Several genome-wide association studies (GWAS) of bone mineral density (BMD) have successfully identified multiple susceptibility genes, yet isolated susceptibility genes are often difficult to interpret biologically. The aim of this study was to unravel the genetic background of BMD at pathway level, by integrating BMD GWAS data with genome-wide expression quantitative trait loci (eQTLs) and methylation quantitative trait loci (meQTLs) data We employed the GWAS datasets of BMD from the Genetic Factors for Osteoporosis Consortium (GEFOS), analysing patients’ BMD. The areas studied included 32 735 femoral necks, 28 498 lumbar spines, and 8143 forearms. Genome-wide eQTLs (containing 923 021 eQTLs) and meQTLs (containing 683 152 unique methylation sites with local meQTLs) data sets were collected from recently published studies. Gene scores were first calculated by summary data-based Mendelian randomisation (SMR) software and meQTL-aligned GWAS results. Gene set enrichment analysis (GSEA) was then applied to identify BMD-associated gene sets with a predefined significance level of 0.05.Objectives
Method
To explore the therapeutic potential of combining bone marrow-derived mesenchymal stem cells (BM-MSCs) and hydroxyapatite (HA) granules to treat nonunion of the long bone. Ten patients with an atrophic nonunion of a long bone fracture were selectively divided into two groups. Five subjects in the treatment group were treated with the combination of 15 million autologous BM-MSCs, 5g/cm3 (HA) granules and internal fixation. Control subjects were treated with iliac crest autograft, 5g/cm3 HA granules and internal fixation. The outcomes measured were post-operative pain (visual analogue scale), level of functionality (LEFS and DASH), and radiograph assessment.Objectives
Methods
To assess the extent of osteointegration in two designs of shoulder
resurfacing implants. Bony integration to the Copeland cylindrical
central stem design and the Epoca RH conical-crown design were compared. Implants retrieved from six patients in each group were pair-matched.
Mean time to revision surgery of Copeland implants was 37 months
(standard deviation (Aims
Patients and Methods
Healing in cancellous metaphyseal bone might be different from
midshaft fracture healing due to different access to mesenchymal
stem cells, and because metaphyseal bone often heals without a cartilaginous
phase. Inflammation plays an important role in the healing of a
shaft fracture, but if metaphyseal injury is different, it is important
to clarify if the role of inflammation is also different. The biology
of fracture healing is also influenced by the degree of mechanical
stability. It is unclear if inflammation interacts with stability-related
factors. We investigated the role of inflammation in three different models:
a metaphyseal screw pull-out, a shaft fracture with unstable nailing
(IM-nail) and a stable external fixation (ExFix) model. For each,
half of the animals received dexamethasone to reduce inflammation,
and half received control injections. Mechanical and morphometric evaluation
was used.Objectives
Methods
Chronic osteomyelitis may recur if dead space management, after
excision of infected bone, is inadequate. This study describes the
results of a strategy for the management of deep bone infection
and evaluates a new antibiotic-loaded biocomposite in the eradication
of infection from bone defects. We report a prospective study of 100 patients with chronic osteomyelitis,
in 105 bones. Osteomyelitis followed injury or surgery in 81 patients.
Nine had concomitant septic arthritis. 80 patients had comorbidities
(Cierny-Mader (C-M) Class B hosts). Ten had infected nonunions. All patients were treated by a multidisciplinary team with a
single-stage protocol including debridement, multiple sampling,
culture-specific systemic antibiotics, stabilisation, dead space
filling with the biocomposite and primary skin closure. Aims
Patients and Methods
The biomembrane (induced membrane) formed around polymethylmethacrylate (PMMA) spacers has value in clinical applications for bone defect reconstruction. Few studies have evaluated its cellular, molecular or stem cell features. Our objective was to characterise induced membrane morphology, molecular features and osteogenic stem cell characteristics. Following Institutional Review Board approval, biomembrane specimens were obtained from 12 patient surgeries for management of segmental bony defects (mean patient age 40.7 years, standard deviation 14.4). Biomembranes from nine tibias and three femurs were processed for morphologic, molecular or stem cell analyses. Gene expression was determined using the Affymetrix GeneChip Operating Software (GCOS). Molecular analyses compared biomembrane gene expression patterns with a mineralising osteoblast culture, and gene expression in specimens with longer spacer duration (> 12 weeks) with specimens with shorter durations. Statistical analyses used the unpaired student Objectives
Methods
The objective of this study was to investigate the therapeutic effect of peripheral blood mononuclear cells (PBMNCs) treated with quality and quantity control culture (QQ-culture) to expand and fortify angiogenic cells on the acceleration of fracture healing. Human PBMNCs were cultured for seven days with the QQ-culture method using a serum-free medium containing five specific cytokines and growth factors. The QQ-cultured PBMNCs (QQMNCs) obtained were counted and characterised by flow cytometry and real-time polymerase chain reaction (RT-PCR). Angiogenic and osteo-inductive potentials were evaluated using tube formation assays and co-culture with mesenchymal stem cells with osteo-inductive medium Objectives
Methods
Regenerative medicine is an emerging field aimed at the repair and regeneration of various tissues. To this end, cytokines (CKs), growth factors (GFs), and stem/progenitor cells have been applied in this field. However, obtaining and preparing these candidates requires invasive, costly, and time-consuming procedures. We hypothesised that skeletal muscle could be a favorable candidate tissue for the concept of a point-of-care approach. The purpose of this study was to characterize and confirm the biological potential of skeletal muscle supernatant for use in regenerative medicine. Semitendinosus muscle was used after harvesting tendon from patients who underwent anterior cruciate ligament reconstructions. A total of 500 milligrams of stripped muscle was minced and mixed with 1 mL of saline. The collected supernatant was analysed by enzyme-linked immunosorbent assay (ELISA) and flow cytometry. The biological effects of the supernatant on cell proliferation, osteogenesis, and angiogenesis in vitro were evaluated using human mesenchymal stem cells (hMSCs) and human umbilical cord vein endothelial cells (HUVECs).Objectives
Methods
Implant-related infection is one of the most devastating complications in orthopaedic surgery. Many surface and/or material modifications have been developed in order to minimise this problem; however, most of the We describe a method for the study of bacterial adherence in the presence of preosteoblastic cells. For this purpose we mixed different concentrations of bacterial cells from collection and clinical strains of staphylococci isolated from implant-related infections with preosteoblastic cells, and analysed the minimal concentration of bacteria able to colonise the surface of the material with image analysis.Objectives
Methods
The aim of this systematic literature review was to assess the clinical level of evidence of commercially available demineralised bone matrix (DBM) products for their use in trauma and orthopaedic related surgery. A total of 17 DBM products were used as search terms in two available databases: Embase and PubMed according to the Preferred Reporting Items for Systematic Reviews and Meta Analyses statement. All articles that reported the clinical use of a DBM-product in trauma and orthopaedic related surgery were included.Objectives
Methods
Recent studies have shown that modulating inflammation-related
lipid signalling after a bone fracture can accelerate healing in
animal models. Specifically, decreasing 5-lipoxygenase (5-LO) activity
during fracture healing increases cyclooxygenase-2 (COX-2) expression
in the fracture callus, accelerates chondrogenesis and decreases
healing time. In this study, we test the hypothesis that 5-LO inhibition
will increase direct osteogenesis. Bilateral, unicortical femoral defects were used in rats to measure
the effects of local 5-LO inhibition on direct osteogenesis. The
defect sites were filled with a polycaprolactone (PCL) scaffold
containing 5-LO inhibitor (A-79175) at three dose levels, scaffold
with drug carrier, or scaffold only. Drug release was assessed Objectives
Methods
Our aim was to examine the clinical and radiographic outcomes
in 257 consecutive Oxford unicompartmental knee arthroplasties (OUKAs)
(238 patients), five years post-operatively. A retrospective evaluation was undertaken of patients treated
between April 2008 and October 2010 in a regional centre by two
non-designing surgeons with no previous experience of UKAs. The
Oxford Knee Scores (OKSs) were recorded and fluoroscopically aligned
radiographs were assessed post-operatively at one and five years.Aims
Patients and Methods
Currently, there is no animal model in which
to evaluate the underlying physiological processes leading to the heterotopic
ossification (HO) which forms in most combat-related and blast wounds.
We sought to reproduce the ossification that forms under these circumstances
in a rat by emulating patterns of injury seen in patients with severe
injuries resulting from blasts. We investigated whether exposure
to blast overpressure increased the prevalence of HO after transfemoral
amputation performed within the zone of injury. We exposed rats
to a blast overpressure alone (BOP-CTL), crush injury and femoral
fracture followed by amputation through the zone of injury (AMP-CTL)
or a combination of these (BOP-AMP). The presence of HO was evaluated
using radiographs, micro-CT and histology. HO developed in none
of nine BOP-CTL, six of nine AMP-CTL, and in all 20 BOP-AMP rats.
Exposure to blast overpressure increased the prevalence of HO. This model may thus be used to elucidate cellular and molecular
pathways of HO, the effect of varying intensities of blast overpressure,
and to evaluate new means of prophylaxis and treatment of heterotopic
ossification. Cite this article:
Construction of a functional skeleton is accomplished
through co-ordination of the developmental processes of chondrogenesis,
osteogenesis, and synovial joint formation. Infants whose movement Cite this article:
The last decade has seen a considerable increase
in the use of in total ankle arthroplasty (TAA) to treat patients
with end-stage arthritis of the ankle. However, the longevity of
the implants is still far from that of total knee and hip arthroplasties. The aim of this review is to outline a diagnostic and treatment
algorithm for the painful TAA to be used when considering revision
surgery. Cite this article:
We report on the outcome of the Synergy cementless femoral stem
with a minimum follow-up of 15 years (15 to 17). A retrospective review was undertaken of a consecutive series
of 112 routine primary cementless total hip arthroplasties (THAs)
in 102 patients (112 hips). There were 60 female and 42 male patients
with a mean age of 61 years (18 to 82) at the time of surgery. A
total of 78 hips in the 69 patients remain Aims
Patients and Methods
This review explores recent advances in fixator design and used in contemporary orthopaedic practice including the management of bone loss, complex deformity and severe isolated limb injury.
We investigated whether strontium-enriched calcium
phosphate cement (Sr-CPC)-treated soft-tissue tendon graft results
in accelerated healing within the bone tunnel in reconstruction
of the anterior cruciate ligament (ACL). A total of 30 single-bundle
ACL reconstructions using tendo Achillis allograft were performed
in 15 rabbits. The graft on the tested limb was treated with Sr-CPC,
whereas that on the contralateral limb was untreated and served
as a control. At timepoints three, six, nine, 12 and 24 weeks after
surgery, three animals were killed for histological examination.
At six weeks, the graft–bone interface in the control group was
filled in with fibrovascular tissue. However, the gap in the Sr-CPC
group had already been completely filled in with new bone, and there
was evidence of the early formation of Sharpey fibres. At 24 weeks,
remodelling into a normal ACL–bone-like insertion was found in the
Sr-CPC group. Coating of Sr-CPC on soft tissue tendon allograft
leads to accelerated graft healing within the bone tunnel in a rabbit
model of ACL reconstruction using Achilles tendon allograft. Cite this article:
The purpose of this study was to compare the results and complications of tibial lengthening over an intramedullary nail with treatment using the traditional Ilizarov method. In this matched case study, 16 adult patients underwent 19 tibial lengthening over nails (LON) procedures. For the matched case group, 17 patients who underwent 19 Ilizarov tibial lengthenings were retrospectively matched to the LON group.Objectives
Methods
Patients with multiple myeloma (MM) develop deposits in the spine
which may lead to vertebral compression fractures (VCFs). Our aim
was to establish which spinopelvic parameters are associated with
the greatest disability in patients with spinal myeloma and VCFs. We performed a retrospective cross-sectional review of 148 consecutive
patients (87 male, 61 female) with spinal myeloma and analysed correlations
between spinopelvic parameters and patient-reported outcome scores.
The mean age of the patients was 65.5 years (37 to 91) and the mean
number of vertebrae involved was 3.7 (1 to 15).Aims
Patients and Methods