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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. 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 Aims
Methods
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. 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.Aims
Methods
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. 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.Aims
Methods
To evaluate the effect of ultrasound-targeted simvastatin-loaded microbubble destruction (UTMD In vitro, OA chondrocytes were treated with ultrasound (US), US-targeted microbubble destruction (UTMD), simvastatin (SV), and UTMDAims
Methods
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. 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
Methods
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. 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.Aims
Methods
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. 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 Aims
Methods
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.
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.
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. 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.Background
Methods
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. 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.Background
Methods
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.
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.
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. 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).Aim
Patients and Methods
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. 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.Objectives
Methods
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. 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, Summary Statement
Introduction
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. 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.Objective
Methods
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. 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.Purpose
Method
