Loss of the glycosyltransferase Galnt11 affects vitamin D homeostasis and bone composition.

O-glycosylation is a conserved posttranslational modification that impacts many aspects of organismal viability and function. Recent studies examining the glycosyltransferase Galnt11 demonstrated that it glycosylates the endocytic receptor megalin in the kidneys, enabling proper binding and reabsorption of ligands, including vitamin D-binding protein (DBP). Galnt11-deficient mice were unable to properly reabsorb DBP from the urine. Vitamin D plays an essential role in mineral homeostasis and its deficiency is associated with bone diseases such as rickets, osteomalacia, and osteoporosis. We therefore set out to examine the effects of the loss of Galnt11 on vitamin D homeostasis and bone composition. We found significantly decreased levels of serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, consistent with decreased reabsorption of DBP. This was accompanied by a significant reduction in blood calcium levels and a physiologic increase in parathyroid hormone (PTH) in Galnt11-deficient mice. Bones in Galnt11-deficient mice were smaller and displayed a decrease in cortical bone accompanied by an increase in trabecular bone and an increase in a marker of bone formation, consistent with PTH-mediated effects on bone. These results support a unified model for the role of Galnt11 in bone and mineral homeostasis, wherein loss of Galnt11 leads to decreased reabsorption of DBP by megalin, resulting in a cascade of disrupted mineral and bone homeostasis including decreased circulating vitamin D and calcium levels, a physiological increase in PTH, an overall loss of cortical bone, and an increase in trabecular bone. Our study elucidates how defects in O-glycosylation can influence vitamin D and mineral homeostasis and the integrity of the skeletal system.

Frequency shifts of free water signals from compact bone: Simulations and measurements using a UTE-FID sequence.

PURPOSE: Free water in cortical bone is either contained in nearly cylindrical structures (mainly Haversian canals oriented parallel to the bone axis) or in more spherically shaped pores (lacunae). Those cavities have been reported to crucially influence bone quality and mechanical stability. Susceptibility differences between bone and water can lead to water frequency shifts dependent on the geometric characteristics. The purpose of this study is to calculate and measure the frequency distribution of the water signal in MRI in dependence of the microscopic bone geometry. METHODS: Finite element modeling and analytical approaches were performed to characterize the free water components of bone. The previously introduced UTE-FID technique providing spatially resolved FID-spectra was used to measure the frequency distribution pixel-wise for different orientations of the bone axis. RESULTS: The frequency difference between free water in spherical pores and in canals parallel to B0 amounts up to approximately 100 Hz at 3T. Simulated resonance frequencies showed good agreement with the findings in UTE-FID spectra. The intensity ratio of the two signal components (parallel canals and spherical pores) was found to vary between periosteal and endosteal regions. CONCLUSION: Spatially resolved UTE-FID examinations allow the determination of the frequency distribution of signals from free water in cortical bone. This frequency distribution indicates the composition of the signal contributions from nearly spherical cavities and cylindrical canals which allows for further characterization of bone structure and status.

Population trends in human rib cross-sectional shapes.

Rib fractures remain the most frequent thoracic injury in motor vehicle crashes. Computational human body models (HBMs) can be used to simulate these injuries and design mitigation strategies, but they require adequately detailed geometry to replicate such fractures. Due to a lack of rib cross-sectional shape data availability, most commercial HBMs use highly simplified rib sections extracted from a single individual during original HBM development. This study provides human rib shape data collected from chest CT scans of 240 females and males across the full adult age range. A cortical bone mapping algorithm extracted cross-sectional geometry from scans in terms of local periosteal position with respect to the central rib axis and local cortex thickness. Principal component analysis was used to reduce the dimensionality of these cross-sectional shape data. Linear regression found significant associations between principal component scores and subject demographics (sex, age, height, and weight) at all rib levels, and predicted scores were used to explore the expected rib cross-sectional shapes across a wide range of subject demographics. The resulting detailed rib cross-sectional shapes were quantified in terms of their total cross-sectional area and their cortical bone cross-sectional area. Average-sized female ribs were smaller in total cross-sectional area than average-sized male ribs by between 20% and 36% across the rib cage, with the greatest differences seen in the central portions of rib 6. This trend persisted although to smaller differences of 14%-29% when comparing females and males of equal intermediate weight and stature. Cortical bone cross-sectional areas were up to 18% smaller in females than males of equivalent height and weight but also reached parity in certain regions of the rib cage. Increased age from 25 to 80 years was associated with reductions in cortical bone cross-sectional area (up to 37% in females and 26% in males at mid-rib levels). Total cross-sectional area was also seen to reduce with age in females but to a lesser degree (of up to 17% in mid-rib regions). Similar regions saw marginal increases in total cross-sectional area for male ribs, indicating age affects rib cortex thickness moreso than overall rib cross-sectional size. Increased subject height was associated with increased rib total and cortical bone cross-sectional areas by approximately 25% and 15% increases, respectively, in mid-rib sections for a given 30 cm increase in height, although the magnitudes of these associations varied by sex and rib location. Increased weight was associated with approximately equal changes in both cortical bone and total cross-sectional areas in males. These effects were most prominent (around 25% increases for an addition of 50 kg) toward lower ribs in the rib cage and had only modest effects (less than 12% change) in ribs 2-4. Females saw greater increases with weight in total rib area compared to cortical bone area, of up to 21% at the eighth rib level. Results from this study show the expected shapes of rib cross-sections across the adult rib cage and across a broad range of demographics. This detailed geometry can be used to produce accurate rib models representing widely varying populations.

Strain-mode-specific mechanical testing and the interpretation of bone adaptation in the deer calcaneus.

The artiodactyl (deer and sheep) calcaneus is a model that helps in understanding how many bones achieve anatomical optimization and functional adaptation. We consider how the dorsal and plantar cortices of these bones are optimized in quasi-isolation (the conventional view) versus in the context of load sharing along the calcaneal shaft by "tension members" (the plantar ligament and superficial digital flexor tendon). This load-sharing concept replaces the conventional view, as we have argued in a recent publication that employs an advanced analytical model of habitual loading and fracture risk factors of the deer calcaneus. Like deer and sheep calcanei, many mammalian limb bones also experience prevalent bending, which seems problematic because the bone is weaker and less fatigue-resistant in tension than compression. To understand how bones adapt to bending loads and counteract deleterious consequences of tension, it is important to examine both strain-mode-specific (S-M-S) testing (compression testing of bone habitually loaded in compression; tension testing of bone habitually loaded in tension) and non-S-M-S testing. Mechanical testing was performed on individually machined specimens from the dorsal "compression cortex" and plantar "tension cortex" of adult deer calcanei and were independently tested to failure in one of these two strain modes. We hypothesized that the mechanical properties of each cortex region would be optimized for its habitual strain mode when these regions are considered independently. Consistent with this hypothesis, energy absorption parameters were approximately three times greater in S-M-S compression testing in the dorsal/compression cortex when compared to non-S-M-S tension testing of the dorsal cortex. However, inconsistent with this hypothesis, S-M-S tension testing of the plantar/tension cortex did not show greater energy absorption compared to non-S-M-S compression testing of the plantar cortex. When compared to the dorsal cortex, the plantar cortex only had a higher elastic modulus (in S-M-S testing of both regions). Therefore, the greater strength and capacity for energy absorption of the dorsal cortex might "protect" the weaker plantar cortex during functional loading. However, this conventional interpretation (i.e., considering adaptation of each cortex in isolation) is rejected when critically considering the load-sharing influences of the ligament and tendon that course along the plantar cortex. This important finding/interpretation has general implications for a better understanding of how other similarly loaded bones achieve anatomical optimization and functional adaptation.

Osteoblastgenic and Osteogenic Effects of KY-273 with CDK8/19 Inhibitory Activity in Bone Marrow Mesenchymal Stem Cells and Female Rats.

Osteoporosis is caused by imbalance between osteogenesis and bone resorption, thus, osteogenic drugs and resorption inhibitors are used for treatment of osteoporosis. The present study examined the effects of (R)-4-(1-hydroxyethyl)-3-{4-[2-(tetrahydropyran-4-yloxy)ethoxy]phenoxy}benzamide (KY-273), a diphenyl ether derivative, on CDK8/19 activity, osteoblast differentiation and femoral bone using micro-computed tomography in female rats. KY-273 potently inhibited CDK8/19 activity, promoted osteoblast differentiation with an increase in alkaline phosphatase (ALP) activity, and gene expression of type I collagen, ALP and BMP-4 in mesenchymal stem cells (ST2 cells). In female rat femur, ovariectomy decreased metaphyseal trabecular bone volume (Tb.BV), mineral content (Tb.BMC), yet had no effect on metaphyseal and diaphyseal cortical bone volume (Ct.BV), mineral content (Ct.BMC) and strength parameters (BSPs). In ovaries-intact and ovariectomized rats, oral administration of KY-273 (10 mg/kg/d) for 6 weeks increased metaphyseal and diaphyseal Ct.BV, Ct.BMC, and BSPs without affecting medullary volume (Med.V), but did not affect Tb.BV and Tb.BMC. In ovariectomized rats, alendronate (3 mg/kg/d) caused marked restoration of Tb.BV, Tb.BMC and structural parameters after ovariectomy, and increased metaphyseal but not diaphyseal Ct.BV, Ct.BMC, and BSPs. In ovaries-intact and ovariectomized rats, by the last week, KY-273 increased bone formation rate/bone surface at the periosteal but not the endocortical side. These findings indicate that KY-273 causes osteogenesis in cortical bone at the periosteal side without reducing Med.V. In conclusion, KY-273 has cortical-bone-selective osteogenic effects by osteoblastogenesis via CDK8/19 inhibition in ovaries-intact and ovariectomized rats, and is an orally active drug candidate for bone diseases such as osteoporosis in monotherapy and combination therapy.

The morphology of alveolar bone of the mandibular second and third molars in skeletal Class III patients.

OBJECTIVES: To investigate the alveolar bone morphology of the mandibular second and third molars in skeletal Class III patients from a buccolingual direction. METHODS: Sixty skeletal Class III patients were recruited. The alveolar bone width, buccal cortical bone thickness and lingual cortical bone thickness were measured in five planes from mesial to distal and at five depths from gingival to root. The effects of the gender of the patients, the second molar lingual inclination and the third molar on alveolar bone width and cortical bone thickness were evaluated. To explore the effect of third molar extraction on alveolar bone morphology, the measurements before and after third molar extraction were compared. RESULTS: The impacted third molar had significantly greater alveolar bone width and thicker buccal cortical bone at the cervical third of the molar, while the erupted third molar had greater alveolar bone width at the apical third. Three weeks after third molar extraction, these advantages would weaken owing to the reconstruction of the alveolar bone. Patients with lingually inclined molar were observed to own thicker lingual cortical bone. Males tended to have greater alveolar bone width, but no significant differences were shown in this study. CONCLUSIONS: The growth of the third molar and the second molar lingual inclination affect the alveolar bone morphology of the mandibular second and third molars significantly, but gender has trivial effects on the morphology. The alveolar bone morphology of the mandibular second and third molars would change 3 weeks after third molar extraction.

Comparison of the clinical and radiographic outcomes of cortical bone trajectory and traditional trajectory pedicle screw fixation in transforaminal lumbar interbody fusion: a randomized controlled trial.

PURPOSE: To compare the clinical outcomes and radiographic outcomes of cortical bone trajectory (CBT) and traditional trajectory (TT) pedicle screw fixation in patients treated with single-level transforaminal lumbar interbody fusion (TLIF). METHODS: This trial included a total of 224 patients with lumbar spine disease who required single-level TLIF surgery. Patients were randomly assigned to the CBT and TT groups at a 1:1 ratio. Demographics and clinical and radiographic data were collected to evaluate the efficacy and safety of CBT and TT screw fixation in TLIF. RESULTS: The baseline characteristic data were similar between the CBT and TT groups. Back and leg pain for both the CBT and TT groups improved significantly from baseline to 24 months postoperatively. The CBT group experienced less pain than the TT group at one week postoperatively. The postoperative radiographic results showed that the accuracy of screw placement was significantly increased in the CBT group compared with the TT group (P < 0.05). The CBT group had a significantly lower rate of FJV than the TT group (P < 0.05). In addition, the rate of fusion and the rate of screw loosening were similar between the CBT and TT groups according to screw loosening criteria. CONCLUSION: This prospective, randomized controlled analysis suggests that clinical outcomes and radiographic characteristics, including fusion rates and caudal screw loosening rates, were comparable between CBT and TT screw fixation. Compared with the TT group, the CBT group showed advantages in the accuracy of screw placement and the FJV rate. CLINICAL TRIALS REGISTRATION: This trial has been registered at the US National Institutes of Health Clinical Trials Registry: NCT03105167.

Biomechanical evaluation of modified and traditional cortical bone trajectory technique on adjacent segment degeneration in transforaminal lumbar interbody fusion-finite element analysis.

OBJECTIVES: Modified cortical bone trajectory (MCBT) technique was proposed by our team in previous studies, but its biomechanical properties at adjacent segments have not been discussed yet. Therefore, the purpose of this study is to investigate the biomechanical properties of modified cortical bone trajectory (MCBT) technique on adjacent segment degeneration (ASD) in transforaminal intradiscal lumbar disc fusion (TLIF) compare to traditional bone trajectory (TT) technique and cortical bone trajectory (CBT) technique. METHODS: The four human cadaveric lumbar specimens were provided by the anatomy teaching and research department of Xinjiang Medical University and four intact finite element models of the L1-S1 segment were generated. For each of these, three transforaminal lumbar interbody fusion procedures with three different fixation techniques were reconstructed at the L4-L5 segment, as follows: TT-TT (TT at both L4 and L5 segments), CBT-CBT (CBT at both L4 and L5 segments), MCBT-MCBT (MCBT at both L4 and L5 segments). The range of motion and von Mises stress of the intervertebral disc of the L3-L4 and L5-S1 segments were recorded with a 400N compressive load and 7.5 Nm moments in flexion, extension, left-right bending, and left-right rotation. RESULTS: The peak ROM of the L3-L4 segment in the MCBT-MCBT group was reduced by 10.5%, 6.1%, 12.2%, 4.1%, and 1.5% in flexion, extension, left-right bending, and left rotation compared to the TT-TT group and reduced by 1.8%, 5.5%, 10.0%, 12.8%, and 8.8% in flexion, left-right bending, and left-right rotation compared to the CBT-CBT group, respectively. The MCBT-MCBT group has the lowest peak ROM of the L3-L4 segment in flexion, left bending, and right rotation, the lowest peak ROM of the L5-S1 segment in extension and right rotation, and the lowest peak von Mises stress of the intervertebral disc at the L5-S1 segment in right rotation compared to the TT-TT and CBT-CBT group. In addition, the peak von Mises stress at the L3-L4 segment was lowest and more dispersed in all motions, the MCBT-MCBT group exhibited lower peak ROM of the L5-S1 segment in flexion, extension, and right rotation, and showed lower peak von Mises stress of the disc at the L5-S1 segment in flexion, extension, and right rotation compared with the TT-TT group. CONCLUSION: The modified cortical bone trajectory technique may have a beneficial effect on reducing the incidence of ASD in the L4-L5 TLIF model compared to the traditional bone trajectory technique and cortical bone trajectory technique.

Cortical bone thickness on preoperative CT scans as predictor of bone quality in distal femur fractures: a retrospective study in Caucasians.

AIM: Distal femur fractures (DFF) are rare, but associated with high complication rates and mortality, particularly in patients with osteoporosis. To improve preoperative assessment, we analyzed if cortical bone thickness on CT and AP radiographs is associated with clinical parameters of bone quality. METHODS: Retrospective single-center study of adult patients presenting at a level-one trauma center, with a DFF between 2011 and 2020. Clinical parameters for bone quality, such as age, sex, body mass index (BMI), energy impact level of trauma, and known history of osteoporosis, were assessed. Mean cortical bone thickness (CBTavg) on AP radiograph was determined using a previously published method. Cortical thickness on CT scan was measured at 8 and 14 cm proximal to the articular surface of the lateral condyle. RESULTS: 71 patients (46 females) between 20 and 100 years were included in the study. Cortical thickness determined by CT correlated significantly with CBTavg measurements on AP radiograph (Spearman r = 0.62 to 0.80; p < 0.001). Cortical thickness was inversely correlated with age (Spearman r = - 0.341 to - 0.466; p < 0.001) and significantly associated with trauma impact level and history of osteoporosis (p = < 0.001). The CT-based values showed a stronger correlation with the clinical parameters than those determined by AP X-ray. CONCLUSION: Our results showed that cortical thickness of the distal femur correlates with clinical parameters of bone quality and is therefore an excellent tool for assessing what surgical care should be provided. Interestingly, our findings indicate that cortical thickness on CT is more strongly correlated with clinical data than AP radiograph measurements.

Correlation Between Acquisition of Dental Implant Stability and Hounsfield Units at Dental Implant Placement.

Alveolar bone quality at the implantation site affects the initial stability of dental implant treatment. However, the relationship between bone quality and osseointegration has yet to be evaluated. Herein, we aimed to investigate the effect of bone quality on dental implant stability in osseointegration formation changes. Patients underwent computed tomography imaging before dental implantation at the posterior. Hounsfield units were measured at the platform, middle, and tip sites. Implant stability was measured using resonance frequency analysis immediately and at 3 months postoperatively, in which the difference in implant stability quotients (ISQ) was defined as the change between primary and secondary fixation. In multiple regression analysis, the dependent variable was the change between the immediate and secondary fixations. We included 81 implants that conformed to the criteria. Primary fixation yielded the following results: R2 = 0.117, F = 2.529, and P = .047. The difference between the maxilla and mandible of the implantation site (P = .02) and the platform-site Hounsfield units (P = .019) were identified as significant factors. The following results were obtained regarding the change between the immediate and secondary fixation: R2 = 0.714, F = 40.964, and P < .001. The difference between diameter (P = .008) and the immediate ISQ (P < .001) were identified as significant factors. Overall, the bone quality of the implantation site affected initial fixation; however, it had limited effect on secondary fixation. Our findings clarified the period where bone quality affects dental implant treatment and is expected to advance dental implant treatment.

Fast bound and pore water mapping of cortical bone with arbitrary slice oriented two-dimensional ultra-short echo time.

PURPOSE: Extend fast, two-dimensional (2D) methods of bound and pore water mapping in bone to arbitrary slice orientation. METHODS: To correct for slice profile artifacts caused by gradient errors of half pulse 2D ultra-short echo time (UTE), we developed a library of predistorted gradient waveforms that can be used to interpolate optimized gradient waveforms for 2D UTE slice selection. We also developed a method to estimate and correct for a bulk phase difference between the two half pulse excitations used for 2D UTE signal excitation. Bound water images were acquired in three healthy subjects with adiabatic inversion recovery prepared 2D UTE, while pore water images were acquired after short-T2 signals were suppressed with double adiabatic inversion recovery preparation. The repeatability of bound and pore water imaging with 2D UTE was tested by repeating acquisitions after repositioning. RESULTS: The library-based interpolation of optimized slice select gradient waveforms combined with the method to estimate bulk phase between two excitations provided compact slice profiles for half pulse excited 2D UTE. Quantitative bound and pore water values were highly repeatable-the pooled SD of bound water across all three subjects was 0.38 mol 1 $$ {}^1 $$ H/L, while pooled SD of pore water was 0.30 mol 1 $$ {}^1 $$ H/L. CONCLUSION: Fast, quantitative, 2D UTE-based bound and pore water images can be acquired at arbitrary oblique orientations after correcting for errors in the slice select gradient waveform and bulk phase shift between the two half acquisitions.

Cortical bone distribution of the proximal phalanges in great apes: implications for reconstructing manual behaviours.

Primate fingers are typically in direct contact with the environment during both locomotion and manipulation, and aspects of external phalangeal morphology are known to reflect differences in hand use. Since bone is a living tissue that can adapt in response to loading through life, the internal bone architecture of the manual phalanges should also reflect differences in manual behaviours. Here, we use the R package Morphomap to analyse high-resolution microCT scans of hominid proximal phalanges of digits 2-5 to determine whether cortical bone structure reflects variation in manual behaviours between bipedal (Homo), knuckle-walking (Gorilla, Pan) and suspensory (Pongo) taxa. We test the hypothesis that relative cortical bone distribution patterns and cross-sectional geometric properties will differ both among extant great apes and across the four digits due to locomotor and postural differences. Results indicate that cortical bone structure reflects the varied hand postures employed by each taxon. The phalangeal cortices of Pongo are significantly thinner and have weaker cross-sectional properties relative to the African apes, yet thick cortical bone under their flexor sheath ridges corresponds with predicted loading during flexed finger grips. Knuckle-walking African apes have even thicker cortical bone under the flexor sheath ridges, as well as in the region proximal to the trochlea, but Pan also has thicker diaphyseal cortices than Gorilla. Humans display a distinct pattern of distodorsal thickening, as well as relatively thin cortices, which may reflect the lack of phalangeal curvature combined with frequent use of flexed fingered hand grips during manipulation. Within each taxon, digits 2-5 have a similar cortical distribution in Pongo, Gorilla and, unexpectedly, Homo, which suggest similar loading of all fingers during habitual locomotion or hand use. In Pan, however, cortical thickness differs between the fingers, potentially reflecting differential loading during knuckle-walking. Inter- and intra-generic variation in phalangeal cortical bone structure reflects differences in manual behaviours, offering a comparative framework for reconstructing hand use in fossil hominins.

3D profiling of mouse epiphyses across ages reveals new potential imaging biomarkers of early spontaneous osteoarthritis.

Worldwide research groups and funding bodies have highlighted the need for imaging biomarkers to predict osteoarthritis (OA) progression and treatment effectiveness. Changes in trabecular architecture, which can be detected with non-destructive high-resolution CT imaging, may reveal OA progression before apparent articular surface damage. Here, we analysed the tibial epiphyses of STR/Ort (OA-prone) and CBA (healthy, parental control) mice at different ages to characterise the effects of mouse age and strain on multiple bony parameters. We isolated epiphyseal components using a semi-automated method, and measured the total epiphyseal volume; cortical bone, trabecular bone and marrow space volumes; mean trabecular and cortical bone thicknesses; trabecular volume relative to cortical volume; trabecular volume relative to epiphyseal interior (trabecular BV/TV); and the trabecular degree of anisotropy. Using two-way ANOVA (significance level ≤0.05), we confirmed that all of these parameters change significantly with age, and that the two strains were significantly different in cortical and trabecular bone volumes, and trabecular degree of anisotropy. STR/Ort mice had higher cortical and trabecular volumes and a lower degree of anisotropy. As the two mouse strains reflect markedly divergent OA predispositions, these parameters have potential as bioimaging markers to monitor OA susceptibility and progression. Additionally, significant age/strain interaction effects were identified for total epiphyseal volume, marrow space volume and trabecular BV/TV. These interactions confirm that the two mouse strains have different epiphyseal growth patterns throughout life, some of which emerge prior to OA onset. Our findings not only propose valuable imaging biomarkers of OA, but also provide insight into ageing 3D epiphyseal architecture bone profiles and skeletal biology underlying the onset and development of age-related OA in STR/Ort mice.

Diversity of cortical bone morphology in anuran amphibians.

The cortical bones of mammals, birds, and reptiles are composed of a complex of woven bone and lamellar bone (fibrolamellar bone) organized into a variety of different patterns; however, it remains unclear whether amphibians possess similar structures. Importantly, to understand the evolutionary process of limb bones in tetrapods, it is necessary to compare the bone structure of amphibians (aquatic to terrestrial) with that of amniotes (mostly terrestrial). Therefore, this study compared the cortical bones in the long bones of several frog species before and after metamorphosis. Using micro-computed tomography (CT), we found that the cortical bones in the fibrolamellar bone of Xenopus tropicalis (Pipoidea superfamily) and Lithobates catesbeianus (Ranoidea superfamily) froglets are dense, whereas those of Ceratophrys cranwelli (Hyloidea superfamily) are porous. To clarify whether these features are common to their superfamily or sister group, four other frog species were examined. Histochemical analyses revealed porous cortical bones in C. ornata and Lepidobatrachus laevis (belonging to the same family, Ceratophryidae, as C. cranwelli). However, the cortical bones of Dryophytes japonicus (Hylidae, a sister group of Ceratophryidae in the Hyloidea superfamily), Microhyla okinavensis (Microhylidae, independent of the Hyloidea superfamily), and Pleurodeles waltl, a newt as an outgroup of anurans, are dense with no observed cavities. Our findings demonstrate that at least three members of the Ceratophryidae family have porous cortical bones similar to those of reptiles, birds, and mammals, suggesting that the process of fibrolamellar bone formation arose evolutionarily in amphibians and is conserved in the common ancestor of amniotes.

Alteration of Volumetric Bone Mineral Density Parameters in Men with Spinal Cord Injury.

Spinal cord injury (SCI) induces severe losses of trabecular and cortical volumetric bone mineral density (vBMD), which cannot be discriminated with conventional dual-energy X-ray absorptiometry (DXA) analysis. The objectives were to: (i) determine the effects of SCI on areal BMD (aBMD) and vBMD determined by advanced 3D-DXA-based methods at various femoral regions and (ii) model the profiles of 3D-DXA-derived parameters with the time since injury. Eighty adult males with SCI and 25 age-matched able-bodied (AB) controls were enrolled in this study. Trabecular and cortical vBMD, cortical thickness and derived strength parameters were assessed by 3D-SHAPER® software at various femoral subregions. Individuals with SCI had significantly lower integral vBMD, trabecular vBMD, cortical vBMD, cortical thickness and derived bone strength parameters (p < 0.001 for all) in total proximal femur compared with AB controls. These alterations were approximately to the same degree for all three femoral subregions, and the difference between the two groups tended to be greater for cortical vBMD than trabecular vBMD. There were minor differences according to the lesion level (paraplegics vs tetraplegics) for all 3D-DXA-derived parameters. For total proximal femur, the decreasing bone parameters tended to reach a new steady state after 5.1 years for integral vBMD, 7.4 years for trabecular vBMD and 9.2 years for cortical vBMD following SCI. At proximal femur, lower vBMD (integral, cortical and trabecular) and cortical thickness resulted in low estimated bone strength in individuals with SCI. It remains to be demonstrated whether these new parameters are more closely associated with fragility fracture than aBMD.

Zero Echo Time vs. T1-Weighted MRI for Assessment of Cortical and Medullary Bone Morphology Abnormalities Using CT as the Reference Standard.

BACKGROUND: Conventional MR pulse sequences result in poor signal from low T2 cortical bone because the minimum achievable echo time is limited. A sequence resulting in improved bone contrast is desirable. PURPOSE: To evaluate the image quality and diagnostic performance of grayscale inversion zero echo time imaging (GI-ZTE) and grayscale inversion T1-weighted imaging (GI-T1WI) compared with computed tomography (CT). STUDY TYPE: Prospective. SUBJECTS: A total of 50 patients with musculoskeletal tumors or tumor-like diseases of the lower extremities having MRI and CT studies. FIELD STRENGTH/SEQUENCE: GI-T1WI and GI-ZTE sequences at 1.5 T. ASSESSMENT: Assessed cortical and medullary bone morphology abnormalities using CT as the reference standard. Three radiologists scored the images quality and recorded nine metrics to assess the diagnostic performance. STATISTICAL TESTS: Differences in image quality were calculated using the Wilcoxon signed-rank test. The intraclass correlation coefficient (ICC) was used to analyze the agreement of quantitative lesion parameters between CT and MR sequences, as well as the interobserver reliability. A P value <0.05 was considered statistically significant. RESULTS: Image quality score was significantly higher for CT images than GI-TIWI images. Except for radiologist 3 [4(0) vs 4 (1)], there was no significant difference in scores between CT and GI-ZTE [radiologist 1: 4 (0) vs 4 (0), P = 0.133; radiologist 2: 4 (0) vs 4 (0), P = 0.085]. There was good-excellent agreement between both MR sequences and CT for size, lesion number, location, sclerotic rim, expanded shell, destruction pattern, and matrix mineralization for all radiologists (ICC: 0.636-1.000). The consistency of periosteal reaction and penetration of the cortex was fair to good (0.481-0.729) between GI-T1WI and CT and good to excellent between GI-ZTE and CT (0.682-0.852). DATA CONCLUSIONS: GI-ZTE images had superior intermodality agreement with CT images and allowed visualization of more cortical bone detail than GI-T1WI images. EVIDENCE LEVEL: 1. TECHNICAL EFFICACY: Stage 2.

Challenges and perspectives on functional interpretations of australopith postcrania and the reconstruction of hominin locomotion.

In 1994, Hunt published the 'postural feeding hypothesis'-a seminal paper on the origins of hominin bipedalism-founded on the detailed study of chimpanzee positional behavior and the functional inferences derived from the upper and lower limb morphology of the Australopithecus afarensis A.L. 288-1 partial skeleton. Hunt proposed a model for understanding the potential selective pressures on hominins, made robust, testable predictions based on Au. afarensis functional morphology, and presented a hypothesis that aimed to explain the dual functional signals of the Au. afarensis and, more generally, early hominin postcranium. Here we synthesize what we have learned about Au. afarensis functional morphology and the dual functional signals of two new australopith discoveries with relatively complete skeletons (Australopithecus sediba and StW 573 'Australopithecus prometheus'). We follow this with a discussion of three research approaches that have been developed for the purpose of drawing behavioral inferences in early hominins: (1) developments in the study of extant apes as models for understanding hominin origins; (2) novel and continued developments to quantify bipedal gait and locomotor economy in extant primates to infer the locomotor costs from the anatomy of fossil taxa; and (3) novel developments in the study of internal bone structure to extract functional signals from fossil remains. In conclusion of this review, we discuss some of the inherent challenges of the approaches and methodologies adopted to reconstruct the locomotor modes and behavioral repertoires in extinct primate taxa, and notably the assessment of habitual terrestrial bipedalism in early hominins.

Diminished cortical bone density of long bones among children with haemophilic arthropathy.

INTRODUCTION: Children with haemophilia (CwH) have lower bone mineral density in the spine (trabecular bone) than healthy children. There are few studies focusing on bone mineral density in long bones (cortical bone). AIM: To evaluate bi-laterally the distal third of radius and midshaft tibias using quantitative ultrasound (QUS) and assess the speed of sound (SoS). METHODS: A cross-sectional study where 91 CwH and 91 age-matched healthy boys were included. Joint evaluation was determined with the Haemophilia Joint Health Score 2.1 and SoS values. The Z scores were measured with the Sunlight Omnisense 8000 S equipment. RESULTS: Ninety-one CwH (haemophilia A) were evaluated (26 mild form, 26 moderate, and 39 severe). Most patients were treated with on-demand factor replacement and had higher total HJHS scores according to severity (4.8, 14.8 and 14.1, respectively). Patients with moderate and severe disease showed a statistical difference in SoS values for both radius and tibias compared to controls. QUS Z-scores ≥-2 were more frequent in radius and tibias in CwH, but were statistically significant only in tibias when compared to controls (in 30% mild, 46% moderate, 28% severe, respectively). CONCLUSIONS: There was diminished cortical bone density in radius and tibias of CwH compared to healthy controls. Changes predominated in tibias, more frequently affected according to the severity of haemophilia. Early intervention with factor replacement combined with physical activity are key aspects to promote bone health.

Exploration of the synergistic role of cortical thickness asymmetry ("Trabecular Eccentricity" concept) in reducing fracture risk in the human femoral neck and a control bone (Artiodactyl Calcaneus).

The mechanobiology of the human femoral neck is a focus of research for many reasons including studies that aim to curb age-related bone loss that contributes to a near-exponential rate of hip fractures. Many believe that the femoral neck is often loaded in rather simple bending, which causes net tension stress in the upper (superior) femoral neck and net compression stress in its inferior aspect ("T/C paradigm"). This T/C loading regime lacks in vivo proof. The "C/C paradigm" is a plausible alternative simplified load history that is characterized by a gradient of net compression across the entire femoral neck; action of the gluteus medius and external rotators of the hip are important in this context. It is unclear which paradigm is at play in natural loading due to lack of in vivo bone strain data and deficiencies in understanding mechanisms and manifestations of bone adaptation in tension vs. compression. For these reasons, studies of the femoral neck would benefit from being compared to a 'control bone' that has been proven, by strain data, to be habitually loaded in bending. The artiodactyl (sheep and deer) calcaneus model has been shown to be a very suitable control in this context. However, the application of this control in understanding the load history of the femoral neck has only been attempted in two prior studies, which did not examine the interplay between cortical and trabecular bone, or potential load-sharing influences of tendons and ligaments. Our first goal is to compare fracture risk factors of the femoral neck in both paradigms. Our second goal is to compare and contrast the deer calcaneus to the human femoral neck in terms of fracture risk factors in the T/C paradigm (the C/C paradigm is not applicable in the artiodactyl calcaneus due to its highly constrained loading). Our third goal explores interplay between dorsal/compression and plantar/tension regions of the deer calcaneus and the load-sharing roles of a nearby ligament and tendon, with insights for translation to the femoral neck. These goals were achieved by employing the analytical model of Fox and Keaveny (J. Theoretical Biology 2001, 2003) that estimates fracture risk factors of the femoral neck. This model focuses on biomechanical advantages of the asymmetric distribution of cortical bone in the direction of habitual loading. The cortical thickness asymmetry of the femoral neck (thin superior cortex, thick inferior cortex) reflects the superior-inferior placement of trabecular bone (i.e., "trabecular eccentricity," TE). TE helps the femoral neck adapt to typical stresses and strains through load-sharing between superior and inferior cortices. Our goals were evaluated in the context of TE. Results showed the C/C paradigm has lower risk factors for the superior cortex and for the overall femoral neck, which is clinically relevant. TE analyses of the deer calcaneus revealed important synergism in load-sharing between the plantar/tension cortex and adjacent ligament/tendon, which challenges conventional understanding of how this control bone achieves functional adaptation. Comparisons with the control bone also exposed important deficiencies in current understanding of human femoral neck loading and its potential histocompositional adaptations.

Effects of different running intensities on the micro-level failure strain of rat femoral cortical bone structures: a finite element investigation.

BACKGROUND: Running with the appropriate intensity may produce a positive influence on the mechanical properties of cortical bone structure. However, few studies have discussed the effects of different running intensities on the mechanical properties at different levels, especially at the micro-level, because the micromechanical parameters are difficult to measure experimentally. METHODS: An approach that combines finite element analysis and experimental data was proposed to predict a micromechanical parameter in the rat femoral cortical bone structure, namely, the micro-level failure strain. Based on the previous three-point bending experimental information, fracture simulations were performed on the femur finite element models to predict their failure process under the same bending load, and the micro-level failure strains in tension and compression of these models were back-calculated by fitting the experimental load-displacement curves. Then, the effects of different running intensities on the micro-level failure strain of rat femoral cortical bone structure were investigated. RESULTS: The micro-level failure strains of the cortical bone structures expressed statistical variations under different running intensities, which indicated that different mechanical stimuli of running had significant influences on the micromechanical properties. The greatest failure strain occurred in the cortical bone structure under low-intensity running, and the lowest failure strain occurred in the structure under high-intensity running. CONCLUSIONS: Moderate and low-intensity running were effective in enhancing the micromechanical properties, whereas high-intensity running led to the weakening of the micromechanical properties of cortical bone. Based on these, the changing trends in the micromechanical properties were exhibited, and the effects of different running intensities on the fracture performance of rat cortical bone structures could be discussed in combination with the known mechanical parameters at the macro- and nano-levels, which provided the theoretical basis for reducing fracture incidence through running exercise.