Usefulness of fat-containing agents: an initial study on estimating fat content for magnetic resonance imaging.

This initial study aimed at testing whether fat-containing agents can be used for the fat mass estimation methods using magnetic resonance imaging (MRI). As an example for clinical application, fat-containing agents (based on soybean oil, 10% and 20%), 100% soybean oil, and saline as reference substances were placed outside the proximal femurs obtained from 14 participants and analyzed by 0.3 T MRI. Fat content was the estimated fat fraction (FF) based on signal intensity (SIeFF, %). The SIeFF values of the femoral bone marrow, including the femoral head, neck, shaft, and trochanter area, were measured. MRI data were compared in terms of bone mineral content (BMC) and bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) in the proximal femur. Twelve pig femurs were also used to confirm the correlation between FF by the DIXON method and SIeFF. According to Pearson's correlation coefficient, the SIeFF and total BMC and BMD data revealed strong and moderate negative correlations in the femoral head (r < - 0.74) and other sites (r = - 0.66 to - 0.45). FF and SIeFF showed a strong correlation (r = 0.96). This study was an initial investigation of a method for estimating fat mass with fat-containing agents and showed the potential for use in MRI. SIeFF and FF showed a strong correlation, and SIeFF and BMD and BMC showed correlation; however, further studies are needed to use SIeFF as a substitute for DXA.

Evaluation of femoral condyle volumes in patients with trochlear dysplasia: a pilot study.

AIM: To examine the volumes of the medial and lateral femoral condyles and the trochlear groove, and to determine their relationship with trochlear dysplasia. MATERIALS AND METHODS: Computed tomography images of the knees of 21 patients with trochlear dysplasia and 18 healthy individuals were analysed retrospectively. According to the modified Dejour classification, the degree of trochlear dysplasia was recorded, such as type A trochlea being low-grade dysplasia and types B, C, and D trochlea being high-grade dysplasia. Volume of the trochlear groove and medial and lateral femoral condyles were calculated using the three-dimensional (3D) volume-rendering method. RESULTS: The volumes of lateral condyle, medial condyle, and trochlear groove were statistically significantly lower in patients with trochlear dysplasia when compared to healthy participants. When compared according to Dejour types, all parameters were statistically significantly lower in both high- and low-grade dysplasia patients (p<0.05). The correlation between femoral condyle volumes and trochlear groove volume was low in the control group, but there was a moderate positive correlation in the patient group (r=0.50-0.75, p<0.05). CONCLUSION: In trochlear dysplasia, the volume of the trochlear groove decreases and hypoplasia may occur in both lateral femoral and medial femoral condyles. Therefore, hypoplasia of only one condyle should not be interpreted as trochlear dysplasia. A holistic approach to patients is required.

Application of 3D-Printed Personalized Guide for Lateral Femoral Positioning in Anterior Cruciate Ligament Reconstruction of the Knee.

Objective: This research aims to investigate the effectiveness of 3D computer-assisted customized guided positioning of the lateral femoral tunnel compared to conventional methods for Anterior Cruciate Ligament (ACL) reconstruction surgery. Methods: A total of 80 patients with a complete ACL tear who underwent arthroscopic reconstruction with autologous tendon transplantation (semitendinosus-gracilis tendon) were included in this study. The patients were admitted to our hospital between March 2020 and January 2022 and were randomly divided into two groups: the conventional group (n = 40) and the personalized guide group (n = 40), based on the positioning method. The conventional group underwent ACL restoration using standard surgical techniques, while the personalized guide group opted for the more precise computer-assisted personalized guide method. The lateral femoral tunnel times were compared between both groups. Additionally, the International Knee Documentation Committee (IKDC) and Lysholm scores were assessed, and the lateral femoral location was evaluated using X-ray imaging at 2 weeks postoperatively. Results: After surgery, both groups showed a statistically significant increase (P < .05) in Lysholm and IKDC scores compared to their pre-surgery scores. However, the two groups had no evident difference (P > .05). X-ray evaluation at 2 weeks post-surgery revealed no significant difference between the two groups in NL/ML, AL/BL, α, and ß angles (P > .05). The preparation time for the femoral tunnel was significantly shorter in the personalized guide group (6.18 ± 0.92 min) compared to the traditional group (15.94 ± 3.12 min) (P < .05). Conclusions: The computer-assisted 3D personalized guide positioning method is more effective in locating the lateral femoral tunnel for ACL reconstruction of the knee and can substantially reduce the positioning time. This study provides valuable insights for clinicians when selecting surgical methods.

Effects of joint loading on the development of capital femoral epiphysis morphology.

INTRODUCTION: The deleterious influence of increased mechanical forces on capital femoral epiphysis development is well established; however, the growth of the physis in the absence of such forces remains unclear. The hips of non-ambulatory cerebral palsy (CP) patients provide a weight-restricted (partial weightbearing) model which can elucidate the influence of decreased mechanical forces on the development of physis morphology, including features related to development of slipped capital femoral epiphysis (SCFE). Here we used 3D image analysis to compare the physis morphology of children with non-ambulatory CP, as a model for abnormal hip loading, with age-matched native hips. MATERIALS AND METHODS: CT images of 98 non-ambulatory CP hips (8-15 years) and 80 age-matched native control hips were used to measure height, width, and length of the tubercle, depth, width, and length of the metaphyseal fossa, and cupping height across different epiphyseal regions. The impact of age on morphology was assessed using Pearson correlations. Mixed linear model was used to compare the quantified morphological features between partial weightbearing hips and full weightbearing controls. RESULTS: In partial weightbearing hips, tubercle height and length along with fossa depth and length significantly decreased with age, while peripheral cupping height increased with age (r > 0.2, P < 0.04). Compared to normally loaded (full weightbearing) hips and across all age groups, partially weightbearing hips' epiphyseal tubercle height and length were smaller (P < .05), metaphyseal fossa depth was larger (P < .01), and posterior, inferior, and anterior peripheral cupping heights were smaller (P < .01). CONCLUSIONS: Smaller epiphyseal tubercle and peripheral cupping with greater metaphyseal fossa size in partial weightbearing hips suggests that the growing capital femoral epiphysis requires mechanical stimulus to adequately develop epiphyseal stabilizers. Deposit low prevalence and relevance of SCFE in CP, these findings highlight both the role of normal joint loading in proper physis development and how chronic abnormal loading may contribute to various pathomorphological changes of the proximal femur (i.e., capital femoral epiphysis).

Smaller epiphyseal tubercle in hips with slipped capital femoral epiphysis compared to the uninvolved contralateral hip.

Recent investigations suggest that physeal morphologic features have a major role in the capital femoral epiphysis stability and slipped capital femoral epiphysis (SCFE) pathology, with a smaller epiphyseal tubercle and larger peripheral cupping of the femoral epiphysis being present in hips with progressive SCFE compared to healthy controls. Yet, little is known on the causal versus remodeling nature of these associations. This study aimed to use preoperative magnetic resonance imaging (MRI) of patients with unilateral SCFE to perform a comparison of the morphology of the epiphyseal tubercle, metaphyseal fossa, and peripheral cupping in hips with SCFE versus the contralateral uninvolved hips. Preoperative MRIs from 22 unilateral SCFE patients were used to quantify the morphological features of the epiphyseal tubercle (height, width, and length), metaphyseal fossa (depth, width, and length), and peripheral cupping height in three dimension. The quantified anatomical features were compared between hips with SCFE and the contralateral uninvolved side across the whole cohort and within SCFE severity subgroups using paired t-test. We found significantly smaller epiphyseal tubercle heights (p < 0.001) across all severities of SCFE when compared to their uninvolved contralateral side. There was a marginally smaller metaphyseal fossa length (p = 0.05) in SCFE hips compared to their contralateral uninvolved hips, with mild SCFE hips specifically having smaller fossa and epiphyseal lengths (p < 0.05) than their contralateral uninvolved side. There were no side-to-side differences in any other features of the epiphyseal tubercle, metaphyseal fossa and peripheral cupping across all severities (p > 0.05). These findings suggest a potential causal role of epiphyseal tubercle in SCFE pathogenesis.

Icariin attenuates thioacetamide­induced bone loss via the RANKL­p38/ERK­NFAT signaling pathway.

There is an increasing incidence of destructive bone disease caused by osteoclast proliferation. This is characterized by reduced bone mass and imbalance of bone homeostasis. Icariin (ICA), a flavonoid compound isolated from Epimedium, has anti­osteoporosis activity and inhibits the formation of osteoclasts and bone resorption. The purpose of the present study was to investigate the protective effect of ICA on osteoclastic differentiation induced by thioacetamide (TAA) and its possible mechanism in Sprague Dawley (SD) rats. In the present study, SD rats were intraperitoneally injected with TAA (300 mg/kg) for the bone loss model, treated with ICA (600 mg/kg, intragastric gavage) in the ICA group and TAA+ICA group for treatment of bone loss for 6 weeks. Indexes associated with bone metabolism, such as alkaline phosphatase, N­terminal telopeptide of type­I collagen (NTX­I), calcium (Ca), phosphorus (P) and magnesium (Mg) in the serum, were detected. Osteoclast differentiation of femoral tissues was detected by hematoxylin and eosin and tartrate­resistant acid phosphatase staining. The femoral bone mass was evaluated using a three­point bending test and micro computed tomography. Western blotting was used to detect the expression levels of osteoclast­related proteins in each group. In the rats treated with TAA, the serum concentrations of Ca, P and Mg were decreased, the serum concentration of NTX­I was increased, osteoclast differentiation of the femur was increased, femur bone stress and bone mass were decreased and the bone loss and osteoclast formation were reduced after ICA treatment. In addition, ICA inhibited the protein expression of receptor activator of nuclear factor κ­Β ligand (RANKL), receptor activator of nuclear factor κ­B (RANK), p38, ERK, c­Fos and nuclear factor of activated T cells 1 (NFATc1) in the femur of rats treated with TAA. The results suggested that ICA may inhibit osteoclast differentiation by downregulating the RANKL­p38/ERK­NFAT signaling pathway and prevent TAA­induced bone loss. The results are helpful to understand the mechanism of osteoclast differentiation induced by TAA, as well as the antiresorptive activity and molecular mechanism of ICA, and to provide new ideas for the treatment of osteolytic diseases.

Proximal femoral changes related to obesity: an analysis of slipped capital femoral epiphysis pathoanatomy.

Recent research has revealed the importance of the femoral epiphyseal tubercle and cupping height in the stability of the physis and its association with capital femoral slippage. To better understand the connection between the pathogenesis of slipped capital femoral epiphysis and obesity, we performed a retrospective analysis of proximal femur and acetabular anatomies using computed tomography (CT) scans in the hips of normal weight and obese pediatric patients. We measured morphologic characteristics of the proximal femur and acetabulum in developing hips of 31 obese adolescent patients and age-matched and sex-matched control group using pelvic CT scans. Measurements included physeal diameter, tubercle height, width, and volume, cupping height, acetabular rotation and inclination, and metaphyseal bone density. Measurements were performed on true coronal and sagittal views through the center of the epiphysis using previously described and validated techniques. Statistical analysis was performed to compare the measurements between obese and nonobese adolescents. The epiphyseal tubercle volume and average cupping size were similar between the two groups. Acetabular inclination and metaphyseal bone density were significantly different between the cohorts. Metaphyseal bone density was lower among obese patients. Obesity does not appear to cause morphologic changes to the capital femoral physis, though it is associated with a decreased metaphyseal bone mineral density which could indicate physeal instability. This could suggest increased metabolic activity in the metaphyseal bone in obese adolescents. Therefore, metabolic factors associated with obesity, rather than anatomical changes, may be responsible for physeal instability seen in obese adolescents.

Dietary Intake of Flaxseed Oil since Early Stages of Life Promotes Femur Quality in Male Rats.

BACKGROUND: Flaxseed oil (FO) is an alpha linolenic acid source important for growth and body development. However, there is little literature on the role of FO in critical stages of bone development and formation. OBJECTIVE: This study evaluated the influence of a diet containing FO on rat femurs. METHODS: After birth, mothers and pups were divided into control and flaxseed groups (n = 6 pups each) fed diets containing 7% soybean oil (C) or 7% FO. At 21 days, pups were weaned and separated from the mothers, and control or experimental diets were continued. At 67 days, the following were analyzed: osteocalcin and osteoprotegerin (OPG) levels, bone mineral density (BMD) and content, and bone area; the dimension, BMD, head radiodensity, and biomechanical proprieties of the right femur; and histomorphometric parameters of the left femur. RESULTS: Compared to the C group, the FO group presented (p < 0.05) a lower body mass (-3.7%) and medullary area (-10.1%) and higher osteocalcin (+36.7%), OPG (+52.5%), femur width (+3.8%), absolute mass (+2.3%), femur BMD (+3.6%), head radiodensity (+6.1%), maximum force (+7.4%), breaking strength (+17.3), and cortical thickness (+7.0). CONCLUSION: The FO diet contributed to femur quality in healthy male Wistar rats.

Regenerating Critical Size Rat Segmental Bone Defects with a Self-Healing Hybrid Nanocomposite Hydrogel: Effect of Bone Condition and BMP-2 Incorporation.

The aim of the current study is to assess the biological performance of self-healing hydrogels based on calcium phosphate (CaP) nanoparticles and bisphosphonate (BP) conjugated hyaluronan (HA) in a critical size segmental femoral bone defect model in rats. Additionally, these hydrogels are loaded with bone morphogenetic protein 2 (BMP-2) and their performance is compared in healthy and osteoporotic bone conditions. Treatment groups comprise internal plate fixation and placement of a PTFE tube containing hydrogel (HABP -CaP) or hydrogel loaded with BMP-2 in two dosages (HABP -CaP-lowBMP2 or HABP -CaP-highBMP2). Twelve weeks after bone defect surgery, bone formation is analyzed by X-ray examination, micro-CT analysis, and histomorphometry. The data show that critical size, segmental femoral bone defects cannot be healed with HABP -CaP gel alone. Loading of the HABP -CaP gel with low dose BMP-2 significantly improve bone formation and resulted in defect bridging in 100% of the defects. Alternatively, high dose BMP-2 loading of the HABP -CaP gel does not improve bone formation within the defect area, but leads to excessive bone formation outside the defect area. Bone defect healing is not affected by osteoporotic bone conditions.

Slipped Capital Femoral Epiphysis Associated With Vitamin C Deficiency in a 7-year-old Boy.

Scurvy is rare in the present world and is mostly found in children with abnormal dietary habits and physical and mental disabilities. Scurvy can present in various forms, mimicking several common diseases, thus making the diagnosis difficult. Spontaneous epiphyseal separation is known to occur in scurvy, although rarely reported. The usual locations of these epiphyseal separations are distal femur and proximal humerus. Our case is unique in that scurvy in a seemingly normal child resulted in proximal femur epiphyseal separation which was not reported previously. We report a case of a 7-year-old boy presenting with pain and swelling in multiple joints for 6 months and later inability to walk. Pseudoparalytic frog-leg posture, dietary history of selective eating, and typical radiologic features made us consider a diagnosis of scurvy which was confirmed by a low serum vitamin C level. He developed epiphyseal separation of proximal femur and was treated with percutaneous screw fixation. Vitamin C supplementation resulted in prompt improvement clinically and radiologically.

ß-Hydroxy-ß-Methylbutyrate (HMB) Supplementation Prevents Bone Loss during Pregnancy-Novel Evidence from a Spiny Mouse (Acomys cahirinus) Model.

The aim of this study was to determine the effects of ß-hydroxy-ß-methylbutyrate (HMB) supplementation during pregnancy on postpartum bone tissue quality by assessing changes in trabecular and compact bone as well as in hyaline and epiphyseal cartilage. The experiment was carried out on adult 6-month-old female spiny mice (Acomys cahirinus) divided into three groups: pregnant control (PregCont), pregnant HMB-treated (supplemented with 0.02 g/kg b.w of HMB during the second trimester of pregnancy, PregHMB), and non-pregnant females (NonPreg). Cross-sectional area and cortical index of the femoral mid-shaft, stiffness, and Young modulus were significantly greater in the PregHMB group. Whole-bone mineral density was similar in all groups, and HMB supplementation increased trabecular number. Growth plate cartilage was the thinnest, while the articular cartilage was the thickest in the PregHMB group. HMB supplementation increased the content of proteoglycans in the articular cartilage and the percentage of immature collagen content in metaphyseal trabeculae and compact bone. In summary, dietary HMB supplementation during the second trimester of pregnancy intensifies bone metabolic processes and prevents bone loss during pregnancy.

Bone mineral density changes in a free vascularised fibular graft in the distal femoral bone after osteosarcoma in a 10-year-old boy: a 7-year follow-up.

A 10-year-old boy presented with continuous reports of pain located to the left knee. Imaging revealed a sclerotic process in the left distal femur, and biopsies were consistent with chondroblastic osteosarcoma. As part of standard treatment the patient underwent neoadjuvant chemotherapy followed by limb sparring surgery and adjuvant chemotherapy. The entire tumour was excised and femoral bone reconstruction was performed with a double barrel free vascularised fibular graft. Bone mineral density (BMD) can be decreased in childhood survivors of cancer. The patient was followed for 7 years with dual-energy X-ray absorptiometry scans in order to assess BMD and graft adaption. Despite two accidental fractures to the graft region local and global BMD underwent an overall increase. Approximately 7 years after tumour resection the patient had a global Z-score of 0.2, which is considered within normal range.

Is an anodizing coating associated to the photobiomodulation able to optimize bone healing in ovariectomized animal model?

This in vivo study investigated whether the bioactivity of anodizing coating, produced by plasma electrolytic oxidation (PEO), on mini-plate in femur fracture could be improved with the association of photobiomodulation (PBM) therapy. From the 20 ovariectomized Wistar female rats, 8 were used for model characterization, and the remaining 12 were divided into four groups according to the use of PBM therapy by diode laser (808 nm; power: 100 mW; energy: 6.0 J; energy density: 212 J/cm2; power density: 3.5 W/cm2) and the type of mini-plate surface (commercially pure titanium mini-plate -cpTi- and PEO-treated mini-plate) as follow: cpTi; PEO; cpTi/PBM; and PEO/PBM. After 60 days of surgery, fracture healing underwent microstructural, bone turnover, histometric, and histologic adjacent muscle analysis. Animals of groups with PEO and PBM showed greater fracture healing than cpTi control group under histometric and microstructural analysis (P < 0.05); however, bone turnover was just improved in PBM's groups (P < 0.05). there was no difference between cpTi and PEO without PBM (P > 0.05). Adjacent muscle analysis showed no metallic particles or muscle alterations in all groups. PEO and PBM are effective strategies for bone repair in fractures, however their association does not provide additional advantages.

Does the Capital Femoral Physis Bony MorphologyDiffer in Children with Symptomatic Cam-type Femoroacetabular Impingement.

BACKGROUND: The epiphyseal tubercle, the corresponding metaphyseal fossa, and peripheral cupping are key stabilizers of the femoral head-neck junction. Abnormal development of these features in the setting of supraphysiologic physeal stress under high forces (for example, forces that occur during sports activity) may result in a cam morphology. Although most previous studies on cam-type femoroacetabular impingement (FAI) have mainly focused on overgrowth of the peripheral cupping, little is known about detailed morphologic changes of the epiphyseal and metaphyseal bony surfaces in patients with cam morphology. QUESTIONS/PURPOSES: (1) Does the CT-based bony morphology of the peripheral epiphyseal cupping differ between patients with a cam-type morphology and asymptomatic controls (individuals who did not have hip pain)? (2) Does the CT-based bony morphology of the epiphyseal tubercle differ between patients with a cam-type morphology and asymptomatic controls? (3) Does the CT-based bony morphology of the metaphyseal fossa differ between patients with a cam-type morphology and asymptomatic controls? METHODS: After obtaining institutional review board approval for this study, we retrospectively searched our institutional database for patients aged 8 to 15 years with a diagnosis of an idiopathic cam morphology who underwent a preoperative CT evaluation of the affected hip between 2005 and 2018 (n = 152). We excluded 96 patients with unavailable CT scans and 40 patients with prior joint diseases other than cam-type FAI. Our search resulted in 16 patients, including nine males. Six of 16 patients had a diagnosis of bilateral FAI, for whom we randomly selected one side for the analysis. Three-dimensional (3-D) models of the proximal femur were generated to quantify the size of the peripheral cupping (peripheral growth of the epiphysis around the metaphysis), epiphyseal tubercle (a beak-like prominence in the posterosuperior aspect of the epiphysis), and metaphyseal fossa (a groove on the metaphyseal surface corresponding to the epiphyseal tubercle). A general linear model was used to compare the quantified anatomic features between the FAI cohort and 80 asymptomatic hips (aged 8 to 15 years; 50% male) after adjusting for age and sex. A secondary analysis using the Wilcoxon matched-pairs signed rank test was performed to assess side-to-side differences in quantified morphological features in 10 patients with unilateral FAI. RESULTS: After adjusting for age and sex, we found that patients with FAI had larger peripheral cupping in the anterior, posterior, superior, and inferior regions than control patients who did not have hip symptoms or radiographic signs of FAI (by 1.3- to 1.7-fold; p < 0.01 for all comparisons). The epiphyseal tubercle height and length were smaller in patients with FAI than in controls (by 0.3- to 0.6-fold; p < 0.02 for all comparisons). There was no difference in tubercle width between the groups. Metaphyseal fossa depth, width, and length were larger in patients with FAI than in controls (by 1.8- to 2.3-fold; p < 0.001 for all comparisons). For patients with unilateral FAI, we saw similar peripheral cupping but smaller epiphyseal tubercle (height and length) along with larger metaphyseal fossa (depth) in the FAI side compared with the uninvolved contralateral side. CONCLUSION: Consistent with prior studies, we observed more peripheral cupping in patients with cam-type FAI than control patients without hip symptoms or radiographic signs of FAI. Interestingly, the epiphyseal tubercle height and length were smaller and the metaphyseal fossa was larger in hips with cam-type FAI, suggesting varying inner bone surface morphology of the growth plate. The docking mechanism between the epiphyseal tubercle and the metaphyseal fossa is important for epiphyseal stability, particularly at early ages when the peripheral cupping is not fully developed. An underdeveloped tubercle and a large fossa could be associated with a reduction in stability, while excessive peripheral cupping growth would be a factor related to improved physeal stability. This is further supported by observed side-to-side differences in tubercle and fossa morphology in patients with unilateral FAI. Further longitudinal studies would be worthwhile to study the causality and compensatory mechanisms related to epiphyseal and metaphyseal bony morphology in pathogenesis cam-type FAI. Such information will lay the foundation for developing imaging biomarkers to predict the risk of FAI or to monitor its progress, which are critical in clinical care planning. LEVEL OF EVIDENCE: Level III, prognostic study.

Regeneration enhanced in critical-sized bone defects using bone-specific extracellular matrix protein.

Extracellular matrix (ECM) products have the potential to improve cellular attachment and promote tissue-specific development by mimicking the native cellular niche. In this study, the therapeutic efficacy of an ECM substratum produced by bone marrow stem cells (BM-MSCs) to promote bone regeneration in vitro and in vivo were evaluated. Fluorescence-activated cell sorting analysis and phenotypic expression were employed to characterize the in vitro BM-MSC response to bone marrow specific ECM (BM-ECM). BM-ECM encouraged cell proliferation and stemness maintenance. The efficacy of BM-ECM as an adjuvant in promoting bone regeneration was evaluated in an orthotopic, segmental critical-sized bone defect in the rat femur over 8 weeks. The groups evaluated were either untreated (negative control); packed with calcium phosphate granules or granules+BM-ECM free protein and stabilized by collagenous membrane. Bone regeneration in vivo was analyzed using microcomputed tomography and histology. in vivo results demonstrated improvements in mineralization, osteogenesis, and tissue infiltration (114 ± 15% increase) in the BM-ECM complex group from 4 to 8 weeks compared to mineral granules only (45 ± 21% increase). Histological observations suggested direct apposition of early bone after 4 weeks and mineral consolidation after 8 weeks implantation for the group supplemented with BM-ECM. Significant osteoid formation and greater functional bone formation (polar moment of inertia was 71 ± 0.2 mm4 with BM-ECM supplementation compared to 48 ± 0.2 mm4 in untreated defects) validated in vivo indicated support of osteoconductivity and increased defect site cellularity. In conclusion, these results suggest that BM-ECM free protein is potentially a therapeutic supplement for stemness maintenance and sustaining osteogenesis.

A predictive model with radiographic signs can be a useful supplementary diagnostic tool for complete discoid lateral meniscus in adults.

PURPOSE: To investigate the diagnostic accuracy of radiographic signs for complete discoid lateral meniscus and whether a predictive model combining the radiographic signs can improve its diagnostic accuracy in adults. METHODS: A total of adult 119 knees with complete discoid lateral meniscus confirmed by arthroscopy and 119 age- and sex-matched knees with normal meniscus were included. The radiographic signs of lateral joint space, fibular head height, lateral tibial spine height, lateral tibial plateau obliquity, lateral femoral condyle squaring, lateral tibial plateau cupping, lateral femoral condyle notching, and the condylar cut-off sign were evaluated. The receiver-operating characteristic (ROC) curves and area under the curve (AUC) were evaluated for best accuracy. A prediction model was developed by multivariable regression with generalized estimating models, and was validated using data from 111 knees of children with complete discoid lateral meniscus and 111 normal controls. RESULTS: The fibular head height, lateral joint space, lateral tibial plateau obliquity, and the condylar cut-off sign were significantly different between the complete discoid lateral meniscus and the normal groups (p < 0.05). Among the four radiographic signs, the fibular head height showed the highest accuracy with 78.9% sensitivity and 57.3% specificity. The prediction models developed by logistic regression showed significantly improved accuracy for complete discoid lateral meniscus compared to the fibular head height (sensitivity: 69.8%, specificity: 82.9%, p = 0.001). For validation, the AUC of children seemed to be larger than that of adults, which indicated that the prediction models could be applied for children to detect complete discoid lateral meniscus. CONCLUSION: Among several radiographic signs, the fibular head height can be used as a screening tool for complete discoid lateral meniscus. The prediction models combined with lateral joint space, fibular head height, lateral tibial plateau obliquity, and/or the condylar cut-off sign yielded a much higher diagnostic value than each radiographic sign. Therefore, fibular head height and prediction models combined with radiographic signs can provide improved diagnostic value for complete discoid lateral meniscus. LEVEL OF EVIDENCE: III.

What Is the Association Among Epiphyseal Rotation, Translation, and the Morphology of the Epiphysis and Metaphysis in Slipped Capital Femoral Epiphysis?

BACKGROUND: Contemporary studies have described the rotational mechanism in patients with slipped capital femoral epiphysis (SCFE). However, there have been limited patient imaging data and information to quantify the rotation. Determining whether the epiphysis is rotated or translated and measuring the epiphyseal displacement in all planes may facilitate planning for surgical reorientation of the epiphysis. QUESTIONS/PURPOSES: (1) How does epiphyseal rotation and translation differ among mild, moderate, and severe SCFE? (2) Is there a correlation between epiphyseal rotation and posterior or inferior translation in hips with SCFE? (3) Does epiphyseal rotation correlate with the size of the epiphyseal tubercle or the metaphyseal fossa or with epiphyseal cupping? METHODS: We identified 51 patients (55% boys [28 of 51]; mean age 13 ± 2 years) with stable SCFE who underwent preoperative CT of the pelvis before definitive treatment. Stable SCFE was selected because unstable SCFE would not allow for accurate assessment of rotation given the complete displacement of the femoral head in relation to the neck. The epiphysis and metaphysis were segmented and reconstructed in three-dimensions (3-D) for analysis in this retrospective study. One observer (a second-year orthopaedic resident) performed the image segmentation and measurements of epiphyseal rotation and translation relative to the metaphysis, epiphyseal tubercle, metaphyseal fossa, and the epiphysis extension onto the metaphysis defined as epiphyseal cupping. To assess the reliability of the measurements, a randomly selected subset of 15 hips was remeasured by the primary examiner and by the two experienced examiners independently. We used ANOVA to calculate the intraclass and interclass correlation coefficients (ICCs) for intraobserver and interobserver reliability of rotational and translational measurements. The ICC values for rotation were 0.91 (intraobserver) and 0.87 (interobserver) and the ICC values for translation were 0.92 (intraobserver) and 0.87 (intraobserver). After adjusting for age and sex, we compared the degree of rotation and translation among mild, moderate, and severe SCFE. Pearson correlation analysis was used to assess the associations between rotation and translation and between rotation and tubercle, fossa, and cupping measurements. RESULTS: Hips with severe SCFE had greater epiphyseal rotation than hips with mild SCFE (adjusted mean difference 21° [95% CI 11° to 31°]; p < 0.001) and hips with moderate SCFE (adjusted mean difference 13° [95% CI 3° to 23°]; p = 0.007). Epiphyseal rotation was positively correlated with posterior translation (r = 0.33 [95% CI 0.06 to 0.55]; p = 0.02) but not with inferior translation (r = 0.16 [95% CI -0.12 to 0.41]; p = 0.27). There was a positive correlation between rotation and metaphyseal fossa depth (r = 0.35 [95% CI 0.08 to 0.57]; p = 0.01), width (r = 0.41 [95% CI 0.15 to 0.61]; p = 0.003), and length (r = 0.56 [95% CI 0.38 to 0.75]; p < 0.001). CONCLUSION: This study supports a rotational mechanism for the pathogenesis of SCFE. Increased rotation is associated with more severe slips, posterior epiphyseal translation, and enlargement of the metaphyseal fossa. The rotational nature of the deformity, with the center of rotation at the epiphyseal tubercle, should be considered when planning in situ fixation and realignment surgery. Avoiding placing a screw through the epiphyseal tubercle-the pivot point of rotation- may increase the stability of the epiphysis. The realignment of the epiphysis through rotation rather than simple translation is recommended during the open subcapital realignment procedure. Enlargement of the metaphyseal fossa disrupts the interlocking mechanism with the tubercle and increases epiphyseal instability. Even in the setting of a stable SCFE, an increased fossa enlargement may indicate using two screws instead of one screw, given the severity of epiphyseal rotation and the risk of instability. Further biomechanical studies should investigate the number and position of in situ fixation screws in relation to the epiphyseal tubercle and metaphyseal fossa. LEVEL OF EVIDENCE: Level III, prognostic study.

Therapeutic potential of Liuwei Dihuang pill against KDM7A and Wnt/ß-catenin signaling pathway in diabetic nephropathy-related osteoporosis.

The effects of Liuwei Dihuang pill (LWDH) on diabetic nephropathy-related osteoporosis (DNOP) are unclear. The present study aimed to evaluate the effects of LWDH on KDM7A and Wnt/ß-catenin signaling pathway in DNOP rats and the high glucose-induced MC3T3-E1 cells. A DNOP model was prepared by streptozotocin in 9-week-old male Sprague-Dawley (SD) rats to evaluate the effects of LWDH. The cell viability and differentiation capacity of high glucose-induced MC3T3-E1 cells were determined by CCK-8 assay, Alizarin Red staining, and alkaline phosphatase (ALP) staining, respectively. Furthermore, the expressions of KDM7A and Wnt1/ß-catenin pathway-related proteins were determined by Western blot analysis. Treatment of DNOP rats with LWDH could significantly ameliorate the general state, degradation of renal function, and renal pathological changes. LWDH decreased the levels of TNF-α, IL-6, IL-8, IL-1ß, ALP, and TRAP, and increased the calcium, phosphorus in serum, as well as decreased the level of the calcium and phosphorus in the urine. Besides, LWDH significantly improved bone mineral density (BMD), bone volume (BV), and the bone microstructure of DNOP rats. Moreover, LWDH increased the levels of the elastic modulus, ultimate load, and bending strength in the femurs. In MC3T3-E1 cells, serum-containing LWDH significantly increases in cell viability and osteoblastic differentiation capability. The expression of α-SMA, vimentin, KDM7A, Wnt1 and ß-catenin were significantly down-regulated, and the E-cadherin, H3K9-Me2, H3K27-Me2, BMP-4, BMP-7, Runx2, osteocalcin, and Col1a1 were significantly up-regulated with LWDH treatment. The present study shows that LWDH has a therapeutic effect on DNOP, in part, through down-regulation of KDM7A and Wnt/ß-catenin pathway.

Evaluation of the therapeutic potential of Epigallocatechin-3-gallate (EGCG) via oral gavage in young adult Down syndrome mice.

Epigallocatechin-3-gallate (EGCG) is a candidate therapeutic for Down syndrome (DS) phenotypes based on in vitro inhibition of DYRK1A, a triplicated gene product of Trisomy 21 (Ts21). Consumption of green tea extracts containing EGCG improved some cognitive and behavioral outcomes in DS mouse models and in humans with Ts21. In contrast, treatment with pure EGCG in DS mouse models did not improve neurobehavioral phenotypes. This study tested the hypothesis that 200 mg/kg/day of pure EGCG, given via oral gavage, would improve neurobehavioral and skeletal phenotypes in the Ts65Dn DS mouse model. Serum EGCG levels post-gavage were significantly higher in trisomic mice than in euploid mice. Daily EGCG gavage treatments over three weeks resulted in growth deficits in both euploid and trisomic mice. Compared to vehicle treatment, EGCG did not significantly improve behavioral performance of Ts65Dn mice in the multivariate concentric square field, balance beam, or Morris water maze tasks, but reduced swimming speed. Furthermore, EGCG resulted in reduced cortical bone structure and strength in Ts65Dn mice. These outcomes failed to support the therapeutic potential of EGCG, and the deleterious effects on growth and skeletal phenotypes underscore the need for caution in high-dose EGCG supplements as an intervention in DS.

Trigonelline Demonstrated Ameliorative Effects in Dexamethasone Induced Osteoporotic Rats.

AIM: Trigonelline is a potent phytochemical present in fenugreek, which has strong anti-oxidant and phytoestrogenic activities. This study was carried out to investigate this estrogenic activity as a possible mechanisms involved in preventing the symptoms of osteoporosis in dexamethasone induced osteoporosis in rats. MATERIALS AND METHODS: Wistar rats were randomly divided into eight groups, six animals in each group. Osteoporosis was induced using dexamethasone 0.1mg/kg subcutaneously in rats for three times per week for 8 consecutive weeks and treatment with drugs up to 12 weeks as per the treatment schedule described. After 12 weeks, rats were sacrificed; blood samples were collected from each rat and the clear, non hemolysed supernatant sera was used for biochemical examinations. Femurs were used for Bone Mineral Density (BMD), microcomputed tomography (Micro CT), histology and biochemical examinations. RESULTS: BMD, bone micro structure, serum calcium, phosphorus level and serum estradiol levels were decreased while serum PTH levels, SAP and acid phosphatase (ACP) were elevated in dexamethasone treated rats as compared to control (p<0.01). Dexmethasone treated animals showed loss of marrow at multifocal area, cartilage and trabeculae and thinning of trabeculae (bone resorption), zone of cartilage was poorly seen and fat cells in marrow. Trigonelline showed significant improvement and prevent the progression of osteoporosis by enhancing the BMD, restoring bone physiology. CONCLUSION: Our results confirm the estrogenic activity of triogonelline, which is responsible for its effects; still, it needs further evaluation in other animal models to provide a more conclusive view for its therapeutic usefulness in osteoporosis.