Assessing osteoporosis in postmenopausal women: preliminary results using a novel lumbar spine phantom-based MRI scoring method.

OBJECTIVE: To develop a novel magnetic resonance imaging (MRI) phantom for producing F-score (for fat) and W-score (for water) and to evaluate the performance of these scores in assessing osteoporosis and related vertebral fractures. MATERIALS AND METHODS: First, a real-time phantom consisting of oil and water tubes was manufactured. Then, 30 female volunteers (age: 62.3 ± 6.3 years) underwent lumbar spine examination with MRI (using a novel phantom) and dual-energy X-ray absorptiometry (DXA), following ethical approval. MRI phantom-based F-score and W-score were defined by normalizing the vertebral signal intensities (SIs) by the oil and water SIs of the phantom on T1- and T2-weighted images, respectively. The diagnostic performances of the new scores for assessing osteoporosis and vertebral fractures were examined using receiver operating characteristic analysis and compared with DXA-measured areal bone mineral density (DXA-aBMD). RESULTS: The F-score and W-score were greater in the osteoporotic patients (3.93 and 2.29) than the non-osteoporotic subjects (3.05 and 1.79) and achieved AUC values of 0.85 and 0.74 (p < 0.05), respectively, when detecting osteoporosis. Similarly, F-score and W-score had greater values for the fracture patients (3.94 and 2.53) than the non-fracture subjects (3.14 and 1.69) and produced better AUC values (0.90 for W-score and 0.79 for F-score) compared to DXA-aBMD (AUC: 0.27, p < 0.05). In addition, the F-score and W-score had a strong correlation (r = 0.77; p < 0.001). CONCLUSION: A novel real-time lumber spine MRI phantom was developed, based upon which newly defined F-score and W-score were able to detect osteoporosis and demonstrated an improved ability over DXA-aBMD in differentiating patients with vertebral fractures.

A Novel Screw Modeling Approach to Study the Effects of Screw Parameters on Pullout Strength.

Screw loosening remains a prominent problem for osteoporotic patients undergoing pedicle screw fixation surgeries and is affected by screw parameters (e.g., diameter, pitch, and thread angle). However, the individual and interactive effects of these parameters on screw fixation are not fully understood. Furthermore, the current finite element modeling of a threaded screw is less computationally efficient. To address these issues, we (1) explored a novel "simulated threaded screw" approach (virtual threads assigned to the contact elements of a simplified screw) and compared its performance with threaded and simplified screws, and (2) examined this approach the individual and interactive effects of altering screw diameter (5.5-6.5 mm), pitch (1-2 mm) and half-thread angle (20-30 deg) on pullout strength of normal vertebrae. Results demonstrated that the "simulated threaded screw" approach equivalently predicted pullout strength compared to the "threaded screw" approach (R2 = 0.99, slope = 1). We further found that the pullout strength was most sensitive to the change in screw diameter, followed by thread angle, pitch, and interactions of diameter*pitch or diameter*angle. In conclusion, the "simulated threaded screw" approach can achieve the same predictive capability compared to threaded modeling of the screw. The current findings may serve as useful references for planning of screw parameters, so as to improve the complication of screw loosening.

Diagnostic Role of Magnetic Resonance Imaging in Low Back Pain Caused by Vertebral Endplate Degeneration.

Low back pain (LBP) is a common health issue worldwide with a huge economic burden on healthcare systems. In the United States alone, the cost is estimated to be $100 billion each year. Intervertebral disc degeneration is considered one of the primary causes of LBP. Moreover, the critical role of the vertebral endplates in disc degeneration and LBP is becoming apparent. Endplate abnormalities are closely correlated with disc degeneration and pain in the lumbar spine. Imaging modalities such as plain film radiography, computed tomography, and fluoroscopy are helpful but not very effective in detecting the causes behind LBP. Magnetic resonance imaging (MRI) can be used to acquire high-quality three-dimensional images of the lumbar spine without using ionizing radiation. Therefore, it is increasingly being used to diagnose spinal disorders. However, according to the American College of Radiology, current referral and justification guidelines for MRI are not sufficiently clear to guide clinical practice. This review aimed to evaluate the role of MRI in diagnosing LBP by considering the correlative contributions of vertebral endplates. The findings of the review indicate that MRI allows for fine evaluations of endplate morphology, endplate defects, diffusion and perfusion properties of the endplate, and Modic changes. Changes in these characteristics of the endplate were found to be closely correlated with disc degeneration and LBP. The collective evidence from the literature suggests that MRI may be the imaging modality of choice for patients suffering from LBP. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 3.

In Vivo Assessment of Age- and Loading Configuration-Related Changes in Multiscale Mechanical Behavior of the Human Proximal Femur Using MRI-Based Finite Element Analysis.

BACKGROUND: MRI-based finite element analysis (MRI-FEA) is the only method able to assess microstructural and whole-bone mechanical properties of the hip in vivo. PURPOSE: To examine whether MRI-FEA is capable of discriminating age-related changes in whole-bone mechanical performance and micromechanical behavior of the proximal femur, particularly considering the most common hip fracture-related sideways fall loading. STUDY TYPE: Retrospective. SUBJECTS: A total of nine younger (27 ± 3.2 years) and nine elderly (61 ± 3.9 years) healthy volunteers. FIELD STRENGTH/SEQUENCE: 3T; 3D fast field echo sequence. ASSESSMENT: The left proximal femurs were scanned and FE models created. FEA was performed to simulate sideways fall and stance loading for each femoral model. Apparent stiffness and high-risk (90th percentile) tensile and compressive strains of the proximal femur as well as the average strains within cubic regions of the femoral neck and greater trochanter were assessed. STATISTICAL TESTS: Paired and unpaired t-tests. RESULTS: Compared to the young group, the femoral stiffness of the elderly decreased by 39% and 40% (both P < 0.05) under the sideways fall and stance conditions, respectively. Accordingly, the high-risk tensile and compressive stains were elevated with aging (40% and 23% for sideways fall, 23% and 11% for stance conditions; all P < 0.05). However, the loading configuration-induced difference was only observed in the elderly group for the high-risk strains (22% for tension and 12% for compression; both P < 0.05). Additionally, compared to the stance condition, the sideways fall increased the average tensile (young: 108%, elderly: 123%; both P < 0.05) and compressive strains (young: 631%, elderly: 617%, both P < 0.05) within the greater trochanter rather than the femoral neck region. DATA CONCLUSION: In vivo MRI-FEA is capable of capturing age-related changes in both apparent-level stiffness and tissue-level micromechanical behavior of the proximal femur. However, the effect of sideways fall loading might be better reflected by tissue-level micromechanics rather than apparent stiffness. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 1.

Disparities in Learning Mode Access Among K-12 Students During the COVID-19 Pandemic, by Race/Ethnicity, Geography, and Grade Level - United States, September 2020-April 2021.

In response to the COVID-19 pandemic, schools across the United States began transitioning to virtual learning during spring 2020. However, schools' learning modes varied during the 2020-21 school year across states as schools transitioned at differing times back to in-person learning, in part reflecting updated CDC guidance. Reduced access to in-person learning is associated with poorer learning outcomes and adverse mental health and behavioral effects in children (1-3). Data on the learning modes available in 1,200 U.S. public school districts (representing 46% of kindergarten through grade 12 [K-12] public school enrollment) from all 50 states and the District of Columbia during September 2020-April 2021 were matched with National Center for Education Statistics (NCES) demographic data. Learning mode access was assessed for K-12 students during the COVID-19 pandemic, over time and by student race/ethnicity, geography, and grade level group. Across all assessed racial/ethnic groups, prevalence of virtual-only learning showed more variability during September-December 2020 but declined steadily from January to April 2021. During January-April 2021, access to full-time in-person learning for non-Hispanic White students increased by 36.6 percentage points (from 38.0% to 74.6%), compared with 31.1 percentage points for non-Hispanic Black students (from 32.3% to 63.4%), 23.0 percentage points for Hispanic students (from 35.9% to 58.9%) and 30.6 percentage points for students of other races/ethnicities (from 26.3% to 56.9%). In January 2021, 39% of students in grades K-5 had access to full-time in-person learning compared with 33% of students in grades 6-8 and 30% of students in grades 9-12. Disparities in full-time in-person learning by race/ethnicity existed across school levels and by geographic region and state. These disparities underscore the importance of prioritizing equitable access to this learning mode for the 2021-22 school year. To increase equitable access to full-time in-person learning for the 2021-22 school year, school leaders should focus on providing safety-optimized in-person learning options across grade levels. CDC's K-12 operational strategy presents a pathway for schools to safely provide in-person learning through implementing recommended prevention strategies, increasing vaccination rates for teachers and older students with a focus on vaccine equity, and reducing community transmission (4).

Highly Photoluminescent CsPbBr3/CsPb2Br5 NCs@TEOS Nanocomposite in Light-Emitting Diodes.

All-inorganic halide perovskite (CsPb2Br5) nanocrystals (NCs) have received widespread attention owing to their unique photoelectric properties. This work reports a novel strategy to control the phase transition from CsPbBr3 to CsPb2Br5 and investigates the effects of different treatment times and treatment temperatures on perovskite NCs formation. By controlling the volume of tetraethoxysilane (TEOS) added, the formation of different phases of perovskite powder can be well controlled. In addition, a white light-emitting diode (WLED) device is designed by coupling the CsPbBr3/CsPbBr3-CsPb2Br5 NCs@TEOS nanocomposite and CaAlSiN3:Eu2+ commercial phosphor with a 460 nm InGaN blue chip, exhibiting a high luminous efficiency of 57.65 lm/W, color rendering index (CRI) of 91, and a low CCT of 5334 K. The CIE chromaticity coordinates are (0.3363, 0.3419). This work provides a new strategy for the synthesis of CsPbBr3/CsPbBr3-CsPb2Br5 NCs@TEOS nanocomposite, which can be applied to the field of WLEDs and display devices.

Enhancing the Efficiency of Distraction Osteogenesis through Rate-Varying Distraction: A Computational Study.

Distraction osteogenesis (DO) is a mechanobiological process of producing new bone and overlying soft tissues through the gradual and controlled distraction of surgically separated bone segments. The process of bone regeneration during DO is largely affected by distraction parameters. In the present study, a distraction strategy with varying distraction rates (i.e., "rate-varying distraction") is proposed, with the aim of shortening the distraction time and improving the efficiency of DO. We hypothesized that faster and better healing can be achieved with rate-varying distractions, as compared with constant-rate distractions. A computational model incorporating the viscoelastic behaviors of the callus tissues and the mechano-regulatory tissue differentiation laws was developed and validated to predict the bone regeneration process during DO. The effect of rate-varying distraction on the healing outcomes (bony bridging time and bone formation) was examined. Compared to the constant low-rate distraction, a low-to-high rate-varying distraction provided a favorable mechanical environment for angiogenesis and bone tissue differentiation, throughout the distraction and consolidation phase, leading to an improved healing outcome with a shortened healing time. These results suggest that a rate-varying clinical strategy could reduce the overall treatment time of DO and decrease the risk of complications related to the external fixator.

[Numerical simulation of fracture healing].

Fracture is a common physical injury. Its healing process involves complex biological activities at tissue, cellular and molecular levels and is affected by mechanical and biological factors. Over recent years, numerical simulation methods have been widely used to explore the mechanisms of fracture healing, design fixators and develop novel treatment strategies, etc. This paper mainly recommend the numerical methods used for simulating fracture healing and their latest research progress, which helps people better understand the mechanism of fracture healing, and also provides direction and guidance for the numerical simulation research of fracture healing in the future. First, the fracture healing process and its relationship with mechanical stimulation and biological factors are described. Then, the numerical models used for simulating fracture healing (including mechano-regulatory model, biological regulatory model and mechano-biological regulatory model) and corresponding modeling techniques (mainly including agent-based techniques and fuzzy logic controlling method) were summarized in particular. Finally, the future research directions in numerical simulation of fracture healing were preliminarily prospected.

KCNQ1OT1 facilitates progression of non-small-cell lung carcinoma via modulating miRNA-27b-3p/HSP90AA1 axis.

Long noncoding RNA KCNQ1OT1 participates in the regulation of imprinted genes within the kcnq1 domain. But its roles in carcinogenesis and metastasis remain largely elusive. Herein, we evaluated its potential in non-small-cell lung cancer (NSCLC) progression. We demonstrated that the KCNQ1OT1 level was upregulated in NSCLC tissues and cell lines. High KCNQ1OT1 level correlated with poor overall and progression-free survival in NSCLC patients. KCNQ1OT1 facilitated proliferation, migration, and invasion in H460 cells. Furthermore, knockdown of KCNQ1OT1 reduced the expression of HSP90AA1. KCNQ1OT1 presented a positive correlation with HSP90AA1 which predicted the tumor progression in NSCLC from The Cancer Genome Atlas database. Intriguingly, KCNQ1OT1 modulated HSP90AA1 expression by sponging miR-27b-3p. MiR-27b-3p counteracted the effect of KCNQ1OT1 on HSP90AA1 expression, H460 cell migration, and invasion. These data revealed a role for KCNQ1OT1 as an oncogene through miR-27b-3p/HSP90AA1 axis during NSCLC progression.

Hemodynamic effects of enhanced external counterpulsation on cerebral arteries: a multiscale study.

BACKGROUND: Enhanced external counterpulsation (EECP) is an effective method for treating patients with cerebral ischemic stroke, while hemodynamics is the major contributing factor in the treatment of EECP. Different counterpulsation modes have the potential to lead to different acute and long-term hemodynamic changes, resulting in different treatment effects. However, various questions about appropriate counterpulsation modes for optimizing hemodynamic effects remain unanswered in clinical treatment. METHODS: A zero-dimensional/three-dimensional (0D/3D) geometric multiscale model of the cerebral artery was established to obtain acute hemodynamic indicators, including mean arterial pressure (MAP) and cerebral blood flow (CBF), as well as localized hemodynamic details for the cerebral artery, which includes wall shear stress (WSS) and oscillatory shear index (OSI). Counterpulsation was achieved by applying pressure on calf, thigh and buttock modules in the 0D model. Different counterpulsation modes including various pressure amplitudes and pressurization durations were applied to investigate hemodynamic responses, which impact acute and long-term treatment effects. Both vascular collapse and cerebral autoregulation were considered during counterpulsation. RESULTS: Variations of pressure amplitude and pressurization duration have different impacts on hemodynamic effects during EECP treatment. There were small differences in the hemodynamics when similar or different pressure amplitudes were applied to calves, thighs and buttocks. When increasing pressure amplitude was applied to the three body parts, MAP and CBF improved slightly. When pressure amplitude exceeded 200 mmHg, hemodynamic indicators almost never changed, demonstrating consistency with clinical data. However, hemodynamic indicators improved significantly with increasing pressurization duration. For pressurization durations of 0.5, 0.6 and 0.7 s, percentage increases for MAP during counterpulsation were 1.5%, 23.5% and 39.0%, for CBF were 1.2%, 23.4% and 41.6% and for time-averaged WSS were 0.2%, 43.5% and 85.0%, respectively. CONCLUSIONS: When EECP was applied to patients with cerebral ischemic stroke, pressure amplitude applied to the three parts may remain the same. Patients may not gain much more benefit from EECP treatment by excessively increasing pressure amplitude above 200 mmHg. However, during clinical procedures, pressurization duration could be increased to 0.7 s during the cardiac circle to optimize the hemodynamics for possible superior treatment outcomes.

Serum KL-6 and the mortality of patients with connective tissue disease-associated interstitial lung disease: A meta-analysis.

Connective tissue disease-associated interstitial lung disease (CTD-ILD) is an important underlying cause of morbidity and mortality in patients with CTD. Serum Krebs von den Lungen-6 (KL-6) is an immune factor which has been related to the severity of ILD. This systematic review and meta-analysis aimed to evaluate the association between serum KL-6 and mortality of patients with CTD-ILD. Longitudinal studies relevant to the aim of the meta-analysis were retrieved by search of electronic databases including PubMed, Web of Science, and Embase. A random-effects model was used to combine the data by incorporating the influence of between-study heterogeneity. Fifteen cohorts involving 1737 patients with CTD-ILD were included. During a mean follow-up of 35.3 months, 430 (24.8%) patients died. Compared to those with a lower KL-6 at admission, patients with a higher KL-6 were associated with a higher mortality risk during follow-up (risk ratio: 2.18, 95% confidence interval: 1.66 to 2.87, P < 0.001; I2 = 20%). Subgroup analysis showed a significant association in studies from Asian countries, but not in those from non-Asian countries; in studies with cutoff of KL-6 derived in receiver operating characteristic (ROC) curve analysis, but not in those derived from other methods; in studies with multivariate analysis, but not in those with univariate analysis (P for subgroup difference all < 0.05). The association was not significantly affected by different CTDs or methods for measuring serum KL-6. In conclusion, a high serum KL-6 may be a risk factor of increased mortality in patients with CTD-ILD.

By-degree Health and Economic Impacts of Lyme Disease, Eastern and Midwestern United States.

Lyme disease (LD) is the most common vector-borne disease in the United States (U.S.). This paper assesses how climate change may influence LD incidence in the eastern and upper Midwestern U.S. and the associated economic burden. We estimated future Ixodes scapularis habitat suitability and LD incidence with a by-degree approach using variables from an ensemble of multiple climate models. We then applied estimates for present-day and projected habitat suitability for I. scapularis, present-day presence of Borrelia burgdorferi, and projected climatological variables to model reported LD incidence at the county level among adults, children, and the total population. Finally, we applied an estimate of healthcare expenses to project economic impacts. We show an overall increase in LD cases with regional variation. We estimate an increase in incidence in New England and the upper Midwestern U.S. and a concurrent decrease in incidence in Virginia and North Carolina. At 3°C of national warming from the 1986-2015 baseline climate, we project approximately 55,000 LD cases, a 38-percent increase from present-day estimates. At 6°C of warming, our most extreme scenario, we project approximately 92,000 LD cases in the region, an increase of 145 percent relative to current levels. Annual LD-related healthcare expenses at 3°C of warming are estimated to be $236 million (2021 dollars), approximately 38 percent greater than present-day. These results may inform decision-makers tasked with addressing climate risks, the public, and healthcare professionals preparing for treatment and prevention of LD.

Non-invasive fractional flow reserve derived from reduced-order coronary model and machine learning prediction of stenosis flow resistance.

BACKGROUND AND OBJECTIVE: Recently, computational fluid dynamics enables the non-invasive calculation of fractional flow reserve (FFR) based on 3D coronary model, but it is time-consuming. Currently, machine learning technique has emerged as an efficient and reliable approach for prediction, which allows saving a lot of analysis time. This study aimed at developing a simplified FFR prediction model for rapid and accurate assessment of functional significance of stenosis. METHODS: A reduced-order lumped parameter model (LPM) of coronary system and cardiovascular system was constructed for rapidly simulating coronary flow, in which a machine learning model was embedded for accurately predicting stenosis flow resistance at a given flow from anatomical features of stenosis. Importantly, the LPM was personalized in both structures and parameters according to coronary geometries from computed tomography angiography and physiological measurements such as blood pressure and cardiac output for personalized simulations of coronary pressure and flow. Coronary lesions with invasive FFR ≤ 0.80 were defined as hemodynamically significant. RESULTS: A total of 91 patients (93 lesions) who underwent invasive FFR were involved in FFR derived from machine learning (FFRML) calculation. Of the 93 lesions, 27 lesions (29.0%) showed lesion-specific ischemia. The average time of FFRML simulation was about 10 min. On a per-vessel basis, the FFRML and FFR were significantly correlated (r = 0.86, p < 0.001). The diagnostic accuracy, sensitivity, specificity, positive predictive value and negative predictive value were 91.4%, 92.6%, 90.9%, 80.6% and 96.8%, respectively. The area under the receiver-operating characteristic curve of FFRML was 0.984. CONCLUSION: In this selected cohort of patients, the FFRML improves the computational efficiency and ensures the accuracy. The favorable performance of FFRML approach greatly facilitates its potential application in detecting hemodynamically significant coronary stenosis in future routine clinical practice.

Biomechanical Study and Analysis for Cardiovascular/Skeletal Materials and Devices.

The Special Issue entitled "Biomechanical Study and Analysis for Cardiovascular/Skeletal Materials and Devices" addresses biological functional materials and devices relevant to cardiovascular diseases and orthopedic conditions [...].

Biomechanical MRI detects reduced bone strength in subjects with vertebral fractures.

Vertebral fracture is one of the most serious consequences of osteoporosis. Estimation of vertebral strength from magnetic resonance imaging (MRI) scans may provide a new approach for the prediction of vertebral fractures. To that end, we sought to establish a biomechanical MRI (BMRI) method to compute vertebral strength and test its ability to distinguish fracture from non-fracture subjects. This case-control study included 30 subjects without vertebral fractures and 15 subjects with vertebral fractures. All subjects underwent MRI with a mDIXON-Quant sequence and quantitative computed tomography (QCT), from which proton fat fraction-based bone marrow adipose tissue (BMAT) content and volumetric bone mineral density (vBMD) were measured, respectively. Nonlinear finite element analysis was applied to MRI and QCT scans of L2 vertebrae to compute vertebral strength (BMRI- and BCT-strength). The differences in BMAT content, vBMD, BMRI-strength and BCT-strength between the two groups were examined by t-tests. Receiver operating characteristic (ROC) analysis was performed to assess the ability of each measured parameter to distinguish fracture from non-fracture subjects. Results showed that the fracture group had 23 % lower BMRI-strength (P < .001) and 19 % higher BMAT content (P < .001) than the non-fracture group, whereas no significant difference in vBMD was detected between the two groups. A poor correlation was found between vBMD and BMRI-strength (R2 = 0.33). Compared to vBMD and BMAT content, BMRI- and BCT-strength had the larger area under the curve (0.82 and 0.84, respectively) and provided better sensitivity and specificity in separating fracture from non-fracture subjects. In conclusion, BMRI is capable of detecting reduced bone strength in patients with vertebral fracture, and may serve as a new approach for risk assessment of vertebral fracture.

Biomechanical CT-computed bone strength predicts the risk of subsequent vertebral fracture.

Following primary fractures and percutaneous kyphoplasty (PKP), patients have a high risk of incurring a subsequent vertebral fracture (SVF). Given that SVF is a consequence of mechanical deterioration of the vertebra, we sought to examine whether vertebral strength derived from QCT-based finite element analysis (i.e., BCT) can predict the risk of SVF. Sixty-six patients who underwent PKP were categorized into two groups: control or non-SVF group (age: 70 ± 7 years; n = 40) and SVF group (age: 69 ± 8 years; n = 26). BCT was performed on L4 or L3 vertebrae to noninvasively measure vertebral strength. Vertebral strength was also estimated based upon the geometry and material properties of the vertebra. Additionally, trabecular volumetric bone mineral density (vBMD) and L1 Hounsfield unit (HU) were measured. t-Test, χ2 test or Mann Whitney U test were used to compare differences in these parameters between the two groups. The predictive abilities of BCT strength and other measured parameters were evaluated using the receiver operating characteristic (ROC) analysis. Results showed no significant difference in either vBMD or L1 HU between the control and SVF groups (p > 0.05), whereas BCT-computed and estimated vertebral strength values were significantly reduced by 33 % and 24 % for the SVF group relative to the non-SVF group, respectively. ROC curve indicated that BCT strength had the largest area under the curve, compared to other parameters. These results suggest that BCT-computed vertebral strength may serve as a surrogate for assessing risk of SVF.

Craniocaudal toggling increases the risk of screw loosening in osteoporotic vertebrae.

BACKGROUND AND OBJECTIVE: Screw loosening remains a prominent problem for osteoporotic patients undergoing pedicle screw fixation surgeries but its underlying mechanisms are not fully understood. This study sought to examine the interactive effect of craniocaudal or axial cyclic loading (toggling) and osteoporosis on screw fixation. METHODS: QCT-based finite element models of normal (n = 7; vBMD = 156 ± 13 mg/cm3) and osteoporotic vertebrae (n = 7; vBMD = 72 ± 6 mg/cm3) were inserted with pedicle screws and loaded with or without craniocaudal toggling. Among them, a representative normal vertebra (age: 55; BMD: 140 mg/cm3) and an osteoporotic vertebra (age: 64; BMD: 79 mg/cm3) were also loaded with or without axial toggling. The individual and interactive effects of craniocaudal toggling and osteoporosis on screw fixation strength (the force when the pull-up displacement of the screw head reached 1 mm) and bone tissue failure (characterized by equivalent plastic strain) were examined by repeated measure ANOVA. RESULTS: A significant interactive effect between craniocaudal toggling and osteoporosis on screw fixation strength was detected (p = 0.008). Specifically, craniocaudal toggling led to a marked decrease in the fixation strength (68%, p < 0.05) and stiffness (83%, p < 0.05) only in the osteoporotic vertebrae but had no effect on screw fixation strength and stiffness of the normal vertebrae (p > 0.05). Likewise, most of the bone tissues around the screw in the osteoporotic vertebrae yielded following craniocaudal toggling whereas this result was not seen in the normal vertebrae. The axial toggling had no significant effect on bone tissue failure as well as pedicle screw fixation in normal or osteoporotic vertebrae. CONCLUSIONS: Craniocaudal toggling substantially reduces the screw fixation strength of the osteoporotic vertebrae by progressively increasing tissue failure around the screw, and therefore may contribute to the higher rates of screw loosening in osteoporotic compared to normal patients, whereas axial toggling is not a risk factor for pedicle screw loosening in normal or osteoporotic patients.

Osteocyte Estrogen Receptor ß (Ot-ERß) Regulates Bone Turnover and Skeletal Adaptive Response to Mechanical Loading Differently in Male and Female Growing and Adult Mice.

Age-related bone loss is a failure of balanced bone turnover and diminished skeletal mechanoadaptation. Estrogen receptors, ERα and ERß, play critical roles in osteoprotective regulation activated by estrogen and mechanical signals. Previous studies mainly focused on ERα and showed that osteocyte-ERα (Ot-ERα) regulated trabecular, but not cortical bone, and played a minor role in load-induced cortical adaptation. However, the role of Ot-ERß in bone mass regulation remains unrevealed. To address this issue, we characterized bone (re)modeling and gene expression in male and female mice with Ot-ERß deletion (ERß-dOT) and littermate control (LC) at 10 weeks (young) or 28 weeks (adult) of age, as well as their responses to in vivo tibial compressive loading. Increased cancellous bone mass appeared in the L4 vertebral body of young male ERß-dOT mice. At the same time, femoral cortical bone gene expression showed signs consistent with elevated osteoblast and osteoclast activities (type-I collagen, Cat K, RANKL). Upregulated androgen receptor (AR) expression was observed in young male ERß-dOT mice relative to LC, suggesting a compensatory effect of testosterone on male bone protection. In contrast, bone mass in L4 decreased in adult male ERß-dOT mice, attributed to potentially increased bone resorption activity (Cat K) with no change in bone formation. There was no effect of ERß-dOT on bone mass or gene expression in female mice. Sex-dependent regulation of Ot-ERß also appeared in load-induced cortical responsiveness. Young female ERß-dOT mice showed an enhanced tibial cortical anabolic adaptation compared with LC. In contrast, an attenuated cortical anabolic response presented at the proximal tibia in male ERß-dOT mice at both ages. For the first time, our findings suggest that Ot-ERß regulates bone (re)modeling and the response to mechanical signals through different mechanisms in males and females. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Effects of dynamization timing and degree on bone healing of different fracture types.

Dynamization, that is, increasing interfragmentary movement (IFM) by reducing fixation stiffness from a rigid to a more flexible state, has been successfully used in clinical practice to promote fracture healing. However, it remains unclear how dynamization timing and degree affect bone healing of different fracture types. Finite element models of tibial fractures based on the OTA/AO classification (Simple: A1-Spiral, A2-Oblique, A3-Transverse; Wedge: B2-Spiral, B3-Fragmented; Complex: C2-Segment, C3-Irregular), in combination with fuzzy logic-based mechano-regulatory tissue differentiation algorithms, were used to simulate the healing process when dynamization of varied degrees (dynamization coefficient or DC = 0-0.9; 0.9 represents 90% reduction in the fixation stiffness relative to a rigid fixation) were applied at different time points after fracture. The fuzzy logic-based algorithms have been validated with a preclinical animal model. The results showed that the healing responses of type A fractures were more sensitive to the changes in dynamization degree and timing comparing with type B or C fractures. Additionally, the optimal dynamization regime for each fracture type was different. For type A fractures, a moderate dynamization degree (e.g., DC = 0.5) applied after Week 1 promoted the recovery of biomechanical integrity. For type B and C fractures, the effective dynamization included a greater dynamization degree (DC = 0.7) applied after Week 2. Our results further demonstrated that the fracture morphology affected interfragmentary strain environments within the callus, leading to varied healing results for different fracture types. These results suggest that the effects of dynamization are highly dependent of the fracture types. Therefore, specific dynamization strategies should be chosen for different fracture types to achieve optimal healing outcomes.