Relationships Between Running Biomechanics and Femoral Articular Cartilage Thickness and Composition in Anterior Cruciate Ligament Reconstruction Patients.

BACKGROUND: Although individuals with anterior cruciate ligament reconstruction (ACLR) are at high risk for posttraumatic osteoarthritis, mechanisms underlying the relationship between running and knee cartilage health remain unclear. OBJECTIVE: We aimed to investigate how 30 min of running influences femoral cartilage thickness and composition and their relationships with running biomechanics in patients with ACLR and controls. METHODS: Twenty patients with ACLR (time post-ACLR: 14.6 ± 6.1 months) and 20 matched controls participated in the study. A running session required both groups to run for 30 min at a self-selected speed. Before and after running, we measured femoral cartilage thickness via ultrasound imaging. A MRI session consisted of T2 mapping. RESULTS: The ACLR group showed longer T2 relaxation times in the medial femoral condyle at resting compared with the control group (central: 51.2 ± 16.6 vs. 34.9 ± 13.2 ms, p = 0.006; posterior: 50.2 ± 10.1 vs. 39.8 ± 7.4 ms, p = 0.006). Following the run, the ACLR group showed greater deformation in the medial femoral cartilage than the control group (0.03 ± 0.01 vs. 0.01 ± 0.01 cm, p = 0.001). Additionally, the ACLR group showed significant negative correlations between resting T2 relaxation time in the medial femoral condyle and vertical impulse (standardized regression coefficients = -0.99 and p = 0.004) during running. CONCLUSIONS: Our findings suggest that those who are between 6 and 24 months post-ACLR have degraded cartilage composition and their cartilage deforms more due to running vGRF.

Osteogenesis Imperfecta type 1: like mother, like daughter - Challenges in the perinatal management.

A third gravida with osteogenesis imperfecta (OI) type 1, in her 20s, was referred from the Medical Genetics department at 12+ weeks with a prenatal diagnosis of OI type 1 in this fetus for further management. She was wheelchair-bound and keen to continue this pregnancy. She had medical termination in her two previous pregnancies for OI in the fetuses. Ultrasound at 12+ weeks revealed a short-bent femur with sparing of the long bones of the upper limb. Serial ultrasound revealed progressive affliction of the long bones with falling growth profile and polyhydramnios. She was delivered at 36 weeks by caesarean for breech in labour under regional anaesthesia.A multidisciplinary approach, patient determination, and good partner support helped in the successful management of this pregnancy.The neonate had blue sclera, dentigerous imperfecta, bowing of the femur and relatively spared upper limbs. Growth was on the third centile. The mother says she brings the girl for follow-up every 3-6 months to give injection zoledronate. The mother confirms her girl can stand with support, crawl, and speak two-syllable words. Her daughter had to undergo femur corrective osteotomy rush nailing and hip spice application for a closed fracture of the left femur.

Impact of the preservation media on ex vivo bone samples for full field mechanical testing.

The preservation method to store bone tissue for posterior analysis is a widespread practice. However, the method's potential influence on the material's mechanical properties is often overlooked during single-point experimentation. Saline and formaldehyde solutions are the most common among the employed preservation media. A full field analysis of the mice femoral bone deformation using non-destructive optical techniques is conducted to assess the influence of the storage media on the viscoelastic properties of the tissue. Three different groups are subjected to a standard three-point bending test. The first group is the control, with fresh post-mortem samples. The second and third groups used saline and formaldehyde solutions, respectively. During the mechanical test, the bone's surface and internal deformation are monitored simultaneously using digital holographic interferometry and Fourier-domain optical coherence tomography. A mechanical comparison among the three groups is presented. The results show that after 48 h of immersion in saline solution, the mice bones keep their viscoelastic behavior similar to fresh bones. Meanwhile, 48 h in formaldehyde modifies the response and affects the marrow structure. The high sensitivity of the optical phase also makes it possible to observe changes in the anisotropy of the samples. As a comparison, Raman spectroscopy analyzes the three bone groups to prove that the preservation media does not affect a single-point inspection.

Establishment of orthotopic osteosarcoma animal models in immunocompetent rats through muti-rounds of in-vivo selection.

Immunodeficient murine models are usually used as the preclinical models of osteosarcoma. Such models do not effectively simulate the process of tumorigenesis and metastasis. Establishing a suitable animal model for understanding the mechanism of osteosarcoma and the clinical translation is indispensable. The UMR-106 cell suspension was injected into the marrow cavity of Balb/C nude mice. Tumor masses were harvested from nude mice and sectioned. The tumor fragments were transplanted into the marrow cavities of SD rats immunosuppressed with cyclosporine A. Through muti-rounds selection in SD rats, we constructed orthotopic osteosarcoma animal models using rats with intact immune systems. The primary tumor cells were cultured in-vitro to obtain the immune-tolerant cell line. VX2 tumor fragments were transplanted into the distal femur and parosteal radius of New Zealand white rabbit to construct orthotopic osteosarcoma animal models in rabbits. The rate of tumor formation in SD rats (P1 generation) was 30%. After four rounds of selection and six rounds of acclimatization in SD rats with intact immune systems, we obtained immune-tolerant cell lines and established the orthotopic osteosarcoma model of the distal femur in SD rats. Micro-CT images confirmed tumor-driven osteolysis and the bone destruction process. Moreover, the orthotopic model was also established in New Zealand white rabbits by implanting VX2 tumor fragments into rabbit radii and femurs. We constructed orthotopic osteosarcoma animal models in rats with intact immune systems through muti-rounds in-vivo selection and the rabbit osteosarcoma model.

Non-linear association of atherogenic index of plasma with bone mineral density a cross-sectional study.

INTRODUCTION: Although there has been abundant evidence of the association between dyslipidemia as a single factor and osteoporosis, the non-linear relationship between osteoporosis and the Atherogenic Index of Plasma (AIP) has not yet been thoroughly investigated. This study aimed to investigate the complex relationship between AIP and bone mineral density (BMD) to elucidate their interrelationship. METHODS: An analysis of 2007-2018 National Health and Nutrition Survey (NHANES) data was conducted for this study. The study enrolled 5,019 participants. Logarithmically multiplying triglycerides and high-density lipoprotein cholesterol yields the AIP (base 10). The measured variables consisted of BMD in the total femur (TF), femoral neck (FN), and lumbar spine (LS). The association between AIP and BMD was examined using a range of statistical models, such as weighted multivariable logistic regression, generalized additive model, etc. RESULTS: It was found that AIP was positively associated with BMD after adjusting for age, gender, race, socioeconomic status, degree of education, income, Consuming alcoholic beverages, osteoporosis status (Yes or No), ALT, AST, serum creatinine, and total calcium levels. Further studies supported the association link between elevated BMD and AIP. Furthermore, compared to men, females had a higher positive connection between AIP and BMD. In general, there was a curve in the reverse L-shape seen, with a point of change around 0.877, indicating a relationship between AIP and TF BMD. Moreover, a curve exhibiting an L-formed pattern, with a point of inflection at around 0.702, was seen between AIP and FN BMD. In addition, a J-shaped curve was seen, with a point of inflection at 0.092, which demonstrates the association between AIP and LS BMD. CONCLUSION: The AIP and TF BMD curves resemble inverted L shapes, as do the AIP and FN BMD curves. The relationship between AIP and LS BMD was further demonstrated by a J-shaped curve. The results indicate a possible association between AIP and bone mineral density, which should be explored in more detail.

Does spinopelvic alignment affect femoral head cartilage and the proximal femoral physis in slipped capital femoral epiphysis? A finite element analysis.

BACKGROUND: Slipped capital femoral epiphysis is a prevalent pediatric hip disorder. Recent studies suggest the spine's sagittal profile may influence the proximal femoral growth plate's slippage, an aspect not extensively explored. This study utilizes finite element analysis to investigate how various spinopelvic alignments affect shear stress and growth plate slip. METHODS: A finite element model was developed from CT scans of a healthy adult male lumbar spine, pelvis, and femurs. The model was subjected to various sagittal alignments through reorientation. Simulations of two-leg stance, one-leg stance, walking heel strike, ascending stairs heel strike, and descending stairs heel strike were conducted. Parameters measured included hip joint contact area, stress, and maximum growth plate Tresca (shear) stress. FINDINGS: Posterior pelvic tilt cases indicated larger shear stresses compared to the anterior pelvic tilt variants except in two leg stance. Two leg stance resulted in decreases in the posterior tilted pelvi variants hip contact and growth plate Tresca stress compared to anterior tilted pelvi, however a combination of posterior pelvic tilt and high pelvic incidence indicated larger shear stresses on the growth plate. One leg stance and heal strike resulted in higher shear stress on the growth plate in posterior pelvic tilt variants compared to anterior pelvic tilt, with a combination of posterior pelvic tilt and high pelvic incidence resulting in the largest shear. INTERPRETATION: Our findings suggest that posterior pelvic tilt and high pelvic incidence may lead to increased shear stress at the growth plate. Activities performed in patients with these alignments may predispose to biomechanical loading that shears the growth plate, potentially leading to slip.

3D-printed titanium porous prosthesis combined with the Masquelet technique for the management of large femoral bone defect caused by osteomyelitis.

BACKGROUND: The treatment of infected bone defects remains a clinical challenge. With the development of three-dimensional printing technology, three-dimensional printed implants have been used for defect reconstruction. The aim of this study was to investigate the clinical outcomes of three-dimensional printed porous prosthesis in the treatment of femoral defects caused by osteomyelitis. METHODS: Eleven patients with femoral bone defects following osteomyelitis who were treated with 3D-printed porous prosthesis at our institution between May 2017 and July 2021, were included. Eight patients were diagnosed with critical-sized defects, and the other three patients were diagnosed with shape-structural defects. A two-stage procedure was performed for all patients, and the infection was eradicated and bone defects were occupied by polymethylmethacrylate spacer during the first stage. The 3D-printed prosthesis was designed and used for the reconstruction of femoral defects in the second stage. Position of the reconstructed prostheses and bone growth were measured using radiography. The union rate, complications, and functional outcomes at the final follow-up were assessed. RESULTS: The mean length of the bone defect was 14.0 cm, union was achieved in 10 (91%) patients. All patients showed good functional performance at the most recent follow-up. In the critical-sized defect group, one patient developed a deep infection that required additional procedures. Two patients had prosthetic dislocations. Radiography demonstrated good osseous integration of the implant-bone interface in 10 patients. CONCLUSION: The 3D printed prostheses enable rapid anatomical and mechanically stable reconstruction of extreme femur bone defects, effectively shortens treatment time, and achieves satisfactory clinical outcomes.

Risk of internal fixation treatment in intertrochanteric fracture based on different lateral femoral wall thickness: finite element analysis.

OBJECTIVE: The thickness of the lateral femoral wall, which is an important indicator for evaluating the stability and integrity of intertrochanteric fractures, has been widely studied in recent years. However, as a typical representative of internal fixation treatment, there are few reports on the biomechanical comparison between PFNA and DHS + CS. This study focused primarily on the biomechanical effects of different lateral femoral wall thicknesses on two types of internal fixation through finite element analysis. METHODS: We randomly recruited a healthy adult and collected his femoral CT data to establish a model of femoral intertrochanteric fracture with different lateral femoral wall thicknesses. Following PFNA and DHS + CS fixation, femoral models were simulated, and variations in stress and displacement of the internal fixation and femoral head were recorded under the same physiological load. RESULTS: First, finite element mechanical analysis revealed that the stress and displacement of the internal fixation and femoral head were lower in the femoral model after PFNA fixation than in the DHS + CS model. Second, as the outer wall thickness decreased, the stress and deformation endured by both types of internal fixation gradually increased. CONCLUSIONS: Finite element analysis determined that PFNA exhibits significantly better biomechanical stability than DHS + CS when subjected to varying lateral femoral wall thicknesses. Moreover, lateral femoral wall thickness substantially affects the stability of the two internal fixation biomechanical environments. When the thickness of the lateral femoral wall is too small, we do not recommend using extramedullary fixation because there is a significant risk of internal fixation fracture.

Femoral anteversion linked to the inability to squat: Analysis of CT images in the patient and control groups.

Many patients who cannot squat well in a neutral toe position can only squat in an excessively out-toeing position. This excessive out-toeing squat is thought to be caused by rotational problems of the lower extremities. In this study, we aimed to identify the cause for the inability to squat by measuring and comparing femoral and tibial torsion between an excessive out-toeing squat patient group and a control group representing the general population. Between 2008 and 2022, a patient group comprising 50 lower extremities with excessive out-toeing squats was established. A control group representing the general population was selected from patients aged 0 to 29 years, who underwent lower-extremity CT angiography between 2012 and 2022, using the Clinical Data Warehouse with exclusion criteria applied. A total of 94 lower extremities were included in the control group. The femoral torsional angle (FTA) and tibial torsional angle (TTA) of both groups were measured and compared using Student t test. Additionally, 30 each of those with the highest and lowest 30 FTA values were selected from the patient and control groups, and the TTA was compared between the high- and low-FTA groups using Student t test. The mean FTA was 0.34° (SD, 11.11°) in the patient group and 10.14° (SD, 11.85°) in the control group, with a mean difference of 9.8° and P < .001. The mean TTA was 27.95° (SD, 7.82°) in the patient group and 32.67 ° (SD, 7.58°) in the control group, with a mean difference of 4.72° (P = .001). The mean TTA was 34.3° (SD, 7.72°) in the high-FTA group and 28.17° (SD, 8.35°) in the low-FTA group, with a mean difference of 6.13° (P = .005). Patients with excessive out-toeing squat showed lower FTA and TTA values than the general population. Furthermore, although a correlation between FTA and TTA was not established through Pearson correlation analysis, a tendency was observed where a decrease in FTA was associated with a decrease in TTA. Based on these results, decreased FTA was demonstrated to be one of the major causes of excessive out-toeing squats.

Relationship between muscle and subcutaneous adipose tissue size and density and proximal femur bone in elderly women with hip fracture.

BACKGROUND: Both osteoporosis and sarcopenia are associated with aging, increasing the likelihood of falls in older adults and consequently raising the risk of hip fractures (HF). AIMS: To explore the relationship between the size and density of muscle and subcutaneous adipose tissue (SAT) and the bone mineral density (BMD) of the proximal femur in elderly women with HF. METHODS: Quantitative computed tomography (QCT) was conducted on the hips of 661 female participants who experienced low-energy acute HFs to measure both areal BMD (aBMD) and volume BMD (vBMD). Measurements were taken for the cross-sectional area (CSA) and density of the muscle around the hip and adjacent SAT. Multivariable linear regression models were applied to assess the relationship between these parameters. RESULTS: Most increases in the density of the gluteus medius and minimus muscle (G.Med/MinM) were correlated with higher BMD in the femoral neck fracture (FNF) group with osteoporosis. In the FNF group, gluteus maximus muscle (G.MaxM) density was negatively associated with the BMD parameters of the proximal femur in individuals with osteoporosis, while they were positively associated with nonosteoporosis. In the intertrochanteric fracture (ITF) group without osteoporosis, both FN aBMD and FN vBMD showed significant correlations with G.Med/MinM density. DISCUSSION: In women with HFs, bone and muscle are closely related. CONCLUSIONS: In older women with HFs, density but not CSA of the G.Med/MinM were associated with BMD parameters of the proximal femur. Osteoporosis may influence the relationship between G.MaxM density and proximal femur BMD in elderly women with FNF.

Photobiomodulation and mesenchymal stem cell-conditioned medium for the repair of experimental critical-size defects.

Orthopedic surgeons face a significant challenge in treating critical-size femoral defects (CSFD) caused by osteoporosis (OP), trauma, infection, or bone tumor resections. In this study for the first time, the application of photobiomodulation (PBM) and bone marrow mesenchymal stem cell-conditioned medium (BM-MSC-CM) to improve the osteogenic characteristics of mineralized bone scaffold (MBS) in ovariectomy-induced osteoporotic (OVX) rats with a CSFD was tested. Five groups of OVX rats with CSFD were created: (1) Control (C); (2) MBS; (3) MBS + CM; (4) MBS + PBM; (5) MBS + CM + PBM. Computed tomography scans (CT scans), compression indentation tests, and histological and stereological analyses were carried out after euthanasia at 12 weeks following implantation surgery. The CT scan results showed that CSFD in the MBS + CM, MBS + PBM, and MBS + CM + PBM groups was significantly smaller compared to the control group (p = 0.01, p = 0.04, and p = 0.000, respectively). Moreover, the CSFD size was substantially smaller in the MBS + CM + PBM treatment group than in the MBS, MBS + CM, and MBS + PBM treatment groups (p = 0.004, p = 0.04, and p = 0.01, respectively). The MBS + PBM and MBS + CM + PBM treatments had significantly increased maximum force relative to the control group (p = 0.01 and p = 0.03, respectively). Bending stiffness significantly increased in MBS (p = 0.006), MBS + CM, MBS + PBM, and MBS + CM + PBM treatments (all p = 0.004) relative to the control group. All treatment groups had considerably higher new trabecular bone volume (NTBV) than the control group (all, p = 0.004). Combined therapies with MBS + PBM and MBS + CM + PBM substantially increased the NTBV relative to the MBS group (all, p = 0.004). The MBS + CM + PBM treatment had a markedly higher NTBV than the MBS + PBM (p = 0.006) and MBS + CM (p = 0.004) treatments. MBS + CM + PBM, MBS + PBM, and MBS + CM treatments significantly accelerated bone regeneration of CSFD in OVX rats. PBM + CM enhanced the osteogenesis of the MBS compared to other treatment groups.

A comparative study on 3D printing-assisted arthroscopic IDEAL point femoral tunnel positioning for anterior cruciate ligament reconstruction versus conventional arthroscopic positioning.

BACKGROUND: This study aimed to investigate the feasibility and precision of using a 3D-printed template for femoral tunnel placement in guiding the optimal positioning of the Internal anatomical stop and Low tension maintenance (IDEAL) bone tunnel during single-bundle anterior cruciate ligament (ACL) reconstruction. METHODS: A retrospective analysis was conducted on 40 patients who underwent arthroscopic single-bundle ACL reconstruction at our hospital between April 2021 and November 2021. In the direct vision group, the IDEAL bone tunnel was positioned using radiofrequency localization directly visualized at the stump. In the 3D-printed positioning group, preoperative CT scans and Digital Imaging and Communications in Medicine (DICOM) data were employed. Following the Quadrant method by Bernard, the femoral tunnel's depth was set at 25% and its height at 29%. Postoperative plain CT scans enabled the reconstruction of 3D models for both groups. The accuracy of femoral tunnel placement was then compared. RESULTS: The central locations of the bone tunnels in the direct vision group were at a mean depth of 25.74 ± 1.84% and a height of 29.22 ± 2.97%. In the 3D printing localization group, these values were 25.39 ± 2.98% for depth and 28.89 ± 2.50% for height, respectively. No significant differences were found in tunnel positioning between the groups. Both groups demonstrated statistically significant improvements in International Knee Documentation Committee Subjective Knee Form (IKDC) and Lysholm scores postoperatively, with no significant differences observed 12 months post-surgery. CONCLUSION: The findings of this study suggest that 3D printing-assisted arthroscopic IDEAL point femoral tunnel positioning and conventional arthroscopic positioning are feasible and effective for ACL reconstruction. Using 3D printing technology to design femoral anchor points in ACL reconstruction allows for the customization of anterior fork reconstruction and precise bone tunnel positioning, supporting the goal of individualized and accurate reconstruction.

Cylindrical depth image based customized helical bone plate design.

Commercial straight metal plates have been generally used to fix fractured bones, but recently, the need for customized and helical metal plates has emerged. Customized metal plates are designed to fit the shape of the fracture area that is a 3D curved surface, making it more difficult than designing on a 2D plane. Helical plates are researched due to their advantage in avoiding blood vessel damage compared to commercially available straight metal plates. In this paper, we propose a novel algorithm to design a customized helical metal plate for the femur using cylindrical depth images and Boolean operations. We also present the results of 3D printing a metal plate designed using the proposed algorithm, and the shape matching is verified by calculating the minimum distance between the surface of the printed plate and the surface of the femur.

The use of hyperbaric oxygen for avascular necrosis of the femoral head and femoral condyle: a single centre's experience over 30 years.

Introduction: Avascular necrosis (AVN) is a rare progressive degenerative disease leading to bone and joint destruction. Patients often require surgical intervention. Femoral AVN is the most common anatomical location. Hyperbaric oxygen treatment (HBOT) has been shown to be effective in AVN. We present data collected from one centre over a 30-year period and compare the results with other published data. Methods: A retrospective chart review of all patients receiving HBOT for AVN at Fremantle and Fiona Stanley Hospitals since 1989 was performed. The primary outcome was radiological appearance using the Steinberg score, with secondary outcomes being subjective improvement, the need for joint replacement surgery and rates of complications. Results: Twenty-one joints in 14 patients (14 femoral heads and seven femoral condyles) were treated with HBOT since 1989. Two patients were excluded. Within the femoral head group, nine of the 14 joints (64%) had stable or improved magnetic resonance imaging (MRI) scans post treatment and at six months (minimum); 10 joints (71%) had good outcomes subjectively, three joints required surgical intervention, and three patients developed mild aural barotrauma. Within the femoral condyle group, all five joints had stable or improved post-treatment MRI scans (four had visible improvement in oedema and/or chondral stability), four joints reported good outcomes subjectively, none of the patients required surgical intervention (follow-up > six months). Conclusions: This single centre retrospective study observed prevention of disease progression in femoral AVN with the use of HBOT, comparable to other published studies. This adds to the body of evidence that HBOT may have a significant role in the treatment of femoral AVN.

Bridging theory and practice: A comprehensive algorithm for imageless total knee arthroplasty.

Total knee arthroplasty (TKA) is a surgical procedure to treat severe knee osteoarthritis. Among several techniques available for performing TKA, imageless TKA is known for achieving precise alignment while minimizing invasiveness. This work proposes a comprehensive algorithm for imageless TKA device to calculate the varus/valgus and flexion/extension angles, as well as resection depths for cutting planes at distal femur and proximal tibia. Moreover, the algorithm calculates the hip-knee-ankle (HKA) and flexion angles of the leg. Initially, the proposed algorithm was validated in a virtual environment using a CT-scanned bone model in Solidworks. Subsequently, for the real-world validation, a SoftBone model was resected with conventional intra and extramedullary rods and cross-checked with the proposed algorithm. For the third validation, another SoftBone model was resected with the proposed algorithm and cuts were measured with a vernier caliper. During this experiment, there was an error of approximately 1 mm for both femoral and tibial resection cases when using an infrared camera with an accuracy of ±0.5 mm. However, this error could be reduced using an infrared camera with higher accuracy.

Technical note: Capturing shape-Linear measurements and geometric morphometrics of the immature femora.

OBJECTIVES: Growth and developmental studies have been a prominent theme in bioarchaeology. These works traditionally focus on metric measurements of long bone length and age-at-death or cross-sectional geometric studies with the use of computed tomography scans for questions on growth and mobility. However, teasing apart aspects of size and shape have been difficult due to the cylindrical nature of immature long bones. This research investigates the methodological use of surface geometries from linear measurements and geometric morphometric methods (GMM) to answer questions on mobility and allometry during childhood. MATERIALS AND METHODS: Left femora were selected from 42 individuals ranging from fetal to 12 years of age from medieval St Gregory's Priory, Canterbury, UK. Femora were digitized with structured-light-scanning for auto3dgm analysis and measurements were obtained from physical caliper measurements. Individuals were put into age groups based on biomechanical milestones during this age range. RESULTS: Ratio and GMM confirm hypotheses of allometry and biomechanical milestones. Geometric morphometrics, however, detects more subtle differences in mobility at each age group. DISCUSSION: The findings of this preliminary study support the potential use of GMM of immature femora, while indicating that the extent in range of mobility that can occur varies at different biological milestones.

gCTRP3 inhibits oophorectomy­induced osteoporosis by activating the AMPK/SIRT1/Nrf2 signaling pathway in mice.

C1q/tumor necrosis factor­related protein 3 (CTRP3) expression is markedly reduced in the serum of patients with osteoporosis. The present study aimed to investigate whether CTRP3 reduces bone loss in oophorectomy (OVX)­induced mice via the AMP­activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/nuclear factor E2­related factor 2 (Nrf2) signaling pathway. Female C57BL/6J mice and MC3T3­E1 cells were used to construct in vivo and in vitro models of osteoporosis, respectively. The left femurs of mice were examined using micro­computed tomography scans and bone­related quantitative morphological evaluation was performed. Pathological changes and the number of osteoclasts in the left femurs of mice were detected using hematoxylin and eosin, and tartrate­resistant acid phosphatase (TRAP) staining. Runt­related transcription factor­2 (RUNX2) expression in the left femurs was detected using immunofluorescence analysis, and the serum levels of bone resorption markers (C­telopeptide of type I collagen and TRAP) and bone formation markers [osteocalcin (OCN) and procollagen type 1 N­terminal propeptide] were detected. In addition, osteoblast differentiation and calcium deposits were examined in MC3T3­E1 cells using alkaline phosphatase (ALP) and Alizarin red staining, respectively. Moreover, RUNX2, ALP and OCN expression levels were detected using reverse transcription­quantitative PCR, and the expression levels of proteins associated with the AMPK/SIRT1/Nrf2 signaling pathway were detected using western blot analysis. The results revealed that globular CTRP3 (gCTRP3) alleviated bone loss and promoted bone formation in OVX­induced mice. gCTRP3 also facilitated the osteogenic differentiation of MC3T3­E1 cells through the AMPK/SIRT1/Nrf2 signaling pathway. The addition of an AMPK inhibitor (Compound C), SIRT1 inhibitor (EX527) or Nrf2 inhibitor (ML385) reduced the osteogenic differentiation of MC3T3­E1 cells via inhibition of gCTRP3. In conclusion, gCTRP3 inhibits OVX­induced osteoporosis by activating the AMPK/SIRT1/Nrf2 signaling pathway.

Super-resolution of clinical CT: Revealing microarchitecture in whole bone clinical CT image data.

Osteoporotic fractures, prevalent in the elderly, pose a significant health and economic burden. Current methods for predicting fracture risk, primarily relying on bone mineral density, provide only modest accuracy. If better spatial resolution of trabecular bone in a clinical scan were available, a more complete assessment of fracture risk would be obtained using microarchitectural measures of bone (i.e. trabecular thickness, trabecular spacing, bone volume fraction, etc.). However, increased resolution comes at the cost of increased radiation or can only be applied at small volumes of distal skeletal locations. This study explores super-resolution (SR) technology to enhance clinical CT scans of proximal femurs and better reveal the trabecular microarchitecture of bone. Using a deep-learning-based (i.e. subset of artificial intelligence) SR approach, low-resolution clinical CT images were upscaled to higher resolution and compared to corresponding MicroCT-derived images. SR-derived 2-dimensional microarchitectural measurements, such as degree of anisotropy, bone volume fraction, trabecular spacing, and trabecular thickness were within 16 % error compared to MicroCT data, whereas connectivity density exhibited larger error (as high as 1094 %). SR-derived 3-dimensional microarchitectural metrics exhibited errors <18 %. This work showcases the potential of SR technology to enhance clinical bone imaging and holds promise for improving fracture risk assessments and osteoporosis detection. Further research, including larger datasets and refined techniques, can advance SR's clinical utility, enabling comprehensive microstructural assessment across whole bones, thereby improving fracture risk predictions and patient-specific treatment strategies.

Automatic segmentation of femoral tumors by nnU-net.

BACKGROUND: Metastatic femoral tumors may lead to pathological fractures during daily activities. A CT-based finite element analysis of a patient's femurs was shown to assist orthopedic surgeons in making informed decisions about the risk of fracture and the need for a prophylactic fixation. Improving the accuracy of such analyses ruqires an automatic and accurate segmentation of the tumors and their automatic inclusion in the finite element model. We present herein a deep learning algorithm (nnU-Net) to automatically segment lytic tumors within the femur. METHOD: A dataset consisting of fifty CT scans of patients with manually annotated femoral tumors was created. Forty of them, chosen randomly, were used for training the nnU-Net, while the remaining ten CT scans were used for testing. The deep learning model's performance was compared to two experienced radiologists. FINDINGS: The proposed algorithm outperformed the current state-of-the-art solutions, achieving dice similarity scores of 0.67 and 0.68 on the test data when compared to two experienced radiologists, while the dice similarity score for inter-individual variability between the radiologists was 0.73. INTERPRETATION: The automatic algorithm may segment lytic femoral tumors in CT scans as accurately as experienced radiologists with similar dice similarity scores. The influence of the realistic tumors inclusion in an autonomous finite element algorithm is presented in (Rachmil et al., "The Influence of Femoral Lytic Tumors Segmentation on Autonomous Finite Element Analyses", Clinical Biomechanics, 112, paper 106192, (2024)).