Trabecular Bone Microstructure Research Articles

TBS correlates with bone density and microstructure at trabecular and cortical bone evaluated by HR-pQCT.

Trabecular bone score (TBS) estimates bone microstructure, which is directly measured by high-resolution peripheral quantitative computed tomography (HRpQCT). We evaluated the correlation between these methods and TBS influence on fracture risk assessed by FRAX. We evaluated 129 individuals (82 women, 43 postmenopausal) 20 to 82.3 years without prevalent clinical or non-clinical morphometric vertebral fractures, using DXA (spine and hip), HR-pQCT at distal radius (R) and tibia (T) and TBS which classifies bone microarchitecture as normal (TBS ≥ 1.350), partially degraded (1.200 < TBS < 1.350), or degraded (TBS ≤ 1.200). Spine and hip BMD and HR-pQCT parameters at cortical bone: area (T), density (R,T) thickness (T) and trabecular bone: density (R,T), number (T) and thickness (R) were significantly better in the 78 individuals with normal TBS (group 1) versus the 51 classified as partially degraded (n = 42) or degraded microarchitecture (n = 9) altogether (group 2). TBS values correlated with age (r = -0.55), positively with spine and hip BMD and all cortical and trabecular bone density and microstructure parameters evaluated, p < 0.05 all tests. Binary logistic regression defined age (p = 0.008) and cortical thickness (p = 0.018) as main influences on TBS, while ANCOVA demonstrated that HR-pQCT data corrected for age were not different between TBS groups 1 and 2. TBS adjustment increased FRAX risk for major osteoporotic fractures and hip fractures. We describe significant association between TBS and both trabecular and cortical bone parameters measured by HR-pQCT, consistent with TBS influence on fracture risk estimation by FRAX, including hip fractures, where cortical bone predominates.

Identification of Drug Targets and Agents Associated with Ferroptosis-related Osteoporosis through Integrated Network Pharmacology and Molecular Docking Technology.

Osteoporosis is a systemic bone disease characterized by progressive reduction of bone mineral density and degradation of trabecular bone microstructure. Iron metabolism plays an important role in bone; its imbalance leads to abnormal lipid oxidation in cells, hence ferroptosis. In osteoporosis, however, the exact mechanism of ferroptosis has not been fully elucidated. The main objective of this project was to identify potential drug target proteins and agents for the treatment of ferroptosis-related osteoporosis. In the current study, we investigated the differences in gene expression of bone marrow mesenchymal stem cells between osteoporosis patients and normal individuals using bioinformatics methods to obtain ferroptosis-related genes. We could predict their protein structure based on the artificial intelligence database of AlphaFold, and their target drugs and binding sites with the network pharmacology and molecular docking technology. We identified five genes that were highly associated with osteoporosis, such as TP53, EGFR, TGFB1, SOX2 and MAPK14, which, we believe, can be taken as the potential markers and targets for the diagnosis and treatment of osteoporosis. Furthermore, we observed that these five genes were highly targeted by resveratrol to exert a therapeutic effect on ferroptosis-related osteoporosis. We examined the relationship between ferroptosis and osteoporosis based on bioinformatics and network pharmacology, presenting a promising direction to the pursuit of the exact molecular mechanism of osteoporosis so that a new target can be discovered for the treatment of osteoporosis.

Deep learning-based harmonization of trabecular bone microstructures between high- and low-resolution CT imaging.

Osteoporosis is a bone disease related to increased bone loss and fracture-risk. The variability in bone strength is partially explained by bone mineral density (BMD), and the remainder is contributed by bone microstructure. Recently, clinical CT has emerged as a viable option for in vivo bone microstructural imaging. Wide variations in spatial-resolution and other imaging features among different CT scanners add inconsistency to derived bone microstructural metrics, urging the need for harmonization of image data from different scanners. This paper presents a new deep learning (DL) method for the harmonization of bone microstructural images derived from low- and high-resolution CT scanners and evaluates the method's performance at the levels of image data as well as derived microstructural metrics. We generalized a three-dimensional (3D) version of GAN-CIRCLE that applies two generative adversarial networks (GANs) constrained by the identical, residual, and cycle learning ensemble (CIRCLE). Two GAN modules simultaneously learn to map low-resolution CT (LRCT) to high-resolution CT (HRCT) and vice versa. Twenty volunteers were recruited. LRCT and HRCT scans of the distal tibia of their left legs were acquired. Five-hundred pairs of LRCT and HRCT image blocks of voxels were sampled for each of the twelve volunteers and used for training in supervised as well as unsupervised setups. LRCT and HRCT images of the remaining eight volunteers were used for evaluation. LRCT blocks were sampled at 32 voxel intervals in each coordinate direction and predicted HRCT blocks were stitched to generate a predicted HRCT image. Mean±standard deviation of structural similarity (SSIM) values between predicted and true HRCT using both 3DGAN-CIRCLE-based supervised (0.84±0.03) and unsupervised (0.83±0.04) methods were significantly (p<0.001) higher than the mean SSIM value between LRCT and true HRCT (0.75±0.03). All Tb measures derived from predicted HRCT by the supervised 3DGAN-CIRCLE showed higher agreement (CCC [0.956 0.991]) with the reference values from true HRCT as compared to LRCT-derived values (CCC [0.732 0.989]). For all Tb measures, except Tb plate-width (CCC=0.866), the unsupervised 3DGAN-CIRCLE showed high agreement (CCC [0.920 0.964]) with the true HRCT-derived reference measures. Moreover, Bland-Altman plots showed that supervised 3DGAN-CIRCLE predicted HRCT reduces bias and variability in residual values of different Tb measures as compared to LRCT and unsupervised 3DGAN-CIRCLE predicted HRCT. The supervised 3DGAN-CIRCLE method produced significantly improved performance (p<0.001) for all Tb measures as compared to the two DL-based supervised methods available in the literature. 3DGAN-CIRCLE, trained in either unsupervised or supervised fashion, generates HRCT images with high structural similarity to the reference true HRCT images. The supervised 3DGAN-CIRCLE improves agreements of computed Tb microstructural measures with their reference values and outperforms the unsupervised 3DGAN-CIRCLE. 3DGAN-CIRCLE offers a viable DL solution to retrospectively improve image resolution, which may aid in data harmonization in multi-site longitudinal studies where scanner mismatch is unavoidable.

Validated, high-resolution, non-linear, explicit finite element models for simulating screw - bone interaction

Background and ObjectivePrimary stability evaluation of screw implants through pull-out or push-in experiments is commonly used to investigate the mechanism of screw loosening. Numerical models simulating these testing methods could provide an enhanced understanding of the underlying attachment mechanisms as well as save time and cost in the development of new screws. However, previous numerical models have been limited by compromises between modelling the trabecular structure at high resolution versus incorporating sophisticated mechanical properties and boundary conditions, leading to overestimated mechanical performance. The aim of this study was to overcome these limitations. MethodsWe developed explicit models incorporating the microstructure of trabecular bone, with frictional contact, and a non-linear material model incorporating damage. One model digitally inserted the screw into the trabecular bone structure using Boolean operations, while another model simulated the screw's rotational insertion. ResultsThe results showed a strong correlation between numerical and experimental results (R2: 0.54–0.93) for force-displacement response in terms of stiffness and strength. We found that the damage induced by the screw insertion process is an important factor to be considered, as the absence of modelling it led to an overestimated stiffness in previous studies. ConclusionsThe study highlights the importance of including frictional contact and also identified screw insertion damage as an important part of the simulating screw-bone interaction. Our findings demonstrate the potential of explicit finite element models for accurately replicating experimental push-in results and optimizing orthopaedic screws. The code is available at https://github.com/zhou436/Bone-Screw-Constructs-eFEM.

Menopause-Associated Changes in Mandibular Bone Microarchitecture Are Site-Specific

BackgroundThere are conflicting reports on the effects of decreased estrogen levels on mandibular bone microarchitecture, and whether these effects are consistent throughout the mandible is unclear and may have important implications for treatment planning. PurposeThe goal of this study was to evaluate trabecular and cortical bone microstructure in the mandibular condyle and the mandibular basal bone and compare these sites between premenopausal and postmenopausal women. Study Design, Setting, SampleParticipants were recruited for a cross-sectional cohort study at Columbia University Irving Medical Center. Each participant had CBCT taken of their mandibular condyles and of the basal bone. Exclusion criteria for the population included a) current chemo- or immunotherapy; b) history of bisphosphonate or other osteoporosis therapy; and c) currently pregnant, nursing, or on hormonal birth control. Independent VariableThe predictor variables are menopausal status (before or after menopause) and mandibular region of interest (condyle/basal bone). Outcome VariableParameters of interest included the following indicators of bone quality: trabecular bone volume fraction (BVF), trabecular thickness, trabecular number, trabecular separation, cortical BVF, cortical thickness, and cortical porosity. CovariatesCovariates included demographic variables such as age, estrogen levels, and ethnicity. AnalysesQuantitative microstructure analyses were conducted on CBCT images, and differences between groups for continuous measures (including age) were assessed with unpaired t-test, and demographic variables were assessed by Chi-square. Statistical significance was recorded at p<0.05. ResultsThe premenopausal and postmenopausal groups each had 31 participants, with the following average age: premenopausal= 43.9±6.9 vs. postmenopausal = 57.5±7.6 years old; p<0.001, and estrogen levels: premenopausal =91.77±80.13 pg/ml vs. postmenopausal= 41.44±61.62 pg/ml; p <0.01). Postmenopausal women had significantly greater condylar trabecular separation (0.61±0.18 vs 0.47±0.11 mm; p<0.001) and lower trabecular number (1.03±0.18 vs 1.21±0.19 1/mm; p<0.001) compared to premenopausal women. There were no significant differences in the basal bone microarchitectural parameters between the menopausal groups. Conclusion and RelevanceMenopause is associated with mandibular condylar trabecular bone loss but has minimal effects on the mandibular basal bone. This may have important ramifications for treatment planning in advanced age individuals.

Association of serum osteocalcin with bone microarchitecture and muscle mass in Beijing community-dwelling postmenopausal women.

Osteoporosis is a systemic skeletal disease with increasing bone fragility and prone to fracture. Osteocalcin (OC), as the most abundant non collagen in bone matrix, has been extensively used in clinic as a biochemical marker of osteogenesis. Two forms of OC were stated on circulation, including carboxylated osteocalcin (cOC) and undercarboxylated osteocalcin (ucOC). OC was not only involved in bone mineralization, but also in the regulation of muscle function. This study explored the relationship between serum OC, cOC, ucOC levels and bone mineral density (BMD), bone microarchitecture, muscle mass and physical activity in Chinese postmenopausal women. 216 community-dwelling postmenopausal women were randomized enrolled. All subjects completed biochemical measurements, including serum β-isomer of C-terminal telopeptides of type I collagen (β-CTX), N-terminal propeptide of type 1 procollagen (P1NP), alkaline phosphatase (ALP), OC, cOC and ucOC. They completed X-ray absorptiometry (DXA) scan to measure BMD, appendicular lean mass (ALM) and trabecular bone score (TBS). They completed high resolution peripheral quantitative CT (HR-pQCT) to assess peripheral bone microarchitectures. Serum OC, cOC and ucOC were elevated in osteoporosis postmenopausal women. In bone geometry, serum ucOC was positively related with total bone area (Tt.Ar) and trabecular area(Tb.Ar). In bone volumetric density, serum OC and ucOC were negatively associated with total volume bone mineral density (Tt.vBMD) and trabecular volume bone mineral density (Tb.vBMD). In bone microarchitecture, serum OC and ucOC were negatively correlative with Tb.N and Tb.BV/TV, and were positively correlated with Tb.Sp. Serum OC and ucOC were positively associated with Tb.1/N.SD. Serum OC was negatively related with Tb.Th. Serum ucOC was positively associated with ALM. The high level of serum OC was the risk factor of osteoporosis. ALM was the protective factor for osteoporosis. All forms of serum OC were negatively associated with BMD. Serum OC and ucOC mainly influenced microstructure of trabecular bone in peripheral skeletons. Serum ucOC participated in modulating both bone microstructure and muscle mass.

Osteonecrosis of the Femoral Head in People Living With Human Immunodeficiency Virus: A Micro-Computed Tomography Study.

The incidence of osteonecrosis of the femoral head (ONFH) in people with human immunodeficiency virus (HIV) is 10-100 times higher than that in the general population. However, the specific bone microstructure and extent of damage within the femoral head in PWH are still unclear. Femoral head samples were obtained by total hip arthroplasty, micro-computed tomography (micro-CT) was employed to investigate the microstructure of trabecular bone across 4 representative regions within necrotic femoral heads, and quantitative analysis was performed. On general observation, different degrees of degenerative cartilage, fibrocartilage, hyperplastic bone, and exposed bone were presented alternately, with a "map-like" appearance. On micro-CT, compared with the normal and necrotic areas, the bone volume/tissue volume and bone mineral density of the sclerotic areas were significantly increased, the number of trabeculae was significantly increased, and the gap was smaller (P < .05). There was no significant difference in trabecular thickness among the groups (P < .05). The systemic immune syndrome caused by HIV itself may interfere with the normal metabolism of bone, including osteoblasts and osteoclasts, and thus participate in HIV-related ONFH.

Six-minute, in vivo MRI quantification of proximal femur trabecular bone 3D microstructure.

Assessment of proximal femur trabecular bone microstructure in vivo by magnetic resonance imaging has recently been validated for acquiring information independent of bone mineral density in osteoporotic patients. However, the requisite signal-to-noise ratio (SNR) and resolution for interrogation of the trabecular microstructure at this anatomical location prolongs the scan duration and renders the imaging protocol clinically infeasible. Parallel imaging and compressed sensing (PICS) techniques can reduce the scan duration of the imaging protocol without substantially compromising image quality. The present work investigates the limits of acceleration for a commonly used PICS technique, ℓ1-ESPIRiT, for the purpose of quantifying measures of trabecular bone microarchitecture. Based on a desired error tolerance, a six-minute, prospectively accelerated variant of the imaging protocol was developed and assessed for intersession reproducibility and agreement with the longer reference scan. To investigate the limits of acceleration for MRI-based trabecular bone quantification by parallel imaging and compressed sensing reconstruction, and to develop a prototypical imaging protocol for assessing the proximal femur microstructure in a clinically practical scan time. Healthy participants (n=11) were scanned by a 3D balanced steady-state free precession (bSSFP) sequence satisfying the Nyquist criterion with a scan duration of about 18min. The raw data were retrospectively undersampled and reconstructed to mimic various acceleration factors ranging from 2 to 6. Trabecular volumes-of-interest in four major femoral regions (greater trochanter, intertrochanteric region, femoral neck, and femoral head) were analyzed and six relevant measures of trabecular bone microarchitecture (bone volume fraction, surface-to-curve ratio, erosion index, elastic modulus, trabecular thickness, plates-to-rods ratio) were obtained for images of all accelerations. To assess agreement, median percent error and intraclass correlation coefficients (ICCs) were computed using the fully-sampled data as reference. Based on this analysis, a prospectively 3-fold accelerated sequence with a duration of about 6min was developed and the analysis was repeated. A prospective acceleration factor of 3 demonstrated comparable performance in reproducibility and absolute agreement to the fully-sampled scan. The median CoV over all image-derived metrics was generally <6% and ICCs >0.70. Also, measurements from prospectively 3-fold accelerated scans demonstrated in general median percent errors of <7% and ICCs >0.70. The present work proposes a method to make in vivo quantitative assessment of proximal femur trabecular microstructure with a clinically practical scan duration of about 6min.

Effects of bisphosphonates and treadmill exercise on bone and kidney in adenine-induced chronic kidney disease rats.

The increasing prevalence of osteoporosis and chronic kidney disease (CKD) due to the aging of society has highlighted the need for development of effective treatments for elderly patients. This study examined whether the combination of treadmill exercise therapy and alendronate (ALN) can improve bone mineral density (BMD) and bone strength without worsening renal function in adenine-induced CKD model rats. 8-week-old male Wistar rats (n = 70) were divided into experimental groups based on the treatment protocol, i.e., non-CKD (control), vehicle only (CKD), ALN only, exercise only, and combined ALN plus exercise. A 0.75% adenine diet was used to induce CKD. Groups were killed at either 20 or 30weeks of age. Comprehensive assessments included serum and urine biochemistry tests, renal histology, bone histomorphometry, BMD measurement, micro-computed tomography examinations, and biomechanical testing. Blood biochemistry tests, urine analyses and histological evaluations of the kidney demonstrated that ALN treatment did not worsen renal function or kidney fibrosis in moderate-stage CKD model rats. Both ALN and treadmill exercise significantly suppressed bone resorption (p < 0.05-p < 0.01). Moreover, ALN monotherapy and combined ALN and treadmill exercise significantly improved BMD of the lumbar spine and femur, bone microstructure, and trabecular bone strength (p < 0.05-p < 0.01). Treadmill exercise was also shown to decrease cortical porosity at the mid-diaphysis of the femur and improve kidney fibrosis. The combination of ALN and treadmill exercise is effective in improving BMD, the microstructure of trabecular and cortical bone, and bone strength, without compromising renal function in adenine-induced CKD model rats.

Development of a semi-anthropomorphic photoacoustic calcaneus phantom based on nano computed tomography and stereolithography 3D printing.

Osteoporosis is a major public health threat with significant physical, psychosocial, and financial consequences. The calcaneus bone has been used as a measurement site for risk prediction of osteoporosis by noninvasive quantitative ultrasound (QUS). By adding optical contrast to QUS, our previous studies indicate that a combination of photoacoustic (PA) and QUS, that is, PAQUS, provides a novel opportunity to assess the health of human calcaneus. Calibration of the PAQUS system is crucial to realize quantitative and repeatable measurements of the calcaneus. Therefore, a phantom which simulates the optical, ultrasound, and architectural properties of the human calcaneus, for PAQUS system calibration, is required. Additionally, a controllable phantom offers researchers a versatile framework for developing versatile structures, allowing more controlled assessment of how varying bone structures cause defined alterations in PA and QUS signals. In this work, we present the first semi-anthropomorphic calcaneus phantom for PAQUS. The phantom was developed based on nano computed-tomography (nano-CT) and stereolithography 3D printing, aiming to maximize accuracy in the approximation of both trabecular and cortical bone microstructures. Compared with the original digital input calcaneus model from a human cadaveric donor, the printed model achieved accuracies of 71.15% in total structure and 87.21% in bone volume fraction. Inorganic materials including synthetic blood, mineral oil, intralipid, and agar gel were used to model the substitutes of bone marrow and soft tissue, filling and covering the calcaneus phantom. The ultrasound and optical properties of this phantom were measured, and the results were consistent with those measured by a commercialized device and from previous in vivo studies. In addition, a short-term stability test was conducted for this phantom, demonstrating that the optical and ultrasound properties of the phantom were stable without significant variation over 1 month. This semi-anthropomorphic calcaneus phantom shows structural, ultrasound, and optical properties similar to those from a human calcaneus in vivo and, thereby, can serve as an effective source for equipment calibration and the comprehensive study of human patients.

A pilot study: effect of irisin on trabecular bone in a streptozotocin-induced animal model of type 1 diabetic osteopathy utilizing a micro-CT.

Osteoporosis is a significant co-morbidity of type 1 diabetes mellitus (DM1) leading to increased fracture risk. Exercise-induced hormone 'irisin' in low dosage has been shown to have a beneficial effect on bone metabolism by increasing osteoblast differentiation and reducing osteoclast maturation, and inhibiting apoptosis and inflammation. We investigated the role of irisin in treating diabetic osteopathy by observing its effect on trabecular bone. DM1 was induced by intraperitoneal injection of streptozotocin 60 mg/kg body weight. Irisin in low dosage (5 µg twice a week for 6 weeks I/P) was injected into half of the control and 4-week diabetic male Wistar rats. Animals were sacrificed six months after induction of diabetes. The trabecular bone in the femoral head and neck was analyzed using a micro-CT technique. Bone turnover markers were measured using ELISA, Western blot, and RT-PCR techniques. It was found that DM1 deteriorates the trabecular bone microstructure by increasing trabecular separation (Tb-Sp) and decreasing trabecular thickness (Tb-Th), bone volume fraction (BV/TV), and bone mineral density (BMD). Irisin treatment positively affects bone quality by increasing trabecular number p < 0.05 and improves the BMD, Tb-Sp, and BV/TV by 21-28%. The deterioration in bone microarchitecture is mainly attributed to decreased bone formation observed as low osteocalcin and high sclerostin levels in diabetic bone samples p < 0.001. The irisin treatment significantly suppressed the serum and bone sclerostin levels p < 0.001, increased the serum CTX1 levels p < 0.05, and also showed non-significant improvement in osteocalcin levels. This is the first pilot study to our knowledge that shows that a low dose of irisin marginally improves the trabecular bone in DM1 and is an effective peptide in reducing sclerostin levels.

THU417 Associations Between Glucose Metabolism And Trabecular Bone Score In Subjects With Acromegaly

Abstract Disclosure: M. Kuzma: None. J. Payer: None. P. Vanuga: None. I. Sagova: None. D. Pavai: None. P. Jackuliak: None. Z. Killinger: None. Introduction: Previously, it was thought that increased risk of vertebral fractures (VF) in acromegaly is associated with impaired trabecular bone. More recently, cortical bone was proposed as one of the fracture risk determinant. However, trabecular compartment is still decreased. Glucose intolerance is a frequent complication of acromegaly and is directly attributable to the excess circulating growth hormone and IGF-1 concentrations and thus possibly lead to trabecular bone detoriation.Objectives: To assess effect of glucose metabolism on DXA-derived bone parameters, such as bone mineral density (BMD), trabecular bone score (TBS), cortical and trabecular vBMD, surface BMD and cortical thickness of proximal femur among patients with acromegaly. Patients and methods: In total, 70 consecutive patients (24 males/56 female, mean age = 55.6 years) with acromegaly based on current ADA guidelines were divided in two subgroups according to glucose metabolism(GM): abnormal GM (n=35; 14 males/21 females; 15 with active disease) and normal GM (n=35;10 Males /25 Females; 11 with active disease). Subjects were prospectively followed up for two years. At baseline and year 2; all subjects had pituitary hormonal measures, fasting plasma glucose (FPG), HBA1c, C-peptide, insulin resistance index (IRI) and DXA measurement performed. From DXA, BMD, TBS and 3D-Shaper parameters were derived. Results: At baseline; subjects with abnormal GM had lower TBS (1.166±0.15) in comparison to normal GM subjects (1.232±0.12; p&amp;lt;0.05). Insulin like growth factor 1 (IGF-1), FPG, HBA1c, C-peptide, IRI and bone parameters was correlated in simple regression model. FPG, HBA1c, C-peptide and IRI was negatively associated with TBS. No correlation between GM parameters and other bone measures was observed. Multiple regression model of all GM parameters weighted by IGF-1 revealed HBA1c as a significant predictor of TBS value (Estimate =-0,054; p=0.04). At year 2; FPG and HBA1c was negatively associated with TBS. In multiple regression IGF-1-weighted model, no significant predictor of TBS was observed. Conclusion: Acromegaly subjects with abnormal GM have lower TBS in comparison to those with normal GM. The best GM parameter to predict TBS in acromegaly was HBA1c. This study showed that trabecular bone microstructure, as indirectly assessed by TBS, is likely resulting of impaired glucose metabolism. Presentation: Thursday, June 15, 2023

Young adult male patients with childhood-onset IBD have increased risks of compromised cortical and trabecular bone microstructures

Young adult male patients with childhood-onset IBD have increased risks of compromised cortical and trabecular bone microstructures

Trabecular Bone Microarchitecture Evaluation in an Osteoporosis Mouse Model.

Bone microstructure refers to the arrangement and quality of bone tissue at the microscopic level. Understanding the bone microstructure of the skeleton is crucial for gaining insight into the pathophysiology of osteoporosis and improving its treatment. However, handling bone samples can be complex due to their hard and dense properties. Secondly, specialized software makes image processing and analysis difficult. In this protocol, we present a cost-effective and easy-to-use solution for trabecular bone microstructure analysis. Detailed steps and precautions are provided. Micro-CT is a non-destructive three-dimensional (3D) imaging technique that provides high-resolution images of trabecular bone structure. It allows for the objective and quantitative evaluation of bone quality, which is why it is widely regarded as the gold standard method for bone quality assessment. However, histomorphometry remains indispensable as it offers crucial cellular-level parameters, bridging the gap between two-dimensional (2D) and 3D assessments of bone specimens. As for the histologic techniques, we chose to decalcify the bone tissue and then perform traditional paraffin embedding. In summary, combining these two methods can provide more comprehensive and accurate information on bone microstructure.

Validation of a Low-Cost Portable Device for Inducing Noninvasive Anterior Cruciate Ligament Injury in Mice.

Noninvasive compression-induced anterior cruciate ligament rupture (ACL-R) is an easy and reproducible model for studying post-traumatic osteoarthritis (PTOA) in mice. However, equipment typically used for ACL-R is expensive, immobile, and not available to all researchers. In this study, we compared PTOA progression in mice injured with a low-cost custom ACL-rupture device (CARD) to mice injured with a standard system (ElectroForce 3200). We quantified anterior-posterior (AP) joint laxity immediately following injury, epiphyseal trabecular bone microstructure, and osteophyte volume at 2 and 6 weeks post injury using micro-computed tomography, and osteoarthritis progression and synovitis at 2 and 6 weeks post injury using whole-joint histology. We observed no significant differences in outcomes in mice injured with the CARD system compared to mice injured with the Electroforce (ELF) system. However, AP joint laxity data and week 2 micro-CT and histology outcomes suggested that injuries may have been slightly more severe and PTOA progressed slightly faster in mice injured with the CARD system compared to the ELF system. Altogether, these data confirm that ACL-R can be successfully and reproducibly performed with the CARD system and that osteoarthritis (OA) progression is mostly comparable to that of mice injured with the ELF system, though potentially slightly faster. The CARD system is low cost and portable, and we are making the plans and instructions freely available to all interested investigators in the hopes that they will find this system useful for their studies of OA in mice.

Radiation-induced changes in load-sharing and structure-function behavior in murine lumbar vertebrae

In this study, we used micro-CT-based finite element analysis to investigate the biomechanical effects of radiation on the microstructure and mechanical function of murine lumbar vertebrae. Specifically, we evaluated vertebral microstructure, whole-bone stiffness, and cortical-trabecular load sharing in the L5 vertebral body of mice exposed to ionizing radiation 11 days post exposure (5 Gy total dose; n = 13) and controls (n = 14). Our findings revealed the irradiated group exhibited reduced trabecular bone volume and microstructure (p < 0.001) compared to controls, while cortical bone volume remained unchanged (p = 0.91). Axially compressive loads in the irradiated group were diverted from the trabecular centrum and into the vertebral cortex, as evidenced by a higher cortical load-fraction (p = 0.02) and a higher proportion of cortical tissue at risk of initial failure (p < 0.01). Whole-bone stiffness was lower in the irradiated group compared to the controls, though the difference was small and non-significant (2045 ± 142 vs. 2185 ± 225 vs. N/mm, irradiated vs. control, p = 0.07). Additionally, the structure-function relationship between trabecular bone volume and trabecular load fraction differed between groups (p = 0.03), indicating a less biomechanically efficient trabecular network in the irradiated group. We conclude that radiation can decrease trabecular bone volume and result in a less biomechanically efficient trabecular structure, leading to increased reliance on the vertebral cortex to resist axially compressive loads. These findings offer biomechanical insight into the effects of radiation on structure-function behavior in murine lumbar vertebrae independent of possible tissue-level material effects.

#5642 ASSOCIATION BETWEEN FIBROBLAST GROWTH FACTOR 23 AND TRABECULAR BONE SCORE IN EARLY STAGES OF CKD

Abstract Background and Aims Newer markers of kidney damage and mineral and bone changes in chronic kidney disease (CKD) are needed. The fracture risk increases with worsening of CKD with highest incidence in later stages. Thus methods for early bone status assessment and laboratory marker of kidney function is needed. Aim of the study was to evaluate bone mineral density (BMD) and trabecular bone score (TBS) – a novel surrogate of trabecular bone microstructure, in relationship with newer laboratory markers of CKD, such as fibroblast growth factor 23 (FGF23) and klotho. Method A cross-sectional study during July 2018-July2019 was conducted. Plasma levels of soluble klotho and FGF23 were determined by ELISA (enzyme-linked immuno -assay). All patients undergone bone mineral density (BMD) and trabecular bone scores (TBS) measurement. Patients were divided into 2 groups as follows: A - patients in stages G1 - G3; B - patients in stages G4 – 5 accoridng to KDIGO. Results A total of 74 CKD patients (42 males and 32 females; mean age 68.8 years) were included in the study. Greater FGF23 levels in group B(N = 15) in comparison to group A (N = 59)(p = .001) were observed. FGF23 was associated with glomerular filtration (GF)(R = -0.43; p = 0.003), with greater levels of FGF23 at GF less than 0.8 ml/s. Significant difference in TBS within first 3 CKD stages (mean TBS in G1 = 1.374 vs. G2 = 1.304 vs. G3a = 1.24; p = 0.03) and negative correlation of FGF23 and TBS (R = -0.33; p = 0.05) and a positive correlation between klotho and TBS (R = 0.419; p = 0.04) was observed. Conclusion This study confirmed that FGF23 is associated with TBS. However, TBS reflects kidney function decline only in first 3 stages of CKD. Thus, FGF23 together with TBS are promising markers of early trabecular bone impairment in CKD.

Effects of Piper sarmentosum on Bone Health and Fracture Healing: A Scoping Review.

Piper sarmentosum (PS) is a traditional herb used by Southeast Asian communities to treat various illnesses. Recent pharmacological studies have discovered that PS possesses antioxidant and anti-inflammatory activities. Since oxidative stress and inflammation are two important processes driving the pathogenesis of bone loss, PS may have potential therapeutic effects against osteoporosis. This review systematically summarised the therapeutic effects of PS on preventing osteoporosis and promoting fracture healing. A systematic literature search was performed in November 2021 using 4 electronic databases and the search string "Piper sarmentosum" AND (bone OR osteoporosis OR osteoblasts OR osteoclasts OR osteocytes). Nine unique articles were identified from the literature. The efficacy of PS has been studied in animal models of osteoporosis induced by ovariectomy and glucocorticoids, as well as bone fracture models. PS prevented deterioration of bone histomorphometric indices, improved fracture healing and restored the biomechanical properties of healed bone in ovariectomised rats. PS also prevented osteoblast/osteocyte apoptosis, increased bone formation and mineralisation and subsequently improved trabecular bone microstructures and strength of rats with osteoporosis induced by glucocorticoids. Apart from its antioxidant and anti-inflammatory activity, PS also suppressed circulating and skeletal expression of corticosterone and skeletal expression of 11β hydroxysteroid dehydrogenase type 1 but increased the enzyme activity in the glucocorticoid osteoporosis model. This review also identified several research gaps about the skeletal effects of PS and suggested future studies to bridge these gaps. PS may be of therapeutic benefit to bone health. However, further research is required to validate this claim.

Shift in Calcium From Peripheral Bone to Axial Bone After Tumor Resection in Patients With Tumor-Induced Osteomalacia.

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by excessive production of fibroblast growth factor 23 (FGF23) by a tumor. After successful tumor resection, patients can recover from hypophosphatemia quicky. However, data on the changes in bone mineral density (BMD) and microstructure in the short term after surgery remained unclear. This work aimed to investigate the postoperative changes in BMD and microstructure both in peripheral and axial bone in TIO patients. We evaluated BMD and microarchitecture in 22 TIO patients using high-resolution peripheral quantitative computed tomography (HR-pQCT) and dual-energy x-ray absorptiometry (DXA) before and 3 months after surgery in this retrospective study. In this study, a total of 22 TIO patients who had recovered serum phosphate levels postoperatively were enrolled. After surgery, areal BMD (aBMD) increased by 21.6% in the femoral neck, by 18.9% in the total hip, and by 29.5% in the lumbar spine. Moreover, TBS increased by 14.1% (all P < .001). In contrast, trabecular or cortical volumetric BMD (vBMD), and microstructure of trabecular bone (trabecular number, separation and bone volume ratio) and cortical bone (cortical thickness and porosity) at the distal radius or tibia were further deteriorated. Correlation analyses found that changes in femoral neck and total hip aBMD were both conversely associated with changes in trabecular vBMD and bone volume ratio, while positively correlated with change in trabecular separation at the distal radius. Although aBMD and microstructure in the axial bone were improved, vBMD and microstructure in the peripheral bone were further impaired shortly after surgery. Correlation of improvement of aBMD in the total hip and femoral neck with deterioration of vBMD and microstructure at the distal radius indicated a shift in calcium from the peripheral bone to the axial bone in the short term after tumor resection in TIO patients.

Microstructural and cellular characterisation of the subchondral trabecular bone in human knee and hip osteoarthritis using synchrotron tomography

It is unclear if different factors influence osteoarthritis (OA) progression and degenerative changes characterising OA disease in hip and knee. We investigated the difference between hip OA and knee OA at the subchondral bone (SCB) tissue and cellular level, relative to the degree of cartilage degeneration. Bone samples were collected from 11 patients (aged 70.4±10.7years) undergoing knee arthroplasty and 8 patients (aged 62.3±13.4years) undergoing hip arthroplasty surgery. Trabecular bone microstructure, osteocyte-lacunar network, and bone matrix vascularity were evaluated using synchrotron micro-CT imaging. Additionally, osteocyte density, viability, and connectivity were determined histologically. The associations between severe cartilage degeneration and increase of bone volume fraction (%) [-8.7, 95% CI (-14.1, -3.4)], trabecular number (#/mm) [-1.5, 95% CI (-0.8, -2.3)], osteocyte lacunar density (#/mm3) [4714.9; 95% CI (2079.1, 7350.6)] and decrease of trabecular separation (mm) [-0.07, 95% CI (0.02, 0.1)] were found in both knee and hip OA. When compared to knee OA, hip OA was characterised by larger (µm3) but less spheric osteocyte lacunae [47.3; 95% CI (11.2, 83.4), -0.04; 95% CI (-0.06, -0.02), respectively], lower vascular canal density (#/mm3) [-22.8; 95% CI (-35.4, -10.3)], lower osteocyte cell density (#/mm2) [-84.2; 95% CI (-102.5, -67.4)], and less senescent (#/mm2) but more apoptotic osteocytes (%) [-2.4; 95% CI (-3.6, -1.2), 24.9; 95% CI (17.7, 32.1)], respectively. SCB from hip OA and knee OA exhibits different characteristics at the tissue and cellular levels, suggesting different mechanisms of OA progression in different joints.