Extensive and Differential Deterioration of Hip Muscles May Preexist in Older Adults with Hip Fractures: Evidence from a Cross-Sectional Study.

Hip muscles play an increasingly important role in lower limb function with aging. Investigating the deterioration of hip muscles and its relationship with hip fracture (HF) may help identify older adults prone to fall. In this study, patients with fall-related HF within 48 h and non-fracture controls aged ≥ 60 years were enrolled. The cross-sectional area (size) and attenuation (density) of the hip flexors, extensors, adductors, and abductors were calculated after segmentation on computed tomography images. The correlation of muscle parameters with HF and age were evaluated using logistic and multiple regression, respectively. Discrimination of HF was analyzed by receiver-operating characteristic analyses. A total of 220 patients and 91 controls were included. The size of the flexors, extensors, and abductors, and the density of the flexors, adductors, and abductors were lower in patients with HF after adjustment for sex, age, and body mass index (BMI). However, decreased muscle size was only observed in hip extensors in patients aged 60-74 years. Decreased muscle size was associated with HF independent of sex, age, BMI, and hip trabecular bone mineral density. Abductor size exhibited a significantly larger negative correlation with age in patients compared to controls. Including abductor size or all muscle size was effective for discrimination of HF in patients aged ≥ 75 years. In conclusion, older adults with HF may have sustained extensive and differential hip muscle deterioration before the injury; extensor atrophy in younger-old age and consideration of a closer relationship between abductor size and age deserve attention.

Exploring the causal relationship between inflammatory bowel disease and sarcopenia-related traits: a two-sample Mendelian randomization analysis.

Previous observational studies have shown an association between inflammatory bowel disease (IBD) and sarcopenia. However, the causal relationship between IBD (including ulcerative colitis and Crohn's disease) and sarcopenia remains unclear. Thus, this study investigated whether genetically predicted IBD play a function in the occurrence of sarcopenia using Mendelian randomization (MR) analysis. This study used independent single nucleotide polymorphisms (SNPs) significantly associated with IBD as instrument variables (IVs). Sarcopenia-related components (hand grip strength, walking space, and appendicular lean mass (ALM)) were investigated as outcome factors, with summary-level data regarding these components of sarcopenia obtained from the UK Biobank. The IVW-MR analysis revealed that there were significant negative associations between IBD and hand grip strength (both left and right) as well as ALM. Besides, the results of IVW-MR analysis provided strong evidence of a causal relationship between genetically predicted Crohn's disease and hand grip strength and ALM. However, there were no significant associations found between ulcerative colitis and sarcopenia-related traits. Sensitivity tests confirmed the accuracy and robustness of the above MR analysis. Conclusions: Our MR analysis showed the causal effect of Crohn's disease on hand grip strength and ALM. This suggests that Crohn's disease may be a potential risk factor for sarcopenia.

The concentrations of bone calcium, phosphorus and trace metal elements in elderly patients with intertrochanteric hip fractures.

Introduction: Trace metal elements may play a crucial role in bone mineralization and metabolism. However, the quantification of trace element concentrations in human bone tissue has received little attention. Materials and methods: Bone tissue samples were collected from 55 elderly patients (15 males and 40 females) with intertrochanteric hip fractures. The calcium, phosphorus, manganese, iron, copper, and zinc concentrations in the cortical bone zone, cancellous bone zone, and junction zone between cortical and cancellous bone were determined by energy-dispersive X-ray fluorescence (EDX). The differences in trace element concentrations in the three regions were compared, and the correlation between gender and bone trace element contents of the bones was analyzed using the Kruskal-Wallis's test. The correlation between age, body mass index (BMI), and bone calcium, phosphorus concentrations, and trace elements in three bone zones was determined using Spearman correlation analysis. Results: The Kruskal-Wallis test showed no difference in bone phosphorus concentration among the three regions. In contrast, the difference in the concentrations of bone calcium and four metal elements was statistically significant (P<0.01). In addition, no statistical differences were observed in the concentrations of trace elements among the three regions in elderly male and female patients. Spearman correlation analysis showed a strong negative correlation between bone calcium and phosphorus in three bone regions (r=-0.999, -0.95, -0.998, P < 0.01) and a significant positive correlation between trace metal elements in the cancellous bone zone. In the junction zone, the BMI showed a strong positive correlation with bone calcium content (r=0.347, P=0.009) and a significant negative correlation with phosphorus content (r=-0.349, P=0.009). Conclusion: Bone calcium and phosphorus were the main components of hydroxyapatite, and these two elements accounted for the majority of bone mineral salts. Trace metal elements are essential for bone metabolism and specific synergistic interactions. BMI may be associated with bone calcium and phosphorus contents in elderly patients with osteoporosis.

Association between bone trace elements and osteoporosis in older adults: a cross-sectional study.

Objectives: Metal micronutrients deficiency may be one of the risk factors for the development of osteoporosis. This study aimed to measure the trace element contents in human bone tissue to analyze the relationship between micronutrients and osteoporosis. Design: A cross-sectional survey was performed on data from 51 elderly patients with proximal femoral fracture. Methods: The concentrations of calcium, phosphorus, manganese, iron, copper, and zinc in bone tissue samples from 51 elderly patients with proximal femoral fracture were determined by energy-dispersive X-ray fluorescence (EDX). Subjects were divided into osteoporosis and non-osteoporosis groups according to their bone mineral density (BMD) T-score values. The difference in metal elements concentrations in bone tissue between the two groups was compared, and the role of metal elements in osteoporosis was discussed. Results: There was no statistical difference in age, sex, body mass index (BMI), serum albumin, biochemical blood indices, and bone turnover markers between the two groups. The Mann-Whitney U test was used to compare the difference in metal elements concentrations in bone tissue samples between the two groups. The results showed that manganese, copper, and zinc concentrations in the cancellous bone were significantly higher in the non-osteoporosis group than in the osteoporosis group. Multivariate logistic regression analysis indicated that high bone zinc concentration [odds ratio = 0.26, 95% confidence interval (CI) = 0.075-0.928, p = 0.038] was negatively correlated with osteoporosis. Conclusion: Manganese, copper, and zinc play an essential role in bone mineralization and metabolism. Among them, zinc may be most closely related to osteoporosis and play a key role in bone development and maintenance of bone mass. Therefore, we believe that the design of zinc-rich compounds or nutrients as a new complementary factor to increase the intake of zinc for the elderly could be able to prevent and intervene in the occurrence of osteoporosis in the early stage.

Development and Verification of a Combined Diagnostic Model for Sarcopenia with Random Forest and Artificial Neural Network.

Background: Sarcopenia is a chronic disease characterized by an age-related decline in skeletal muscle mass and function, and diagnosis is challenging owing to the lack of a clear "gold standard" assessment method. Objective: This study is aimed at combining random forest (RF) and artificial neural network (ANN) methods to screen key potential biomarkers and establish an early sarcopenia diagnostic model. Methods: Three gene expression datasets were downloaded and merged by searching the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) in the merged dataset were identified by R software and subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Afterward, the STRING database was employed for interaction analysis of the differentially encoded proteins. Then, RF was used to identify key genes from the DEGs, and a sarcopenia diagnostic model was constructed by ANN. Finally, the diagnostic model was assessed using a validation dataset, while its diagnostic performance was evaluated by the area under curve (AUC) value. Results: 107 sarcopenia-related DEGs were identified, and they were mainly enriched in the FoxO and AMPK signaling pathways involved in the molecular pathogenesis of sarcopenia. Thereafter, seven key genes (MT1X, FAM171A1, ZNF415, ARHGAP36, CISD1, ETNPPL, and WISP2) were identified by the RF classifier. The proteins encoded by three of these genes (CISD1, ETNPPL, and WISP2) may be potential biomarkers for sarcopenia. Finally, a diagnostic model for sarcopenia was successfully designed by ANN, achieving an AUC of 0.999 and 0.85 in the training and testing datasets, respectively. Conclusion: We identified several potential genetic biomarkers and successfully developed an early predictive model with high diagnostic performance for sarcopenia. Moreover, our results provide a valuable reference for the early diagnosis and screening of sarcopenia in the future.

Screening Potential Diagnostic Biomarkers for Age-Related Sarcopenia in the Elderly Population by WGCNA and LASSO.

Background: Sarcopenia is a common chronic disease characterized by age-related decline in skeletal muscle mass and function, and the lack of diagnostic biomarkers makes community-based screening problematic. Methods: Three gene expression profiles related with sarcopenia were downloaded and merged by searching the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and eigengenes of a module in the merged dataset were identified by differential expression analysis and weighted gene coexpression network analysis (WGCNA), and common genes (CGs) were defined as the intersection of DEGs and eigengenes of a module. CGs were subjected to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Subsequently, the least absolute shrinkage and selection operator (LASSO) analysis was performed to screen the CGs for identifying the diagnostic biomarkers of sarcopenia. Based on the diagnostic biomarkers, we established a novel nomogram model of sarcopenia. At last, we validated the diagnostic biomarkers and evaluated the diagnostic performance of the nomogram model by the area under curve (AUC) value. Results: We screened out 107 DEGs and 788 eigengenes in the turquoise module, and 72 genes were selected as CGs of sarcopenia by intersection. GO analysis showed that CGs were mainly involved in metal ion detoxification and mitochondrial structure, and KEGG analysis revealed that CGs were mainly enriched in the mineral absorption, glucagon signaling pathway, FoxO signaling pathway, insulin signaling pathway, AMPK signaling pathway, and estrogen signaling pathway. Then, six diagnostic biomarkers (ARHGAP36, FAM171A1, GPCPD1, MT1X, ZNF415, and RXRG) were identified by LASSO analysis. Finally, the validation AUC values indicated that the six diagnostic biomarkers had high diagnostic accuracy for sarcopenia. Conclusion: We identified six diagnostic biomarkers with high diagnostic performance, providing new insights into the incidence and progression of sarcopenia in future research.

Association between bone turnover markers, BMD and height loss of cemented vertebrae after percutaneous vertebroplasty in patients with osteoporotic vertebral compression fractures.

INTRODUCTION: Percutaneous vertebroplasty (PVP) was recently performed for treating patients with osteoporotic vertebral compression fractures (OVCF). However, recompression of cemented vertebra with significant vertebral height loss occurred in the patients after PVP was observed during the follow-up period. The purpose is to explore the risk factors among several potential predictors for the height loss of treated vertebral bodies after PVP in patients with OVCF. METHODS: A study of 93 patients who had undergone PVP between May 1, 2016, and March 1, 2019, at the Spine Center of Huadong Hospital Affiliated to Fudan University was conducted. The fractured vertebral height loss ratio ≥ 15% at final follow-up were defined as cemented vertebra recompression. The following variables were measured and collected: age, gender, body mass index (BMI), bone mineral density (BMD), volume of bone cement injected, bone cement leakage, fractured vertebra segment, contact between bone cement and endplates, serum of calcium and phosphorus, and six kinds of bone turnover markers. RESULTS: Mann-Whitney U test and Univariate Logistic regression analysis showed that the cemented vertebra recompression was correlated with BMD, contact between bone cement and endplates, parathyroid hormone (PTH), and 25-hydroxy vitamin D3 (25-OH-D3). Following multivariate modeling, multiple factors logistic regression elucidated that high BMD (P < 0.001, OR = 0.089) and high level of serum 25-OH-D3 (P = 0.012, OR = 0.877) were negatively correlated with the cemented vertebra recompression after PVP. CONCLUSION: Decreased BMD and lower level of serum 25-OH-D3 might be two critical and significant risk factors for the height loss of cemented vertebrae after PVP.

Icariin-Loaded Hydrogel Regulates Bone Marrow Mesenchymal Stem Cell Chondrogenic Differentiation and Promotes Cartilage Repair in Osteoarthritis.

Intra-articular injection of mesenchymal stem cells is a potential therapeutic strategy for cartilage protection and symptom relief for osteoarthritis (OA). However, controlling chondrogenesis of the implanted cells in the articular cavity remains a challenge. In this study, hydrogels containing different concentrations of icariin were prepared by in situ crosslinking of hyaluronic acid and Poloxamer 407. This injectable and thermoresponsive hydrogel, as a 3D cell culture system, showed good biocompatibility with chondrocytes and bone marrow mesenchymal stem cells (BMSCs), as well as promoted proliferation and chondrogenesis of BMSCs through the Wnt/ß-catenin signaling pathway. Intra-articular injection of this kind of BMSC-loaded composite hydrogel can significantly prevent cartilage destruction by inducing chondrogenic differentiation of BMSCs, and relieve pain through regulating the expression of inflammatory cytokines (e.g., IL-10 and MMP-13) in the OA model. Incorporating BMSCs into this novel icariin-loaded hydrogel indicates a more superior efficacy than the single BMSC injection, which suggests a great potential for its application in OA.

Development and validation of a novel diagnostic model for musculoskeletal aging (sarcopenia) based on cuproptosis-related genes associated with immunity.

OBJECTIVE: Sarcopenia is a geriatric disease characterized by accelerated skeletal muscle mass and function loss due to aging. Cell death plays a pivotal role in the onset and progress of sarcopenia. The purpose of this study was to investigate the role of cuproptosis-related genes (CRGs) and immune infiltration in sarcopenia development. METHODS: Three microarray expression datasets from the Gene Expression Omnibus (GEO) database were merged and batch-corrected by R software to identify differentially expressed genes (DEGs) between old and young skeletal muscles. Subsequently, DEGs were subjected to functional enrichment and gene set enrichment analysis (GSEA) to investigate the roles of DEGs and immune infiltration in the pathogenesis of musculoskeletal aging. Then, ssGSEA was performed to calculate the proportion of immune cells and functions within each muscle sample to analyze the differences between the older and young healthy muscle groups. In order to select candidate CRGs, the correlation between CRGs and immune infiltration was analyzed. Finally, a novel nomogram model of musculoskeletal aging was constructed based on candidate CRGs associated with immunity. Additionally, the diagnostic model based on key CRGs was tested using a validation dataset, and its diagnostic performance was evaluated by the area under curve (AUC) value. RESULTS: 141 DEGs were identified between 45 older samples and 50 young healthy samples. Compared to young healthy muscle tissues, significantly lower infiltration levels of T-regulatory cells were identified in older muscle tissues, while dendritic cells (DCs) and mast cells were relatively higher. Based on the CRGs from seven candidates, a novel model with high prediction efficiency (AUC = 0.856) was established to diagnose and screen for sarcopenia. CONCLUSION: The CRGs associated with immunity may play a vital role in the development of musculoskeletal aging, providing a novel avenue for early diagnosis. Furthermore, immune cell infiltration is essential for the progression of musculoskeletal aging.

Spatial distribution of hip cortical thickness in postmenopausal women with different osteoporotic fractures.

Few studies h ave discussed the association between cortical bone outside the fracture site and the fracture itself. Focusing on hip cortical thickness, this study revealed distinct distributions of the parameters for hip (trochanteric or femoral neck), vertebral, and peripheral osteoporotic fractures and suggested that the spatial distribution of hip cortical thickness was fracture-specific. PURPOSE: Cortical bone is critical for bone strength. Hip cortical thickness is reported to be closely associated with the incidence of hip fractures, but its relationship with nonhip fractures is rarely studied. As the hip is a major site for fracture risk assessment, it would be of great benefit to investigate the association between hip cortical thickness and different osteoporotic fractures. METHODS: One hundred age-matched postmenopausal women were equally assigned to 4 osteoporotic fracture groups (trochanteric, femoral neck, vertebral, and peripheral fractures) and a nonfracture group. Each subject had a clinical quantitative computed tomography scan of the bilateral hips and the lumbar spine. A cortical bone mapping algorithm was adopted to calculate hip cortical thickness. Hip and lumbar trabecular density and the hip cortical thickness distribution were compared among the groups. RESULTS: All the fracture groups presented lower lumbar trabecular density. Compared with nonfracture controls, patients with hip or vertebral fractures but not peripheral fractures showed decreased cortical thickness and trabecular density of the hip. Fracture-specific distributions of cortical thickness were revealed, including zonal defects on the neck-intertrochanter junction, greater trochanter, and the periphery of the lesser trochanter for trochanteric fractures, a focal defect on the anterosuperior neck for femoral neck fractures, a moderate and average distribution for vertebral fractures, and focally thicker cortices on the anterosuperior greater trochanter and the periphery of the lesser trochanter for peripheral fractures. CONCLUSION: The spatial distribution of hip cortical thickness was different for each type of osteoporotic fracture, and patients with centrally located fractures demonstrated more severe cortical deterioration. This finding needs to be validated in a larger sample.

ZEB1 Mediates Bone Marrow Mesenchymal Stem Cell Osteogenic Differentiation Partly via Wnt/ß-Catenin Signaling.

Zinc finger E-box-binding homebox 1 (ZEB1) is a zinc-finger transcription factor best known for its role in promoting the epithelial-mesenchymal transition, which is also related to osteogenesis. Here, ZEB1 was investigated for its role in the commitment of bone marrow mesenchymal stem cells (BMSCs) to osteoblasts. In vitro, ZEB1 expression decreased following osteogenic differentiation. Furthermore, silencing of ZEB1 in BMSCs promoted osteogenic activity and mineralization. The increase in osteogenic differentiation induced by si-ZEB1 could be partly rescued by the inhibition of Wnt/ß-catenin (si-ß-catenin). In vivo, knockdown of ZEB1 in BMSCs inhibited the rapid bone loss of ovariectomized (OVX) mice. ZEB1 expression has also been negatively associated with bone mass and bone formation in postmenopausal women. In conclusion, ZEB1 is an essential transcription factor in BMSC differentiation and may serve as a potential anabolic strategy for treating and preventing postmenopausal osteoporosis (PMOP).

Publication Trends and Hot Spots in Femoroacetabular Impingement Research: A 20-Year Bibliometric Analysis.

BACKGROUND: Femoroacetabular impingement (FAI) has attracted increasing attention over the past few decades. We aim to evaluate FAI research and predict research hot spots quantitatively and qualitatively. METHODS: The publications in FAI research between 2000 and 2019 were assimilated from the Web of Science Core Collection of Clarivate Analytics. The retrieved data were evaluated by the bibliometric method. Software CiteSpace 5.7.R1, VOSviewer 1.6.15, and the Online Analysis Platform of Literature Metrology (http://bibliometric.com/) were used to analyze and identify the hot spots and trends in this field. RESULTS: A total of 2471 originals articles that fulfilled the study requirements were obtained. The number of manuscripts on FAI has experienced rapid growth, especially after 2009. The United States of America was the leading country for publication and to the collaboration network. FAI, osteoarthritis, hip arthroscopy, labral reconstruction, pathomorphology, outcome, rehabilitation, and joint cartilage are some of the high-frequency keywords in co-occurrence cluster analysis and cocited reference cluster analysis. Burst detection analysis of top keywords revealed that outcomes, instability, labral reconstruction, adolescent, and risk factor were newly emerged research hot spots. CONCLUSION: The understanding of FAI has been improved significantly during the past two decades. Present studies focused on identifying the optimal method to treat labral pathology, outcome assessment of either surgeries or conservative managements, and predicting midterm and long-term outcomes. Together these studies exert critical implications for decision-making and management for FAI.

The comparison of bone mineral density of femoral head between non-hip fracture side and hip fracture side.

We aimed to analyze the associations of bone mineral density (BMD) of femoral heads, age and gender, and compare the differences in BMD between fracture side and non-fracture side by "3D Spine Exam Analysis" module in QCT Pro software. In this study, we identified patients who had undergone quantitative computed tomography (QCT) examinations between March 2016 and July 2018 and measured their trabecular volumetric BMD (vBMD) of femoral heads. This retrospective study enrolled 367 subjects. A total of 149 participants with images were randomly selected to verify the repeatability of this method. The relationship among the vBMD, age and gender was analyzed (n = 367), and the difference of vBMD between non-fracture side and fracture side were studied in subjects (n = 75) with low-energy hip fracture on one side and compared the image quality of bilateral hip joints. The intraclass correlation coefficients (ICCs) between the results measured by 2 operators and the results measured by the same operator showed excellent agreement (ICCs > 0.9). Multivariate regression equation of vBMD of femoral head, age and gender showed statistical significance (P < 0.05). vBMD showed negative correlation with age (P < 0.05), and showed no statistically significant relation with gender (P > 0.05). vBMD of non-fracture side was higher than that of fracture side, but the difference was statistically significant only at the middle layer (Pmiddle < 0.05). In conclusions, the vBMD of femoral head as measured by "3D Spine Exam Analysis" module in QCT Pro software showed good repeatability. The trabecular vBMD of femoral head was negatively correlated with age, and not related with gender. The vBMD of femoral head was higher on non-fracture side than that on the fracture side.

Intra-Articular Tranexamic Acid Injection During the Hip Hemi-Arthroplasty in Elderly Patients: A Retrospective Study.

INTRODUCTION: The objective was to evaluate the safety and efficacy of intra-articular injection of tranexamic acid (TXA) in patients between 80 and 100 years of age with femoral neck fracture undergoing hip hemi-arthroplasty (HA). MATERIAL AND METHODS: We conducted a retrospective review to assess perioperative blood loss and transfusion rate after intra-articular injection of TXA during HA. This was a single-center, retrospective, single-surgeon, and standard care cohort study covering the period between January and December 2016. One hundred three consecutive patients undergoing HA under spinal or general anesthesia were included. Fifty-four and 49 patients received and did not receive intra-articular injection of TXA during the HA, respectively. After closing the capsule, 50 mL of a TXA solution at a concentration of 1 g/100 mL of saline was injected into joint capsule. We compared the following outcomes: preoperative hemoglobin (HB) level, postoperative day 1 HB level, postoperative day 3 HB level, the net reduction of HB level by postoperative day 3, transfusion rate, and 30- and 90-day postoperative mortality rates. In addition, we use logistic regression to analyze the factors affecting the transfusion rate. RESULT: Day 3 postoperative HB level and the net reduction in HB level within 3 days following surgery were 93.22 ± 11.70 g/L and 25.98 ± 6.29 g/L in TXA group, respectively, while were 87.10 ± 10.52 g/L and 35.44±8.61 g/L in no-TXA group. Transfusion rate was 9% (5/54) in TXA group and 24% (12/49) in no-TXA group, respectively. The differences were statistically significant between the both groups. Logistic regression indicated that the topical administration of TXA would reduce the risk for transfusion, while in male diabetes mellitus would increase the risk. There were no significant differences in the deep venous thrombosis, pulmonary embolism, and mortality rates of 30 and 90 days postoperatively (P > .05). DISCUSSION: Because of lower systemic absorption and a higher concentration in the wound, topical use of TXA is safer for elderly patients who may have renal or liver dysfunction. TXA at therapeutic concentration does not affect platelet count, platelet aggregation, or coagulation parameters, and is of value in elderly patients who take antiplatelet drug for secondary prevention of cardiovascular diseases. CONCLUSION: For patients between 80 and 100 years of age with femoral neck fracture undergoing HA, intra-articular injection of TXA may reduce the perioperative blood loss and transfusion rate without increasing risk of thrombosis.

Bone Marrow-derived Endothelial Progenitor Cells Are Associated with Bone Mass and Strength.

OBJECTIVE: Blood vessels of bone are thought to influence osteogenesis of bone. No clinical studies have determined whether angiogenesis is related to bone mass and gene expression of growth factors. We compared bone marrow endothelial progenitor cells (EPC), which control angiogenesis of bone in postmenopausal women incurring fragility fracture, with osteoporosis or traumatic fracture with normal bone mass (COM). METHODS: Bone specimens were obtained from age-matched women with osteoporosis or COM. Mononuclear cells were isolated and EPC were detected by flow cytometry. The expression levels of specific genes were measured. Bone mineral density (BMD) was determined, and serum markers of bone turnover also were measured. Differences between OP and COM were assessed with Student t test or Mann-Whitney U test, and correlations were determined using Spearman's correlation. RESULTS: Compared with COM, patients with OP had significantly lower levels of serum osteocalcin, procollagen type-1 N-terminal propeptide, and 25-hydroxy vitamin D, as well as decreased BMD of total hip and femoral neck and fewer bone marrow EPC. Expression levels of vascular endothelial growth factor, angiopoietin-1 (Ang-1), angiopoietin 2 (Ang-2), and the osteoblast-specific genes runt-related transcription factor 2 (RUNX2) and osterix in bone were significantly lower in OP than in COM. We determined that mature EPC were correlated positively with BMD of the femoral neck and total hip, gene expression of Ang-1, RUNX2, and CD31, and negatively with gene expression of receptor activator of nuclear factor-κB ligand and Ang-2. CONCLUSION: Our results demonstrate correlations of bone marrow EPC with bone mass and gene expression of growth factors, which support a hypothesis of crosstalk between angiogenesis and osteogenesis in bone health.

Efficacy and Safety of 3 Different Anesthesia Techniques Used in Total Hip Arthroplasty.

BACKGROUND This study compared the efficacy and safety of 3 different anesthesia techniques used in total hip arthroplasty (THA). MATERIAL AND METHODS We allocated 198 patients preparing to undertake THA into 3 groups: general anesthesia group (GA group, n=66), caudal epidural anesthesia group (CEA group, n=66), and spinal-epidural anesthesia group (SEA group, n=66). We compared postoperative adverse effects occurring in patients of the 3 anesthesia groups. The Visual Analog Scale (VAS) score, Minimum Mental State Examination (MMSE) score, and ß-amyloid (Aß) expression were calculated to determine the effects of different anesthesia on the postoperative pain and cognitive dysfunction of patients. RESULTS The CEA and SEA groups had lower rates of perioperative adverse effects than in the GA group. Patients in the GA group required significantly higher administration of analgesics after the surgery than those in CEA and SEA groups. Higher Aß expression levels and VAS scores, as well as lower MMSE scores, were also seen in the GA group compared with the other 2 groups. CONCLUSIONS CEA and SEA were more effective than GA in THA, and CEA seemed to be a better anesthesia technique than SEA.

Plasma homocysteine level is a risk factor for osteoporotic fractures in elderly patients.

OBJECTIVE: To study the relationship of plasma homocysteine (Hcy), bone turnover biomarkers (BTB), and bone mineral density (BMD) with osteoporotic fracture (OPF) in elderly people. METHODS: Eighty-two patients (aged 65 years or older) admitted to our orthopedics department between October 2014 and May 2015 were randomly divided into three groups: 1) OPF group: 39 cases with the mean age 81.82±5.49 years, which included 24 females and 15 males; 2) high-energy fracture (HEF) group: 22 cases with the mean age 78.88±5.75 years, which included 16 females and six males; 3) non-bone-fracture group: 21 cases with mean age 79.75±5.47 years without bone fracture, which included 14 females and seven males. Plasma Hcy, BTB, and BMD were measured. Analysis of variance and multiple regression analysis were used in the statistical analysis. RESULTS: There was no significant difference in either age or sex among the three groups. There were significant differences in plasma Hcy and hip BMD between the OPF and HEF groups; there was also significant difference in plasma Hcy, 25-(OH) Vit D, and hip BMD between the OPF and non-fracture groups. There was no difference in lumbar spine BMD between the OPF group and the other two groups. There was no significant difference in plasma Hcy, 25-(OH) Vit D, hip or lumbar spine BMD between the HEF and non-fracture group. There was no significant difference in procollagen type I N-propeptide of type I collagen, serum C-terminal cross-linking telopeptide of type I collagen, and parathyroid hormone among the three groups. Plasma Hcy was linearly correlated with age and serum C-terminal cross-linking telopeptide of type I collagen, but not correlated with either hip or lumbar spine BMD or any other BTBs. CONCLUSION: In this study, we found that the plasma Hcy level in elderly patients with OPF is higher than that of nonosteoporotic patients. It is not correlated with BMD, but positively correlated with bone resorption markers. An increased Hcy level appears to be a risk factor for OPFs in elderly people.

Deferoxamine released from poly(lactic-co-glycolic acid) promotes healing of osteoporotic bone defect via enhanced angiogenesis and osteogenesis.

The regeneration capacity of osteoporotic bones is generally lower than that of normal bones. Current methods of osteoporotic bone defect treatment are not always satisfactory. Recent studies demonstrate that activation of the hypoxia inducible factor-1α (HIF-1α) pathway, by genetic methods or hypoxia-mimicking agents, could accelerate bone regeneration. However, little is known as to whether modulating the HIF-1α pathway promotes osteoporotic defect healing. To address this problem in the present study, we first demonstrated that HIF-1α and vascular endothelial growth factor expression levels are lower in osteoporotic bones than in normal bones. Second, we loaded poly(Lactic-co-glycolic acid) (PLGA) with the hypoxia-mimetic agent deferoxamine (DFO). DFO released from PLGA had no significant effect on the proliferation of mesenchymal stem cells (MSCs); however, DFO did enhance the osteogenic differentiation of MSCs. In addition, DFO upregulated the mRNA expression levels of angiogenic factors in MSCs. Endothelial tubule formation assays demonstrate that DFO promoted angiogenesis in human umbilical vein endothelial cells. Third, untreated PLGA scaffolds (PLGA group) or DFO-containing PLGA (PLGA + DFO group) were implanted into critically sized osteoporotic femur defects in ovariectomized rats. After treatment periods of 14 or 28 days, micro-CT, histological, CD31 immunohistochemical, and dynamic bone histomorphometric analyses showed that DFO dramatically stimulated bone formation and angiogenesis in a critically sized osteoporotic femur defect model. Our in vitro and in vivo results demonstrate that DFO may promote the healing of osteoporotic bone defects due to enhanced angiogenesis and osteogenesis. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2515-2527, 2016.

Gab1 regulates SDF-1-induced progression via inhibition of apoptosis pathway induced by PI3K/AKT/Bcl-2/BAX pathway in human chondrosarcoma.

In recent decades, the stromal cell-derived factor-l (SDF-1) and Gab1 have been investigated to be involved in oncogenesis. However, it is scarcely reported that SDF-1-Gab1 pathway mediates proliferation and apoptosis in human chondrosarcoma (CS). In this study, we assessed the expression of Gab1 in 90 CS solid tumors by immunohistochemistry, immunoblotting, and qRT-PCR, and then, some in vitro assays were also applied to CS cells treated with SDF-1. We observed that the overexpression of Gab1 was positively correlated with lung metastasis and recurrence, and acts as an independent prognostic factor for CS patients. Gab1 expression was up-regulated in response to SDF-1 stimulation in CS cell line JJ012, SW1353, L3252. Overexpression of Gab1 increased Bcl-2/BAX ratio to promote cell growth via PI3K/AKT. On the other hand, silencing of Gab1 accelerated apoptosis and repressed the growth of CS cells, which further caused the inhibition of G1/S phase transition and decreased invasion capacity in CS cell lines. In vivo assay identified that the knockdown of Gab1 interfered with the tumor mass formation. In conclusion, our data identified overexpression of Gab1 in CS tissues, and Gab1 can be recommended as a novel biomarker for diagnosis and prognosis in patients with CS. Additionally, PI3K/AKT/Bcl-2/BAX axis was involved in Gab1-induced CS progression, indicating Gab1 might act as a new target for the treatment of CS patients.