Mechanical effect of changed femoral neck ante-version angles on the stability of an intertrochanteric fracture fixed with PFNA: A finite element analysis.

Objective: Change of femoral neck ante-version angle postoperatively due to inadequate reduction could result in unsatisfying treatment outcome of intertrochanteric fracture. However, the influence of increased or decreased femoral neck ante-version on the biomechanical stability of the bone-implant complex has rarely been studied. Methods: A finite element model of a complete normal human femur with normal femoral neck ante-version as 13° was established accurately by scanning a 64 year old female femur. The models of 31-A1.1 intertrochanteric fractures with different femoral neck ante-version angles of 3°, 5.5°, 8°, 10.5°, 13°, 15.5°, 18°, 20.5°, 23° were created. They were assembled with a proximal femoral nail anti-rotation (PFNA) device. The biomechanical differences with varying femoral neck ante-version angles were compared using finite element analysis method. Results: As the femoral neck ante-version angle gradually increased from 13° to 23°with a gradient of 2.5°, the peak von Mises stress was gradually increased from 137.82 MPa to 276.02 MPa. Similarly, the peak von Mises stress was gradually increased from 137.82 MPa to 360.12 MPa with the femoral neck ante-version angle decreased from 13° to 3°. When decreased ante-version angle of 7.5° and increased ante-version angle of 10° will exceed the yield strength of femoral (240.32 MPa), the risk of femoral fracture will increase significantly. The maximum displacement of the femur was significantly reduced for increased ante-version models than for decreased ante-version models, whether the changes of ante-version angles were 2.5°, 5°, 7.5° or 10°. The maximum stress of PFNA was found in the intersection of main nail and helical blade, and became greater gradually as the ante-version angle increased or decreased with a gradient of 2.5°. The maximum stress of PFNA was presented in the model 5.5° with the maximum stress of 724.42 MPa (near to the yield strength of titanium alloy of 700-1000 MPa), producing the breakage risk of PFNA. The maximum displacement of the PFNA was significantly reduced for increased ante-version models than for decreased ante-version models, whether the changes of ante-version angles were 2.5°, 5°, 7.5° or 10°. Conclusion: Based on the results of present study, it was demonstrated that the anatomical reduction of femoral neck ante-version was vital to secure the optimal stability. Abnormal femoral ante-version could increase the potential risk of failure for intertrochanteric fracture after PFNA. The stability of increased femoral ante-version (less than 10°) was superior to the stability of decreased ante-version (less than 5°) for the cases of difficulty to acquire anatomical reduction. The clinical implication of the finding was that increased femoral neck ante-version had an advantage of mechanical stability towards the decreased femoral neck ante-version for the cases of comminuted intertrochanteric fracture and failure of anatomical reduction.

A novel surgical planning system using an AI model to optimize planning of pedicle screw trajectories with highest bone mineral density and strongest pull-out force.

OBJECTIVE: The purpose of this study was to evaluate the ability of a novel artificial intelligence (AI) model in identifying optimized transpedicular screw trajectories with higher bone mineral density (BMD) as well as higher pull-out force (POF) in osteoporotic patients. METHODS: An innovative pedicle screw trajectory planning system called Bone's Trajectory was developed using a 3D graphic search and an AI-based finite element analysis model. The preoperative CT scans of 21 elderly osteoporotic patients were analyzed retrospectively. The AI model automatically calculated the number of alternative transpedicular trajectories, the trajectory BMD, and the estimated POF of L3-5. The highest BMD and highest POF of optimized trajectories were recorded and compared with AO standard trajectories. RESULTS: The average patient age and average BMD of the vertebral bodies were 69.6 ± 7.8 years and 55.9 ± 17.1 mg/ml, respectively. On both sides of L3-5, the optimized trajectories showed significantly higher BMD and POF than the AO standard trajectories (p < 0.05). On average, the POF of optimized trajectory screws showed at least a 2.0-fold increase compared with AO trajectory screws. CONCLUSIONS: The novel AI model performs well in enabling the selection of optimized transpedicular trajectories with higher BMD and POF than the AO standard trajectories.

Focal osteoporosis defect is associated with vertebral compression fracture prevalence in a bone mineral density-independent manner.

Introduction: Focal osteoporosis defect has shown a high association with the bone fragility and osteoporotic fracture prevalence. However, no routine computed tomography (CT)-based vertebral focal osteoporosis defect measurement and its association with vertebral compression fracture (VCF) were discussed yet. This study aimed to develop a routine CT-based measurement method for focal osteoporosis defect quantification, and to assess its association with the VCF prevalence. Materials and Methods: A total of 205 cases who underwent routine CT scanning, were retrospectively reviewed and enrolled into either the VCF or the control group. The focal bone mineral content loss (focal BMC loss), measured as the cumulated demineralization within bone void space, was proposed for focal osteoporosis defect quantification. Its scan-rescan reproducibility and its correlation with trabecular bone mineral density (BMD) and apparent microarchitecture parameters were evaluated. The association between focal BMC loss and the prevalence of VCF was studied by logistic regression. Results: The measurement of focal BMC loss showed high reproducibility (RMSSD = 0.011 mm, LSC = 0.030 mm, ICC = 0.97), and good correlation with focal bone volume fraction (r = 0.79, P < 0.001), trabecular bone separation (r = 0.76, P < 0.001), but poor correlation with trabecular BMD (r = 0.37, P < 0.001). The focal BMC loss was significantly higher in the fracture group than the control (1.03 ± 0.13 vs. 0.93 ± 0.11 mm; P < 0.001), and was associated with prevalent VCF (1.87, 95% CI = 1.31-2.65, P < 0.001) independent of trabecular BMD level. Discussion: As a surrogate measure of focal osteoporosis defect, focal BMC Loss independently associated with the VCF prevalence. It suggests that focal osteoporosis defect is a common manifestation that positively contributed to compression fracture risk and can be quantified with routine CT using focal BMC Loss.

Prevent action of magnoflorine with hyaluronic acid gel from cartilage degeneration in anterior cruciate ligament transection induced osteoarthritis.

According to the Chinese medicine, magnoflorine exerted significant anti-inflammatory effects and potentially promoted synthesis of proteoglycans in chondrocytes to reverse the progression of rheumatoid arthritis. However, the latent beneficial effect of magnoflorine for the treatment of traumatic osteoarthritis (OA) is still unknown. Therefore, we aim to demonstrate the efficacy of magnoflorine combined with HA-gel in attenuating cartilage degeneration in anterior cruciate ligament transection (ACLT) induced OA rat model. We found that the histological results showed the elevated cartilage matrix, chondrogenic signals and chondroprogenitor cells in HA-gel + magnoflorine treatment. HA-gel + magnoflorine treatment resulted in a decreased modified Mankin's score, and a higher volume ratio of hyaline cartilage (HC)/calcified cartilage (CC) and HC/Sum (whole cartilage), compared to ACLT and HA-gel groups. Furthermore, both the volume ratios of HC/Sum and HC/CC were negatively correlated with modified Mankin's scores. Finally, HA-gel + magnoflorine could significantly increase the BV/TV, Tb.Th, and decrease the Tb.Pf, Po(tot), Conn.Dn and Tb.Sp. In vitro, 50 µg/ml magnoflorine treatment could significantly increase the viability, S-phase, migration rate and chondrogenesis of chondroprogenitor cells. There were significant downregulations of MAPK/NF-κB signaling, and upregulations of chondrogenic signals in 50 µg/ml magnoflorine treatment. There were significant downregulations of proinflammatory cytokines and upregulation of IL-10 in HA-gel + magnoflorine treated group. Therefore, our study elucidated a protective effect of HA-gel + magnoflorine on attenuating cartilage degradation and maintaining SCB stabilization in ACLT induced OA.

Failure mechanisms of pedicle screws and cortical screws fixation under large displacement: A biomechanical and microstructural study based on a clinical case scenario.

STUDY DESIGN: Cadaveric biomechanical with imaging analysis. OBJECTIVE: This study aims to compare the fixation failure between pedicel screws (PS) and cortical screws (CS), thus to investigate their failure mechanisms under vertical migration. SUMMARY OF BACKGROUND DATA: Due to their minimal invasive nature, CS are gaining popularity. However, contradictions exist in the literature regarding whether CS may have superior fixation failure resistance compared to PS under vertical migration. METHODS: Human vertebral specimens were examined under Dual-energy X-ray. For each specimen, PS were inserted on the left and CS on the right with rods secured. Vertical force-displacement tests were applied to rods. MicroCT images were taken pre and post-MTS® for microstructural analysis. RESULTS: The average T-scores of the specimens were -4±0.25. Three phases of force-displacement behaviour featuring different PS and CS failure-resistance were discovered. For phase I, the force required to migrate PS tended to be slightly higher than CS. However, during phase II, a fixation instability occurred for PS and the CS fixation strength was superior. For phase III under large displacement, CS did not require increased force to displace, whereas PS re-stabilised and revealed improved displacement resistance. Both force analysis and microstructural analysis indicated that PS migrated along the direction of the vertical loading, whereas CS had a force component in the longitudinal axis of the screw. CONCLUSIONS: Different failure mechanisms underlay PS and CS under large vertical displacement. PS fail with trabecular bone compaction possibly altering the initial material property surround the screw. CS fail with screw cut-out due to the force component along the screw axis.

Magnoflorine with hyaluronic acid gel promotes subchondral bone regeneration and attenuates cartilage degeneration in early osteoarthritis.

OBJECTIVE: To investigate efficacy of Chinese medicine magnoflorine combined with hyaluronic acid (HA)-gel in promoting subchondral bone (SCB) regeneration and attenuating cartilage degeneration in early osteoarthritis (OA). METHODS: MC3T3-E1 under magnoflorine treatment was assayed by XTT to determine cell viability. Cell proliferation was reflected through cell cycle. Osteoblast mineralization was stained by Alizarin Red. Standardized bone canal of 1 mm in diameter and 4 mm in depth was made on tibial medial plateau of 4-month-old Dunkin-Hartley spontaneous knee OA guinea pigs. Guinea pigs (n = 5/group) were treated once intra-bone canal injection of 2 µl HA-gel, 2 µl HA-gel+50 ng magnoflorine and null (Defect) respectively, except sham group. The left hind limbs were harvested for µCT scan and histopathological staining 2-month post-surgery. RESULTS: 25 µg/ml magnoflorine treatment significantly increased cell viability, S-phase and mineralization of MC3T3-E1 cells. In vivo, HA-gel + magnoflorine treatment significantly altered SCB microstructure; changes included increase in bone volume fraction (BV/TV), trabecular number (Tb.N), connectivity density (Conn.Dn), and decrease in degree of anisotropy (DA), which implied trabecular bone regeneration. Treatment also resulted in a decrease in modified Mankin's scores, and an increase in volume ratio of hyaline cartilage (HC)/calcified cartilage (CC) and fractal dimension (FD, roughness indicator of osteochondral conjunction), compared to Defect and HA groups. Furthermore, FD was positively associated with volume ratio of HC/CC and negatively associated with modified Mankin's scores. Finally, histological results showed that due to a faster regeneration of SCB with the HA-gel + magnoflorine treatment, the reduction of cartilage matrix and the decreased expression of chondrogenic signals were attenuated. CONCLUSION: Our study elucidated the potential benefits of HA-gel + magnoflorine in promoting SCB regeneration and revealed a protective effect of stimulating recovery of the SCB integrity on attenuating cartilage degradation to prevent OA progression.

Effects of Combined Magnetic Fields Treatment and Nano-Hydroxyapatite Coating on Porous Biphasic Calcium Phosphate Bone Graft in Rabbit Spinal Fusion Model.

STUDY DESIGN: An animal experimental study was designed to investigate the efficacy of combined magnetic fields (CMF) treatment and nano-hydroxyapatite (HA) coating in the biphasic calcium phosphate (BCP) graft in posterolateral lumbar fusion. OBJECTIVE: To evaluate the effects of CMF treatment and nano-HA/BCP and their combination effect in posterolateral lumbar fusion. SUMMARY OF BACKGROUND DATA: Enhancement of artificial bone graft bioeffects could improve spinal fusion outcomes. The bone graft integration is vital in spinal fusion, nano-HA coating, and CMF treatment were reported as effective methods to improve bone graft integration. METHODS: A bilateral transverse process fusion model was performed on 32 rabbits. The CMF treatment was performed for 30 minutes per day postoperation. The fusion rate, new bone formation, artificial bone graft-autologous bone fusion interface in x-ray and scanning electron microscopy, biomechanics property of fusion rate, histological fusion condition, artificial bone residual rate, and immunohistochemistry assessment of bone morphogenetic protein 2 (BMP-2) and Transforming growth factor beta 1 (TGF-ß1) expression were observed at 9th week after surgery. RESULTS: CMF treatment and nano-HA coating increased the fusion rate, adjusted optical density index, intensity of binding of artificial and autologous bone, bone growth rate, and bending stiffness. CMF treatment also significantly increased BMP-2 and TGF-ß1 expression in fusion region while nano-HA coating significantly decreased artificial bone residual rate. CONCLUSION: Our findings suggest that porous nano-HA/BCP graft could significantly improve spine fusion outcome with excellent bioactivity, biocompatibility and degradability and CMF treatment could significantly improve spine fusion outcome by improving bioactivity and biocompatibility of artificial bone graft in rabbit. Combination of CMF treatment with nano-HA/BCP graft could significantly increase posterolateral lumbar fusion rate in rabbit, which would be a potential strategy for spine fusion preclinical study. LEVEL OF EVIDENCE: N/A.

Using 3D finite element models verified the importance of callus material and microstructure in biomechanics restoration during bone defect repair.

BACKGROUND: There is lack of further observations on the microstructure and material property of callus during bone defect healing and the relationships between callus properties and the mechanical strength. METHODS: Femur bone defect model was created in rabbits and harvested CT data to reconstruct finite element models at 1 and 2 months. Three types of assumed finite element models were compared to study the callus properties, which assumed the material elastic property as heterogeneous (R-model), homogenous (H-model) or did not change from 1 to 2 months (U-model). RESULTS:  The apparent elastic moduli increased at 2 months (from 355.58 ± 132.67 to 1139.30 ± 967.43 MPa) in R-models. But there was no significant difference in apparent elastic moduli between R-models (355.58 ± 132.67 and 1139.30 ± 967.43 MPa) and H-models (344.79 ± 138.73 and 1001.52 ± 692.12 MPa) in 1 and 2 months. A significant difference of apparent elastic moduli was found between the R-model (1139.30 ± 967.43 MPa) and U-model group (207.15 ± 64.60 MPa) in 2 months. CONCLUSIONS: This study showed that the callus structure stability remodeled overtime to achieve a more effective structure, while the material quality of callus tissue is a very important factor for callus strength. At the meantime, this study showed an evidence that the material heterogeneity maybe not as important as it is in bone fracture model.

miR-375-3p negatively regulates osteogenesis by targeting and decreasing the expression levels of LRP5 and ß-catenin.

Wnt signaling pathways are essential for bone formation. Previous studies showed that Wnt signaling pathways were regulated by miR-375. Thus, we aim to explore whether miR-375 could affect osteogenesis. In the present study, we investigated the roles of miR-375 and its downstream targets. Firstly, we revealed that miR-375-3p negatively modulated osteogenesis by suppressing positive regulators of osteogenesis and promoting negative regulators of osteogenesis. In addition, the results of TUNEL cell apoptosis assay showed that miR-375-3p induced MC3T3-E1 cell apoptosis. Secondly, miR-375-3p targeted low-density lipoprotein receptor-related protein 5 (LRP5), a co-receptor of the Wnt signaling pathways, and ß-catenin as determined by luciferase activity assay, and it decreased the expression levels of LRP5 and ß-catenin. Thirdly, the decline of protein levels of ß-catenin was determined by immunocytochemistry and immunofluorescence. Finally, silence of LRP5 in osteoblast precursor cells resulted in diminished cell viability and cell proliferation as detected by WST-1-based colorimetric assay. Additionally, all the parameters including the relative bone volume from µCT measurement suggested that LRP5 knockout in mice resulted in a looser and worse-connected trabeculae. The mRNA levels of important negative modulators relating to osteogenesis increased after the functions of LRP5 were blocked in mice. Last but not least, the expression levels of LRP5 increased during the osteogenesis of MC3T3-E1, while the levels of ß-catenin decreased in bone tissues from osteoporotic patients with vertebral compression fractures. In conclusion, we revealed miR-375-3p negatively regulated osteogenesis by targeting LRP5 and ß-catenin. In addition, loss of functions of LRP5 damaged bone formation in vivo. Clinically, miR-375-3p and its targets might be used as diagnostic biomarkers for osteoporosis and might be also as novel therapeutic agents in osteoporosis treatment. The relevant products of miR-375-3p might be developed into molecular drugs in the future. These molecules could be used in translational medicine.

Notch signaling represses hypoxia-inducible factor-1α-induced activation of Wnt/ß-catenin signaling in osteoblasts under cobalt-mimicked hypoxia.

The modification of Wnt and Notch signaling pathways by hypoxia, and its association with osteoblast proliferation and apoptosis remain to be fully elucidated. To investigate Wnt-Notch crosstalk, and its role in hypoxia-induced osteoblast proliferation and apoptosis regulation, the present study investigated the effects of cobalt­mimicked hypoxia on the mouse pre-osteoblast-like cell line, MC3T3­E1, when the Notch signals were repressed using a γ­secretase inhibitor DAPT. The data showed that the cobalt­mimicked hypoxia suppressed cell proliferation under normal conditions, but increased cell proliferation under conditions of Notch repression, in a concentration­dependent manner. The results of western blot and reverse transcription­quantitative polymerase chain reaction analyses showed that the cobalt treatment increased the levels of activated ß­catenin protein and the expression levels of the target genes, axis inhibition protein 2 and myelocytomatosis oncogene, under DAPT­induced Notch repression. However, no significant changes were found in the expression levels of the Notch intracellular domain protein or the Notch target gene, hes1. In a ß­catenin gene­knockdown experiment, the proliferation of the MC3T3­E1 cells under hypoxia were decreased by DAPT treatment, and knockdown of the expression of hypoxia­inducible factor­1α (HIF­1α) suppressed the cobalt­induced increase in Wnt target gene levels. No significant difference in cell proliferation rate was found following DAPT treatment when the expression of HIF­1α was knocked down. The results of the present study showed the opposing effects of Wnt and Notch signaling under cobalt­mimicked hypoxia, which were partially regulated by HIF­1α, The results also showed that osteoblast proliferation was dependent on Wnt-Notch signal crosstalk.