Construction of the Femoral Neck During Growth Determines its Strength in Old Age

Study of the design of the FN in vivo in 697 women and in vitro in 200 cross-sections of different sizes and shapes along each of 13 FN specimens revealed that strength in old age was largely achieved during growth by differences in the distribution rather than the amount of bone material in a given FN cross-section from individual to individual. Introduction: We studied the design of the femoral neck (FN) to gain insight into the structural basis of FN strength in adulthood and FN fragility in old age. Materials and Methods: Studies in vivo were performed using densitometry in 697 women and in vitro using high-resolution μCT and direct measurements in 13 pairs of postmortem specimens. Results: The contradictory needs of strength for loading yet lightness for mobility were met by varying FN size, shape, spatial distribution, and proportions of its trabecular and cortical bone in a cross-section, not its mass. Wider and narrower FNs were constructed with similar amounts of bone material. Wider FNs were relatively lighter: a 1 SD higher FN volume had a 0.67 (95% CI, 0.61-0.72) SD lower volumetric BMD (vBMD). A 1 SD increment in height was achieved by increasing FN volume by 0.32 (95% CI, 0.25-0.39) SD with only 0.15 (95% CI, 0.08-0.22) SD more bone, so taller individuals had a relatively lighter FN (vBMD was 0.13 [95% CI, 0.05-0.20 SD] SD lower). Greater periosteal apposition constructing a wider FN was offset by even greater endocortical resorption so that the same net amount of bone was distributed as a thinner cortex further from the neutral axis, increasing resistance to bending and lowering vBMD. This was recapitulated at each point along the FN; varying absolute and relative degrees of periosteal apposition and endocortical resorption focally used the same amount of material to fashion an elliptical FN of mainly cortical bone near the femoral shaft to offset bending but a more circular FN of proportionally more trabecular and less cortical bone to accommodate compressive loads adjacent to the pelvis. This structural heterogeneity was largely achieved by adaptive modeling and remodeling during growth-most of the variance in FN volume, BMC, and vBMD was growth related. Conclusions: Altering structural design while minimizing mass achieves FN strength and lightness. Bone fragility may be the result of failure to adapt bone's architecture to loading, not just low bone mass

Method and system for image analysis

A computer-implemented method for analyzing a sample comprising a first material and a second material of generally different densities and having a junction therebetween. The method comprises: defining automatically a plurality of regions of interest within an image of the sample, each of said regions of interest having a width of one or more voxels or pixels; determining respective density, intensity or attenuation profiles within the regions of interest; determining a location of said junction including defining a first reference point within one of said first and second materials and employing the first reference point as current reference point, and (i) determining a closest point to said current reference point that is on said respective profile and in the other of said first and second materials to that of the current reference point; (ii) locating a greatest difference in values of the respective profile between an adjacent peak and trough in a segment of the respective profile between said current reference point and said closest point; and (iii) locating a point of inflexion in said segment

Assessment of the effects of sulfate and nitrate on the temporal evolution of Klebsiella oxytoca and Staphylococcus aureus abundance under shaking conditions, in aquatic microcosm

Most chemicals in natural aquatic media can be assimilated by bacteria. The impact of various environmental conditions on this microbial process is not always clear. This study aimed at investigating changes in the abundance of Klebsiella oxytoca and Staphylococcus aureus under different shaking conditions, in aquatic microcosms containing nitrate and sulfate. Sodium chloride solution (8.5 g NaCl•L-1), and nitrate and sulfate solutions (0.005, 0.05, 0.5 and 5 g•L-1) containing bacteria were supplemented with tryptic peptone at a final concentration of 10 g•L-1. The solutions were incubated under shaking conditions (300, 350 and 400 rev•min-1). Bacteriological analyses were performed hourly over a 6-h period. During the first 3 h of incubation, results showed that the highest values of the apparent cell growth rates (CAGRs) with K2SO4 in pure cultures, at a shaking speed 400 rev•min-1, were 0.656 h-1 for S. aureus, and 0.364 h-1 for K. oxytoca. In mixed culture, the CAGR was 0.235 h-1 for S. aureus, and 0.388 h-1 for K. oxytoca, both recorded at 300 rev•min-1. With KNO3 in pure culture solutions, the CAGR was 0.353 h-1 for S. aureus at 300 rev•min-1, and 0.367 h-1 for K. oxytoca at 350 rev•min-1. In mixed culture it was 0.454 h-1 for S. aureus and 0.393 h-1 for K. oxytoca, both recorded at 350 rev•min-1. The highest value of the apparent cell inhibition rate (CAIR) for S. aureus was 0.520 h-1 in K2SO4 (5 g•L-1, 400 rev•min-1), and 0.115 h-1 in KNO3 (5 g•L-1, 300 rev•min-1). For K. oxytoca, it was 0.07 h-1 in K2SO4 in pure culture (0.05 g•L-1, 300 rev•min-1), and 0.044 h-1 in mixed culture (0.05 g•L-1, 350 rev•min-1). In KNO3 it was 0.239 h-1 in mixed culture (5 g•L-1, 300 rev•min-1). The growth and inhibition potentials of different microbial species were impacted by the chemical concentrations and the movement speeds.L’impact de diverses conditions environnementales sur l’assimilation bactérienne dans l’eau, des composés chimiques est peu connu. La présente étude a visé l’évaluation de la dynamique d’abondance de Klebsiella oxytoca et Staphylococcus aureus sous diverses conditions, en milieu aquatique microcosme contenant du sulfate ou nitrate. Des solutions du NaCl (8,5 g•L-1), sulfate et nitrate (0,005, 0,05, 0,5 et 5 g•L-1) contenant des cellules ont été enrichies à la peptone trypsique (concentration finale 10 g•L-1), puis incubées sous conditions dynamiques (300, 350 et 400 tr•min-1). Les analyses bactériologiques ont été effectuées pendant 6 h. Il ressort qu’au cours des trois premières heures d'incubation, le taux de croissance cellulaire apparent (TCCA) le plus élevé en culture pure, contenant du K2SO4, est de 0,656 h-1 pour S. aureus, et 0,364 h-1 pour K. oxytoca, enregistrés à 400 tr•min-1. En culture mixte, il est de 0,235 h-1 pour S. aureus, et 0,388 h-1 pour K. oxytoca, enregistrés à 300 tr•min-1. Avec du KNO3, en culture pure, le TCCA est de 0,353 h-1 pour S. aureus à 300 tr•min-1, et 0,367 h-1 à 350 tr•min-1 pour K. oxytoka. En culture mixte, il est de 0,454 h-1 pour S. aureus et 0,393 h-1 pour K. oxytoca, enregistrés à 350 tr•min-1. Le taux d’inhibition cellulaire apparent (TICA) le plus élevé de S. aureus est de 0,520 h-1 en présence du K2SO4 (5 g•L-1, 400 tr•min-1), et 0,115 h-1 en présence de KNO3 (5 g•L-1, 300 tr•min-1). Pour K. oxytoca, il est de 0,07 h-1 avec du K2SO4 en culture pure (0,05 g•L-1, 300 tr•min-1), et 0,044 h-1 en culture mixte (0,05 g•L-1, 350 tr•min-1). Avec du KNO3, il est de 0,239 h-1 en culture mixte (5 g•L-1, 300 tr•min-1). La croissance et l’inhibition des microorganismes sont affectées par les concentrations en sels et la vitesse de mouvements du milieu

Adding marrow adiposity and cortical porosity to femoral neck areal bone mineral density improves the discrimination of women with nonvertebral fractures from controls

Advancing age is accompanied by a reduction in bone formation and remodeling imbalance, which produces microstructural deterioration. This may be partly caused by a diversion of mesenchymal cells towards adipocytes rather than osteoblast lineage cells. We hypothesized that microstructural deterioration would be associated with an increased marrow adiposity, and each of these traits would be independently associated with nonvertebral fractures and improve discrimination of women with fractures from controls over that achieved by femoral neck (FN) areal bone mineral density (aBMD) alone. The marrow adiposity and bone microstructure were quantified from HR‐pQCT images of the distal tibia and distal radius in 77 women aged 40 to 70 years with a recent nonvertebral fracture and 226 controls in Melbourne, Australia. Marrow fat measurement from HR‐pQCT images was validated using direct histologic measurement as the gold standard, at the distal radius of 15 sheep, with an agreement (R2 = 0.86, p < 0.0001). Each SD higher distal tibia marrow adiposity was associated with 0.33 SD higher cortical porosity, and 0.60 SD fewer, 0.24 SD thinner, and 0.72 SD more‐separated trabeculae (all p < 0.05). Adjusted for age and FN aBMD, odds ratios (ORs) (95% CI) for fracture per SD higher marrow adiposity and cortical porosity were OR, 3.39 (95% CI, 2.14 to 5.38) and OR, 1.79 (95% CI, 1.14 to 2.80), respectively. Discrimination of women with fracture from controls improved when cortical porosity was added to FN aBMD and age (area under the receiver‐operating characteristic curve [AUC] 0.778 versus 0.751, p = 0.006) or marrow adiposity was added to FN aBMD and age (AUC 0.825 versus 0.751, p = 0.002). The model including FN aBMD, age, cortical porosity, trabecular thickness, and marrow adiposity had an AUC = 0.888. Results were similar for the distal radius. Whether marrow adiposity and cortical porosity indices improve the identification of women at risk for fractures requires validation in prospective studies. © 2019 American Society for Bone and Mineral Research

Are the Relationships of Lean Mass and Fat Mass With Bone Microarchitecture Causal or Due to Familial Confounders? A Novel Study of Adult Female Twin Pairs

It is not known whether the relationships of lean mass (LM) and fat mass (FM) with bone microarchitecture and geometry are causal and/or are because of confounders, including familial confounders arising from genetic and environment effects shared by relatives. We tested the hypotheses that: (i) LM is associated with cortical bone traits, (ii) FM is associated with trabecular bone traits, and (iii) these relationships of LM and FM with bone microarchitecture and geometry have a causal component. Total body composition was quantified for 98 monozygotic (MZ) and 54 dizygotic (DZ) white female twin pairs aged 31 to 77 years. Microarchitecture at the distal tibia and distal radius was quantified using HRpQCT and StrAx software. We applied the Inference about Causation through Examination of FAmiliaL CONfounding (ICE FALCON) method. Within‐individuals, distal tibia total bone area, cortical area, cortical thickness, and trabecular number were positively associated with LM (standardized regression coefficient (β) = 0.13 to 0.43; all p < 0.05); porosity of the inner transitional zone (ITZ) was negatively associated with LM (β = −0.22; p < 0.01). Trabecular number was positively associated with FM (β = 0.40; p < 0.001), and trabecular thickness was negatively associated with FM (β = −0.27; p < 0.001). For porosity of ITZ and trabecular number, the cross‐pair cross‐trait association with LM was significant before and after adjustment for the within‐individual association with LM (all ps < 0.05). For trabecular number, the cross‐pair cross‐trait association with FM was significant before and after adjustment for the within‐individual association with FM (p < 0.01). There were no significant changes in these cross‐pair cross‐trait associations after adjustment for the within‐individual association (p = 0.06 to 0.99). Similar results were found for distal radius measures. We conclude that there was no evidence that the relationships of LM and FM with bone microarchitecture and geometry are causal; they must in part due to by familial confounders affecting both bone architecture and body composition. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research

Mechanical loading of the femoral neck in human locomotion

Advancing age and reduced loading are associated with a reduction in bone formation. Conversely, loading increases periosteal apposition and may reduce remodeling imbalance and slow age‐related bone loss, an important outcome for the proximal femur, which is a common site of fracture. The ability to take advantage of bone's adaptive response to increase bone strength has been hampered by a lack of knowledge of which exercises and specific leg muscles load the superior femoral neck: a common region of microcrack initiation and progression following a sideways fall. We used an in vivo method of quantifying focal strains within the femoral neck in postmenopausal women during walking, stair ambulation, and jumping. Relative to walking, stair ambulation and jumping induced significantly higher strains in the anterior and superior aspects of the femoral neck, common regions of microcrack initiation and progression following a fall. The gluteus maximus, a hip extensor muscle, induced strains in the femoral neck during stair ambulation and jumping, in contrast to walking which induced strains via the iliopsoas, a hip flexor. The ground reaction force was closely associated with the level of strain during each task, providing a surrogate indicator of the potential for a given exercise to load the femoral neck. The gluteal muscles combined with an increased ground reaction force relative to walking induce high focal strains within the anterosuperior region of the femoral neck and therefore provide a target for exercise regimens designed to slow bone loss and maintain or improve microstructural strength. Model files used for calculating femoral neck strains are available at uitbl.mechse.illinois.edu/download

Mechanical loading of the femoral neck in human locomotion

Advancing age and reduced loading are associated with a reduction in bone formation. Conversely, loading increases periosteal apposition and may reduce remodeling imbalance and slow age‐related bone loss, an important outcome for the proximal femur, which is a common site of fracture. The ability to take advantage of bone's adaptive response to increase bone strength has been hampered by a lack of knowledge of which exercises and specific leg muscles load the superior femoral neck: a common region of microcrack initiation and progression following a sideways fall. We used an in vivo method of quantifying focal strains within the femoral neck in postmenopausal women during walking, stair ambulation, and jumping. Relative to walking, stair ambulation and jumping induced significantly higher strains in the anterior and superior aspects of the femoral neck, common regions of microcrack initiation and progression following a fall. The gluteus maximus, a hip extensor muscle, induced strains in the femoral neck during stair ambulation and jumping, in contrast to walking which induced strains via the iliopsoas, a hip flexor. The ground reaction force was closely associated with the level of strain during each task, providing a surrogate indicator of the potential for a given exercise to load the femoral neck. The gluteal muscles combined with an increased ground reaction force relative to walking induce high focal strains within the anterosuperior region of the femoral neck and therefore provide a target for exercise regimens designed to slow bone loss and maintain or improve microstructural strength. Model files used for calculating femoral neck strains are available at uitbl.mechse.illinois.edu/download

Regional heterogeneity in the configuration of the intracortical canals of the femoral shaft

Three-dimensional (3D) characterization of cortical porosity, most of which is under 100 µm in diameter, is usually confined to measurements made in 3–4 mm diameter cylinders of bone. We used micro-computed tomography (micro-CT) scanning of entire transaxial cross sections of human proximal femoral shafts (30–35 mm diameter) to quantify regional variation in porosity within the same scan. Complete, up to 10-mm-thick, transaxial slices of femoral upper shafts from 8 female cadavers were studied (n = 3 aged 29–37 years, n = 5 aged 72–90 years). Scanning was performed using high-resolution micro-CT (8.65 µm/voxel). Micro-CT volumes (10 × 10 × 5 mm) were selected via software in the anterior, medial and lateral regions. Images were segmented with voids appearing as 3D-interconnected canals. The percent void-to-tissue volume (Vo.V/TV) and the corresponding void surface area/TV were 86–309 % higher in older than younger subjects in anterior (p = 0.034), medial (p = 0.077), and lateral aspects (p = 0.034). Although not significant, void separation was reciprocally lower by 19–39 %, and void diameter was 65 % larger in older than younger subjects; void number tended to be 24–25 % higher medially and laterally but not anteriorly. For all specimens combined, medially there was higher Vo.V/TV and void surface area/TV than anteriorly (+48 %, p = 0.018; +33 %, p = 0.018) and laterally (+56 %, p = 0.062; +36 %, p = 0.043). There is regional heterogeneity in the 3D microarchitecture of the intracortical canals of the femoral shaft. The higher void volume in advanced age appears to be due to larger, rather than more, pores. However, creation of new canals from existing canals may contribute, depending on the location. High-resolution micro-computed tomography scanning of entire bone segments enables quantification of the 3D microanatomy of the intracortical void network at multiple locations