Given the possible radiation damage and inaccuracy of radiological investigations, particularly in children, ultrasound and superb microvascular imaging (SMI) may offer alternative methods of evaluating new bone formation when limb lengthening is undertaken in paediatric patients. The aim of this study was to assess the use of ultrasound combined with SMI in monitoring new bone formation during limb lengthening in children. In this retrospective cohort study, ultrasound and radiograph examinations were performed every two weeks in 30 paediatric patients undergoing limb lengthening. Ultrasound was used to monitor new bone formation. The number of vertical vessels and the blood flow resistance index were compared with those from plain radiographs.Aims
Methods
To investigate the effects of senescent osteocytes on bone homeostasis in the progress of age-related osteoporosis and explore the underlying mechanism. In a series of in vitro experiments, we used tert-Butyl hydroperoxide (TBHP) to induce senescence of MLO-Y4 cells successfully, and collected conditioned medium (CM) and senescent MLO-Y4 cell-derived exosomes, which were then applied to MC3T3-E1 cells, separately, to evaluate their effects on osteogenic differentiation. Furthermore, we identified differentially expressed microRNAs (miRNAs) between exosomes from senescent and normal MLO-Y4 cells by high-throughput RNA sequencing. Based on the key miRNAs that were discovered, the underlying mechanism by which senescent osteocytes regulate osteogenic differentiation was explored. Lastly, in the in vivo experiments, the effects of senescent MLO-Y4 cell-derived exosomes on age-related bone loss were evaluated in male SAMP6 mice, which excluded the effects of oestrogen, and the underlying mechanism was confirmed.Aims
Methods
cAMP response element binding protein (CREB1) is involved in the progression of osteoarthritis (OA). However, available findings about the role of CREB1 in OA are inconsistent. 666-15 is a potent and selective CREB1 inhibitor, but its role in OA is unclear. This study aimed to investigate the precise role of CREB1 in OA, and whether 666-15 exerts an anti-OA effect. CREB1 activity and expression of a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4) in cells and tissues were measured by immunoblotting and immunohistochemical (IHC) staining. The effect of 666-15 on chondrocyte viability and apoptosis was examined by cell counting kit-8 (CCK-8) assay, JC-10, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) staining. The effect of 666-15 on the microstructure of subchondral bone, and the synthesis and catabolism of cartilage, in anterior cruciate ligament transection mice were detected by micro-CT, safranin O and fast green (S/F), immunohistochemical staining, and enzyme-linked immunosorbent assay (ELISA).Aims
Methods
3D Printed polyether-ether-ketone (PEEK) has gained widespread use in clinical practice due to its excellent biocompatibility, biomechanical compatibility, and personalization. However, pre-printed PEEK implants are not without their flaws, including bioinert, optimization distortion of 3D printing digital model and prosthetic mismatching. Recent advancements in mechanical processing technology have made it possible to print bone implants with PEEK fused deposition, allowing for the construction of mechanically adaptable implants. In this study, we aimed to synthesize silanized polycitrate (PCS) via thermal polymerization and in situ graft it to PEEK surface to construct an elastomer coating for 3D printed PEEK implants (PEEK-PCS). This incorporation of PCS allows the implant to exhibit adaptive space filling ability and stress dispersal. In vivo and in vitro results, PEEK-PCS exhibited exceptional osseointegration and osteogenesis properties along with macrophage M2 phenotypic polarization, inflammatory factors reducing, promotion of osteogenic differentiation in bone marrow mesenchymal stem cells (BMSCs). Additionally, PEEK-PCS displays good autofluorescence properties in vitro and in vivo, with stable fluorescence for 14 days, suggesting potential bioimaging applications. The study confirms that PEEK in situ grafting with thermo-polymerized PCS elastomers is a viable approach for creating multifunctional (bone defect adaptation, bioimaging, immune regulation, and osseointegration) implants for bone tissue engineering.
Distal arthrogryposis (DA) is a collection of rare developmental disorders characterized by congenital joint contractures. Most arthrogryposis mutations are in muscle- and joint-related genes, and the anatomical defects originate cell-autonomously within the musculoskeletal tissues. However, gain-of-function (GOF) mutations in PIEZO2, a principal mechanosensor in somatosensation, cause DA subtype 5 via unknown mechanisms. We show that expression of a GOF PIEZO2 mutation in proprioceptive sensory neurons mainly innervating muscle spindles and tendons is sufficient to induce DA5-like phenotypes in mice. Overactive PIEZO2 causes anatomical defects via increased activity within the peripheral nervous system during postnatal development. Surprisingly, overactive PIEZO2 is likely to cause joint abnormalities via increased exocytosis from sensory neuron endings without involving motor circuitry. This reveals a role for somatosensory neurons: excessive mechanosensation within these neurons disrupts musculoskeletal development. We also present proof-of-concept that Botox injection or dietary treatment can counteract the effect of overactive PIEZO2 function to evade DA-like phenotypes in mice when applied during a developmental critical period. These approaches might have clinical applications. Beyond this, our findings call attention to the importance of considering sensory mechanotransduction when diagnosing and treating other musculoskeletal disorders.
To explore the novel molecular mechanisms of histone deacetylase 4 (HDAC4) in chondrocytes via RNA sequencing (RNA-seq) analysis. Empty adenovirus (EP) and a Aims
Methods
Adequate visual clarity is paramount to performing arthroscopic shoulder surgery safely, efficiently, and effectively. The addition of epinephrine in irrigation fluid, and the intravenous or local administration of tranexamic acid (TXA) have independently been reported to decrease bleeding thereby improving the surgeon's visualization during arthroscopic shoulder procedures. No study has compared the effect of systemic administered TXA, epinephrine added in the irrigation fluid or the combination of both TXA and epinephrine on visual clarity during shoulder arthroscopy with a placebo group. The purpose of this study is to determine if intravenous TXA is a safe alternative to epinephrine delivered by a pressure-controlled pump in improving arthroscopic shoulder visualization during arthroscopic procedures and whether using both TXA and epinephrine together has an additive effect in improving visualization. The design of the study was a double-blinded, randomized controlled trial with four 1:1:1:1 parallel groups conducted at one center. Patients aged ≥18 years undergoing arthroscopic shoulder procedures including rotator cuff repair, arthroscopic biceps tenotomy/tenodesis, distal clavicle excision, subacromial decompression and labral repair by five fellowship-trained upper extremity surgeons were randomized into one of four arms: Pressure pump-controlled regular saline irrigation fluid (control), epinephrine (1ml of 1:1000) mixed in irrigation fluid (EPI), 1g intravenous TXA (TXA), and epinephrine and TXA (EPI/TXA). Visualization was rated on a 4-point Likert scale every 15 minutes with 0 indicating ‘poor’ quality and 3 indicating ‘excellent’ quality. The primary outcome measure was the unweighted mean of these ratings. Secondary outcomes included mean arterial blood pressure (MAP), surgery duration, surgery complexity, and adverse events within the first postoperative week. One hundred and twenty-eight participants with a mean age (± SD) of 56 (± 11) years were randomized. Mean visualization quality for the control, TXA, EPI, and EPI/TXA groups were 2.1 (±0.40), 2.1 (±0.52), 2.6 (±0.37), 2.6 (±0.35), respectively. In a regression model with visual quality as the dependent variable, the presence/absence of EPI was the most significant predictor of visualization quality (R=0.525; p < 0 .001). TXA presence/absence had no effect, and there was no interaction between TXA and EPI. The addition of MAP and surgery duration strengthened the model (R=0.529; p < 0 .001). Increased MAP and surgery duration were both associated with decreased visualization quality. When surgery duration was controlled, surgery complexity was not a significant predictor of visualization quality. No adverse events were recorded in any of the groups. Intravenous administration of TXA is not an effective alternative to epinephrine in the irrigation fluid to improve visualization during routine arthroscopic shoulder surgeries although its application is safe. There is no additional improvement in visualization when TXA is used in combination with epinephrine beyond the effect of epinephrine alone.
Tissue inhibitors of metalloproteinases (TIMPs) are the endogenous inhibitors of the zinc-dependent matrix metalloproteinases (MMP) and A disintegrin and metalloproteinases (ADAM) involved in extracellular matrix modulation. The present study aims to develop the TIMPs as biologics for osteoclast-related disorders. We examine the inhibitory effect of a high affinity, glycosyl-phosphatidylinositol-anchored TIMP variant named ‘T1PrαTACE’ on receptor activator of nuclear factor kappa-Β ligand (RANKL)-induced osteoclast differentiation.Aims
Methods
This study aims to report the outcomes in the treatment of unstable proximal third scaphoid nonunions with arthroscopic curettage, non-vascularized bone grafting, and percutaneous fixation. This was a retrospective analysis of 20 patients. All cases were delayed presentations (n = 15) or failed nonoperatively managed scaphoid fractures (n = 5). Surgery was performed at a mean duration of 27 months (7 to 120) following injury with arthroscopic debridement and arthroscopic iliac crest autograft. Fracture fixation was performed percutaneously with Kirschner (K)-wires in 12 wrists, a headless screw in six, and a combination of a headless screw and single K-wire in two. Clinical outcomes were assessed using grip strength, patient-reported outcome measures, and wrist range of motion (ROM) measurements.Aims
Methods
Correct femoral tunnel position in anterior cruciate ligament reconstruction (ACLR) is critical in obtaining good clinical outcomes. We aimed to delineate whether any difference exists between the anteromedial (AM) and trans-tibial (TT) portal femoral tunnel placement techniques on the primary outcome of ACLR graft rupture. Adult patients (>18year old) who underwent primary ACLR between January 2011 – January 2018 were identified and divided based on portal technique (AM v TT). The primary outcome measure was graft rupture. Univariate analysis was used to delineate association between independent variables and outcome. Binary logistic regression was utilised to delineate odds ratios of significant variables. 473 patients were analysed. Median age at surgery was 27 years old (range 18–70). A total of 152/473, (32.1%) patients were AM group compared to 321/473 (67.9%) TT. Twenty-five patients (25/473, 5.3%) sustained graft rupture. Median time to graft rupture was 12 months (IQR 9). A higher odds for graft rupture was associated with the AM group, which trended towards significance (OR 2.03; 95% CI 0.90 – 4.56, p=0.081). Older age at time of surgery was associated with a lower odds of rupture (OR 0.92, 95% CI 0.86 – 0.98, p=0.014). There is no statistically significant difference in ACLR graft rupture rates when comparing anteromedial and trans-tibial portal technique for femoral tunnel placement. There was a trend towards higher rupture rates in the anteromedial portal group.
LY3023414 is a novel oral phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) dual inhibitor designed for advanced cancers, for which a phase II clinical study was completed in March 2020; however, little is known about its effect on bone modelling/remodelling. In this study, we aimed to explore the function of LY3023414 in bone modelling/remodelling. The function of LY3023414 was explored in the context of osteogenesis (bone formation by osteoblasts) and osteoclastogenesis (osteoclast formation and bone resorption). Murine preosteoblast MC3T3-E1 cell line and murine bone marrow-derived macrophage cells (BMMs) were subjected to different treatments. An MTS cell proliferation assay was used to examine the cytotoxicity. Thereafter, different induction conditions were applied, such as MCSF and RANKL for osteoclastogenesis and osteogenic media for osteogenesis. Specific staining, a bone resorption assay, and quantitative real-time polymerase chain reaction (qRT-PCR) were subsequently used to evaluate the effect of LY3023414. Moreover, small interfering RNA (siRNA) was applied to knockdown Akt1 or Akt2 for further validation. Lastly, western blot was used to examine the exact mechanism of action.Aims
Methods
Parathyroid hormone (PTH) (1-34) exhibits potential in preventing degeneration in both cartilage and subchondral bone in osteoarthritis (OA) development. We assessed the effects of PTH (1-34) at different concentrations on bone and cartilage metabolism in a collagenase-induced mouse model of OA and examined whether PTH (1-34) affects the JAK2/STAT3 signalling pathway in this process. Collagenase-induced OA was established in C57Bl/6 mice. Therapy with PTH (1-34) (10 μg/kg/day or 40 μg/kg/day) was initiated immediately after surgery and continued for six weeks. Cartilage pathology was evaluated by gross visual, histology, and immunohistochemical assessments. Cell apoptosis was analyzed by TUNEL staining. Microcomputed tomography (micro-CT) was used to evaluate the bone mass and the microarchitecture in subchondral bone.Aims
Methods
The purpose of our study was to determine whether mesenchymal stem cells (MSCs) are an effective and safe therapeutic agent for the treatment of knee osteoarthritis (OA), owing to their cartilage regeneration potential. We searched PubMed, Embase, and the Cochrane Library, with keywords including “knee osteoarthritis” and “mesenchymal stem cells”, up to June 2019. We selected randomized controlled trials (RCTs) that explored the use of MSCs to treat knee OA. The visual analogue scale (VAS), Western Ontario and McMaster University Osteoarthritis Index (WOMAC), adverse events, and the whole-organ MRI score (WORMS) were used as the primary evaluation tools in the studies. Our meta-analysis included a subgroup analysis of cell dose and cell source.Aims
Methods
Ulnar shortening osteotomy (USO) is a procedure performed to alleviate ulnar sided wrist pain caused by ulnar impaction syndrome (UIS) and/or triangular fibrocartilage complex (TFCC) injury. Presently, non-union rates for ulnar shortening osteotomy is quoted to be 0–18% in the literature. However, there is a dearth of literature on the effect of site of osteotomy and plate placement on the rate of complications like a delayed union, symptomatic hardware and need for second surgery for hardware removal. In this study, we performed a multi-centered institutional review of ulnar shortening osteotomies performed, focusing on plate placement (volar vs. dorsal) and osteotomy site (distal vs. proximal) and determining if it plays a role in reducing complications. This study was a multi-centered retrospective chart review. All radiographs and charts for patients that have received USO for UIS or TFCC injury between 2013 and 2017 from hand and wrist fellowship-trained surgeons in Calgary, Alberta and Winnipeg, Manitoba were examined. Basic patient demographics including age, sex, past medical history, and smoking history were recorded. Postoperative complications such as delayed union, non-union, infection, chronic regional pain syndrome, hardware irritation requiring removal were evaluated with a two-year follow-up period. Osteotomy sites were analyzed based on the location in relation to the entire length of the ulna on forearm radiographs. Surgical techniques including volar vs. dorsal plating, oblique vs. transverse osteotomy cuts, and plate type were documented. Continuous variables of interest were summarized as mean or medians with standard deviation or inter-quartile range as appropriate. Differences in baseline characteristics were determined by t-test or one-way ANOVA for continuous variables and chi-square or Fischer exact test for dichotomous variables. All analyses were conducted using SPSS V24.0 (Chicago, IL, USA). All statistical tests were considered significant if p < 0.05. Between 2013–2017 there were 117 ulnar shortening osteotomies performed. The average age of patients was 46.2 ± 16.2, with 62.4% being female. The mean pre-operative ulnar variance was +3.89 ± 2.17 mm and post-operative ulnar variance was −1.90 ± 1.80 mm. 84.6% of the plates were placed on the volar aspect of the ulna and 14.5% were placed on the dorsal aspect. An oblique osteotomy was made 99.1% of the time. In measuring osteotomy placement, the average placement was made in the distal 1/3 of the ulna. Overall, there was a 40% complication rate. Hardware irritation requiring removal encompassed 23%, non-union 14%, and wound infection covered 0.8%. When comparing dorsal vs volar plating, there was no statistically significant difference for non-union or hardware removal. Similarly, in evaluating osteotomy level, there was no statistical difference between proximal vs distal osteotomy for non-union and hardware removal. In this multi-centered retrospective review of ulnar shortening osteotomies, we found that there was an overall complication rate of 40%. There was no statistically significant difference in complication rates between dorsal vs volar plate placement or proximal vs distal osteotomy sites. Further studies examining other potential risk factors in lowering the complication rate would be beneficial.
Tibial plateau fractures (TPFs) are complex injuries around the knee caused by high- or low-energy trauma. In the present study, we aimed to define the distribution and frequency of TPF lines using a 3D mapping technique and analyze the rationalization of divisions employed by frequently used classifications. In total, 759 adult patients with 766 affected knees were retrospectively reviewed. The TPF fragments on CT were multiplanar reconstructed, and virtually reduced to match a 3D model of the proximal tibia. 3D heat mapping was subsequently created by graphically superimposing all fracture lines onto a tibia template.Aims
Methods
During the pandemic of COVID-19, some patients with COVID-19 may need emergency surgeries. As spine surgeons, it is our responsibility to ensure appropriate treatment to the patients with COVID-19 and spinal diseases. A protocol for spinal surgery and related management on patients with COVID-19 has been reviewed. Patient preparation for emergency surgeries, indications, and contraindications of emergency surgeries, operating room preparation, infection control precautions and personal protective equipments (PPE), anesthesia management, intraoperative procedures, postoperative management, medical waste disposal, and surveillance of healthcare workers were reviewed. It should be safe for surgeons with PPE of protection level 2 to perform spinal surgeries on patients with COVID-19. Standardized and careful surgical procedures should be necessary to reduce the exposure to COVID-19.
Chondrocyte hypertrophy represents a crucial turning point during endochondral bone development. This process is tightly regulated by various factors, constituting a regulatory network that maintains normal bone development. Histone deacetylase 4 (HDAC4) is the most well-characterized member of the HDAC class IIa family and participates in different signalling networks during development in various tissues by promoting chromatin condensation and transcriptional repression. Studies have reported that HDAC4-null mice display premature ossification of developing bones due to ectopic and early-onset chondrocyte hypertrophy. Overexpression of HDAC4 in proliferating chondrocytes inhibits hypertrophy and ossification of developing bones, which suggests that HDAC4, as a negative regulator, is involved in the network regulating chondrocyte hypertrophy. Overall, HDAC4 plays a key role during bone development and disease. Thus, understanding the role of HDAC4 during chondrocyte hypertrophy and endochondral bone formation and its features regarding the structure, function, and regulation of this process will not only provide new insight into the mechanisms by which HDAC4 is involved in chondrocyte hypertrophy and endochondral bone development, but will also create a platform for developing a therapeutic strategy for related diseases.
There is an increasing demand for hip arthroplasty in China. We aimed to describe trends in in-hospital mortality after this procedure in China and to examine the potential risk factors. We included 210 450 patients undergoing primary hip arthroplasty registered in the Hospital Quality Monitoring System in China between 2013 and 2016. In-hospital mortality after hip arthroplasty and its relation to potential risk factors were assessed using multivariable Poisson regression.Aims
Patients and Methods
The sacrum is frequently invaded by a pelvic tumour. The aim
of this study was to review our experience of treating this group
of patients and to identify the feasibility of a new surgical classification
in the management of these tumours. We reviewed 141 patients who, between 2005 and 2014, had undergone
surgical excision of a pelvic tumour with invasion of the sacrum. In a new classification, pelvisacral (Ps) I, II, and III resections
refer to a sagittal osteotomy through the ipsilateral wing of the
sacrum, through the sacral midline, or lateral to the contralateral
sacral foramina, respectively. A Ps a resection describes a pelvic
osteotomy through the ilium and a Ps b resection describes a concurrent
resection of the acetabulum with osteotomies performed through the
pubis and ischium or the pubic symphysis. Within each type, surgical
approaches were standardized to guide resection of the tumour.Aims
Patients and Methods
The aims of this retrospective study were to report the feasibility
of using 3D-printing technology for patients with a pelvic tumour
who underwent reconstruction. A total of 35 patients underwent resection of a pelvic tumour
and reconstruction using 3D-printed endoprostheses between September
2013 and December 2015. According to Enneking’s classification of
bone defects, there were three Type I lesions, 12 Type II+III lesions,
five Type I+II lesions, two Type I+II+III lesions, ten type I+II+IV
lesions and three type I+II+III+IV lesions. A total of three patients
underwent reconstruction using an iliac prosthesis, 12 using a standard
hemipelvic prosthesis and 20 using a screw-rod connected hemipelvic
prosthesis.Aims
Patients and Methods
