Silicone rubber sealed channel induced self-healing of large bone defects: Where is the limit of self-healing of bone?

Background: Large defects of long tubular bones due to severe trauma, bone tumor resection, or osteomyelitis debridement are challenging in orthopedics. Bone non-union and other complications often lead to serious consequences. At present, autologous bone graft is still the gold standard for the treatment of large bone defects. However, autologous bone graft sources are limited. Silicon rubber (SR) materials are widely used in biomedical fields, due to their safety and biocompatibility, and even shown to induce nerve regeneration. Materials and methods: We extracted rat bone marrow mesenchymal stem cells (BMMSCs) in vitro and verified the biocompatibility of silicone rubber through cell experiments. Then we designed a rabbit radius critical sized bone defect model to verify the effect of silicone rubber sealed channel inducing bone repair in vivo. Results: SR sealed channel could prevent the fibrous tissue from entering the fracture end and forming bone nonunion, thereby inducing self-healing of long tubular bone through endochondral osteogenesis. The hematoma tissue formed in the early stage was rich in osteogenesis and angiogenesis related proteins, and gradually turned into vascularization and endochondral osteogenesis, and finally realized bone regeneration. Conclusions: In summary, our study proved that SR sealed channel could prevent the fibrous tissue from entering the fracture end and induce self-healing of long tubular bone through endochondral osteogenesis. In this process, the sealed environment provided by the SR channel was key, and this might indicate that the limit of self-healing of bone exceeded the previously thought. The translational potential of this article: This study investigated a new concept to induce the self-healing of large bone defects. It could avoid trauma caused by autologous bone extraction and possible rejection reactions caused by bone graft materials. Further research based on this study, including the innovation of induction materials, might invent a new type of bone inducing production, which could bring convenience to patients. We believed that this study had significant meaning for the treatment of large bone defects in clinical practice.

Gamma Nail Combined with One Cannulated Compression Screw Fixation for Treating Pauwels Type III Femoral Neck Fractures in Young and Middle-Aged Adults: Clinical Follow-Up and Biomechanical Studies.

OBJECTIVE: Recently, some clinical studies have reported the use of an intramedullary nailing system for treating unstable femoral neck fractures or femoral neck fractures combined with femoral shaft fractures in young adults, and the results have indicated certain advantages. However, no study has investigated the mechanical properties of this method. We aimed to evaluate the mechanical stability and clinical efficacy of the Gamma nail combined with one cannulated compression screw (CCS) fixation for treating Pauwels type III femoral neck fracture in young and middle-aged adults. METHODS: This study consists of two parts: a clinical retrospective study and randomized controlled biomechanical test. Twelve adult cadaver femora were used to test and compare the biomechanical properties among three fixation methods: three parallel CCS (group A), Gamma nail (group B), and Gamma nail combined with one cannulated compression screw (group C). The single continuous compression test, cyclic load test, and ultimate vertical load test were used to evaluate the biomechanical performance of the three fixation methods. We also conducted a retrospective study of 31 patients with Pauwels type III femoral neck fractures, including 16 patients with fractures fixed with three parallel CCS (CCS group) and 15 patients with fractures fixed with Gamma nail combined with one CCS (Gamma nail + CCS group). The patients were followed up for at least 3 years, and all were evaluated for surgical time (from skin incision to closure), surgical blood loss, hospital stay, and the Harris hip score. RESULTS: In mechanical experiments, we have found that the mechanical advantages of Gamma nail fixation are not as good as those of conventional CCS fixation. However, the mechanical properties of Gamma nail fixation combined with one cannulated screw perpendicular to the fracture line are much better than those of Gamma nail fixation and CCS fixation. No significant difference was found in the incidence of femoral head necrosis and nonunion between the CCS and Gamma nail + CCS groups. Moreover, there was no statistically significant difference in the Harris hip scores between the two groups. One patient in the CCS group showed significant withdrawal of cannulated screws at 5 months after surgery, whereas in the Gamma nail + CCS group, all patients, including those with femoral neck necrosis, showed no loss of stability of the fixation. CONCLUSION: Among the two fixation methods evaluated in this study, Gamma nail combined with one CCS fixation showed better biomechanical properties and may reduce complications associated with unstable fixation devices.

Efficacy of the Combination of Teriparatide and Denosumab in the Treatment of Postmenopausal Osteoporosis: A Meta-Analysis.

Aim: Evidence on the efficacy of combination treatment of teriparatide and denosumab for osteoporosis remains controversial. We aim to compare the efficacy between the combination treatment and monotherapy among patients with postmenopausal osteoporosis. Methods and results: We systematically searched PubMed, EMBASE, the Cochrane Library, and Web of Science up to 26 January 2022, for relevant studies. This meta-analysis reviewed all randomized controlled trials (RCTs) that reported on the combination treatment of teriparatide and denosumab in patients with postmenopausal osteoporosis. The articles were examined individually by two reviewers, and the relevant data was extracted. We combined weighted mean difference (WMD) for bone mineral density (BMD) using random- or fixed- effect models and conducted subgroup analyses. Sensitivity analyses were performed, and possible publication bias was also assessed. Overall, combination treatment enhanced the mean percent change of bone mineral density in lumbar spine than monotherapy (WMD = 2.91, 95%CI: 1.983.83; p = 0.00). And, combination treatment has been beneficial for enhancing the mean percent change of BMD in hip (WMD = 3.19, 95%CI: 2.25∼4.13; p = 0.00). There was no significant difference between combination treatment and monotherapy in terms of the adverse events (RR = 0.81, 95%CI: 0.45∼1.45; p = 0.472). Conclusion: The meta-analysis indicates that combination treatment led to greater BMD at the lumbar spine and hip in comparison to monotherapy, without an increased incidence of adverse events. Systematic Review Registration: (https://inplasy.com/), identifier (Inplasy Protocol 2734).

Minimally Invasive Percutaneous TightRope® System Fixation for an Unstable Posterior Pelvic Ring: Clinical Follow-up and Biomechanical Studies.

OBJECTIVE: To evaluate the mechanical stability and clinical efficacy of minimally invasive percutaneous TightRope® systems applied via gun-shaped reduction forceps for unstable posterior pelvic ring fractures. MATERIALS AND METHODS: This study consists of two parts: a clinical retrospective study and a randomized controlled biomechanical test. For the clinical study, a retrospective analysis of posterior pelvic ring fractures was performed between June 2015 and May 2020. Eighteen patients underwent surgery using two TightRope® systems to fix a broken posterior pelvic ring because of unstable AO type C1 and C2 pelvic ring fractures. The patients were followed up for at least 2 years, and all patients were evaluated using the Majeed scoring system and vertical displacement. In the biomechanical tests, six embalmed adult pelvic specimens were used. The fractures were subjected to TightRope®, IS screw, and TBP fixation in a randomized block design. The specimens were placed in a biomechanical testing machine in a standing neutral posture. A cyclic vertical load of up to 500 N was applied, and the displacement of the specimens was recorded by the testing machine. The ultimate load in each group of specimens was recorded. The displacement and ultimate load were compared and analyzed by statistical methods. RESULTS: At a mean follow-up of 38.89 ± 8.72 months, the functional Majeed score was excellent in 14 patients and good in four patients. The final radiological examinations showed that the outcome was excellent in 14 patients and good in four patients. In these patients, no serious clinical complications were found. Weight-bearing was delayed in four patients. In biomechanical tests, the displacement of the specimens fixed with TightRope® was significantly lower than that of the specimens fixed with TBP (P < 0.05) when the load ranged from 300 to 500 N. The displacement in the IS screw group was significantly lower than that in either the TBP or TightRope® group (P < 0.05) when the load ranged from 0 to 500 N. The ultimate load in the IS screw group (1798 ± 83.53 N) was significantly greater than that in the TBP group (1352 ± 74.41 N) (t = 9.78, P < 0.0001) and the TightRope® group (1347 ± 54.28 N) (t = 11.11, P < 0.0001). However, no significant difference was observed between the TightRope® and TBP groups (t = 0.13, P = 0.90). CONCLUSION: Percutaneous posterior TightRope® system shows strong stability in mechanical experiments and shows good results in clinical follow-up while this system has certain advantages in lower surgical requirements and lower risk of related nerve and vascular structural damage.

Fracture risks in patients with atrial fibrillation treated with different oral anticoagulants: a meta-analysis and systematic review.

AIMS: evidence on the difference in fracture risks for patients with atrial fibrillation (AF) receiving direct oral anticoagulants (DOACs) versus warfarin remains controversial. We aim to compare the fracture risks between the DOAC and warfarin prescriptions among the AF patients. METHODS AND RESULTS: we systematically searched PubMed, EMBASE, the Cochrane Library and Web of Science up to 19 April 2021 for relevant studies. And the observational studies regarding the relationship between the DAOC versus warfarin prescriptions and fracture risks among the patients with AF were included in this meta-analysis. Two investigators independently screened the articles and extracted the relevant data. A random- or fixed-effect model was applied to calculate the pooled hazard ratio/relative ratios with 95% confidence intervals of fracture risks associated with the DOAC and warfarin prescriptions. Six studies comprising 351,208 patients and 9,424 fractures were included in this meta-analysis. Overall, the AF patients treated with DOACs tend to present a lower risk of any fracture compared with those treated with warfarin (relative ratio: 0.82, 95% confidence interval (CI): 0.74-0.91). Sub-analyses for each individual DOAC indicate that apixaban and rivaroxan are associated with lower risk of any fracture compared with warfarin (HR: 0.75, 95% CI: 0.60-0.92, and HR: 0.79, 95% CI: 0.71-0.88, respectively). CONCLUSION: this meta-analysis suggests that DOAC users have a lower risk of fractures than the warfarin users. The results of this study may provide optimal anticoagulation opportunities for AF patients with high fracture risk factors.

Changes of Migration, Immunoregulation and Osteogenic Differentiation of Mesenchymal Stem Cells in Different Stages of Inflammation.

Bone infection has always been the focus of orthopedic research. Mesenchymal stem cells (MSCs) are the natural progenitors of osteoblasts, and the process of osteogenesis is triggered in response to different signals from the extracellular matrix. MSCs exert important functions including secretion and immune regulation and also play a key role in bone regeneration. The biological behavior of MSCs in acute and chronic inflammation, especially the transformation between acute inflammation and chronic inflammation, has aroused great interest among researchers. This paper reviews the recent literature and summarizes the behavior and biological characteristics of MSCs in acute and chronic inflammation to stimulate further research on MSCs and treatment of bone diseases.

Recent Advances in Osteoclast Biological Behavior.

With the progress of the aging population, bone-related diseases such as osteoporosis and osteoarthritis have become urgent problems. Recent studies have demonstrated the importance of osteoclasts in bone homeostasis, implying these will be an important mediator in the treatment of bone-related diseases. Up to now, several reviews have been performed on part of osteoclast biological behaviors such as differentiation, function, or apoptosis. However, few reviews have shown the complete osteoclast biology and research advances in recent years. Therefore, in this review, we focus on the origin, differentiation, apoptosis, behavior changes and coupling signals with osteoblasts, providing a simple but comprehensive overview of osteoclasts for subsequent studies.

Macrophage-Osteoclast Associations: Origin, Polarization, and Subgroups.

Cellular associations in the bone microenvironment are involved in modulating the balance between bone remodeling and resorption, which is necessary for maintaining a normal bone morphology. Macrophages and osteoclasts are both vital components of the bone marrow. Macrophages can interact with osteoclasts and regulate bone metabolism by secreting a variety of cytokines, which make a significant contribution to the associations. Although, recent studies have fully explored either macrophages or osteoclasts, indicating the significance of these two types of cells. However, it is of high importance to report the latest discoveries on the relationships between these two myeloid-derived cells in the field of osteoimmunology. Therefore, this paper reviews this topic from three novel aspects of the origin, polarization, and subgroups based on the previous work, to provide a reference for future research and treatment of bone-related diseases.

MicroRNAs as Biomarkers for the Diagnosis of Ankylosing Spondylitis: A Systematic Review and Meta-Analysis.

Background: Abnormal expression levels of microRNAs (miRNAs) were observed in ankylosing spondylitis (AS) in recent articles, suggesting that miRNAs may be used as biomarkers for AS diagnoses. In this paper, we conducted a meta-analysis to identify the overall diagnostic accuracy of miRNA biomarkers in AS patients. Methods: An extensive search was undertaken in PubMed, Embase, Cochrane databases, and Wan Fang database up to 30 December 2020 using the following key words: ("microRNAs" or "microRNA" or "miRNA" or "miR" or "RNA, Micro" or "Primary MicroRNA") and ("Spondylitis Ankylosing" or "Spondyloarthritis Ankylopoietica" or "Ankylosing Spondylarthritis" or "Ankylosing Spondylarthritides" or "Spondylarthritides Ankylosing" or "Ankylosing Spondylitis") and ("blood" or "serum" or "plasma"). Statistical evaluation of dysregulated miRNAs using the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the area under the curve (AUC). Results: Twenty-nine articles reporting on the miRNAs of AS were included. A total of 42 miRNAs were observed to be up-regulated and 45 miRNAs were down-regulated in the AS cases compared with the controls. Besides, 29 studies from nine articles were included in our meta-analysis. The pooled sensitivity, specificity, PLR, NLR, DOR, and AUC were 0. 76 (95% CI, 0.70-0.81), 0.80 (95% CI, 0.74-0.85), 3.75 (95% CI, 2.82-5.01), 0.30 (95% CI, 0.24-0.39), 12.32 (95% CI, 7.65-19.83), 0.85 (95% CI, 0.81-0.88), respectively, suggesting a good diagnostic accuracy of miRNAs for AS. Conclusions: Circulating miRNAs are deregulated in AS patients. miRNAs may be used as a relatively non-invasive biomarkers for the detection of AS.

Acid-Suppressive Drugs and Risk of Fracture in Children and Young Adults: A Meta-Analysis of Observational Studies.

Background: Recent studies have suggested that proton pump inhibitors (PPIs) and histamine type 2 receptor antagonists (H2RAs) may increase the risk of fracture. We performed a meta-analysis to evaluate the risk of fracture with PPIs and H2RAs use in children and young adults. Methods: PubMed, EMBASE database, Cochrane Library, and Web of Science for relevant articles published before May 2021 were searched. We included all the observational studies reporting on the risk of fracture with acid-suppressive drug (PPIs and H2RAs) use in children and young adults. We calculated pooled risk ratios (RRs) for fracture using random-effects models and conducted subgroup analyses. Results: A total of six studies were included in our analysis. Pooled analysis of PPIs use showed significant risk for fracture (RR = 1.23; 95% CI, 1.12-1.34; I 2 = 79.3), but not significant for PPIs combined with H2RAs use (RR = 1.22; 95% CI, 0.94-1.60; I 2 = 44.0%), as well as for H2RAs use alone (RR = 1.08; 95% CI, 0.94-1.24; I 2 = 84.1%). Grouping of studies by region showed a significantly increased fracture risk with PPIs use in North America (RR = 1.24; 95% CI, 1.16-1.32; I 2 =0.0%) than in Europe (RR = 1.23; 95% CI, 1.00-1.52; I 2 = 94.6%) and Asia (RR = 1.10; 95% CI, 0.96-1.25). However, there was no significant association between the H2RAs use and the fracture risk in North America (RR = 1.08; 95% CI, 1.00-1.09; I 2 = 0.0%). Moreover, PPIs use showed an increased risk of fracture in women (RR = 1.13; 95% CI, 1.07-1.19; I 2 = 0.0%), whereas there was no significant association between the PPIs use and the risk of fracture in men (RR = 0.93; 95% CI, 0.66-1.31; I 2 = 0.0%). Conclusion: PPIs use alone could increase the risk of fracture in children and young adults, but not for PPIs combined with H2RAs use or H2RAs use alone. Clinicians should exercise caution when prescribing PPIs for patients.

Genetic Determinants for Bacterial Osteomyelitis: A Focused Systematic Review of Published Literature.

Background: Osteomyelitis is an inflammatory process characterized by progressive bone destruction. Moreover, chronic bacterial osteomyelitis is regarded as a difficult-to-treat clinical entity due to its long-standing course and frequent infection recurrence. However, the role of genetic factors in the occurrence and development of bacterial osteomyelitis is poorly understood. Methods: We performed a systematic review to assess the frequency of individual alleles and genotypes of single-nucleotide polymorphisms (SNPs) among patients with bacterial osteomyelitis and healthy people to identify whether the SNPs are associated with the risk of developing bacterial osteomyelitis. Then, gene ontology and Kyoto Encyclopedia of Gene and Genomes analyses were performed to identify the potential biological effects of these genes on the pathogenesis of bacterial osteomyelitis. Result: Fourteen eligible studies containing 25 genes were analyzed. In this review, we discovered that the SNPs in IL1B, IL6, IL4, IL10, IL12B, IL1A, IFNG, TNF, PTGS2, CTSG, vitamin D receptor (VDR), MMP1, PLAT, and BAX increased the risk of bacterial osteomyelitis, whereas those in IL1RN and TLR2 could protect against osteomyelitis. The bioinformatic analysis indicated that these osteomyelitis-related genes were mainly enriched in inflammatory reaction pathways, suggesting that inflammation plays a vital role in the development of bacterial osteomyelitis. Furthermore, functional notation for 25 SNPs in 17 significant genes was performed using the RegulomeDB and NCBI databases. Four SNPs (rs1143627, rs16944, rs2430561, and rs2070874) had smaller scores from regulome analysis, implying significant biological function. Conclusion: We systematically summarized several SNPs linked to bacterial osteomyelitis and discovered that these gene polymorphisms could be a genetic factor for bacterial osteomyelitis. Moreover, further large-scale cohort studies are needed to enhance our comprehensive understanding of the development of osteomyelitis to provide earlier individualized preventions and interventions for patients with osteomyelitis in clinical practice.

Comparison of single versus double TightRope system in the treatment of acute acromioclavicular joint dislocation.

BACKGROUND: Reconstruction of the coracoclavicular (CC) ligament using a single TightRope (ST) system has some complications. We attempted to use a double TightRope (DT) system to reduce complications and obtain the ideal therapeutic effect. PURPOSE: This investigation aimed to compare the ST and DT systems in terms of efficacy and safety in treating acromioclavicular (AC) joint dislocation. METHODS: Sixty-six cases of acute AC joint dislocation between January 2013 and January 2018 were retrospectively reviewed. All patients were divided into 2 groups based on treatment with the ST or DT system. Patients were evaluated radiologically and clinically using the Disability of Arm, Shoulder, and Hand, Constant, and visual analog scale scores as clinical outcome measures at 1 day, 3 weeks, 6 weeks, 3 months, 6 months, 1 year, and 2 years after surgery. The CC distance and displacement ratio were assessed radiologically. RESULTS: The mean follow-up period was 49 months. Satisfactory clinical outcomes were obtained after CC fixation in both groups. No intergroup difference was found regarding the visual analog scale (P = .80), Disability of Arm, Shoulder, and Hand (P = .42), or Constant score (P = .28) at 2 years. However, there was a significant difference in the displacement ratio at 6 weeks (P < .0001), 3 months (P < .0001), 6 months (P < .0001), 1 year (P < .0001), and 2 years (P < .0001) postoperatively between the 2 groups. There were 3 complications in the ST group, including 1 case of secondary coracoid fracture, 1 case of AC joint arthrosis combined with ossification of the CC ligaments, and 1 case of clavicular erosion. All complications occurred in the ST group. CONCLUSIONS: Both surgical methods are effective in treating AC joint dislocation, but the DT system is more reliable for reduction maintenance.

The Process of Osteoblastic Infection by Staphylococcus Aureus.

Bone infection is difficult to cure, and relapse frequently occurs, which is a major treatment problem. One of the main reasons for the refractory and recurrent nature of bone infection is that bacteria, such as Staphylococcus aureus (S. aureus), can be internalized into osteoblasts after infecting bone tissue, thereby avoiding attack by the immune system and antibiotics. Understanding how bacteria (such as S. aureus) are internalized into osteoblasts is key to effective treatment. S. aureus is the most common pathogenic bacterium that causes bone infection. This paper reviews the literature, analyzes the specific process of osteoblastic S. aureus infection, and summarizes specific treatment strategies to improve bone infection treatment.