Identification of ALK in Thinness.

There is considerable inter-individual variability in susceptibility to weight gain despite an equally obesogenic environment in large parts of the world. Whereas many studies have focused on identifying the genetic susceptibility to obesity, we performed a GWAS on metabolically healthy thin individuals (lowest 6th percentile of the population-wide BMI spectrum) in a uniquely phenotyped Estonian cohort. We discovered anaplastic lymphoma kinase (ALK) as a candidate thinness gene. In Drosophila, RNAi mediated knockdown of Alk led to decreased triglyceride levels. In mice, genetic deletion of Alk resulted in thin animals with marked resistance to diet- and leptin-mutation-induced obesity. Mechanistically, we found that ALK expression in hypothalamic neurons controls energy expenditure via sympathetic control of adipose tissue lipolysis. Our genetic and mechanistic experiments identify ALK as a thinness gene, which is involved in the resistance to weight gain.

On the Functional and Extra-Functional Properties of IMU Fusion Algorithms for Body-Worn Smart Sensors.

In this work, four sensor fusion algorithms for inertial measurement unit data to determine the orientation of a device are assessed regarding their usability in a hardware restricted environment such as body-worn sensor nodes. The assessment is done for both the functional and the extra-functional properties in the context of human operated devices. The four algorithms are implemented in three data formats: 32-bit floating-point, 32-bit fixed-point and 16-bit fixed-point and compared regarding code size, computational effort, and fusion quality. Code size and computational effort are evaluated on an ARM Cortex M0+. For the assessment of the functional properties, the sensor fusion output is compared to a camera generated reference and analyzed in an extensive statistical analysis to determine how data format, algorithm, and human interaction influence the quality of the sensor fusion. Our experiments show that using fixed-point arithmetic can significantly decrease the computational complexity while still maintaining a high fusion quality and all four algorithms are applicable for applications with human interaction.

Application of micro-computed tomography to microstructure studies of the medicinal fungus Hericium coralloides.

The potential of 3-D nondestructive imaging techniques such as micro-computed tomography (micro-CT) was evaluated to study morphological patterns of the potential medicinal fungus Hericium coralloides (Basidiomycota). Micro-CT results were correlated with histological information gained from scanning electron microscopy (SEM) and light microscopy (LM). It is demonstrated that the combination of these imaging methods results in a more distinct picture of the morphology of the edible and potentially medicinal Hericium coralloides basidiomata. In addition we have created 3-D reconstructions and visualizations based on micro-CT imagery from a randomly selected part of the upper region of a fresh H. coralloides basidioma: Analyses for the first time allowed an approximation of the evolutionary effectiveness of this bizarrely formed basidioma type in terms of the investment of tissue biomass and its reproductive output (production of basidiospores).

The adaptation of nitrifying microorganisms to inhibiting substances at meso- and psychrophilic temperature conditions.

This paper deals with adaption capacity of nitrifiers to allylthiourea (ATU) as a model inhibitor at two temperature levels. Nitrifying communities were developed at 15 (BM15) and 30 °C (BM30). The activity of the nitrifiers was determined by using short-time respiration (STR) tests, oxygen monitoring and in-situ measurements. The oxygen monitoring provided information about the temperature-dependent time delay between the dosage of NH4(+)-N or ATU and reaching its characteristic level of effect. The greatly scattered results from the STR tests for BM15 were thus explained by the time delay, which was two to three times higher than for BM30. Furthermore, combining the results of oxygen-monitoring and in-situ measurements it can be stated that an adaption to ATU at psychrophilic temperature conditions was not achieved, whereby up to 40% of nitrification was sustained for BM30 at an ATU-concentration over 7 mg/l. The nitrification by BM15 did not start until ATU was degraded to 1-2 mg/l, the typical inhibition concentration for ATU. Hence, the results indicate a population drift to adapted nitrifiers at mesophilic conditions and ATU-degrading microorganisms at psychrophilic temperature conditions, which can have a considerable influence on domestic wastewater treatment in cold climates receiving industrial effluents.

The negative adipogenesis regulator Dlk1 is transcriptionally regulated by Ifrd1 (TIS7) and translationally by its orthologue Ifrd2 (SKMc15).

Delta-like homolog 1 (Dlk1), an inhibitor of adipogenesis, controls the cell fate of adipocyte progenitors. Experimental data presented here identify two independent regulatory mechanisms, transcriptional and translational, by which Ifrd1 (TIS7) and its orthologue Ifrd2 (SKMc15) regulate Dlk1 levels. Mice deficient in both Ifrd1 and Ifrd2 (dKO) had severely reduced adipose tissue and were resistant to high-fat diet-induced obesity. Wnt signaling, a negative regulator of adipocyte differentiation, was significantly upregulated in dKO mice. Elevated levels of the Wnt/ß-catenin target protein Dlk1 inhibited the expression of adipogenesis regulators Pparg and Cebpa, and fatty acid transporter Cd36. Although both Ifrd1 and Ifrd2 contributed to this phenotype, they utilized two different mechanisms. Ifrd1 acted by controlling Wnt signaling and thereby transcriptional regulation of Dlk1. On the other hand, distinctive experimental evidence showed that Ifrd2 acts as a general translational inhibitor significantly affecting Dlk1 protein levels. Novel mechanisms of Dlk1 regulation in adipocyte differentiation involving Ifrd1 and Ifrd2 are based on experimental data presented here.

Correlation of Pulse Wave Transit Time with Pulmonary Artery Pressure in a Porcine Model of Pulmonary Hypertension.

For the non-invasive assessment of pulmonary artery pressure (PAP), surrogates like pulse wave transit time (PWTT) have been proposed. The aim of this study was to invasively validate for which kind of PAP (systolic, mean, or diastolic) PWTT is the best surrogate parameter. To assess both PWTT and PAP in six healthy pigs, two pulmonary artery Mikro-Tip™ catheters were inserted into the pulmonary vasculature at a fixed distance: one in the pulmonary artery trunk, and a second one in a distal segment of the pulmonary artery. PAP was raised using the thromboxane A2 analogue U46619 (TXA) and by hypoxic vasoconstriction. There was a negative linear correlation between PWTT and systolic PAP (r = 0.742), mean PAP (r = 0.712) and diastolic PAP (r = 0.609) under TXA. During hypoxic vasoconstriction, the correlation coefficients for systolic, mean, and diastolic PAP were consistently higher than for TXA-induced pulmonary hypertension (r = 0.809, 0.778 and 0.734, respectively). Estimation of sPAP, mPAP, and dPAP using PWTT is feasible, nevertheless slightly better correlation coefficients were detected for sPAP compared to dPAP. In this study we establish the physiological basis for future methods to obtain PAP by non-invasively measured PWTT.

Structural asymmetry between the hips and its relation to experimental fracture type.

Experimental analysis with paired femurs provides the opportunity to study within-person differences in fracture type and associated structural side differences. We hypothesized that different fracture types in the hips of a subject are associated with structural asymmetry. Bone mineral density (BMD) and structural measurements of paired cadaver femurs (32 females, 24 males) were performed before mechanical testing in a side-impact configuration. Fractures were classified (cervical or trochanteric) and differences in structural parameters, BMD, and failure load were evaluated between the left and right hips as well as between experimental fracture types. We observed larger dimensions (P < 0.05-0.01), thicker cortices (P < 0.05-0.001), and a smaller femoral shaft diameter (FSD) (P < 0.01) in the left hip than in the right. Seventeen pairs (30.4%) had trochanteric fractures on one side and cervical on the contralateral side. The asymmetric trochanteric fracture side had a higher head/neck diameter ratio (HD/ND) (P < 0.05) and a trend toward a lower neck-shaft angle (NSA) (P = 0.066) than its collateral cervical side in females and a lower HD and higher FSD (P < 0.05) in males. In females, asymmetric fracture cases displayed lower NSA (P < 0.001) and HD/ND (P < 0.01) than symmetric cervical ones. In males, asymmetric fracture cases showed larger dimensions than the other groups (P < 0.05-0.01). BMD increased from symmetric cervical to asymmetric and then to symmetric trochanteric cases (P < 0.05-0.01), with the experimental failure load showing a similar trend. In conclusion, intrasubject structural asymmetry is associated with asymmetric fracture types. Asymmetry should be considered when using the opposite side as control in clinical studies.

Assessment of the individual fracture risk of the proximal femur by using statistical appearance models.

PURPOSE: Standard diagnostic techniques to quantify bone mineral density (BMD) include dual-energy x-ray absorptiometry (DXA) and quantitative computed tomography. However, BMD alone is not sufficient to predict the fracture risk for an individual patient. Therefore, the development of tools, which can assess the bone quality in order to predict individual biomechanics of a bone, would mean a significant improvement for the prevention of fragility fractures. In this study, a new approach to predict the fracture risk of proximal femora using a statistical appearance model will be presented. METHODS: 100 CT data sets of human femur cadaver specimens are used to create statistical appearance models for the prediction of the individual fracture load (FL). Calculating these models offers the possibility to use information about the inner structure of the proximal femur, as well as geometric properties of the femoral bone for FL prediction. By applying principal component analysis, statistical models have been calculated in different regions of interest. For each of these models, the individual model parameters for each single data set were calculated and used as predictor variables in a multilinear regression model. By this means, the best working region of interest for the prediction of FL was identified. The accuracy of the FL prediction was evaluated by using a leave-one-out cross validation scheme. Performance of DXA in predicting FL was used as a standard of comparison. RESULTS: The results of the evaluative tests demonstrate that significantly better results for FL prediction can be achieved by using the proposed model-based approach (R = 0.91) than using DXA-BMD (R = 0.81) for the prediction of fracture load. CONCLUSIONS: The results of the evaluation show that the presented model-based approach is very promising and also comparable to studies that partly used higher image resolutions for bone quality assessment and fracture risk prediction.

Operational experience with a full-scale anaerobic baffled reactor treating municipal wastewater.

The aim of the study was to investigate the influence of moderate temperatures on the efficiency of a full-scale anaerobic treatment system consisting of a primary sedimentation unit (PST) and an anaerobic baffled reactor (ABR, approx. 10 m3 ). Therefore, two trials with different test setups in series were carried out (1st trial: continuous load; 2nd trial: diurnal variation load). The plant was fed with municipal wastewater and operated at temperatures between 8 and 24°C. The mean efficiency of the ABR was low, compared to the one of the PST. At 10°C, only 10% of the COD was removed. The COD (chemical oxygen demand) removal efficiency of the plant (PST + ABR) averaged 50%. At low temperatures, volatile fatty acids began to accumulate. In both trials, the contents of total suspended solids in the sludge bed differed distinctly and influenced the effort for desludging. PRACTITIONER POINTS: The operation of ABR in combined collection systems depends on the efficiency of the pretreatment unit. At cold temperatures, an ABR has no advantages compared to conventional pretreatment processes. For use under moderate conditions, the design must be adjusted.

Proximal femur segmentation in conventional pelvic x ray.

A solid and accurate proximal femur segmentation technique using the popular active shape model (ASM) is proposed. For generating an optimal shape prior, the minimum description length, based on 200 supervised manual segmented proximal femur shapes, is used. The segmentation is based on a coarse to fine scaling technique including a profile scale space method. The segmentation results are compared using an optimal defined initial pose and a pose based on a registration technique. Using ideal template initialization, 95% of the shapes have been recovered exactly (average point-to-point error approximately 13 pixels, average point-to-boundary error approximately 7 pixels). Using a template-based initialization based on a registration technique, a successful segmentation rate of approximately 89% is achieved, with an average point-to-point error approximately 12 pixels, and an average point-to-boundary error approximately 8 pixels. With an adequate template initialization and an improved ASM, this method seems to provide an accurate tool for segmentation of the proximal femur shapes on conventional hip overview x-ray images.

Knowledge-based femur detection in conventional radiographs of the pelvis.

In this paper we present a knowledge-based femur detection algorithm. The algorithm uses femur corpus constraints, Canny edge detection and Hough lines. For optimal femur template placement in the local area we use cross-correlation. The segmentation itself is done with an optimized active shape modeling technique. Using the knowledge-based technique we have located 95% of the femur shapes of N=117 X-rays. From those 83% of the target femur shapes have been segmented successfully (point-to-point error: approximately 14 pixels, point-to-boundary error = approximately 9 pixels).

Sex differences of human trabecular bone microstructure in aging are site-dependent.

UNLABELLED: In this study, we characterize bone microstructure, specifically sex differences, at multiple skeletal sites in 165 subjects >52 yr of age, using microCT technology in vitro. Significant sex differences are observed at the distal radius, femoral neck, and femoral trochanter, but not at the iliac crest, calcaneus, and lumbar vertebral body. Correlations in BV/TV between sites ranged from r = 0.13 to 0.56. INTRODUCTION: The goals of this study were (1) to assess potential sex differences of bone microstructure and their difference between skeletal sites and (2) to explore the relationship of trabecular microstructural properties between relevant skeletal sites. MATERIALS AND METHODS: Trabecular bone microstructural properties were measured in vitro in 165 subjects 52-99 yr of age using microCT. Defined volumes of interest (cylinders with 6 mm diameter and 6 mm length) were scanned at a resolution of 26 microm (isotropic) in six different anatomical sites: distal radius, femoral neck and trochanter, iliac crest, calcaneus, and second lumbar vertebral body. RESULTS: At the radius and femoral neck, trabecular bone displayed a more plate-like structure, thicker trabeculae, smaller separation/higher trabecular number, higher connectivity, and a higher degree of anisotropy in men than in women (p < 0.05). At the trochanter, men displayed more plate-like structure and thicker trabeculae (p < 0.05), but no differences in trabecular separation or other parameters compared with the women. At the calcaneus, iliac crest, and second lumbar vertebra none of the bone parameters displayed significant differences between sexes. The BV/TV at one site explained a range of only 2-32% of the variability at other sites. CONCLUSIONS: These results suggest that trabecular bone microstructural properties are remarkably heterogeneous throughout the skeleton. Significant differences between men and women are observed at some, but not at all, sites. The magnitude of sex differences in trabecular microstructure coincides with that of fracture incidence observed for some of the sites in epidemiological studies.

Association of geometric factors and failure load level with the distribution of cervical vs. trochanteric hip fractures.

UNLABELLED: We experimentally studied the distribution of hip fracture types at different structural mechanical strength. Femoral neck fractures were dominant at the lowest structural strength levels, whereas trochanteric fractures were more common at high failure loads. The best predictor of fracture type across all failure loads and in both sexes was the neck-shaft angle. INTRODUCTION: Bone geometry has been shown to be a potential risk factor for osteoporotic fractures. Risk factors have been shown to differ between cervical and trochanteric hip fractures. However, the determinants of cervical and trochanteric fractures at different levels of structural mechanical strength are currently unknown. In addition, it is not known if the distribution of fracture types differs between sexes. The aim of this experimental study on excised femora was to investigate whether there exist differences in the distribution of cervical and trochanteric fractures between different structural mechanical strength levels and different sexes and to identify the geometric determinants that predict a fracture type. MATERIALS AND METHODS: The sample was comprised of 140 cadavers (77 females: mean age, 81.7 years; 63 males: mean age, 79.1 years) from whom the left femora were excised for analysis. The bones were radiographed, and geometrical parameters were determined from the digitized X-rays. The femora were mechanically tested in a side impact configuration, simulating a sideways fall. After the mechanical test, the fracture patterns were classified into cervical and trochanteric. RESULTS: The overall proportion of cervical fractures was higher in females (74%) than in males (49%) (p = 0.002). The fracture type distribution differed significantly across load quartiles in females (p = 0.025), but not in males (p = 0.205). At the lowest load quartiles, 94.7% of fractures in female and 62.5% in males were femoral neck fractures. At the highest quartiles, in contrast, only 52.6% of fractures in females and 33.3% in males were cervical fractures. Among geometric variables, the neck-shaft angle was the best predictor of fracture type, with higher values in subjects with cervical fractures. This finding was made in females (p < 0.001) and males (p = 0.02) and was consistent across all failure load quartiles. CONCLUSIONS: Femoral neck fractures predominate at the lowest structural mechanical strength levels, whereas trochanteric fractures are more common at high failure loads. Females are more susceptible to femoral neck fractures than males. The best predictor of fracture type across all structural strength levels and both sexes was the neck-shaft angle.

Comparison of different radiography systems in an experimental study for detection of forearm fractures and evaluation of the Müller-AO and Frykman classification for distal radius fractures.

OBJECTIVES: We sought to compare the diagnostic performance of screen-film radiography, storage-phosphor radiography, and a flat-panel detector system in detecting forearm fractures and to classify distal radius fractures according to the Müller-AO and Frykman classifications compared with the true extent, depicted by anatomic preparation. MATERIALS AND METHODS: A total of 71 cadaver arms were fractured in a material testing machine creating different fractures of the radius and ulna as well as of the carpal bones. Radiographs of the complete forearm were evaluated by 3 radiologists, and anatomic preparation was used as standard of reference in a receiver operating curve analysis. RESULTS: The highest diagnostic performance was obtained for the detection of distal radius fractures with area under the receiver operating curve (AUC) values of 0.959 for screen-film radiography, 0.966 for storage-phosphor radiography, and 0.971 for the flat-panel detector system (P > 0.05). Exact classification was slightly better for the Frykman (kappa values of 0.457-0.478) compared with the Müller-AO classification (kappa values of 0.404-0.447), but agreement can be considered as moderate for both classifications. CONCLUSIONS: The 3 imaging systems showed a comparable diagnostic performance in detecting forearm fractures. A high diagnostic performance was demonstrated for distal radius fractures and conventional radiography can be routinely performed for fracture detection. However, compared with anatomic preparation, depiction of the true extent of distal radius fractures was limited and the severity of distal radius fractures tends to be underestimated.

Improved performance of hip DXA using a novel region of interest in the upper part of the femoral neck: in vitro study using bone strength as a standard of reference.

We tested the hypothesis that bone mineral density (BMD) and bone mineral content (BMC) in proximal human femur specimens in the upper neck region of interest (ROI) and femoral neck axis length (FNAL) provide a significantly better prediction of femoral bone strength than standard ROIs in vitro. BMD and BMC were measured in 110 proximal femur specimens using a standard dual-energy X-ray absorptiometry (DXA) scanner. The analysis included a new ROI in the upper neck as well as the standard ROIs. FNAL was obtained from the scan images. The specimens' failure-load was measured in a mechanical loading device, simulating a fall on the greater trochanter. For the standard ROIs, correlations between failure-load and BMD ranged from R2 = 0.64 (shaft ROI) to R2 = 0.70, p < 0.001 (femoral neck). Prediction of strength by BMD did not significantly differ from those of BMC (R2 ranging from 0.65 to 0.75, p < 0.001). In the upper neck ROI, for both BMD and BMC correlations with failure-load were higher (R2 = 0.76 and 0.81, respectively; p < 0.001). A lower, yet still significant, correlation was found between FNAL and bone strength (R2 = 0.23, p < 0.001). Normalization of failure-load with respect to FNAL did not significantly increase the correlations with densitometric measures. This study provides in vitro evidence indicating that among the ROIs of the proximal femur the newly defined upper neck ROI provides the best prediction of bone strength. Only a weak association was observed between failure load and FNAL.

Reproducibility and side differences of mechanical tests for determining the structural strength of the proximal femur.

UNLABELLED: In this experimental study, we evaluated the reproducibility error of mechanical strength tests of the proximal femur when simulating a fall on the trochanter. Based on side differences in femoral failure loads in 55 pairs of femora, we estimated the upper limit of the precision error to be 15% for the side impact test, whereas the intersubject variability was >40%. INTRODUCTION: Mechanical tests are commonly used as the gold standard for determining one of the main functions of bones, that is, to provide mechanical strength. However, it is unknown what magnitude of error is associated with these tests. Here we investigate the precision error and side difference of a side impact test of the proximal femur. MATERIALS AND METHODS: BMC was measured using DXA in 54 pairs of femora from donors 79.0 +/- 10.6 years of age. Bones were tested to failure, simulating a fall on the greater trochanter. RESULTS: Failure loads were 3951 +/- 1659N (CV% = 42%) on the right and 3900 +/- 1652N (CV% = 42%) on the left (no significant side difference). The average random difference of femoral BMC was 7 +/- 7% and that of femoral failure loads was 17 +/- 12%. The correlation between BMC and failure load was 79% (r2), but the association between side differences in failure load with those in BMC was only 4%. When confining the analysis to pairs with less than 5% differences in BMC (n = 31), side differences in failure loads were 15 +/- 13%. When correcting failure loads for side differences of BMC, the difference was 16 +/- 15% CONCLUSIONS: These results suggest that the upper limit of the precision error for femoral strength tests is approximately 15% in a side impact configuration. Given the large intersubject variability of failure loads, this test provides an efficient tool for determining the structural strength of the proximal femur in a fall.

Can novel clinical densitometric techniques replace or improve DXA in predicting bone strength in osteoporosis at the hip and other skeletal sites?

New peripheral techniques are now available for the diagnosis of osteoporosis, but their value in the clinical management of the disease remains controversial. This study tests the hypothesis that peripheral quantitative computed tomography (pQCT) at the distal radius and/or quantitative ultrasound (QUS) at the calcaneus can serve as replacement or improvement of current methodology (QCT and DXA) for predicting bone strength at the hip and other sites. In 126 human cadavers (age, 80.2 +/- 10.4 years), DXA of the femur, spine, and radius and pQCT of the radius were acquired with intact soft tissues. QCT (spine) and QUS (calcaneus) were performed ex situ in degassed specimens. Femoral failure loads were assessed in side impact and vertical loading. Failure loads of the thoracolumbar spine were determined at three levels in compression and those of the radius by simulating a fall. Site-specific DXA explained approximately 55% of the variability in femoral strength, whereas pQCT and QUS displayed a lower association (15-40%). QUS did not provide additional information on mechanical strength of the femur, spine, or radius. All techniques displayed similar capability in predicting a combined index of failure strength at these three sites, with only QUS exhibiting significantly lower associations than other methods. These experimental results suggest that clinical assessment of femoral fracture risk should preferably rely on femoral DXA, whereas DXA, QCT, and pQCT display similar capability of predicting a combined index of mechanical strength at the hip, spine, and radius.

Radius bone strength in bending, compression, and falling and its correlation with clinical densitometry at multiple sites.

This study comprehensively analyzes the ability of site-specific and nonsite-specific clinical densitometric techniques for predicting mechanical strength of the distal radius in different loading configurations. DXA of the distal forearm, spine, femur, and total body and peripheral quantitative computed tomography (pQCT) measurements of the distal radius (4, 20, and 33%) were obtained in situ (with soft tissues) in 129 cadavers, aged 80.16 +/- 9.8 years. Spinal QCT and calcaneal quantitative ultrasound (QUS) were performed ex situ in degassed specimens. The left radius was tested in three-point bending and axial compression, and the right forearm was tested in a fall configuration, respectively. Correlation coefficients with radius DXA were r = 0.89, 0.84, and 0.70 for failure in three-point bending, axial compression, and the fall simulation, respectively. The correlation with pQCT (r = 0.75 for multiple regression models with the fall) was not significantly higher than for DXA. Nonsite-specific measurements and calcaneal QUS displayed significantly (p < 0.01) lower correlation coefficients, and QUS did only contribute to the prediction of axial failure stress but not of failure load. We conclude that a combination of pQCT parameters involves only marginal improvement in predicting mechanical strength of the distal radius, nonsite-specific measurements are less accurate for this purpose, and QUS adds only little independent information to site-specific bone mass. Therefore, the noninvasive diagnosis of loss of strength at the distal radius should rely on site-specific measurements with DXA or pQCT and may be the earliest chance to detect individuals at risk of osteoporotic fracture.

Bone strength at clinically relevant sites displays substantial heterogeneity and is best predicted from site-specific bone densitometry.

In this study we test the hypotheses that mechanical bone strength in elderly individuals displays substantial heterogeneity among clinically relevant skeletal sites, that ex situ dual-energy X-ray absorptiometry (DXA) provides better estimates of bone strength than in situ DXA, but that a site-specific approach of bone densitometry is nevertheless superior for optimal prediction of bone failure under in situ conditions. DXA measurements were obtained of the lumbar spine, the left femur, the left radius, and the total body in 110 human cadavers (age, 80.6 +/- 10.5 years; 72 female, 38 male), including the skin and soft tissues. The bones were then excised, spinal and femoral DXA being repeated ex situ. Mechanical failure tests were performed on thoracic vertebra 10 and lumbar vertebra 3 (compressive loading of a functional unit), the left and right femur (side impact and vertical loading configuration), and the left and right distal radius (fall configuration, axial compression, and 3-point-bending). The failure loads displayed only very moderate correlation among sites (r = 0.39 to 0.63). Ex situ DXA displayed slightly higher correlations with failure loads compared with those of in situ DXA, but the differences were not significant and relatively small. Under in situ conditions, DXA predicted 50-60% of the variability in bone failure loads at identical (or closely adjacent) sites, but only around 20-35% at distant sites, advocating a site-specific approach of densitometry. These data suggest that mechanical competence in the elderly is governed by strong regional variation, and that its loss in osteoporosis may not represent a strictly systemic process.

Determinants and heterogeneity of mechanical competence throughout the thoracolumbar spine of elderly women and men.

Vertebral fractures represent the hallmark of osteoporosis. Here, we test the hypotheses that (sub)cortical bone strength and density predict failure better than trabecular core strength and density, and that elderly women display lower failure stress of thoracic vertebrae than men. We examined the vertebral bodies T3 to L5 in 39 spines from elderly donors (23 women; 16 men; age 79 +/- 11 years). Peripheral quantitative computed tomography was used to measure total, trabecular, and (sub)cortical bone density. Mechanical tests were performed in functional spinal units, planoparallel sections of vertebrae, trabecular cores, and (sub)cortical ring specimens. The failure stress decreased with descending vertebral level. Failure stress was highest for the (sub)cortical rings and planoparallel sections and lowest for the trabecular core. The failure stress did not differ significantly between men and women. Mechanical strength of the functional unit was more strongly correlated with the strength of the (sub)cortical ring (r = 0.78) than with that of the trabecular core (r = 0.62). However, total density was more highly correlated with mechanical strength of the same and remote vertebrae (r = 0.63) than trabecular (r = 0.50) or (sub)cortical density (r = 0.36), respectively. The results show that vertebral strength is similar in elderly women and men. Strength of (sub)cortical bone provides significantly better prediction of strength of functional spinal units than that of the trabecular core. However, total density predicts functional segment failure stress with higher accuracy than (sub)cortical or trabecular density and is thus recommended for predicting fracture strength clinically.