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The Bone & Joint Journal
Vol. 106-B, Issue 6 | Pages 613 - 622
1 Jun 2024
Shen J Wei Z Wu H Wang X Wang S Wang G Luo F Xie Z

Aims

The aim of the present study was to assess the outcomes of the induced membrane technique (IMT) for the management of infected segmental bone defects, and to analyze predictive factors associated with unfavourable outcomes.

Methods

Between May 2012 and December 2020, 203 patients with infected segmental bone defects treated with the IMT were enrolled. The digital medical records of these patients were retrospectively analyzed. Factors associated with unfavourable outcomes were identified through logistic regression analysis.


Bone & Joint Research
Vol. 13, Issue 3 | Pages 124 - 126
11 Mar 2024
Shen J Wei Z Sun D Wu H Wang X Wang S Luo F Xie Z

Cite this article: Bone Joint Res 2024;13(3):124–126.


Bone & Joint Research
Vol. 12, Issue 11 | Pages 677 - 690
1 Nov 2023
Wang X Jiang W Pan K Tao L Zhu Y

Aims

Currently, the effect of drug treatment for osteoporosis is relatively poor, and the side effects are numerous and serious. Melatonin is a potential drug to improve bone mass in postmenopausal women. Unfortunately, the mechanism by which melatonin improves bone metabolism remains unclear. The aim of this study was to further investigate the potential mechanism of melatonin in the treatment of osteoporosis.

Methods

The effects of melatonin on mitochondrial apoptosis protein, bmal1 gene, and related pathway proteins of RAW264.7 (mouse mononuclear macrophage leukaemia cells) were analyzed by western blot. Cell Counting Kit-8 was used to evaluate the effect of melatonin on cell viability. Flow cytometry was used to evaluate the effect of melatonin on the apoptosis of RAW264.7 cells and mitochondrial membrane potential. A reactive oxygen species (ROS) detection kit was used to evaluate the level of ROS in osteoclast precursors. We used bmal1-small interfering RNAs (siRNAs) to downregulate the Bmal1 gene. We established a postmenopausal mouse model and verified the effect of melatonin on the bone mass of postmenopausal osteoporosis in mice via micro-CT. Bmal1 lentiviral activation particles were used to establish an in vitro model of overexpression of the bmal1 gene.


Bone & Joint Research
Vol. 12, Issue 9 | Pages 546 - 558
12 Sep 2023
Shen J Wei Z Wang S Wang X Lin W Liu L Wang G

Aims

This study aimed to evaluate the effectiveness of the induced membrane technique for treating infected bone defects, and to explore the factors that might affect patient outcomes.

Methods

A comprehensive search was performed in PubMed, Embase, and the Cochrane Central Register of Controlled Trials databases between 1 January 2000 and 31 October 2021. Studies with a minimum sample size of five patients with infected bone defects treated with the induced membrane technique were included. Factors associated with nonunion, infection recurrence, and additional procedures were identified using logistic regression analysis on individual patient data.


Bone & Joint Research
Vol. 12, Issue 8 | Pages 467 - 475
2 Aug 2023
Wu H Sun D Wang S Jia C Shen J Wang X Hou C Xie Z Luo F

Aims

This study was designed to characterize the recurrence incidence and risk factors of antibiotic-loaded cement spacer (ALCS) for definitive bone defect treatment in limb osteomyelitis.

Methods

We included adult patients with limb osteomyelitis who received debridement and ALCS insertion into the bone defect as definitive management between 2013 and 2020 in our clinical centre. The follow-up time was at least two years. Data on patients’ demographics, clinical characteristics, and infection recurrence were retrospectively collected and analyzed.


The Bone & Joint Journal
Vol. 105-B, Issue 4 | Pages 439 - 448
15 Mar 2023
Hong H Pan X Song J Fang N Yang R Xiang L Wang X Huang C

Aims

The prevalence of scoliosis is not known in patients with idiopathic short stature, and the impact of treatment with recombinant human growth hormone on those with scoliosis remains controversial. We investigated the prevalence of scoliosis radiologically in children with idiopathic short stature, and the impact of treatment with growth hormone in a cross-sectional and retrospective cohort study.

Methods

A total of 2,053 children with idiopathic short stature and 4,106 age- and sex-matched (1:2) children without short stature with available whole-spine radiographs were enrolled in the cross-sectional study. Among them, 1,056 with idiopathic short stature and 790 controls who had radiographs more than twice were recruited to assess the development and progression of scoliosis, and the need for bracing and surgery.


Bone & Joint Research
Vol. 11, Issue 4 | Pages 251 - 251
30 Apr 2022
Wang X Wang D Xia P Cheng K Wang Q Wang X Lin Q Song J Chen A Li X


Bone & Joint Research
Vol. 10, Issue 10 | Pages 693 - 703
1 Oct 2021
Wang X Wang D Xia P Cheng K Wang Q Wang X Lin Q Song J Chen A Li X

Aims

To evaluate the effect of ultrasound-targeted simvastatin-loaded microbubble destruction (UTMDSV) for alleviation of the progression of osteoarthritis (OA) in rabbits through modulation of the peroxisome proliferator-activated receptor (PPARγ).

Methods

In vitro, OA chondrocytes were treated with ultrasound (US), US-targeted microbubble destruction (UTMD), simvastatin (SV), and UTMDSV on alternate days for four weeks. Chondrocytes were also treated with PPARγ inhibitor, PPARγ inhibitor+ UTMDSV, and UTMDSV. The cholesterol efflux rate and triglyceride levels were measured using an assay kit and oil red O staining, respectively. In vivo, the OA rabbits were treated with a single intra-articular injection of UTMD, SV, and UTMDSV every seven days for four weeks. Cartilage histopathology was assessed by safranin-O staining and the Mankin score. Total cholesterol (TC) and high-density lipoprotein-cholesterol (HDL-C) in rabbit knee synovial fluid were detected by enzyme-marker assay. Aggrecan, collagen II, and PPARγ expression levels were analyzed by Western blotting (WB).


Bone & Joint Research
Vol. 10, Issue 7 | Pages 380 - 387
5 Jul 2021
Shen J Sun D Fu J Wang S Wang X Xie Z

Aims

In contrast to operations performed for other fractures, there is a high incidence rate of surgical site infection (SSI) post-open reduction and internal fixation (ORIF) done for tibial plateau fractures (TPFs). This study investigates the effect of induced membrane technique combined with internal fixation for managing SSI in TPF patients who underwent ORIF.

Methods

From April 2013 to May 2017, 46 consecutive patients with SSI post-ORIF for TPFs were managed in our centre with an induced membrane technique. Of these, 35 patients were included for this study, with data analyzed in a retrospective manner.


Aims

Treatment of chronic osteomyelitis (COM) for young patients remains a challenge. Large bone deficiencies secondary to COM can be treated using induced membrane technique (IMT). However, it is unclear which type of bone graft is optimal. The goal of the study was to determine the clinical effectiveness of bone marrow concentrator modified allograft (BMCA) versus bone marrow aspirate mixed allograft (BMAA) for children with COM of long bones.

Methods

Between January 2013 and December 2017, 26 young patients with COM were enrolled. Different bone grafts were applied to repair bone defects secondary to IMT procedure for infection eradication. Group BMCA was administered BMCA while Group BMAA was given BMAA. The results of this case-control study were retrospectively analyzed.


Bone & Joint Research
Vol. 9, Issue 9 | Pages 578 - 586
1 Sep 2020
Ma M Liang X Wang X Zhang L Cheng S Guo X Zhang F Wen Y

Aims

Kashin-Beck disease (KBD) is a kind of chronic osteochondropathy, thought to be caused by environmental risk factors such as T-2 toxin. However, the exact aetiology of KBD remains unclear. In this study, we explored the functional relevance and biological mechanism of cartilage oligosaccharide matrix protein (COMP) in the articular cartilage damage of KBD.

Methods

The articular cartilage specimens were collected from five KBD patients and five control subjects for cell culture. The messenger RNA (mRNA) and protein expression levels were detected by quantitative reverse transcription PCR (qRT-PCR) and western blot. The survival rate of C28/I2 chondrocyte cell line was detected by MTT assay after T-2 toxin intervention. The cell viability and mRNA expression levels of apoptosis related genes between COMP-overexpression groups and control groups were examined after cell transfection.


The Bone & Joint Journal
Vol. 102-B, Issue 8 | Pages 981 - 996
1 Aug 2020
Yang Y Zhao H Chai Y Zhao D Duan L Wang H Zhu J Yang S Li C Chen S Chae S Song J Wang X Yu X

Aims

Whether to perform hybrid surgery (HS) in contrast to anterior cervical discectomy and fusion (ACDF) when treating patients with multilevel cervical disc degeneration remains a controversial subject. To resolve this we have undertaken a meta-analysis comparing the outcomes from HS with ACDF in this condition.

Methods

Seven databases were searched for studies of HS and ACDF from inception of the study to 1 September 2019. Both random-effects and fixed-effects models were used to evaluate the overall effect of the C2-C7 range of motion (ROM), ROM of superior/inferior adjacent levels, adjacent segment degeneration (ASD), heterotopic ossification (HO), complications, neck disability index (NDI) score, visual analogue scale (VAS) score, Japanese Orthopaedic Association (JOA) score, Odom’s criteria, blood loss, and operating and hospitalization time. To obtain more credible results contour-enhanced funnel plots, Egger’s and Begg’s tests, meta-regression, and sensitivity analyses were performed.


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_7 | Pages 64 - 64
1 Jul 2020
Wang X Aubin C Rawlinson J Armstrong R
Full Access

In posterior fixation for deformity correction and spinal fusion, there is increasing discussion around auxiliary rods secured to the pedicle screws, sharing the loads, and reducing stresses in the primary rods. Dual-rod, multiaxial screws (DRMAS) provide two rod mounting points on a single screw shaft to allow unique constructs and load-sharing at specific vertebrae. These implants provide surgical flexibility to add auxiliary rods across a pedicle subtraction osteotomy (PSO) or over multiple vertebral levels where higher bending loads are anticipated in primary rods. Other options include fixed-angle devices as multiple rod connectors (MRC) and variable-angle dominoes (VAD) with a single-axis rotation in the connection. The objective in this simulation study was to assess rod bending in adult spinal instrumentation across an osteotomy using constructs with DRMAS, MRC, or VAD multi-rod connections.

The study was performed using computer biomechanical models of two adult patients having undergone posterior instrumented spinal fusion for deformity. The models were patient-specific, incorporating the biomechanics of the spine, have been calibrated to assess deformity correction and intra- and postoperative loads across the instrumented spine. One traditional bilateral-rod construct was used as a control for six multi-rod configurations. Spinal fixation scenarios from T10 through S1 with the PSO at L4 were simulated on each patient-specific model. The multi-rod configurations were bilateral and unilateral DRMAS at L2 through S1 (B-DRMAS and U-DRMAS), bilateral DRMAS at L3 and L5 (Hybrid), bilateral MRC over L3-L5, bilateral and unilateral VAD over L3-L5 (B-VAD and U-VAD). Postoperative gravity plus 8-Nm flexion and extension loads were simulated and bending moments in the rods were computed and compared.

In the simulated control for each case (#1 & #2), average rod bending moments (of the right and left rods) at the PSO level were 6.7Nm & 5.5Nm, respectively, in upright position, 8.8Nm & 7.3Nm in 8-Nm flexion, and 4.6Nm & 3.7Nm in 8-Nm extension. When the primary rods of the multi-rod constructs were normalized to this control, the bending moments in the primary rods of Case #1 & #2 were respectively 57% & 58% (B-DRMAS), 54% & 62% (B-VAD), 60% & 61% (MRC), 72% & 69% (Hybrid), 81% & 70% (U-DRMAS), and 81% & 73% (U-VAD). Overall, the reduction in primary rod bending moments ranged from 19–46% for standing loads. Under simulated 8-Nm functional moments, the primary rod moments were reduced by 18–46% in flexion and 17–48% in extension. More rods and stiffer connections produced the largest reductions for the primary rods, but auxiliary rods had bending moments that varied from 49% lower to 13% higher than the primary ones.

Additional rods through DRMAS, MRC, and VAD connections noticeably reduced the bending loads in the primary rods compared with a standard bilateral-rod construct. Yet, bending loads in the auxiliary rods were higher or lower than those in the primary rods depending on the 3D spinal deformity and stiffness of the auxiliary rod connections. Additional studies and patient-specific analyses are needed to optimize instrumentation parameters that may improve load-sharing in these constructs.


Bone & Joint Research
Vol. 9, Issue 2 | Pages 82 - 89
1 Feb 2020
Chen Z Zhang Z Guo L Wei X Zhang Y Wang X Wei L

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.

Cite this article: Bone Joint Res. 2020;9(2):82–89.


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_6 | Pages 26 - 26
1 May 2019
King R Wang X Qureshi A Vepa A Rahman U Palit A Williams M Elliott M
Full Access

Background

Over 10% of total hip arthroplasty (THA) surgeries performed in England and Wales are revision procedures1. Malorientation of the acetabular component in THA may contribute to premature failure due to mechanisms such as edge loading and prosthetic impingement. It is known that the pelvis flexes and extends during activities of daily living (ADLs), and excessive pelvic motion can contribute to functional acetabular malorientation. Preoperative radiographs can be performed to measure changes in pelvic tilt during ADLs to identify high risk individuals and inform surgical decision making. However, radiographs require time-consuming radiation exposure, and are unable to provide truly dynamic 3-dimensional analysis. The purpose of this study was to develop and evaluate a motion capture method using inertial measurement units (IMUs). This would provide a rapid, non-invasive analysis of pelvic tilt which could be used to support surgical planning.

Methods

Patients awaiting THA were fitted with a bespoke device consisting of a 3D-printed clamp which housed the IMU and positioned over the sacrum. A wide elastic belt was fitted around the patient's waist to keep the device in place. Movement data was transmitted wirelessly to a tablet computer. Pelvic tilt was measured in standing, flexed seated and step-up positions while undergoing X-rays with the IMU capturing the data in parallel. Statistical analysis included measures of correlation between the X-ray and IMU measurements.


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_5 | Pages 126 - 126
1 Apr 2019
Elliott MT King R Wang X Qureshi A Vepa A Rahman U Palit A Williams MA
Full Access

Background

Over 10% of total hip arthroplasty (THA) surgeries performed in England and Wales are revision procedures1. Malorientation of the acetabular component in THA may contribute to premature failure. Yet with increasingly younger populations receiving THA surgery (through higher incidences of obesity) and longer life expectancy in general, the lifetime of an implant needs to increase to avoid a rapid increase in revision surgery in the future.

The Evaluation of X-ray, Acetabular Guides and Computerised Tomography in THA (EXACT) trial is assessing the pelvic tilt of a patient by capturing x-rays from the patient in sitting, standing and step-up positions. It uses this information, along with a CT scan image, to deliver a personalised dynamic simulation that outputs an optimised position for the hip replacement. A clinical trial is currently in place to investigate how the new procedure improves patient outcomes2.

Our aim in this project was to assess whether accurate functional assessment of pelvic tilt could be further obtained using inertial measurement units (IMUs). This would provide a rapid, non-invasive triaging method such that only patients with high levels of tilt measured by the sensors would then receive the full assessment with x-rays.

Methods

Recruited patients were fitted with a bespoke device consisting of a 3D-printed clamp which housed the IMU and fitted around the sacrum area. A wide elastic belt was fitted around the patient's waist to keep the device in place. Pelvic tilt is measured in a standing, flexed seated and step-up position while undergoing X-rays with the IMU capturing the data in parallel. Patients further completed another five repetitions of the movements with the IMU but without the x-ray to test repeatability of the measurements. Statistical analysis included measures of correlation between the X-ray and IMU measurements.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_16 | Pages 58 - 58
1 Nov 2018
Wang X Bian Z Li M Zhu L
Full Access

Aging has been associated with decreases in muscle strength and bone quality. In elderly patients, paravertebral muscle atrophy is accompanied by vertebral osteoporosis. The purpose of this study was to use paravertebral injection of botulinum toxin-A (BTX) to investigate the effects of paravertebral muscle atrophy on lumbar vertebral bone quality. Forty 16-week-old female SD rats were randomly divided into four groups: (1) a control group (CNT); (2) a resection of erector spinae muscles group (RESM); (3) a botulinum toxin-A group (BTX) that was treated with local injection of 5U BTX into the paravertebral muscles bilaterally; and (4) a positive control group (OVX) that underwent bilateral ovariectomy. At 3 months post-surgery the lumbar vertebrae (L3 – L6) were collected. The BMDs of the RESM and BTX groups were significantly lower than that of the CNT group (P < 0.01). Micro-CT scans showed that rats in the three experimental groups had fewer trabeculae and trabecular connections than rats in the CNT group. The bone loss trend of the trabecular networks was most obvious in the OVX rats. Vertebral compression testing revealed that the three experimental groups had significantly lower maximum load, energy absorption, maximum stress, and elastic modulus values than the CNT group (P < 0.01), and these parameters were lowest in the OVX group (P < 0.05). Our results demonstrate that the new paravertebral muscle atrophy model using local BTX injection causes sufficient muscle atrophy and dysfunction to result in local lumbar vertebral bone loss and quality deterioration.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_14 | Pages 115 - 115
1 Nov 2018
Müller S Nicholson L Jone E Dickinson A Dalgarno K Wang X
Full Access

Mesenchymal stromal cells (MSCs) are widely used in clinical trials for the treatment of many bone defects. Apatite-wollastonite glass ceramic (A-W) is an osteoconductive biomaterial shown to be compatible with MSCs. This is the first study comparing the osteogenic potential of two MSC populations, heterogeneous plastic adherence MSCs (PA-MSCs) and CD271-enriched MSCs (CD271-MSCs), when cultured on A-W 3D scaffold. The paired MSC populations were assessed for their attachment, growth kinetics and ALP activity using confocal or scanning electron microscopy and the quantifications of DNA contents and p-nitrophenyl (pNP) production. While the PA-MSCs and CD271-MSCs had similar expansion and tri-lineage differentiation capacity during standard 2D culture, they showed different proliferation kinetics when seeded on the A-W scaffolds. PA-MSCs displayed a well-spread attachment with more elongated morphology compared to CD271-MSCs, signifying a different level of interaction between the cell populations and the scaffold surface. PA-MSCs also fully integrated into the scaffold surface and showed a stronger propensity for osteogenic differentiation on the A-W scaffold as indicated by higher ALP activity than CD271-MSCs. Furthermore, A-W scaffold seeded uncultured bone marrow mononuclear cells (BM-MNCs) demonstrated a higher proliferation rate and greater ALP activity compared to freshly isolated CD271-enriched BM-MNCs. Our findings suggest that enrichment of CD271-positive population is not beneficial for osteogenesis when the cells are seeded on A-W scaffold. Furthermore, unselected heterogeneous MSCs or BM-MNCs are more promising for A-W scaffold-based bone regeneration, providing novel insight with potential clinical implications in regenerative medicine for bone defects using an innovative tissue engineering approach.


Bone & Joint Research
Vol. 7, Issue 5 | Pages 343 - 350
1 May 2018
He A Ning Y Wen Y Cai Y Xu K Cai Y Han J Liu L Du Y Liang X Li P Fan Q Hao J Wang X Guo X Ma T Zhang F

Aim

Osteoarthritis (OA) is caused by complex interactions between genetic and environmental factors. Epigenetic mechanisms control the expression of genes and are likely to regulate the OA transcriptome. We performed integrative genomic analyses to define methylation-gene expression relationships in osteoarthritic cartilage.

Patients and Methods

Genome-wide DNA methylation profiling of articular cartilage from five patients with OA of the knee and five healthy controls was conducted using the Illumina Infinium HumanMethylation450 BeadChip (Illumina, San Diego, California). Other independent genome-wide mRNA expression profiles of articular cartilage from three patients with OA and three healthy controls were obtained from the Gene Expression Omnibus (GEO) database. Integrative pathway enrichment analysis of DNA methylation and mRNA expression profiles was performed using integrated analysis of cross-platform microarray and pathway software. Gene ontology (GO) analysis was conducted using the Database for Annotation, Visualization and Integrated Discovery (DAVID).


Bone & Joint Research
Vol. 5, Issue 3 | Pages 101 - 105
1 Mar 2016
Wang X Luo F Huang K Xie Z

Objectives

Induced membrane technique is a relatively new technique in the reconstruction of large bone defects. It involves the implantation of polymethylmethacrylate (PMMA) cement in the bone defects to induce the formation of membranes after radical debridement and reconstruction of bone defects using an autologous cancellous bone graft in a span of four to eight weeks. The purpose of this study was to explore the clinical outcomes of the induced membrane technique for the treatment of post-traumatic osteomyelitis in 32 patients.

Methods

A total of 32 cases of post-traumatic osteomyelitis were admitted to our department between August 2011 and October 2012. This retrospective study included 22 men and ten women, with a mean age of 40 years (19 to 70). Within this group there were 20 tibias and 12 femurs with a mean defect of 5 cm (1.5 to 12.5). Antibiotic-loaded PMMA cement was inserted into the defects after radical debridement. After approximately eight weeks, the defects were implanted with bone graft.


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 11 - 11
1 Jul 2014
Guo B Wang X Hong A Lu A Zhang B Zhang G
Full Access

Summary Statement

The stable inhibition of miR-214 in the aged osteoporotic rats induced by OVX could be achieved by periodic administration of AntagomiR-214 at a dosage of 4 mg/kg and at an interval of 7 days, which will provide a potential bone anabolic strategy for treatment of osteoprosis.

Introduction

MiR-214 has a crucial role in suppressing bone formation and miR-214 inhibition in osteogenic cells may be a potential anabolic strategy for ameliorating osteoporosis (Wang X, et al. 2013). An aged ovariectomised rat has been regarded as a golden model to test bone anabolic agents for reversing established osteoporosis in aged postmenopausal women (Li X, et al. 2009). However, there is still lack of evidence to demonstrate bone anabolic potential of therapeutic inhibition of miR-214 within osteogenic cells in the golden model. So, it should be necessary to establish RNAi-based administration protocol toward stable inhibition of miR-214 at a low level in the golden model. A targeted delivery system specifically facilitating Antagomir-214 approaching osteogenic cells, i.e. (Asp-Ser-Ser)6-liposome (Zhang G, et al 2012), was employed in this study.


Bone & Joint Research
Vol. 2, Issue 12 | Pages 255 - 263
1 Dec 2013
Zhang Y Xu J Wang X Huang J Zhang C Chen L Wang C Ma X

Objective

The objective of this study was to evaluate the rotation and translation of each joint in the hindfoot and compare the load response in healthy feet with that in stage II posterior tibial tendon dysfunction (PTTD) flatfoot by analysing the reconstructive three-dimensional (3D) computed tomography (CT) image data during simulated weight-bearing.

Methods

CT scans of 15 healthy feet and 15 feet with stage II PTTD flatfoot were taken first in a non-weight-bearing condition, followed by a simulated full-body weight-bearing condition. The images of the hindfoot bones were reconstructed into 3D models. The ‘twice registration’ method in three planes was used to calculate the position of the talus relative to the calcaneus in the talocalcaneal joint, the navicular relative to the talus in talonavicular joint, and the cuboid relative to the calcaneus in the calcaneocuboid joint.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVIII | Pages 139 - 139
1 Sep 2012
Filomeno PA Dayan V Kandel RA Wang X Felizardo TC Salomeh J Filomeno AE Medin J Keating A Ferguson P
Full Access

Purpose

Mesenchymal stromal cells (MSCs) are an attractive choice for regenerative medicine. We previously showed that MSCs enhance wound healing in animals after radiotherapy. The effect of MSCs on tumor growth is not well understood. The potential use of MSCs to enhance wound healing after radiotherapy (RT) and resection of soft tissue sarcoma (STS) is dependent on a satisfactory safety profile to ensure that tumor proliferation does not occur and recurrence is not increased.

Method

Primary cell lines (human myxofibrosarcoma and undifferentiated sarcoma) derived from sarcoma bearing patients and a commercialized human fibrosarcoma cell line (HT1080) were used. Cell line proliferation assay after co-culture with MSCs was done using flow cytometry (CFSE) and bioluminescence emission (BLI) (using eGFP/Fluc transduced cell lines).

Five xenograft models were developed with NOD/SCID gc-null mice (n=164) harbouring primary tissue lines obtained from patients biopsies (myxofibrosarcoma and three pleomorphic undifferentiated sarcoma [PUS A, B and C]) and a a fibrosarcoma cell line previously transduced with eGFP/Fluc. Tumors were passaged to three mouse generations before a tissue line was established and the model was then used. For the fibrosarcoma model, eGFP/Fluc HT1080 were injected under the dorsal skin. When tumors reached 1cm in diameter, they received localized RT and 48hr later were resected. MSCs (n=82) or medium alone (n=82) was injected subcutaneously adjacent to the wound after tumor resection. Histological and in vivo BLI analysis were performed 3 and 12 weeks after surgery.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 8 | Pages 1077 - 1085
1 Aug 2012
Yin Z Zhang J Kan S Wang X

Follow-up radiographs are usually used as the reference standard for the diagnosis of suspected scaphoid fractures. However, these are prone to errors in interpretation. We performed a meta-analysis of 30 clinical studies on the diagnosis of suspected scaphoid fractures, in which agreement data between any of follow-up radiographs, bone scintigraphy, magnetic resonance (MR) imaging, or CT could be obtained, and combined this with latent class analysis to infer the accuracy of these tests on the diagnosis of suspected scaphoid fractures in the absence of an established standard. The estimated sensitivity and specificity were respectively 91.1% and 99.8% for follow-up radiographs, 97.8% and 93.5% for bone scintigraphy, 97.7% and 99.8% for MRI, and 85.2% and 99.5% for CT. The results were generally robust in multiple sensitivity analyses. There was large between-study heterogeneity for the sensitivity of follow-up radiographs and CT, and imprecision about their sensitivity estimates.

If we acknowledge the lack of a reference standard for diagnosing suspected scaphoid fractures, MRI is the most accurate test; follow-up radiographs and CT may be less sensitive, and bone scintigraphy less specific.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_VIII | Pages 59 - 59
1 Mar 2012
Cui F Wang X Dighe A Balian G Cui Q
Full Access

Introduction

Enhanced angiogenesis and osteogenesis may provide new strategies for the treatment of osteonecrosis.

Methods

Synergistic effects of vascular endothelial growth factor (VEGF) and bone morphogenetic protein - 6 (BMP-6) on in vitro osteogenic differentiation and in vivo ectopic bone formation mediated by a cloned mouse bone marrow stromal cell line, D1, previously isolated from Balb/c mice in our laboratory, were determined.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_VIII | Pages 56 - 56
1 Mar 2012
Zawodny SR Wang X Balian G Cui Q
Full Access

Introduction

Osteonecrosis of the femoral head is a devastating disease in young patients and remains a challenge for clinicians and researchers alike. To increase understanding of the disease and produce effective treatments that preserve a patient's native hip, an animal model that mimics the disease process in humans, including collapse of the femoral head, is essential. Our goal was to create such a bipedal model by surgically inducing osteonecrosis in the femoral heads of chickens.

Methods

A lateral approach to the proximal femur was used to access the hip, dislocate the femoral head, and sever the periosteal network of blood vessels. At 4, 8, 12, and 20 weeks after surgery, both the left (experimental) and right (control) femoral heads were harvested from 6 chickens for micro-CT and histological analysis.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 4 | Pages 558 - 565
1 Apr 2011
Xie X Wang X Zhang G Liu Z Yao D Hung L Hung VW Qin L

Corticosteroids are prescribed for the treatment of many medical conditions and their adverse effects on bone, including steroid-associated osteoporosis and osteonecrosis, are well documented. Core decompression is performed to treat osteonecrosis, but the results are variable. As steroids may affect bone turnover, this study was designed to investigate bone healing within a bone tunnel after core decompression in an experimental model of steroid-associated osteonecrosis. A total of five 28-week-old New Zealand rabbits were used to establish a model of steroid-induced osteonecrosis and another five rabbits served as controls. Two weeks after the induction of osteonecrosis, core decompression was performed by creating a bone tunnel 3 mm in diameter in both distal femora of each rabbit in both the experimental osteonecrosis and control groups. An in vivo micro-CT scanner was used to monitor healing within the bone tunnel at four, eight and 12 weeks postoperatively. At week 12, the animals were killed for histological and biomechanical analysis.

In the osteonecrosis group all measurements of bone healing and maturation were lower compared with the control group. Impaired osteogenesis and remodelling within the bone tunnel was demonstrated in the steroid-induced osteonecrosis, accompanied by inferior mechanical properties of the bone.

We have confirmed impaired bone healing in a model of bone defects in rabbits with pulsed administration of corticosteroids. This finding may be important in the development of strategies for treatment to improve the prognosis of fracture healing or the repair of bone defects in patients receiving steroid treatment.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 4 | Pages 545 - 549
1 Apr 2010
Li W Chi Y Xu H Wang X Lin Y Huang Q Mao F

We reviewed the outcome of a retrospective case series of eight patients with atlantoaxial instability who had been treated by percutaneous anterior transarticular screw fixation and grafting under image-intensifier guidance between December 2005 and June 2008.

The mean follow-up was 19 months (8 to 27). All eight patients had a solid C1–2 fusion. There were no breakages or displacement of screws. All the patients with pre-operative neck pain had immediate relief from their symptoms or considerable improvement. There were no major complications. Our preliminary clinical results suggest that percutaneous anterior transarticulation screw fixation is technically feasible, safe, useful and minimally invasive when using the appropriate instruments allied to intra-operative image intensification, and by selecting the correct puncture point, angle and depth of insertion.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_III | Pages 523 - 523
1 Aug 2008
Robb C Bradish C Wang X
Full Access

Purpose of study: To report the use of a forearm fascial strip to repair the annular ligament and treat late diagnosed or irreducible Monteggia fracture.

Methods: Through Boyd’s approach nineteen patients with Monteggia fractures were treated with a technique to reconstruct the annular ligament using forearm fascia, retaining its proximal attachment to the ulna. The radial head was dislocated and the fascial strip wound around the neck of the radius. After reducing the radial head, forearm rotation was checked. The strip was sutured to the residual annular ligament on the proximal ulna after correction of any ulna deformity. In late diagnosis, the ulna deformity was managed with ulna lengthening of approximately 0.5 cm and stabilization with a 4- or 5- hole semi-tubular AO plate. The stability of the radial head was then assessed using intra-operative fluoroscopy.

Results: Stability of the radial head was achieved in all cases. According to the Anderson classification, the final outcome was excellent in ten cases satisfactory in eight cases and unsatisfactory in one late diagnosed patient with an associated radioulnar synostosis secondary to a compartment syndrome. There were no failures. Two radiocapitellar K-wires broke while in plaster in the initial period, so the use of a K wire was subsequently abandoned.

Conclusions: We have found this technique to be reliable for stabilizing the proximal radioulnar joint. The length of the incision is less than that required for the Bell Tawse (triceps tendon) technique and permits a tourniquet on the upper arm. Poorer results were achieved with delay in diagnosis beyond 6 months.

Patients must be warned of potential reduction of forearm rotation.


The Journal of Bone & Joint Surgery British Volume
Vol. 85-B, Issue 6 | Pages 879 - 882
1 Aug 2003
Peng B Wu W Hou S Shang W Wang X Yang Y

We examined the pathogenesis of Schmorl’s nodes, correlating the histological findings from 12 lumbar vertebrae with the corresponding conventional radiographs, tomographs, MR images and CT scans. The last revealed round, often multiple cystic lesions with indistinct sclerotic margins beneath the cartilaginous endplate. The appearances are similar to the typical CT changes of osteonecrosis. Histological examination of en-bloc slices through Schmorl’s nodes gave clear evidence of subchondral osteonecrosis. Beneath the cartilage endplate, we found fibrosis within the marrow cavities with the disappearance of fat cells. Osteocytes within bone trabeculae were either dead or had disappeared. We suggest that Schmorl’s nodes are the end result of ischaemic necrosis beneath the cartilaginous endplate and that herniation into the body of the vertebra is secondary.


Orthopaedic Proceedings
Vol. 85-B, Issue SUPP_III | Pages 191 - 191
1 Mar 2003
Bagnall K Demianczuk D Wang X Moreau M Raso J Mahood J
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Introduction: No appropriate animal model for studying adolescent idiopathic scoliosis (AIS) exists and this hampers research. In recent years, we have been examining a model in which scoliosis consistently develops in young chickens following pinealectomy and which has been shown to have many characteristics similar to those seen in AIS. Not all of the pinealectomised chickens develop scoliosis following the pinealectomy and so we have the opportunity to examine differences between the two groups. The obvious candidate for study of the mechanism underlying this phenomenon is melatonin which is the principal product of the pineal gland. In this study we have measured the serum melatonin levels of pinealectomised chickens that have developed scoliosis and compared these with similar measurements taken from chickens that have developed scoliosis.

Methods and results: Newly-hatched chickens were obtained from a local hatchery and kept in a single pen with standard heating and lighting. A 12:12 light dark cycle was introduced immediately and the two-thirds of the chickens were pinealectomised three days later. The remainder acted as controls. At weekly intervals following surgery, the chickens were radiographed in a supine position while anaesthetised and the presence of scoliosis was determined from the radiographs. Three weeks after surgery the chickens were euthanised and blood samples were collected and analysed using radioimmunological techniques to determine levels of serum melatonin. The samples were collected in the presence of red light in the middle of the dark cycle when melatonin levels have been shown to be at their highest.

Approximately 55% of the pinealectomised chickens developed scoliosis within the three weeks following surgery whereas none of the control chickens developed scoliosis. The results showed that the serum melatonin levels of pinealectomised chickens were significantly lower than the normal controls and were in fact all close to zero. However, there was no significant difference in serum melatonin levels between those chickens that developed scoliosis and those that did not.

Conclusion: The results of this study have shown that pinealectomy significantly reduces serum melatonin levels close to zero in all chickens. The results also show that there is no significant difference in serum melatonin levels between those pinealectomised chickens that develop scoliosis and those that do not. Unless there is a subtle threshold level that is unable to be detected using our methodology or that melatonin levels in the days immediately after surgery are of critical importance, these results suggest that other causes for this phenomenon need to be examined. An understanding of the underlying cause would be of great importance and might represent a significant breakthrough in the study of AIS.