell can be improved over a baseline button cell by 9–17% in current density and by 7–19% in power density. [ABSTRACT FROM AUTHOR]

Cells and tissues are intrinsically adapted to molecular gradients and use them to maintain or change their activity. The effect of such gradients is particularly important for cell populations that have an intrinsic capacity to differentiate into multiple cell lineages, such as bone marrow derived mesenchymal stromal cells (MSCs). Our results showed that nutrient gradients prompt the spatiotemporal organization of MSCs in 3D culture. Cells adapted to their 3D environment without significant cell death or cell differentiation. Kinetics data and whole-genome gene expression analysis suggest that a low proliferation activity phenotype predominates in stromal cells cultured in 3D, likely due to increasing nutrient limitation. These differences implied that despite similar surface areas available for cell attachment, higher cell concentrations in 3D reduced MSCs proliferation, while activating hypoxia related-pathways. To further understand the in vivo effects of both proliferation and cell concentrations, we increased cell concentrations in small (1.8 μl) implantable wells. We found that MSCs accumulation and conditioning by nutrient competition in small volumes leads to an ideal threshold of cell-concentration for the induction of blood vessel formation, possibly signaled by the hypoxia-related stanniocalcin-1 gene. [ABSTRACT FROM AUTHOR]

The advent of multicore and manycore processors, including GPUs, in the customer market encouraged developers to focus on extraction of parallelism. While it is certainly true that parallelism can deliver performance boosts, parallelization is also a very complex and error- prone task, and any applications are still dominated by sequential sections. Micro-architectures have become extremely complex, and they usually do a very good job at executing fast a given sequence of instructions. When they occasionally fail, however, the penalty is severe. Pathological behaviors often have their roots in very low-level details of the micro-architecture, hardly available to the programmer. We argue that the impact of these low-level features on performance has been overlooked, often relegated to experts. We show that a few metrics can be easily defined to help assess the overall performance of an application, and quickly diagnose a problem. Finally, we illustrate our claim with a simple prototype, along with use cases. [ABSTRACT FROM AUTHOR]

Context Various fat depots have differential effects on bone. Visceral adipose tissue (VAT) is deleterious to bone, whereas subcutaneous adipose tissue (SAT) has positive effects. Also, marrow adipose tissue (MAT), a relatively newly recognized fat depot is inversely associated with bone mineral density (BMD). Bone mass in athletes depends on many factors including gonadal steroids and muscle mass. Exercise increases muscle mass and BMD, whereas, estrogen deficiency decreases BMD. Thus, the beneficial effects of weight-bearing exercise on areal and volumetric BMD (aBMD and vBMD) in regularly menstruating (eumenorrheic) athletes (EA) are attenuated in oligo-amenorrheic athletes (OA). Of note, data regarding VAT, SAT, MAT and regional muscle mass in OA compared with EA and non-athletes (C), and their impact on bone are lacking. Methods We used (i) MRI to assess VAT and SAT at the L4 vertebra level, and cross-sectional muscle area (CSA) of the mid-thigh, (ii) 1H-MRS to assess MAT at L4, the proximal femoral metaphysis and mid-diaphysis, (iii) DXA to assess spine and hip aBMD, and (iv) HRpQCT to assess vBMD at the distal radius (non-weight-bearing bone) and tibia (weight-bearing bone) in 41 young women (20 OA, 10 EA and 11 C 18–25 years). All athletes engaged in weight-bearing sports for ≥ 4 h/week or ran ≥ 20 miles/week. Main outcome measures VAT, SAT and MAT at L4; CSA of the mid-thigh; MAT at the proximal femoral metaphysis and mid-diaphysis; aBMD, vBMD and bone microarchitecture. Results Groups had comparable age, menarchal age, BMI, VAT, VAT/SAT and spine BMD Z-scores. EA had higher femoral neck BMD Z-scores than OA and C. Fat mass was lowest in OA. SAT was lowest in OA (p = 0.048); L4 MAT was higher in OA than EA (p = 0.03). We found inverse associations of (i) VAT/SAT with spine BMD Z-scores (r = − 0.42, p = 0.01), (ii) L4 MAT with spine and hip BMD Z-scores (r = − 0.44, p = 0.01; r = − 0.36, p = 0.02), and vBMD of the radius and tibia (r = − 0.49, p = 0.002; r = − 0.41, p = 0.01), and (iii) diaphyseal and metaphyseal MAT with vBMD of the radius (r ≤ − 0.42, p ≤ 0.01) and tibia (r ≤ − 0.34, p ≤ 0.04). In a multivariate model including VAT/SAT, L4 MAT and thigh CSA, spine and hip BMD Z-scores were predicted inversely by L4 MAT and positively by thigh CSA, and total and cortical radius and total tibial vBMD were predicted inversely by L4 MAT. VAT/SAT did not predict radius or tibia total vBMD in this model, but inversely predicted spine BMD Z-scores. When L4 MAT was replaced with diaphyseal or metaphyseal MAT in the model, diaphyseal and metaphyseal MAT did not predict aBMD Z-scores, but diaphyseal MAT inversely predicted total vBMD of the radius and tibia. These results did not change after adding percent body fat to the model. Conclusions VAT/SAT is an inverse predictor of lumbar spine aBMD Z-scores, while L4 MAT is an independent inverse predictor of aBMD Z-scores at the spine and hip and vBMD measures at the distal tibia and radius in athletes and non-athletes. Diaphyseal MAT independently predicts vBMD measures of the distal tibia and radius. [ABSTRACT FROM AUTHOR]

Introduction Age and gender have been reported to have a remarkable impact on bone homeostasis. However, subchondral bone, which plays a pivotal role in the initiation and progression of OA, has been poorly investigated. This study was to investigate age- and gender-related changes of microarchitecture and bone remodeling in subchondral bone in OA. Methods Subchondral trabecular bone (STB) and deeper trabecular bone (DTB) specimens were extracted in the load-bearing region of femoral heads from 110 patients with OA. Micro-CT and histomorphometry were performed to analyze microarchitectural and bone remodeling changes of all specimens. Results Compared to DTB, STB showed more sclerotic microarchitecture, more active bone remodeling and higher frequency of bone cysts. There were no gender differences for both microarchitecture and bone remodeling in STB. However, gender differences were found in DTB, with thinner Tb.Th, higher Tb.N, higher OS/BV and ES/BV in males. In both STB and DTB, no correlation between microarchitecture and age was found in both genders. However, bone remodeling of STB increased significantly with age in males, while bone remodeling of DTB increased significantly with age in females. No age or gender preference was found in subchondral bone cyst (SBC) frequency. The cyst volume fraction was correlated with neither age nor gender. Conclusions There were differences in microarchitecture and bone remodeling between STB and DTB, which may be due to the distinct biomechanical and biochemical functions of these two bone structures in maintaining joint homeostasis. OA changed the normal age- and gender-dependence of bone homeostasis in joints, in a site-specific manner. [ABSTRACT FROM AUTHOR]

Individuals with sickle cell disease often experience acute and chronic bone pain due to occlusive events within the tissue vasculature that result in ischemia, necrosis, and organ degeneration. Macroscopically, sickle bone is identified in clinical radiographs by its reduced mineral density, widening of the marrow cavity, and thinning of the cortical bone due to the elevated erythroid hyperplasia accompanying the disease. However, the microstructural architecture of sickle bone and its role in mechanical functionality is largely unknown. This study utilized micro-CT and biomechanical testing to determine the relationship between the bone morphology, tissue mineral density, and trabecular and cortical microarchitecture of 10- and 21-week-old femurs from transgenic sickle male mice and littermates with sickle trait, as well as a wild-type control. While bone tissue mineral density did not vary among the genotypes at either age, variation in bone microstructure were observed. At 10 weeks, healthy and trait mice exhibited similar morphology within the cortical and trabecular bone, while sickle mice exhibited highly connected trabeculae. Within older femurs, sickle and trait specimens displayed significantly fewer trabeculae, and the remaining trabeculae had a more deteriorated geometry based on the structure model index. Thinning of the cortical region in sickle femurs contributed to the displayed flexibility with a significantly lower elastic modulus than the controls at both 10- and 21-weeks old. Wild-type and trait femurs generally demonstrated similar mechanical properties; however, trait femurs had a significantly higher modulus than sickle and wild-type control at 21-weeks. Overall, these data indicate that the progressive damage to the microvasculature caused by sickle cell disease, results in deleterious structural changes in the bone tissue׳s microarchitecture and mechanics. [ABSTRACT FROM AUTHOR]

A macro–micro–nano–multi-level study was conducted to explore age-related structural and mechanical properties of bone, as well as the effects of aging on bone properties. A total of 70 male Wistar rats were used, ranging in the ages of 1, 3, 5, 7, 9, 11, 14, 15, 16, and 17 months ( n = 7/age group). After micro-computed tomography (CT) scanning, longitudinal cortical bone specimens with a length of 5 mm were cut along the femoral shaft axis from left femur shafts for mechanical testing, and the cross-sectional areas were measured. The macro-mechanical properties obtained in mechanical testing and microarchitecture parameters measured by micro-CT were significantly correlated with the animal age (r 2 = 0.96, p < 0.001). Scanning electron microscopy was used for detecting the microarchitecture features of the fractured surfaces, which exhibited age-related plate-fibrous-mixed fibrous-plate texture, resulting in changes in macro-mechanical properties (r 2 > 0.90, p < 0.001). The mineral phase of the left femoral shaft and head was analyzed by atomic force microscopy. Longitudinal and transverse trabecular bone tissues, as well as longitudinal cortical bone tissue, were used for nanoindentation test, and the chemical composition was evaluated by quantitative chemical analyses. The correlations between mineral content and bone material properties (i.e., elastic properties of the bone tissue and size and roughness of bone mineral grains) were highly significant (r > 0.95, p < 0.001). Multi-level femur morphology, mechanical property, and mineral content were significantly correlated with the animal age. The correlations between bone mineral content and bone material morphological and mechanical properties may partly explain the increase in bone fragility with aging, which will provide a theoretical basis for the investigation of age-related bone properties in clinics. [ABSTRACT FROM AUTHOR]

Decline in bone formation is a major contributing factor to the loss of bone mass associated with aging. We previously showed that the genetic ablation of the tissue-restricted and multifunctional Ca 2 + /calmodulin (CaM)-dependent protein kinase kinase 2 (CaMKK2) stimulates trabecular bone mass accrual, mainly by promoting anabolic pathways and inhibiting catabolic pathways of bone remodeling. In this study, we investigated whether inhibition of this kinase using its selective cell-permeable inhibitor STO-609 will stimulate bone formation in 32 week old male WT mice and reverse age-associated of decline in bone volume and strength. Tri-weekly intraperitoneal injections of saline or STO-609 (10 μM) were performed for six weeks followed by metabolic labeling with calcein and alizarin red. New bone formation was assessed by dynamic histomorphometry whereas micro-computed tomography was employed to measure trabecular bone volume, microarchitecture and femoral mid-shaft geometry. Cortical and trabecular bone biomechanical properties were assessed using three-point bending and punch compression methods respectively. Our results reveal that as they progress from 12 to 32 weeks of age, WT mice sustain a significant decline in trabecular bone volume, microarchitecture and strength as well as cortical bone strength. However, treatment of the 32 week old WT mice with STO-609 stimulated apposition of new bone and completely reversed the age-associated decrease in bone volume, quality, as well as trabecular and cortical bone strength. We also observed that regardless of age, male Camkk2 −/− mice possessed significantly elevated trabecular bone volume, microarchitecture and compressive strength as well as cortical bone strength compared to age-matched WT mice, implying that the chronic loss of this kinase attenuates age-associated decline in bone mass. Further, whereas STO-609 treatment and/or the absence of CaMKK2 significantly enhanced the femoral mid-shaft geometry, the mid-shaft cortical wall thickness and material bending stress remained similar among the cohorts, implying that regardless of treatment, the material properties of the bone remain similar. Thus, our cumulative results provide evidence for the pharmacological inhibition of CaMKK2 as a bone anabolic strategy in combating age-associated osteoporosis. [ABSTRACT FROM AUTHOR]

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 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 (r 2 = 0.97) and yield strength (r 2 = 0.96) were found between the PR FE model predictions and experimental measures, suggesting that trabecular plate and rod 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 (r 2 = 0.99, r 2 = 0.98, respectively), resulted from the original 3D images without the PR segmentation. In conclusion, the ITS-based PR models predicted accurately both elastic modulus and yield strength determined experimentally across three distinct anatomic sites. Trabecular plates and rods accurately determine elastic modulus and yield strength of human trabecular bone. [ABSTRACT FROM AUTHOR]

For cancellous bone screws, the respective roles of the applied insertion torque ( T Insert ) and of the quality of the host bone (microarchitecture, areal bone mineral density (aBMD)), in contributing to the mechanical holding strength of the bone-screw construct ( F Pullout ), are still unclear. During orthopaedic surgery screws are tightened, typically manually, until adequate compression is attained, depending on surgeons’ manual feel. This corresponds to a subjective insertion torque control, and can lead to variable levels of tightening, including screw stripping. The aim of this study, performed on cancellous screws inserted in human femoral heads, was to investigate which, among the measurements of aBMD, bone microarchitecture, and the applied T Insert , has the strongest correlation with F Pullout . Forty six femoral heads were obtained, over which microarchitecture and aBMD were evaluated using micro-computed tomography and dual X-ray absorptiometry. Using an automated micro-mechanical test device, a cancellous screw was inserted in the femoral heads at T Insert set to 55% to 99% of the predicted stripping torque beyond screw head contact, after which F Pullout was measured. F Pullout exhibited strongest correlations with T Insert ( R =0.88, p <0.001), followed by structure model index (SMI, R =−0.81, p <0.001), bone volume fraction (BV/TV, R =0.73, p <0.001) and aBMD ( R =0.66, p <0.01). Combinations of T Insert with microarchitectural parameters and/or aBMD did not improve the prediction of F Pullout . These results indicate that, for cancellous screws, F Pullout depends most strongly on the applied T Insert , followed by microarchitecture and aBMD of the host bone. In trabecular bone, screw tightening increases the holding strength of the screw-bone construct. [ABSTRACT FROM AUTHOR]

• Elucidates geometrical features of microarchitecture in cancellous bone mechanics. • Compression testing for 5-mm cubes of bovine femoral cancellous bone. • Combinations of geometrical features accurately expressed cancellous stiffness. • Significant contribution of bifurcation characteristics to cancellous stiffness. • Contributions of trabecular shape and orientation to cancellous stiffness. This study aims to describe the geometrical features of single trabeculae and their network to explain cancellous stiffness as a representative mechanical function from a strength of materials perspective. Compression tests were performed on cancellous bone specimens dissected from a bovine femur as 5-mm cubes to measure cancellous stiffness. The microarchitecture was determined by microfocus X-ray computed tomography, and conventional morphological indicators were analyzed. The length, orientation, and bifurcation characteristics of each trabecula were analyzed by skeletonizing and linearizing the cancellous bone volume. Multiple regression analyses revealed a significant contribution made to cancellous stiffness by the compressive shape factor of the stiffness of single trabeculae, the trabecular orientation, and the bifurcation count, which evaluated the mean number of connected trabeculae at bifurcation points. Bifurcation count made the most significant contribution to cancellous stiffness. The combination of these geometrical indicators expressed the cancellous stiffness (R 2 = 0.85), which indicated as high accuracy as that explained by bone volume fraction, in specific bones that were not affected by bone disease or aging. The present study demonstrated mechanically important geometrical features of the microarchitecture and indicated their complex contributions to cancellous stiffness underlying the contribution of bone volume fraction. [Display omitted] [ABSTRACT FROM AUTHOR]

Trabecular bone is a random cellular solid with an interconnected network of plate-like and rod-like components. However, the structural randomness and complexity have hindered rigorous mathematical modeling of trabecular bone microarchitecture. Recent advancements in imaging processing techniques have enabled us to define the size, orientation, and spatial location of individual trabecular plates and rods in trabecular bone. Based on the essential information, this study proposed a probability-based approach to define the size, orientation, and spatial distributions of trabecular plates and rods for trabecular bone cubes (N = 547) acquired from six human cadaver proximal femurs. Using two groups of probability-based parameters, it was attempted to capture microarchitectural details, which could not be captured by the existing histomorphometric parameters, but crucial to the elastic properties of trabecular bone. The elastic properties of the trabecular bone cubes in three principal axes were estimated using microCT based finite element (FE) simulations. Based on the results of multivariate multiple regression modeling, the efficacy of the two groups of probability-based parameters in prediction of the elastic properties was verified in comparison with that of the existing histomorphometric parameters (BV/TV, Tb.Th, Tb.Sp, DA, EF.Med, and Conn.D). The results indicated that the regression models trained using the probability-based parameters had a comparable and even better accuracy (rMSE = 0.621 and 0.548) than that of the histomorphometric parameters (rMSE = 0.647). More importantly, the probability-based parameters could provide more insights into some unexplored microarchitectural features, such as individual trabecular size, orientation, and spatial distributions, which are also critical to the elastic properties of trabecular bone. [ABSTRACT FROM AUTHOR]

The amount of microdamage in bone tissue impairs mechanical performance and may act as a stimulus for bone remodeling. Here we determine how loading mode (tension vs. compression) and microstructure (trabecular microarchitecture, local trabecular thickness, and presence of resorption cavities) influence the number and volume of microdamage sites generated in cancellous bone following a single overload. Twenty paired cylindrical specimens of human vertebral cancellous bone from 10 donors (47-78 years) were mechanically loaded to apparent yield in either compression or tension, and imaged in three dimensions for microarchitecture and microdamage (voxel size 0.7×0.7×5.0 µm³). We found that the overall proportion of damaged tissue was greater (p=0.01) for apparent tension loading (3.9±2.4%, mean±SD) than for apparent compression loading (1.9±1.3%). Individual microdamage sites generated in tension were larger in volume (p<0.001) but not more numerous (p=0.64) than sites in compression. For both loading modes, the proportion of damaged tissue varied more across donors than with bone volume fraction, traditional measures of microarchitecture (trabecular thickness, trabecular separation, etc.), apparent Youngs modulus, or strength. Microdamage tended to occur in regions of greater trabecular thickness but not near observable resorption cavities. Taken together, these findings indicate that, regardless of loading mode, accumulation of microdamage in cancellous bone after monotonic loading to yield is influenced by donor characteristics other than traditional measures of microarchitecture, suggesting a possible role for tissue material properties. [ABSTRACT FROM AUTHOR]

This paper presents an approach for incorporating the effect of various logic synthesis options and logic level implementations into the custom instruction (CI) selection for extensible processors. This effect translates into the availability of a piecewise continuous spectrum of delay versus area choices for each CI, which in turn influences the selection of the CI set that maximizes the speedup per area cost (SPA) metric. The effectiveness of the proposed approach is evaluated by applying it to several benchmarks and comparing the results with those of a conventional technique. We also apply the methodology to the existing serialization algorithms aimed at relaxing register file constraints in multi-cycle custom instruction design. The comparison shows considerable improvements in the speedup per area compared to the custom instruction selection algorithms under the same area-budget constraint. [ABSTRACT FROM AUTHOR]

The purpose was to assess whether precision of bone properties derived via the use of high-resolution peripheral quantitative computed tomography (HR-pQCT) differs between postmenopausal women and young adults. Using HR-pQCT, we scanned the distal radius and tibia at 2 time points in 34 postmenopausal women (74 ± 7 years) and 30 young adults (mean age ± SD: 27 ± 9 years). Standard protocols were used to acquire bone area, density, and microarchitectural properties. We calculated coefficients of variation (CV; percentage CV and percentage CV of the root mean square) and 95% limits of agreement (95% LOA) to assess precision errors. The 95% LOA is the magnitude of individual change needed to be observed to ensure that a real change has occurred. Multiple Mann-Whitney U -tests (with the use of Bonferroni correction for multiple comparisons) were used to compare percentage CV between the 2 groups. Significance was set to p < 0.004. All standard outcome variables were not significantly different between the groups. The 95% LOA confirmed that the measurement bias between the groups did not differ. These results suggest that short-term precision errors in HR-pQCT–derived bone outcomes are similar between postmenopausal women and young adults. [ABSTRACT FROM AUTHOR]

Objectives The role of subchondral bone in osteoarthritis (OA) development is well admitted. Cross-talk between subchondral bone and cartilage may be disrupted in OA, leading to altered subchondral bone remodeling. Osteocytes are involved in bone remodeling control and could play a key role in OA progression. Our purpose of this study was to evaluate the preventive effect of interval-training exercise on subchondral bone and osteocyte in monosodium iodoacetate (MIA) model of experimental OA. Methods At baseline, 48 male Wistar rats (8 weeks old) were separated into two groups: interval-training exercise or no exercise for 10 weeks. After this training period, each group was divided into two subgroups: MIA-injected knee (1 mg/100 µl saline) and saline-injected knee. Four weeks later, rats were sacrificed and carefully dissected. Evaluated parameters were: cartilage degeneration by OA scoring, bone mineral density (BMD) by Dual energy X-ray Absorptiometry (DXA), trabecular subchondral bone microarchitecture by micro-computed tomography (µCT), cortical subchondral bone lacunar osteocyte occupancy (by Toluidine Blue staining) and cleaved caspase-3 positive apoptosis (by epifluorescence). Results Our results showed deleterious effects of MIA on cartilage. OA induced a decrease in proximal tibia (PT) BMD which was prevented by exercise. Exercise induced increase in full osteocyte lacunae surface and osteocyte occupancy (+60%) of cortical subchondral bone independently of OA. Osteocyte apoptosis (<1%) in cortical subchondral bone was not different whatever the group at sacrifice. Conclusion Our results suggest that preliminary interval-training improved BMD and osteocytes lacunar occupancy in subchondral bone. Our interval-training did not prevent MIA-induced cartilage degeneration. [ABSTRACT FROM AUTHOR]

Osteoporosis is a bone disease resulting in increased fracture risk as a result of alterations in both 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 for evaluating potential treatments of this disease. Large animals, such as the ovariectomized sheep, have been used as models 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 femoral condyles and vertebral bodies of sheep that were sacrificed one or two years following ovariectomy. In the vertebral body, microarch-itectural 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 architectural changes stabilize after the first year. [ABSTRACT FROM AUTHOR]

During insertion of a cancellous bone screw, the torque level reaches a plateau, at the engagement of all the screw threads prior to the screw head contact. This plateau torque (TPlateau) was found to be a good predictor of the insertion failure torque (stripping) and also exhibited strong positive correlations with areal bone mineral density (aBMD) in ovine bone. However, correlations between TPlateau and aBMD, as well as correlations between TPlateau and bone microarchitecture, have never been explored in human bone. The aim of this study was to determine whether TPlateau, a predictor of insertion failure torque, depends on aBMD and/or bone microarchitecture in human femoral heads. Fifty-two excised human femoral heads were obtained. The aBMD and microarchitecture of each specimen were evaluated using dual X-ray Absorptiometry and micro-computed tomography. A cancellous screw was inserted into specimens using an automated micro-mechanical test device, and Tplateau was calculated from the insertion profile. Tplateau exhibited the strongest correlation with the structure model index (SMI, R =-0.82, p < 0.001), followed by bone volume fraction (BV/TV, R=0.80, p < 0.01) and aBMD (R = 0.76, p < 0.01). Stepwise forward regression analysis showed an increase for the prediction of TPlateau when aBMD was combined with microarchitectural parameters, i.e., aBMD combined with SMI (R² increased from 0.58 to 0.72) and aBMD combined with BV/TV and BS/TV (R² increased from 0.58 to 0.74). In conclusion, TPlateau, a strong predictor for insertion failure torque, is significantly dependent on bone microarchitecture (particularly SMI and BV/TV) and aBMD. [ABSTRACT FROM AUTHOR]

Abstract: Bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) is used to diagnose osteoporosis and assess fracture risk. However, DXA cannot evaluate trabecular microarchitecture. This study used a novel software program (TBS iNsight; Med-Imaps, Geneva, Switzerland) to estimate bone texture (trabecular bone score [TBS]) from standard spine DXA images. We hypothesized that TBS assessment would differentiate women with low trauma fracture from those without. In this study, TBS was performed blinded to fracture status on existing research DXA lumbar spine (LS) images from 429 women. Mean participant age was 71.3 yr, and 158 had prior fractures. The correlation between LS BMD and TBS was low (r = 0.28), suggesting these parameters reflect different bone properties. Age- and body mass index–adjusted odds ratios (ORs) ranged from 1.36 to 1.63 for LS or hip BMD in discriminating women with low trauma nonvertebral and vertebral fractures. TBS demonstrated ORs from 2.46 to 2.49 for these respective fractures; these remained significant after lowest BMD T-score adjustment (OR = 2.38 and 2.44). Seventy-three percent of all fractures occurred in women without osteoporosis (BMD T-score > −2.5); 72% of these women had a TBS score below the median, thereby appropriately classified them as being at increased risk. In conclusion, TBS assessment enhances DXA by evaluating trabecular pattern and identifying individuals with vertebral or low trauma fracture. TBS identifies 66–70% of women with fracture who were not classified with osteoporosis by BMD alone. [Copyright &y& Elsevier]

With the ever-increasing energy-efficiency requirements for the computing platforms at the edge, precision tuning techniques highlight the possibility of improving the efficiency of floating-point computations by selectively lowering the precision of intermediate operations without affecting the accuracy of the final result. Recent trends also demonstrated the possibility of successfully employing fixed-point computations in place of floating-point ones to further optimize the efficiency in the high-performance computing (HPC) domain. However, the use of integer functional units to support the execution of fixed-point operations in embedded platforms can severely degrade the energy-delay product (EDP). This work presents a cost-effective architecture to efficiently support fixed-point computations in embedded systems with two goals. On the one hand, it allows replacing the floating-point computations, with meaningful area and EDP improvements. On the other hand, it can complement the FPU, providing flexibility in selecting the best arithmetic for the target applications depending on their accuracy and performance requirements. Experimental results were collected from a representative set of floating-point-intensive applications executed on six variants of the baseline system-on-chip (SoC). We compared the efficiency of different floating- and fixed-point architectures in terms of accuracy, area, and EDP. Our fixed-point solution demonstrated a 0.651 EDP, normalized with respect to a SoC that featured a binary32 FPU, while achieving a negligible accuracy loss, i.e., 0.0003% on average (0.004% peak), compared to binary32 execution. In contrast, a SoC employing the integer functional units for fixed-point execution reports a 1.796 normalized EDP to achieve the same accuracy loss. Compared to the baseline SoC implementing only the integer units, the proposed architecture shows an area overhead limited to 4%, while the SoC featuring binary32 floating-point hardware support requires 32% more resources. • Substituting floating-point with fixed-point computations optimizes efficiency. • Supporting fixed-point operations via integer functional units decreases efficiency. • Fixed-point hardware support enables precision tuning in embedded systems. • Fixed-point hardware support saves area over FPU implementations. • Negligible accuracy loss considering a set of floating-point-intensive benchmarks. [ABSTRACT FROM AUTHOR]

Abstract: Bone defects can occur in various forms and present challenges to performing a standard micro-CT evaluation of bone quality because most measures are suited to homogeneous structures rather than ones with spatially focal abnormalities. Such defects are commonly associated with pain and fragility. Research involving bone defects requires quantitative approaches to be developed if micro-CT is to be employed. In this study, we demonstrate that measures of inter-microarchitectural bone spacing are sensitive to the presence of focal defects in the proximal tibia of two distinctly different mouse models: a burr-hole model for fracture healing research, and a model of osteolytic bone metastases. In these models, the cortical and trabecular bone compartments were both affected by the defect and were, therefore, evaluated as a single unit to avoid splitting the defects into multiple analysis regions. The burr-hole defect increased mean spacing (Sp) by 27.6%, spacing standard deviation (SpSD) by 113%, and maximum spacing (Spmax) by 72.8%. Regression modeling revealed SpSD (β =0.974, p <0.0001) to be a significant predictor of the defect volume (R 2 =0.949) and Spmax (β =0.712, p <0.0001) and SpSD (β =0.271, p =0.022) to be significant predictors of the defect diameter (R 2 =0.954). In the mice with osteolytic bone metastases, spacing parameters followed similar patterns of change as reflected by other imaging technologies, specifically bioluminescence data which is indicative of tumor burden. These data highlight the sensitivity of spacing measurements to bone architectural abnormalities from 3D micro-CT data and provide a tool for quantitative evaluation of defects within a bone. [Copyright &y& Elsevier]

Abstract: Objective: Fractal bone analysis (Hmean) is a texture parameter reflecting bone microarchitecture. The BMA device (D3A™ Medical Systems, Orléans, France) is a high-resolution X-ray device that allows assessment of bone texture analysis. We aimed to measure Hmean in rheumatoid arthritis patients at the second and third metacarpal bones, at baseline and after 1year of follow-up, and to assess the relationship of Hmean and rheumatoid arthritis disease parameters. Methods: Patients with rheumatoid arthritis according to ACR criteria were included. They were assessed over 1year, in the context of a prospective study conducted in Maastricht. For this substudy, activity of the disease was assessed by erythrocyte sedimentation rate, C-reactive protein and Disease Activity Score 28 performed at each visit. Radiographic bone damage was assessed using hand and feet radiographs at baseline and on a 1-year basis. The bone texture parameters were evaluated on the second and third metacarpal heads of the left hand using BMA device. Results: One hundred and sixty-five rheumatoid arthritis patients were included in this study. At baseline, Hmean was negatively correlated with age [r =−0.22 (P =0.013)] and erythrocyte sedimentation rate [r =−0.16 (P =0.039)]. No significant correlation was found between Hmean and Disease Activity Score, disease activity Visual Analog Scale, daily corticosteroid dose and C-reactive protein. There was a significant increase in Hmean of second and third metacarpal bones over 1year (1.6% and 1.3%, P <0.01) except in patients with local second and third metacarpal bones erosion. Conclusion: The bone texture parameter Hmean is influenced by age, inflammation and local erosions in rheumatoid arthritis. [Copyright &y& Elsevier]