Effect of different constraining boundary conditions on simulated femoral stresses and strains during gait.

Finite element analysis (FEA) is commonly used in orthopaedic research to estimate localised tissue stresses and strains. A variety of boundary conditions have been proposed for isolated femur analysis, but it remains unclear how these assumed constraints influence FEA predictions of bone biomechanics. This study compared the femoral head deflection (FHD), stresses, and strains elicited under four commonly used boundary conditions (fixed knee, mid-shaft constraint, springs, and isostatic methods) and benchmarked these mechanics against the gold standard inertia relief method for normal and pathological femurs (extreme anteversion and retroversion, coxa vara, and coxa valga). Simulations were performed for the stance phase of walking with the applied femoral loading determined from patient-specific neuromusculoskeletal models. Due to unrealistic biomechanics observed for the commonly used boundary conditions, we propose a novel biomechanical constraint method to generate physiological femur biomechanics. The biomechanical method yielded FHD (< 1 mm), strains (approaching 1000 µÎµ), and stresses (< 60 MPa), which were consistent with physiological observations and similar to predictions from the inertia relief method (average coefficient of determination = 0.97, average normalized root mean square error = 0.17). Our results highlight the superior performance of the biomechanical method compared to current methods of constraint for  both healthy and pathological femurs.

Robot-assisted total knee arthroplasty system provides more precise control of the femoral rotation angle: A retrospective study.

BACKGROUND: Rotational alignment in total knee arthroplasty (TKA) is a crucial technical point that needs attention. We conducted a retrospective study to investigate whether a new robot-assisted TKA (RA-TKA) could improve the accuracy of rotational alignment and whether rotational alignment affects postoperative pain and functional evaluation of the knee. METHODS: A total of 136 consecutive patients who underwent TKA were included in this study. Half of the patients underwent RA-TKA and the other half underwent conventional TKA (CON-TKA) by the same group of surgeons. Collect the relevant parameters. RESULTS: The postoperative femoral rotation angle (FRA) was -0.72 ± 2.59° in the robot-assisted group and 1.13 ± 2.73° in the conventional group, and were statistically significantly different (p < 0.001). CONCLUSION: This study provides preliminary evidence that the RA-TKA provides more precise control of FRA than CON-TKA, and verifies that tibial rotation angle and combined rotation angle affect postoperative knee pain and functional evaluation.

Biomechanical changes in the proximal femur before and after removal of femoral neck system.

BACKGROUND: As an innovative internal fixation system, FNS (femoral neck system) is increasingly being utilized by surgeons for the treatment of femoral neck fractures. At present, there have been numerous finite element analysis experiments studying the immediate stability of FNS and CSS in treating femoral neck fractures. However, there is scarce mechanical analysis available regarding the effects post internal fixation removal. This study aimed to investigate the alterations in mechanical parameters of the proximal femur before and after the removal of FNS (femoral neck system), and to assess potential distinctions in indicators following the extraction of CSS (Cannulated Screws). METHODS: A proximal femur model was reconstructed using finite element numerical techniques. The models for CSS and FNS were formulated utilizing characteristics and parametric definitions. The internal fixation was combined with a normal proximal femur model to simulate the healing state after fracture surgery. Within the framework of static analysis, consistent stress burdens were applied across the entirety of the models. The total deformation and equivalent stress of the proximal femur were recorded before and after the removal of internal fixation. RESULTS: Under the standing condition, the total deformation of the model before and after removing CSS was 0.99 mm and 1.10 mm, respectively, indicating an increase of 12%. The total deformation of the model before and after removing FNS was 0.65 mm and 0.76 mm, respectively, indicating an increase of 17%. The equivalent stress for CSS and FNS were 55.21 MPa and 250.67 MPa, respectively. The average equivalent stress on the cross-section of the femoral neck before and after removal of CSS was 7.76 MPa and 6.11 MPa, respectively. The average equivalent stress on the cross-section of the femoral neck before and after removal of FNS was 9.89 MPa and 8.79 MPa, respectively. CONCLUSIONS: The retention of internal fixation may contribute to improved stability of the proximal femur. However, there still existed risks of stress concentration in internal fixation and stress shielding in the proximal femur. Compared to CSS, the removal of FNS results in larger bone tunnels and insufficient model stability. Further clinical interventions are recommended to address this issue.

SIRT1 maintains bone homeostasis by regulating osteoblast glycolysis through GOT1.

The silent information regulator T1 (SIRT1) is linked to longevity and is a crucial mediator of osteoblast function. We investigated the direct role of Sirt1 during bone modeling and remodeling stages in vivo using Tamoxifen-inducible osteoblast-specific Sirt1 conditional knockout (cKO) mice. cKO mice exhibited lower trabecular and cortical bone mass in the distal femur. These phenotypes were coupled with lower bone formation and bone resorption. Metabolomics analysis revealed that the metabolites involved in glycolysis were significantly decreased in cKO mice. Further analysis of the quantitative acetylome revealed 11 proteins with upregulated acetylation levels in both the femur and calvaria of cKO mice. Cross-analysis identified four proteins with the same upregulated lysine acetylation site in both the femur and calvaria of cKO mice. A combined analysis of the metabolome and acetylome, as well as immunoprecipitation, gene knockout, and site-mutation experiments, revealed that Sirt1 deletion inhibited glycolysis by directly binding to and increasing the acetylation level of Glutamine oxaloacetic transaminase 1 (GOT1). In conclusion, our study suggested that Sirt1 played a crucial role in regulating osteoblast metabolism to maintain bone homeostasis through its deacetylase activity on GOT1. These findings provided a novel insight into the potential targeting of osteoblast metabolism for the treatment of bone-related diseases.

Productizing Nano-Bioactive Glass-Based Bilayer Scaffolds: A Graft for Reconstruction of Mandibular and Femoral Bone Defects.

This investigation aimed to construct a bilayer scaffold integrating alginate and gelatin with nanobioactive glass (BG), recognized for their efficacy in tissue regeneration and drug delivery. Scaffolds, namely, alginate/gelatin (AG), alginate-/actonel gelatin (AGD), alginate actenol/gelatin-45S5 BG (4AGD), and alginate-actonel/gelatin-59S BG (5AGD), were assembled using a cost-effective freeze-drying method, followed by detailed structural investigation via powder X-ray diffraction as well as morphological characterization using field emission scanning electron microscopy (FESEM). FESEM revealed a honeycomb-like morphology with distinct pore sizes for nutrient, oxygen, and drug transport. The scaffolds evidently exhibited hemocompatibility, high porosity, good swelling capacity, and biodegradability. In vitro studies demonstrated sustained drug release, particularly for scaffolds containing actonel. In vivo tests showed that the bilayer scaffold promoted new bone formation, surpassing the control group in bone area increase. The interaction of the scaffold with collagen and released ions improved the osteoblastic function and bone volume fraction. The findings suggest that this bilayer scaffold could be beneficial for treating critical-sized bone defects, especially in the mandibular and femoral regions.

Synergistic effect of umbilical cord extracellular vesicles and rhBMP-2 to enhance the regeneration of a metaphyseal femoral defect in osteoporotic rats.

BACKGROUND: The aim of this study was to evaluate potential synergistic effects of a single, local application of human umbilical cord MSC-derived sEVs in combination with a low dose of recombinant human rhBMP-2 to promote the regeneration of a metaphyseal femoral defect in an osteoporotic rat model. METHODS: 6 weeks after induction of osteoporosis by bilateral ventral ovariectomy and administration of a special diet, a total of 64 rats underwent a distal femoral metaphyseal osteotomy using a manual Gigli wire saw. Defects were stabilized with an adapted Y-shaped mini-locking plate and were subsequently treated with alginate only, or alginate loaded with hUC-MSC-sEVs (2 × 109), rhBMP-2 (1.5 µg), or a combination of sEVs and rhBMP-2 (n = 16 for each group). 6 weeks post-surgery, femora were evaluated by µCT, descriptive histology, and biomechanical testing. RESULTS: Native radiographs and µCT analysis confirmed superior bony union with callus formation after treatment with hUC-MSC-sEVs in combination with a low dose of rhBMP-2. This finding was further substantiated by histology, showing robust defect consolidation 6 weeks after treatment. Torsion testing of the explanted femora revealed increased stiffness after application of both, rhBMP-2 alone, or in combination with sEVs, whereas torque was only significantly increased after treatment with rhBMP-2 together with sEVs. CONCLUSION: The present study demonstrates that the co-application of hUC-MSC-sEVs can improve the efficacy of rhBMP-2 to promote the regeneration of osteoporotic bone defects.

Simultaneous medial closing wedge distal femoral varus osteotomy and double-bundle anterior cruciate ligament reconstruction in the symptomatic femoral valgus deformity: A case report.

Distal femoral varus osteotomy (DFVO) is a widely recognized surgical procedure used to address valgus malalignment in patients with knee joint disorders. However, it still remains unclear whether anterior cruciate ligament (ACL) reconstruction can be performed in a single procedure along with DFVO. Herein, we present a 73-year-old female patient who developed lateral osteoarthritis of the knee with valgus alignment due to chronic ACL deficiency following a twisting injury during skiing. She was physiologically very active, and strongly demanded to return to sports. We performed a combined procedure involving a medial closing wedge DFVO using an anatomical locking plate, along with double-bundle ACL reconstruction. The postoperative radiograph confirmed successful correction of knee alignment, specifically achieving varus alignment with precise conformance of the anatomical plate to the medial contour of the distal femur following the osteotomy. The patient resumed her previous sports activities without experiencing knee pain. The operated knee demonstrated restored anterior stability, as indicated by negative Lachman test results, and regained full range of motion. Both the Knee Injury and Osteoarthritis Outcome Score and the 2011 Knee Society score demonstrated continuous postoperative improvements over the three-year follow-up period, indicating positive functional outcomes and joint preservation. To the best of our knowledge, this is the first case of medial closing wedge DFVO with anatomic double-bundle ACL reconstruction in the symptomatic femoral valgus deformity with chronic ACL deficiency in the literature.

Impact of postoperative femorotibial axis on functional outcomes in unicompartmental knee arthroplasty.

OBJECTIVES: This study aimed to compare the functional outcomes of patients undergoing fixed-bearing medial unicompartmental knee arthroplasty (UKA) classified as either varus or neutral based on their postoperative femorotibial angle (FTA), with the goal of evaluating the impact of FTA on functional results. PATIENTS AND METHODS: A total of 38 knees of 35 patients (27 females, 8 males; mean age: 63.6±7.1 years; range, 52 to 75 years) were included in this retrospective study. The data was collected between December 15, 2020, and January 15, 2021. Patients were categorized into two groups based on their postoperative FTA. The neutral group consisted of patients with an FTA range of 5.1° to 7.4°, while the varus group included patients with an FTA range of 0.1° to 4.8°. Knee Outcome Osteoarthritis Score (KOOS), Visual Analog Scale (VAS) scores, sit to stand test results, and six minute walk test data were analyzed. RESULTS: The mean follow-up was 42.0±19.3 months. The postoperative VAS score for the varus group was 0.95±0.99, whereas the neutral group had a VAS score of 2.19±1.83 (p=0.021). The mean KOOS for the varus group was 88.01±7.88, whereas the neutral group had a mean KOOS score of 78.46±13.69 (p=0.006). CONCLUSION: In patients undergoing UKA, mild varus alignment could yield superior early and midterm functional outcomes compared to a neutral femorotibial angle.

Numerical evaluation of internal femur osteosynthesis based on a biomechanical model of the loading in the proximal equine hindlimb.

Femoral fractures are often considered lethal for adult horses because femur osteosynthesis is still a surgical challenge. For equine femur osteosynthesis, primary stability is essential, but the detailed physiological forces occurring in the hindlimb are largely unknown. The objective of this study was to create a numerical testing environment to evaluate equine femur osteosynthesis based on physiological conditions. The study was designed as a finite element analysis (FEA) of the femur using a musculoskeletal model of the loading situation in stance. Relevant forces were determined in the musculoskeletal model via optimization. The treatment of four different fracture types with an intramedullary nail was investigated in FEA with loading conditions derived from the model. The analyzed diaphyseal fracture types were a transverse (TR) fracture, two oblique fractures in different orientations (OB-ML: medial-lateral and OB-AP: anterior-posterior) and a "gap" fracture (GAP) without contact between the fragments. For the native femur, the most relevant areas of increased stress were located distally to the femoral head and proximally to the caudal side of the condyles. For all fracture types, the highest stresses in the implant material were present in the fracture-adjacent screws. Maximum compressive (-348 MPa) and tensile stress (197 MPa) were found for the GAP fracture, but material strength was not exceeded. The mathematical model was able to predict a load distribution in the femur of the standing horse and was used to assess the performance of internal fixation devices via FEA. The analyzed intramedullary nail and screws showed sufficient stability for all fracture types.

Evaluating the reliability of the lateral femoral condyle measuring methods by different modalities for patients with lateral patellar dislocation.

BACKGROUND: A variety of measurement methods and imaging modalities are in use to quantify the morphology of lateral femoral condyle (LFC), but the most reliable method remains elusive in patients with lateral patellar dislocation (LPD). The purpose of this study was to determine the intra- and inter-observer reliability of different measurement methods for evaluating the morphology of LFC on different imaging modalities in patients with LPD. METHODS: Seventy-three patients with LPD were included. Four parameters for quantifying the morphology of LFC were retrospectively measured by three observers on MRI, sagittal CT image, conventional radiograph (CR), and three-dimensional CT (3D-CT). The intra-class correlation coefficient was calculated to determine the intra- and inter-observer reliability. Bland-Altman analysis was conducted to identify the bias between observers. RESULTS: The lateral femoral condyle index (LFCI) showed better intra- and inter-observer reliability on MRI and 3D-CT than on CR and sagittal CT images. The mean difference in the LFCI between observers was lowest on 3D-CT (0.047), higher on MRI (0.053), and highest on sagittal CT images (0.062). The LFCI was associated with the lateral femoral condyle ratio (ρ = 0.422, P = 0.022), lateral condyle index (r = 0.413, P = 0.037), and lateral femoral condyle distance (r = 0.459, P = 0.014). The LFCI could be reliably measured by MRI and 3D-CT. CONCLUSION: The LFCI could be reliably measured by MRI and 3D-CT. The LFCI was associated with both the height and length of LFC and could serve as a comprehensive parameter for quantifying the morphology of LFC in patients with LPD.

Immunohistochemical and Morphometric Assessment on the Biological Function and Vascular Endothelial Cells in the Initial Process of Cortical Porosity in Mice With PTH Administration.

To clarify the cellular mechanism of cortical porosity induced by intermittent parathyroid hormone (PTH) administration, we examined the femoral cortical bone of mice that received 40 µg/kg/day (four times a day) human PTH (hPTH) (1-34). The PTH-driven cortical porosity initiated from the metaphyseal region and chronologically expanded toward the diaphysis. Alkaline phosphatase (ALP)-positive osteoblasts in the control mice covered the cortical surface, and endomucin-positive blood vessels were distant from these osteoblasts. In PTH-administered mice, endomucin-reactive blood vessels with TRAP-positive penetrated the ALP-positive osteoblast layer, invading the cortical bone. Statistically, the distance between endomucin-positive blood vessels and the cortical bone surface abated after PTH administration. Transmission electron microscopic observation demonstrated that vascular endothelial cells often pass through the flattened osteoblast layer and accompanied osteoclasts in the deep region of the cortical bone. The cell layers covering mature osteoblasts thickened with PTH administration and exhibited ALP, α-smooth muscle actin (αSMA), vascular cell adhesion molecule-1 (VCAM1), and receptor activator of NF-κB ligand (RANKL). Within these cell layers, osteoclasts were found near endomucin-reactive blood vessels. In PTH-administered femora, osteocytes secreted Dkk1, a Wnt inhibitor that affects angiogenesis, and blood vessels exhibited plasmalemma vesicle-associated protein, an angiogenic molecule. In summary, endomucin-positive blood vessels, when accompanied by osteoclasts in the ALP/αSMA/VCAM1/RANKL-reactive osteoblastic cell layers, invade the cortical bone, potentially due to the action of osteocyte-derived molecules such as DKK1.

Evaluation of the Effects of Whey Protein and Moringa Oleifera Leaves Extract Mixture on Osseointegration in Rabbits.

Background: Osteogenic, antioxidant and anti-inflammatory effects of Whey protein and M. oleifera gel prompted us to evaluate their role alone or in combination on osseointegration in rabbits. Methods: In this study, 24 titanium implants were inserted in the femurs of six rabbits. One implant was placed without treatment, and another one was coated with a mixture of whey protein and M. oleifera gel for each side. The animals were divided into two groups of 2- and 6-week intervals and evaluated using histopathological and immunohistochemical techniques. Results: Histological evaluation revealed a significant difference between the experimental and the control groups after two weeks in osteoblast and osteocyte counts. The experimental group had mature bone development after six weeks of implantation, while the control group had a woven bone. Immunohistochemical results showed that the experimental group, compared to the control group, exhibited early positive expression of osteoblast cells at two weeks after the experiment. Based on histopathological observations, the experimental group showed a tiny area of collagenous fiber in 6th week after the implantation. Conclusion: A mixture of whey protein and M. oleifera could accelerate osseointegration and healing processes.

Anterior cruciate ligament femoral side retained stump technique reduces enlargement of the femoral bone tunnel after anterior cruciate ligament reconstruction.

BACKGROUND: Enlargement of the bone tunnel has become an unavoidable early complication after anterior cruciate ligament (ACL) reconstruction, whether it is a single or double-bundle ACL reconstruction. Preservation of the ACL stump in ACL reconstruction reduces enlargement of the bone tunnel. The purpose of this study was to investigate the question of whether single-bundle ACL reconstruction using the ACL femoral side retained stump technique reduces enlargement of the femoral tunnel. METHODS: Forty patients who underwent single-bundle reconstruction of the ACL were included in this study. The patients were categorized into a Remnant preservation group (Group R) and the Non-remnant preservation group (Group N). In the Remnant preservation group, a high-flexion femoral side retained stump technique was used intraoperatively for the establishment of the femoral side bone tunnel, and in the Non-remnant preservation group, the conventional femoral positioning method was used (we used a femoral positioning drill for localization and drilling of the femoral bone tunnel), and MRI of the operated knee joints was performed at 6 months postoperatively. We measured the internal diameter of the femoral bone tunnel at 5 mm from the intra-articular outlet of the femoral bone tunnel on an MRI scan image perpendicular to the femoral bone tunnel. The size of the tunnel was compared between the intraoperative drilling of the bone tunnel and the size of the bone tunnel at 6 months postoperatively. Postoperative clinical assessment was Lysholm score. RESULTS: After a 6-month follow-up of 40 patients, the diameter of the femoral tunnel at a distance of 5 mm from the inner opening of the femoral tunnel was 10.96 ± 0.67 mm and 10.11 ± 0.62 mm in patients of group N and group R, respectively, and the difference was statistically significant (P < 0.05).The diameter of the femoral tunnel at 6 months postoperatively in group N and group R compared to the intraoperative bone tunnel increased by 2.58 ± 0.24 mm and 1.94 ± 0.31 mm, and the difference was statistically significant (P < 0.05).The femoral tunnel enlargement rates of group N and group R were 30.94 ± 3.00% and 24.02 ± 5.10%, respectively, and the differences were significant (P < 0.05). CONCLUSION: ACL femoral side retained stump technique does not sacrifice the ideal location of the femoral tunnel and is able to preserve the possible benefits of the ACL stump: reduced femoral tunnel enlargement.

External fixator versus elastic stable intramedullary nail for treatment of metaphyseal-diaphyseal junction fractures of the pediatric distal femur: a case-control study.

BACKGROUND: Several methods have been used for the treatment of pediatric distal femoral fractures, such as elastic stable intramedullary nail (ESIN), external fixator (EF) and plate osteosynthesis, but there has been no consensus about the optimal method. The purpose of this study was to compare the clinical outcome between EF and ESIN techniques used in metaphyseal-diaphyseal junction (MDJ) fractures of the pediatric distal femur. METHODS: We retrospectively analyzed operatively treated MDJ fractures of pediatric distal femur between January 2015 and January 2022. Patient charts were reviewed for demographics, injury and data of radiography. All of the patients were divided into EF and ESIN groups according to the operation techniques. Malalignment was defined as more than 5 degrees of angular deformity in either plane. Clinical outcomes were measured by Flynn scoring system. RESULTS: Thirty-eight patients were included in this study, among which, 23 were treated with EF, and 15 with ESIN. The mean follow-up time was 18 months (12-24 months). At the final follow-up, all of the fractures were healed. Although there were no statistical differences between the two groups in demographic data, length of stay, estimated blood loss (EBL), rate of open reduction, time to fracture healing and Flynn score, the EF was superior to ESIN in operative time, fluoroscopic exposure and time to partial weight-bearing. The EF group had a significantly higher rate of skin irritation, while the ESIN had a significantly higher rate of malalignment. CONCLUSION: EF and ESIN are both effective methods in the treatment of MDJ fractures of the pediatric distal femur. ESIN is associated with lower rates of skin irritation. However, EF technique has the advantages of shorter operative time, reduced fluoroscopic exposure, and shorter time to partial weight-bearing, as well as lower incidence of malalignment. LEVEL OF EVIDENCE: Level III.

Factors influencing the posterior cruciate ligament buckling phenomenon-a multiple linear regression analysis of bony and soft tissue structures of the knee joint.

PURPOSE: To determine whether posterior cruciate ligament (PCL) buckling (angular change) is associated with anterior cruciate ligament (ACL) status (intact or ruptured), meniscal bone angle (MBA), anterior tibial translation (ATT), body weight, femoral-tibial rotation (FTR), posterior tibial slope (PTS), PCL length and femoral-tibial distance (FTD) and to identify the factors that have the greatest influence. METHODS: All enrolled participants were scanned with a 3.0 T, 8-channel coil MRI system (Magnetom Verio; Siemens). Bone and soft tissue parameters were measured by MIMICS software for each subject and each measured parameter was correlated with PCL buckling phenomena. The correlated and statistically significant parameters were then analyzed by multiple linear regression to determine the magnitude of the effect of the different parameters on the PCL buckling phenomenon. RESULTS: A total of 116 subjects (50 ACL ruptured and 66 age, weight and height matched volunteers with uninjured knees) were enrolled. Among all measured parameters, there were 8 parameters that correlated with PCL angle (PCLA), of which ACL status had the strongest correlation with PCLA (r = - 0.67, p = < 0.001); and 7 parameters that correlated with PCL-posterior femoral cortex angle (PCL-PCA), of which ATT had the strongest correlation with PCL-PCA (r = 0.69, p = < 0.001). PCLIA was not significantly correlated with any of the measured parameters. Multiple linear regression analyses revealed four parameters can explain PCLA, of which ACL status had the strongest effect on PCLA (absolute value of standardized coefficient Beta was 0.508). Three parameters can explain PCL-PCA, of which ATT had the strongest effect on PCLIA (r = 0.69, p = < 0.001), ATT has the greatest effect on PCL-PCA (absolute value of normalized coefficient Beta is 0.523). CONCLUSIONS: PCLA may be a simple and easily reproducible and important supplement for the diagnosis of ACL injury; PCL-PCA is a simple and easily reproducible and important complementary tool for the detection of ATT. The use of PCLA is more recommended to aid in the diagnosis of ACL injury.

Evaluation optimum ratio of synthetic bone graft material and platelet rich fibrin mixture in a metal 3D printed implant to enhance bone regeneration.

BACKGROUND: This study aims to evaluate the optimal ratio of synthetic bone graft (SBG) material and platelet rich fibrin (PRF) mixed in a metal 3D-printed implant to enhance bone regeneration. METHODS: Specialized titanium hollow implants (5 mm in diameter and 6 mm in height for rabbit; 6 mm in diameter and 5 mm in height for pig) were designed and manufactured using 3D printing technology. The implants were divided into three groups and filled with different bone graft combinations, namely (1) SBG alone; (2) PRF to SBG in 1:1 ratio; (3) PRF to SBG in 2:1 ratio. These three groups were replicated tightly into each bone defect in distal femurs of rabbits (nine implants, n = 3) and femoral shafts of pigs (fifteen implants, n = 5). Animal tissue sections were obtained after euthanasia at the 8th postoperative week. The rabbit specimens were stained with analine blue, while the pig specimens were stained with Masson-Goldner's trichrome stain to perform histologically examination. All titanium hollow implants were well anchored, except in fracture specimens (three in the rabbit and one fracture in the pig). RESULT: Rabbit specimens under analine blue staining showed that collagen tissue increased by about 20% and 40% in the 1:1 ratio group and the 2:1 ratio group, respectively. Masson-Goldner's trichrome stain results showed that new bone growth increased by 32% in the 1:1 ratio PRF to SBG, while - 8% in the 2:1 ratio group. CONCLUSION: This study demonstrated that placing a 1:1 ratio combination of PRF and SBG in a stabilized titanium 3D printed implant resulted in an optimal increase in bone growth.

Relationship Between Prepatellar Fat Thickness and Bone Mineral Density.

OBJECTIVE: To evaluate the relationship between bone mineral density (BMD) by measuring the prepatellar fat thickness with knee radiography and to gain a measurement method that has not been done before in the literature. STUDY DESIGN: Cross-sectional descriptive study. Place and Duration of the Study: Department of Physical Medicine and Rehabilitation, Training and Research Hospital, Sanliurfa, Turkiye, between January and June 2020. METHODOLOGY: Patients' age, body mass index (BMI) data, prepatellar fat thickness (mm), L1-L4 total, bone mineral density femoral neck, femur trochanter major, and femur total T scores were recorded. The relationships between these three groups (normal, osteopenia, osteoporosis) and between prepatellar fat tissue measurement were evaluated. One-way analysis of variance (ANOVA) and Post Hoc Tukey tests were used in the analysis. RESULTS:  A statistically significant difference was found in terms of trochanter major T score measurements (X2 = 20.435; p <0.001) and BMI (X2 = 66.535; p <0.001) measurements of prepatellar fat thickness measurement. A statistically significant difference was found between the three groups in terms of prepatellar fat thickness measurement, L1-4 T-score, femoral neck, and femur total values (p <0.001). CONCLUSION:  Prepatellar fat thickness in postmenopausal Turkish women was positively correlated with BMD; BMD increases as the prepatellar fat thickness increases. This explains that perapatellar fat thickness creates a mechanical load on the bones and causes an increase in BMD. KEY WORDS: Osteoporosis, Fat thickness, Bone mineral density.

Hydrolyzed egg yolk peptide prevented osteoporosis by regulating Wnt/ß-catenin signaling pathway in ovariectomized rats.

Hydrolyzed egg yolk peptide (YPEP) was shown to increase bone mineral density in ovariectomized rats. However, the underlying mechanism of YPEP on osteoporosis has not been explored. Recent studies have shown that Wnt/ß-catenin signaling pathway and gut microbiota may be involved in the regulation of bone metabolism and the progression of osteoporosis. The present study aimed to explore the preventive effect of the YPEP supplementation on osteoporosis in ovariectomized (OVX) rats and to verify whether YPEP can improve osteoporosis by regulating Wnt/ß-catenin signaling pathway and gut microbiota. The experiment included five groups: sham surgery group (SHAM), ovariectomy group (OVX), 17-ß estradiol group (E2: 25 µg /kg/d 17ß-estradiol), OVX with low-dose YPEP group (LYPEP: 10 mg /kg/d YPEP) and OVX with high-dose YPEP group (HYPEP: 40 mg /kg/d YPEP). In this study, all the bone samples used were femurs. Micro-CT analysis revealed improvements in both bone mineral density (BMD) and microstructure by YPEP treatment. The three-point mechanical bending test indicated an enhancement in the biomechanical properties of the YPEP groups. The serum levels of bone alkaline phosphatase (BALP), bone gla protein (BGP), calcium (Ca), and phosphorus (P) were markedly higher in the YPEP groups than in the OVX group. The LYPEP group had markedly lower levels of alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP) and C-terminal telopeptide of type I collagen (CTX-I) than the OVX group. The YPEP groups had significantly higher protein levels of the Wnt3a, ß-catenin, LRP5, RUNX2 and OPG of the Wnt/ß-catenin signaling pathway compared with the OVX group. Compared to the OVX group, the ratio of OPG/RANKL was markedly higher in the LYPEP group. At the genus level, there was a significantly increase in relative abundance of Lachnospiraceae_NK4A136_group and a decrease in Escherichia_Shigella in YPEP groups, compared with the OVX group. However, in the correlation analysis, there was no correlation between these two bacteria and bone metabolism and microstructure indexes. These findings demonstrate that YPEP has the potential to improve osteoporosis, and the mechanism may be associated with its modulating effect on Wnt/ß-catenin signaling pathway.

Cytokine Receptor-like Factor 1 (CRLF1) and Its Role in Osteochondral Repair.

BACKGROUND: Since cytokine receptor-like factor 1 (CRLF1) has been implicated in tissue regeneration, we hypothesized that CRLF1 released by mesenchymal stem cells can promote the repair of osteochondral defects. METHODS: The degree of a femoral osteochondral defect repair in rabbits after intra-articular injections of bone marrow-derived mesenchymal stem cells (BMSCs) that were transduced with empty adeno-associated virus (AAV) or AAV containing CRLF1 was determined by morphological, histological, and micro computer tomography (CT) analyses. The effects of CRLF1 on chondrogenic differentiation of BMSCs or catabolic events of interleukin-1beta-treated chondrocyte cell line TC28a2 were determined by alcian blue staining, gene expression levels of cartilage and catabolic marker genes using real-time PCR analysis, and immunoblot analysis of Smad2/3 and STAT3 signaling. RESULTS: Intra-articular injections of BMSCs overexpressing CRLF1 markedly improved repair of a rabbit femoral osteochondral defect. Overexpression of CRLF1 in BMSCs resulted in the release of a homodimeric CRLF1 complex that stimulated chondrogenic differentiation of BMSCs via enhancing Smad2/3 signaling, whereas the suppression of CRLF1 expression inhibited chondrogenic differentiation. In addition, CRLF1 inhibited catabolic events in TC28a2 cells cultured in an inflammatory environment, while a heterodimeric complex of CRLF1 and cardiotrophin-like Cytokine (CLC) stimulated catabolic events via STAT3 activation. CONCLUSION: A homodimeric CRLF1 complex released by BMSCs enhanced the repair of osteochondral defects via the inhibition of catabolic events in chondrocytes and the stimulation of chondrogenic differentiation of precursor cells.

Modulate stress distribution with bio-inspired irregular architected materials towards optimal tissue support.

Natural materials typically exhibit irregular and non-periodic architectures, endowing them with compelling functionalities such as body protection, camouflage, and mechanical stress modulation. Among these functionalities, mechanical stress modulation is crucial for homeostasis regulation and tissue remodeling. Here, we uncover the relationship between stress modulation functionality and the irregularity of bio-inspired architected materials by a generative computational framework. This framework optimizes the spatial distribution of a limited set of basic building blocks and uses these blocks to assemble irregular materials with heterogeneous, disordered microstructures. Despite being irregular and non-periodic, the assembled materials display spatially varying properties that precisely modulate stress distribution towards target values in various control regions and load cases, echoing the robust stress modulation capability of natural materials. The performance of the generated irregular architected materials is experimentally validated with 3D printed physical samples - a good agreement with target stress distribution is observed. Owing to its capability to redirect loads while keeping a proper amount of stress to stimulate bone repair, we demonstrate the potential application of the stress-programmable architected materials as support in orthopedic femur restoration.