Characteristics Of Trabecular Bone Research Articles

Application of Fractal Analysis in Detecting Trabecular Bone Characteristics Around Mandibular Impacted Third Molars on Dental Panoramic Radiographs

Purpose: Surgical extraction of third molars can be difficult for many reasons, including increased bone density, which causes bone structures to lose their elastic properties. The aim of this study is to compare the trabecular structure around the impacted mandibular third molar(M3M) and the normal alveolar trabecular pattern using the fractal analysis method. Materials and Methods: Panoramic images of 47 patients were included in the study. ROI1 is the area between the distal root of the second molar and the mesial of the third molar tooth. On the other hand, ROI2 was selected between the distal root of the first molar tooth and the mesial root of the second molar tooth. Fractal Dimension (FD) and Bone Marrow Dimension analyzes were applied to the selected ROIs using the ImageJ software. Results: The mean FD values of 47 patients were found to be 1.135 for ROI1 and 1.105 for ROI2, respectively (p=0,078).The mean Bone Marrow Dimension values were found to be 1.591 for ROI1 and 1.587 for ROI2(p=0.731). There was no significant difference in FD and Bone Marrow Dimension analysis when ROI1 and ROI2 were compared. It is very important to know the pattern of trabecular structure before surgical procedure on M3M. The bone density around the impacted M3M may be higher than the healthy alveolar bone, however, the fact that males have denser bone than females should not be ignored during the operation. Conclusion: The method of FD analysis can be useful for evaluating the trabecular structure of impacted M3M. Key words: fractal dimension; bone structure; panoramic imaging; impacted tooth; third molars

A Comprehensive Mechanical Characterization of Subject-Specific 3D Printed Scaffolds Mimicking Trabecular Bone Architecture Biomechanics.

This study presents a polymeric scaffold designed and manufactured to mimic the structure and mechanical compressive characteristics of trabecular bone. The morphological parameters and mechanical behavior of the scaffold were studied and compared with trabecular bone from bovine iliac crest. Its mechanical properties, such as modulus of elasticity and yield strength, were studied under a three-step monotonic compressive test. Results showed that the elastic modulus of the scaffold was 329 MPa, and the one for trabecular bone reached 336 MPa. A stepwise dynamic compressive test was used to assess the behavior of samples under various loading regimes. With microcomputed tomography (µCT), a three-dimensional reconstruction of the samples was obtained, and their porosity was estimated as 80% for the polymeric scaffold and 88% for trabecular bone. The full-field strain distribution of the samples was measured using in situ µCT mechanics and digital volume correlation (DVC). This provided information on the local microdeformation mechanism of the scaffolds when compared to that of the tissue. The comprehensive results illustrate the potential of the fabricated scaffolds as biomechanical templates for in vitro studies. Furthermore, there is potential for extending this structure and fabrication methodology to incorporate suitable biocompatible materials for both in vitro and in vivo clinical applications.

3D strain analysis of trabecular bone within the osteoarthritic humeral head subjected to stepwise compressive loads

Understanding the local mechanical properties of trabecular bone at the humeral head-neck junction is essential for the safe design of stemless humeral head implants. Recent advancements in mechanical testing coupled with volumetric imaging have allowed for the ability to quantify full-field strain distributions throughout trabecular bone. Within this study, digital volume correlation (DVC) was applied to micro-computed tomography images to investigate the local load carrying characteristics of trabecular bone within osteoarthritic (OA) humeral heads subjected to stepwise loading. A multi-pegged indenter was used to transfer loads from a custom-fabricated loading apparatus to trabecular bone on the resection surface of OA humeral head osteotomies retrieved from patients undergoing total shoulder arthroplasty (TSA). In regions of trabecular bone that eventually fractured, third principal strains were significantly higher (95th percentile third principal strain = −12,558 μstrain, p < 0.001) compared to regions that did not fracture (95th percentile third principal strain = −7,806 μstrain). As well, bone volume fraction (p = 0.012), trabecular separation (p = 0.014), and trabecular number (p = 0.007) were found to influence the likelihood of trabecular bone fracture. Collectively, this work has led to a deeper understanding of the local load carrying characteristics of trabecular bone specific to patients receiving TSA for osteoarthritis.

A simple and effective 1D-element discrete-based method for computational bone remodeling

In-silico models applied to bone remodeling are widely used to investigate bone mechanics, bone diseases, bone-implant interactions, and also the effect of treatments of bone pathologies. This article proposes a new methodology to solve the bone remodeling problem using one-dimensional (1D) elements to discretize trabecular structures more efficiently for 2D and 3D domains. An Euler integration scheme is coupled with the momentum equations to obtain the evolution of material density at each step. For the simulations, the equations were solved by using the finite element method, and two benchmark tests were solved varying mesh parameters. Proximal femur and calcaneus bone were selected as study cases given the vast research available on the topology of these bones, and compared with the anatomical features of trabecular bone reported in the literature. The presented methodology has proven to be efficient in optimizing topologies of lattice structures; It can predict the trend of formation patterns of the main trabecular groups from two different cancellous bones (femur and calcaneus) using domains set up by discrete elements as a starting point. Preliminary results confirm that the proposed approach is suitable and useful in bone remodeling problems leading to a considerable computational cost reduction. Characteristics similar to those encountered in topological optimization algorithms were identified in the benchmark tests as well, showing the viability of the proposed approach in other applications such as bio-inspired design.

Automated simulation techniques for uncovering high-performance bioinspired cellular structures under blast loads

Trabecular bone possesses a complex hierarchical structure of plate- and strut-like elements, which is analogous to structural systems encountered in engineering practice. In this work, key structural features of trabecular bone are mimicked to uncover effective energy dissipation mechanisms under blast loading. To this end, several key design parameters were identified to develop a bone-like unit cell. A computer script was then developed to automatically generate bone-like finite element models with many combinations of these design parameters, which were simulated under blast loading. The optimal structure was identified and its performance was benchmarked against traditional engineered cellular structures, including those with hexagonal, re-entrant and square cellular geometries. The bone-like structure showed superior performance over its engineered counterparts using the peak transmitted reaction force and energy dissipation as the key performance criteria.

Bone targeting nanocarrier-assisted delivery of adenosine to combat osteoporotic bone loss

Extracellular adenosine has been shown to play a key role in maintaining bone health and could potentially be used to treat bone loss. However, systemic administration of exogenous adenosine to treat bone disorders remains a challenge due to the ubiquitous presence of adenosine receptors in different organs and the short half-life of adenosine in circulation. Towards this, we have developed a bone-targeting nanocarrier and determined its potential for systemic administration of adenosine. The nanocarrier, synthesized via emulsion suspension photopolymerization, is comprised of hyaluronic acid (HA) copolymerized with phenylboronic acid (PBA), a moiety that can form reversible bonds with adenosine. The bone binding affinity of the nanocarrier was achieved by alendronate (Aln) conjugation. Nanocarriers functionalized with the alendronate (Aln-NC) showed a 45% higher accumulation in the mice vertebrae in vivo compared to those lacking alendronate molecules (NCs). Systemic administration of adenosine via bone-targeting nanocarriers (Aln-NC) attenuated bone loss in ovariectomized (OVX) mice. Furthermore, bone tissue of mice treated with adenosine-loaded Aln-NC displayed trabecular bone characteristics comparable to healthy controls as shown by microcomputed tomography, histochemical staining, bone labeling, and mechanical strength. Overall, our results demonstrate the use of a bone-targeting nanocarrier towards systemic administration of adenosine and its application in treating bone degenerative diseases such as osteoporosis.

Microstructural and mechanical evaluations of region segmentation methods in classifications of osteonecrosis

Measuring the location of necrotic lesions is necessary to diagnosis of osteonecrosis. Different region segmentation methods of the femoral head were proposed to quantitatively measure necrotic lesions including Japanese Investigation Committee for Avascular Necrosis (JIC) classification and China-Japan Friendship Hospital (CJFH) classification. Biomechanical methods could bring important information to evaluate the reasonability of these classifications. In this study, microstructural and mechanical properties of trabecular bone were quantitatively analyzed according to the region segmentation methods described in these classifications. Microstructural parameters of trabecular bone were analyzed based on micro-CT scanning. Mechanical properties were measured through Nanoindentation and micro-finite element analysis. It was found that microstructural and mechanical properties of trabecular bone in the middle region was more adaptive to load bearing than the medial and lateral regions according to the CJFH classification; lesions in the middle region could bring more changes to microstructure and stress distribution. According to JIC classification, differences of microstructural and mechanical properties among the three regions were not significant. Biomechanical characteristics of trabecular bones could be better distinguished with CJFH classification.

A Combination Treatment of Raloxifene and Vitamin D Enhances Bone-to-Tendon Healing of the Rotator Cuff in a Rat Model

Background: Tearing and degeneration of the rotator cuff at the tendon-to-bone junction are common in adults aged ≥50 years. Few studies have reported on the relationship between estrogen and the rotator cuff enthesis. In addition to preventing bone loss, selective estrogen receptor modulators have been shown to improve tendon and muscle quality. Purpose: To evaluate the effects of raloxifene (RLX) and vitamin D on rotator cuff tendon-to-bone healing in a rat model. Study Design: Controlled laboratory study. Methods: A total of 29 female rats (58 shoulders) were assigned to 4 groups: (1) control group, (2) ovariectomy (OVX)–only group, (3) no RLX group (OVX and rotator cuff repair [RCR]), and (4) RLX group (OVX, RCR, and RLX). Rats that did not undergo rotator cuff tear (RCT) surgery were divided into the control and OVX-only groups according to OVX surgery. Rats that underwent RCT surgery and RCR were divided into the no RLX and RLX groups according to RLX and vitamin D administration. An estrogen-deficient state was induced by OVX at 12 weeks of age. Bone mineral density (BMD) and trabecular bone characteristics were measured by micro–computed tomography, and healing of the tendon-to-bone junction was evaluated by biomechanical testing, histomorphometry, and micro–magnetic resonance imaging (MRI). Results: The mean final body weight (BW; 461.6 ± 47.3 g) of the OVX-only group was significantly higher and BMD (0.25 ± 0.07 g/cm3) was significantly lower (P < .001) than the mean final BW (338.5 ± 35.1 g) and BMD (0.48 ± 0.05 g/cm3) of the control group. In contrast, the RLX group showed that the BW (369.6 ± 35.8 g) and BMD (0.41 ± 0.08 g/cm3) were not significantly different from the control group. The RLX group had a significantly higher histomorphometric total score (8.50 ± 1.05) than the no RLX group (4.83 ± 2.48). On biomechanical testing, the RLX group (29.7 ± 9.1 N) showed a significantly higher load to failure than the no RLX group (19.4 ± 8.8 N). On micro-MRI, the RLX group had a more homogeneous low signal and tendon continuity than the no RLX group. Conclusion: The combination treatment of RLX and vitamin D prevented a decrease in local BMD (greater tuberosity of the proximal humerus) and enhanced tendon-to-bone healing of the rotator cuff in a rat model. Clinical Relevance: This study induced an estrogen-deficient state similar to the human postmenopausal state and used drugs that are actually being prescribed in a clinical situation.

The body composition analysis as a complementary tool in the screening of bone structural abnormalities.

Purpose. The importance of early diagnosis, bone-healthy lifestyle and medication is required for remaining fracture free. Dual-energy X-ray absorptiometry and ultrasound densitometry are widely used to screen osteoporosis and other bone structural diseases. Bioelectrical impedance analysis (BIA) devices can also estimate bone mineral content (BMC), but it has not been recommended for diagnostic purposes. The aim was to analyse whether low levels of the body composition' components and low bone mineral content can predict bone structural risk. Methods. Healthy pre- (n: 235, 18-45 years) and postmenopausal women (n: 137, 46-78 years) were enrolled to the analysis. BMC (kg) was estimated by InBody 720 analyser. Bone structure was measured by ultrasound DTU-One osteometer. Broadband ultrasound attenuation (BUA, dB/MHz), which estimates structural characteristics of trabecular bone, was used to assess bone structure. Body mass components were estimated by Drinkwater-Ross method. Results. Age changes of BMC, absolute and relative bone mass, muscle mass and bone structural parameters were analysed in women. BMC (r = 0.43, p < 0.01), absolute muscle mass (r = 0.41, p < 0.01) and absolute bone mass (r = 0.37, p < 0.01) were highly correlated (Pearson correlation) with BUA in premenopausal women. In postmenopausal women weaker relationship was identified between BUA and its hypothetical predictive factors. Conclusion. BMC and other studied body mass components alone do not provide enough information to identify osteoporosis, but can complete and widen the screening methods for bone structural diseases. Bone mineral density of healthy premenopausal women with low BMC, low bone mass and/or low muscle mass values should be measured regularly.

Deciphering an extreme morphology: bone microarchitecture of the hero shrew backbone (Soricidae: Scutisorex).

Biological structures with extreme morphologies are puzzling because they often lack obvious functions and stymie comparisons to homologous or analogous features with more typical shapes. An example of such an extreme morphotype is the uniquely modified vertebral column of the hero shrew Scutisorex, which features numerous accessory intervertebral articulations and massively expanded transverse processes. The function of these vertebral structures is unknown, and it is difficult to meaningfully compare them to vertebrae from animals with known behavioural patterns and spinal adaptations. Here, we use trabecular bone architecture of vertebral centra and quantitative external vertebral morphology to elucidate the forces that may act on the spine of Scutisorex and that of another large shrew with unmodified vertebrae (Crocidura goliath). X-ray micro-computed tomography (µCT) scans of thoracolumbar columns show that Scutisorex thori is structurally intermediate between C. goliath and S. somereni internally and externally, and both Scutisorex species exhibit trabecular bone characteristics indicative of higher in vivo axial compressive loads than C. goliath. Under compressive load, Scutisorex vertebral morphology is adapted to largely restrict bending to the sagittal plane (flexion). Although these findings do not solve the mystery of how Scutisorex uses its byzantine spine in vivo, our work suggests potentially fruitful new avenues of investigation for learning more about the function of this perplexing structure.

Differential effects of jump versus running exercise on trabecular bone architecture and strength in rats.

PurposeThis study compared differences in trabecular bone architecture and strength caused by jump and running exercises in rats.MethodsTen-week-old male Wistar rats (n=45) were randomly assigned to three body weight-matched groups: a sedentary control group (CON, n=15); a treadmill running group (RUN, n=15); and a jump exercise group (JUM, n=15). Treadmill running was performed at 25 m/min without inclination, 1 h/day, 5 days/week for 8 weeks. The jump exercise protocol comprised 10 jumps/day, 5 days/week for 8 weeks, with a jump height of 40 cm. We used microcomputed tomography to assess microarchitecture, mineralization density, and fracture load as predicted by finite element analysis (FEA) at the distal femoral metaphysis.ResultsBoth jump and running exercises produced significantly higher trabecular bone mass, thickness, number, and fracture load compared to the sedentary control group. The jump and running exercises, however, showed different results in terms of the structural characteristics of trabecular bone. Jump exercises enhanced trabecular bone mass by thickening the trabeculae, while running exercises did so by increasing the trabecular number. FEA-estimated fracture load did not differ significantly between the exercise groups.ConclusionThis study elucidated the differential effects of jump and running exercise on trabecular bone architecture in rats. The different structural changes in the trabecular bone, however, had no significant impact on trabecular bone strength.

Multiscale bone quality analysis in osteoarthritic knee joints reveal a role of the mechanosensory osteocyte network in osteophytes

Osteophytes - bony outgrowths on joint structures - are found in healthy individuals but are specifically present in late osteoarthritis (OA). Osteophyte development and function is not well understood, yet biomechanical stimuli are thought to be critical. Bone adapts to mechanical forces via the cellular network of osteocytes. The involvement of osteocytes in osteophyte formation and maturation has not been unravelled. Forty-three osteophytes from tibias of 23 OA patients (65 ± 9 years) were analysed. The trabecular bone structure of osteophytes presented with fewer trabeculae of lower bone mineral density compared to subchondral bone. We identified 40% early stage and 60% late stage osteophytes that significantly differed in their trabecular bone characteristics. Osteophyte bone revealed a higher number of osteocytes and a lower number of empty osteocyte lacunae per bone area than the subchondral bone. We found that OA osteophytes consist of younger bone material comprised of woven and lamellar bone with the capacity to develop into a late stage osteophyte potentially via the involvement of the osteocyte network. Our analysis of OA osteophytes implies a transition from woven to lamellar bone as in physiological bone growth within a pathological joint. Therefore, osteophyte development and growth present a valuable research subject when aiming to investigate the osteogenic signalling cascade.

Sclerostin Antibody Mitigates Estrogen Deficiency-Inducted Marrow Lipid Accumulation Assessed by Proton MR Spectroscopy.

Sclerostin knock-out mice or sclerostin antibody (Scl-Ab) treated wild-type mice displayed decreased marrow adiposity. But the effects of Scl-Ab on estrogen deficiency-induced marrow fat expansion remain elusive. In this work, 45 female New Zealand rabbits were equally divided into sham-operation, ovariectomy controls, and ovariectomy treated with Scl-Ab for 5 months. MR spectroscopy was performed to longitudinally assess marrow fat fraction at baseline conditions, 2.5 and 5 months post-operatively, respectively. We evaluated bone mineral density (BMD), bone structural parameters, serum bone biomarkers, and quantitative parameters of marrow adipocytes. Ovariectomized rabbits markedly exhibited expansion of marrow fat in a time-dependent manner, with a variation of marrow fat fraction (+17.8%) at 2.5 months relative to baseline and it was maintained until 5 months (+30.4%, all P < 0.001), which was accompanied by diminished BMD and deterioration of trabecular microstructure. Compared to sham controls, adipocyte mean diameter, adipocyte density and adipocytes area percentage was increased by 42.9, 68.3, and 108.6% in ovariectomized rabbits, respectively. Scl-Ab treatment increased serum bone formation marker and alleviated the ovariectomy escalation of serum bone resorption marker. It remarkably lessened the ovariectomy-mediated deterioration of BMD, and morphometric characteristics of trabecular bone. Marrow fat fraction was decreased significantly with Scl-Ab to levels matching that of sham-operated controls and correlated positively with reductions in adipocyte mean diameter, percentage adipocyte volume per marrow volume, and adipocyte density. Taken together, early Scl-Ab treatment reverts marrow fat expansion seen in ovariectomized rabbits in addition to having a beneficial effect on bone mass and microstructural properties.

Analysis of bone density in a group of patients with dental inclusion

Background/Aim: Genetic and environmental etiologic factors have been described for maxillary canine impaction, except for the trabecular bone characteristics in the impacted area. The aim of this study was to evaluate the surface area and bone density using cone-beam computed tomography (CBCT) images of patients with maxillary impacted canines. Material and Methods: The sample comprised preorthodontic treatment, CBCT images of 24 participants with unilateral maxillary impacted canines, using the impacted side as study group and the non-impacted side as control group. CBCT images were acquired in portrait mode (17 x 23 cm high field of view) at 120 kV, 5 mA, 8.9 seconds exposure time, and 0.3 mm voxel size. Each root was divided into three levels (cervical, intermediate, and apical) to determine whether the bone density change varied with the tooth level. Moreover, each level was divided into four regions (palatal, distal, mesial, and buccal sides). Bone density was measured using Hounsfield Units. Comparisons were made using paired t tests and linear regression. Repeated measurements were obtained randomly from about 20% of the sample. Results: In subjects with unilateral impactions, the maxillary bone density was higher in the impacted side, with a mean difference of 350 HU. Bone density increases in the corono-apical direction of about 100 HU in the impaction site and about 50 HU in the site of the erupted canine. The repeated measurements showed similar results. Conclusions: The maxillary alveolar bone area and bone density are increased in the impacted side compared with the nonimpacted side.

Trabecular Titanium acetabular cups in hip revision surgery: mid-term clinical and radiological outcomes.

Severe acetabular bone loss during revision hip arthroplasty can be restored with different surgical techniques. Best results have been observed using porous tantalum cementless cups. Trabecular Titanium (TT) cups were designed to reproduce the structure, mechanical and biological characteristics of trabecular bone. Few clinical studies have been published with these cups. The aim of this study is to evaluate the clinical and radiological outcome of patients with large acetabular defects (Paprosky IIb or higher) revised using TT cups. 64 consecutive patients who underwent revision for total hip arthroplasty (THA) between 2011 and 2015 at our institution were enrolled. All were classified as Paprosky IIb, IIc, IIIa and IIIb. Periprosthetic joint infections and fractures were not included in this study. Radiographic and clinical (Harris Hip Score (HHS)) outcomes were evaluated. Kaplan-Meyer survivorship curve was performed. Complete data of 58 patients (mean follow-up 48.3 months) were analysed. 6 patients underwent a further revision (10.3%). Causes of re-revision were instability (5.2%), infection (3.4%) and aseptic loosening (1.7%). No radiolucent lines or signs of migration were observed. Survivorship was 94.8%. HHS Improved from a mean of 36.5-83.7. TT cups demonstrated encouraging results at mid-term follow-up. Cup modularity represented a helpful tool to restore hip rotation centre and to reduce the risk of dislocation. The capacity of trabecular titanium to induce bone growth and the versatility of modularity, make the Delta TT System a very useful aid for surgeons who are more frequently faced with complex revision.

Alternative cone-beam computed tomography method for the analysis of bone density around impacted maxillary canines.

Genetic and environmental etiologic factors have been described for maxillary canine impaction, except for the trabecular bone characteristics in the impacted area. The aim of this study was to evaluate the surface area and fractal dimension of the alveolar bone on cone-beam computed tomography (CBCT) images of patients with maxillary impacted canines. The sample comprised preorthodontic treatment CBCT images of 49 participants with maxillary impacted canines (31 unilateral and 18 bilateral). CBCT images were acquired in portrait mode (17×23cm high field of view) at 120kV, 5mA, 8.9-seconds exposure time, and 0.3-mm voxel size. Coronal slices (0.3mm) were obtained from the right and left alveolar processes between the first and second maxillary premolars. We collected 64×64-pixel regions of interest between the premolars to assess maxillary bone area and fractal dimension using ImageJ software (National Institutes of Health, Bethesda, Md). Comparisons were made using paired t tests and linear regression. Repeated measurements were obtained randomly from about 20% of the sample. In subjects with unilateral impactions, the maxillary bone area (P=0.0227) was higher in the impacted side, with a mean difference of 245.5 pixels (SD, 569.2), but the fractal dimension (P=0.9822) was not, -0.0003 pixels (SD, 0.082). Comparisons of unilateral and bilateral subjects using a general linear mixed model test confirmed the increased bone area in the impacted side (P=0.1062). The repeated measurements showed similar results. The maxillary alveolar bone area is increased in the impacted side compared with the nonimpacted side.

Fluoride intake and cortical and trabecular bone characteristics in adolescents at age 17: A prospective cohort study.

To investigate the associations between period-specific and cumulative fluoride (F) intakes from birth to age 17years, and radial and tibial bone measures obtained using peripheral quantitative computed tomography (pQCT). Participants (n=380) were recruited from hospitals at birth and continued their participation in the ongoing Iowa Fluoride Study/Iowa Bone Development Study until age 17. Fluoride intakes from water, other beverages, selected foods, dietary fluoride supplements and dentifrice were determined every 1.5-6months using detailed questionnaires. Associations between F intake and bone measures (cortical and trabecular bone mineral content [BMC], density and strength) were determined in bivariate and multivariable analyses adjusted for height, weight, maturity offset, physical activity, and daily calcium and protein intake using robust regression analysis. Fluoride intake ranged from 0.7 to 0.8mg F/d for females and from 0.7 to 0.9mg F/d for males. Spearman correlations between daily F intake and pQCT bone measures were weak. For females, Spearman correlations ranged from r=-.08 to .21, and for males, they ranged from r=-.03 to .30. In sex-specific, height-, weight- and maturity offset- partially adjusted regression analyses, associations between females' fluoride intake and bone characteristics were almost all negative; associations for males were mostly positive. In the fully adjusted models, which also included physical activity, and protein and calcium intakes, no significant associations were detected for females; significant positive associations were detected between F intake from 14 to 17years and tibial cortical bone content (β=21.40, P<.01) and torsion strength (β=175.06, P<.01) for males. In this cohort of 17-year-old adolescents, mostly living in optimally fluoridated areas, lifelong F intake from combined sources was weakly associated with bone pQCT measures.

Sclerostin vaccination mitigates estrogen deficiency induction of bone mass loss and microstructure deterioration.

Sclerostin (SOST) is a Wnt signaling inhibitor detrimental to osteogenic differentiation and bone mineral acquisition. While control of SOST action delays the pathogenesis of skeletal disorders, the effects of SOST vaccination on the estrogen deficiency-induced bone deterioration remain elusive. In this study, we generated a SOST-Fc fusion protein which was composed of a SOST peptide Pro-Asn-Ala-Ile-Gly along with an IgG Fc fragment. SOST-Fc vaccination increased serum anti-SOST antibody levels and reduced serum SOST concentrations in mice. In vitro, anti-SOST serum attenuated the SOST-induced inhibition of osteogenic gene expression in osteoblast cultures. Administration with SOST-Fc increased serum levels of bone formation marker osteocalcin and alleviated the ovariectomy escalation of serum resorption markers CTX-1 and TRAP5b concentrations. It remarkably lessened the estrogen deficiency-mediated deterioration of bone mineral density, morphometric characteristics of trabecular bone, and mechanical strength of femurs and lumbar spines. The SOST-Fc-treated skeletal tissue exhibited moderate responses to the adverse actions of ovariectomy to bone mineral accretion, osteoclast surface, trabecular separation, and fatty marrow histopathology. SOST-Fc treatment increased serum osteoclast-inhibitory factor osteoprotegrin levels in conjunction with strong Wnt3a, β-catenin, and TCF4 immunostaining in osteoblasts, whereas it weakened the estrogen deficiency enhancement of osteoclast-promoting factor receptor activator of nuclear factor-κB ligand. Taken together, blockade of SOST action by SOST-Fc vaccination sustains Wnt signaling, which harmonizes bone mineral accretion and resorption reactions and thereby ameliorates ovariectomy-induced bone loss. This study highlights SOST-Fc fusion protein as a new molecular therapeutic potential for preventing from osteoporotic disorders.

Inférence causale dans les essais cliniques et la recherche épidémiologique

Sclerostin (SOST) is a Wnt signaling inhibitor detrimental to osteogenic differentiation and bone mineral acquisition. While control of SOST action delays the pathogenesis of skeletal disorders, the effects of SOST vaccination on the estrogen deficiency-induced bone deterioration remain elusive. In this study, we generated a SOST-Fc fusion protein which was composed of a SOST peptide Pro-Asn-Ala-Ile-Gly along with an IgG Fc fragment. SOST-Fc vaccination increased serum anti-SOST antibody levels and reduced serum SOST concentrations in mice. In vitro, anti-SOST serum attenuated the SOST-induced inhibition of osteogenic gene expression in osteoblast cultures. Administration with SOST-Fc increased serum levels of bone formation marker osteocalcin and alleviated the ovariectomy escalation of serum resorption markers CTX-1 and TRAP5b concentrations. It remarkably lessened the estrogen deficiency-mediated deterioration of bone mineral density, morphometric characteristics of trabecular bone, and mechanical strength of femurs and lumbar spines. The SOST-Fc-treated skeletal tissue exhibited moderate responses to the adverse actions of ovariectomy to bone mineral accretion, osteoclast surface, trabecular separation, and fatty marrow histopathology. SOST-Fc treatment increased serum osteoclast-inhibitory factor osteoprotegrin levels in conjunction with strong Wnt3a, β-catenin, and TCF4 immunostaining in osteoblasts, whereas it weakened the estrogen deficiency enhancement of osteoclast-promoting factor receptor activator of nuclear factor-κB ligand. Taken together, blockade of SOST action by SOST-Fc vaccination sustains Wnt signaling, which harmonizes bone mineral accretion and resorption reactions and thereby ameliorates ovariectomy-induced bone loss. This study highlights SOST-Fc fusion protein as a new molecular therapeutic potential for preventing from osteoporotic disorders.

Ultrasonic Estimation of Volume Fraction of Kelvin Structure Using Micro-Structural Model

A quantitative ultrasound (QUS) method is developed for estimation of volume fraction of porous Kelvin structure to understand acoustic characteristics of trabecular bone. A Kelvin cellular specimen composed of isotropic tetra-kaidecahedron was produced by 3D printer with ABS plastic material to simulate artificial trabecular bone. The unit cell of Kelvin specimen has a size of 3.4mm and 81% of porosity. The specimen was completely filled with paraffin wax as a substitute of bone marrow. The speed of sound (SOS) of the wax-filled Kelvin specimen was measured using the time-of-flight (TOF) of ultrasound. Based on micro-structural model, shape parameters of Kelvin specimen is correlated with SOS and elastic constant to evaluate volume fraction of the specimen quantitatively. 25.8% of volume fraction was estimated for the Kelvin specimen which has actual volume fraction of 19%. It is concluded from experiment that the ultrasonic method developed in this study is effective and can be applied to diagnose and monitor osteoporosis.