Objectives. Bisphosphonates are widely used as first-line treatment for primary and secondary prevention of fragility fractures. Whilst they have proved effective in this role, there is growing concern over their long-term use, with much evidence linking bisphosphonate-related suppression of bone remodelling to an increased risk of atypical subtrochanteric
Objectives. The annual incidence of hip fracture is 620 000 in the European Union. The cost of this clinical problem has been estimated at 1.75 million disability-adjusted life years lost, equating to 1.4% of the total healthcare burden in established market economies. Recent guidance from The National Institute for Health and Clinical Excellence (NICE) states that research into the clinical and cost effectiveness of total hip arthroplasty (THA) as a treatment for hip fracture is a priority. We asked the question: can a trial investigating THA for hip fracture currently be delivered in the NHS?. Methods. We performed a contemporaneous process evaluation that provides a context for the interpretation of the findings of WHiTE Two – a randomised study of THA for hip fracture. We developed a mixed methods approach to situate the trial centre within the context of wider United Kingdom clinical practice. We focused on fidelity, implementation, acceptability and feasibility of both the trial processes and interventions to stakeholder groups, such as healthcare providers and patients. Results. We have shown that patients are willing to participate in this type of research and that surgeons value being part of a team that has a strong research ethos. However, surgical practice does not currently reflect NICE guidance. Current models of service delivery for hip fractures are unlikely to be able to provide timely total hip arthroplasty for suitable patients. Conclusions. Further observational research should be conducted to define the population of interest before future interventional studies are performed. Cite this article: C. Huxley, J. Achten, M. L. Costa, F. Griffiths, X. L. Griffin. A process evaluation of the WHiTE Two trial comparing total hip arthroplasty with and without dual mobility component in the treatment of displaced intracapsular
Objectives. In this prospective cohort study, we investigated whether patient-specific finite element (FE) models can identify patients at risk of a pathological femoral fracture resulting from metastatic bone disease, and compared these FE predictions with clinical assessments by experienced clinicians. Methods. A total of 39 patients with non-fractured femoral metastatic lesions who were irradiated for pain were included from three radiotherapy institutes. During follow-up, nine pathological fractures occurred in seven patients. Quantitative CT-based FE models were generated for all patients. Femoral failure load was calculated and compared between the
Open lower limb fracture is a life-changing injury affecting 11.5 per 100,000 adults each year, and causes significant morbidity and resource demand on trauma infrastructures. This study aims to identify what, and how, outcomes have been reported for people following open lower limb fracture over ten years. Systematic literature searches identified all clinical studies reporting outcomes for adults following open lower limb fracture between January 2009 and July 2019. All outcomes and outcome measurement instruments were extracted verbatim. An iterative process was used to group outcome terms under standardized outcome headings categorized using an outcome taxonomy.Aims
Methods
Previous studies have suggested that selenium as a trace element is involved in bone health, but findings related to the specific effect of selenium on bone health remain inconclusive. Thus, we performed a meta-analysis by including all the relevant studies to elucidate the association between selenium status (dietary intake or serum selenium) and bone health indicators (bone mineral density (BMD), osteoporosis (OP), or fracture). PubMed, Embase, and Cochrane Library were systematically searched to retrieve relevant articles published before 15 November 2022. Studies focusing on the correlation between selenium and BMD, OP, or fracture were included. Effect sizes included regression coefficient (β), weighted mean difference (WMD), and odds ratio (OR). According to heterogeneity, the fixed-effect or random-effect model was used to assess the association between selenium and bone health.Aims
Methods
Research into COVID-19 has been rapid in response to the dynamic global situation, which has resulted in heterogeneity of methodology and the communication of information. Adherence to reporting standards would improve the quality of evidence presented in future studies, and may ensure that findings could be interpreted in the context of the wider literature. The COVID-19 pandemic remains a dynamic situation, requiring continued assessment of the disease incidence and monitoring for the emergence of viral variants and their transmissibility, virulence, and susceptibility to vaccine-induced immunity. More work is needed to assess the long-term impact of COVID-19 infection on patients who sustain a hip fracture. The International Multicentre Project Auditing COVID-19 in Trauma & Orthopaedics (IMPACT) formed the largest multicentre collaborative audit conducted in orthopaedics in order to provide an emergency response to a global pandemic, but this was in the context of many vital established audit services being disrupted at an early stage, and it is crucial that these resources are protected during future health crises. Rapid data-sharing between regions should be developed, with wider adoption of the revised 2022 Fragility Fracture Network Minimum Common Data Set for Hip Fracture Audit, and a pragmatic approach to information governance processes in order to facilitate cooperation and meta-audit. This editorial aims to: 1) identify issues related to COVID-19 that require further research; 2) suggest reporting standards for studies of COVID-19 and other communicable diseases; 3) consider the requirement of new risk scores for hip fracture patients; and 4) present the lessons learned from IMPACT in order to inform future collaborative studies. Cite this article:
We aimed to evaluate the utility of 68Ga-citrate positron emission tomography (PET)/CT in the differentiation of periprosthetic joint infection (PJI) and aseptic loosening (AL), and compare it with 99mTc-methylene bisphosphonates (99mTc-MDP) bone scan. We studied 39 patients with suspected PJI or AL. These patients underwent 68Ga-citrate PET/CT, 99mTc-MDP three-phase bone scan and single-photon emission CT (SPECT)/CT. PET/CT was performed at ten minutes and 60 minutes after injection, respectively. Images were evaluated by three nuclear medicine doctors based on: 1) visual analysis of the three methods based on tracer uptake model, and PET images attenuation-corrected with CT and those not attenuation-corrected with CT were analyzed, respectively; and 2) semi-quantitative analysis of PET/CT: maximum standardized uptake value (SUVmax) of lesions, SUVmax of the lesion/SUVmean of the normal bone, and SUVmax of the lesion/SUVmean of the normal muscle. The final diagnosis was based on the clinical and intraoperative findings, and histopathological and microbiological examinations.Aims
Methods
There is an increasing concern of osteoporotic fractures in the ageing population. Low-magnitude high-frequency vibration (LMHFV) was shown to significantly enhance osteoporotic fracture healing through alteration of osteocyte lacuno-canalicular network (LCN). Dentin matrix protein 1 (DMP1) in osteocytes is known to be responsible for maintaining the LCN and mineralization. This study aimed to investigate the role of osteocyte-specific DMP1 during osteoporotic fracture healing augmented by LMHFV. A metaphyseal fracture was created in the distal femur of ovariectomy-induced osteoporotic Sprague Dawley rats. Rats were randomized to five different groups: 1) DMP1 knockdown (KD), 2) DMP1 KD + vibration (VT), 3) Scramble + VT, 4) VT, and 5) control (CT), where KD was performed by injection of short hairpin RNA (shRNA) into marrow cavity; vibration treatment was conducted at 35 Hz, 0.3 g; 20 minutes/day, five days/week). Assessments included radiography, micro-CT, dynamic histomorphometry and immunohistochemistry on DMP1, sclerostin, E11, and fibroblast growth factor 23 (FGF23). In vitro, murine long bone osteocyte-Y4 (MLO-Y4) osteocyte-like cells were randomized as in vivo groupings. DMP1 KD was performed by transfecting cells with shRNA plasmid. Assessments included immunocytochemistry on osteocyte-specific markers as above, and mineralized nodule staining.Aims
Methods
Bone turnover markers (BTMs) follow distinct trends after fractures and limited evidence suggests differential levels in BTMs in patients with delayed healing. The effect of vitamin D, and other factors that influence BTMs and fracture healing, is important to elucidate the use of BTMs as surrogates of fracture healing. We sought to determine whether BTMs can be used as early markers of delayed fracture healing, and the effect of vitamin D on BTM response after fracture. A total of 102 participants aged 18 to 50 years (median 28 years (interquartile range 23 to 35)), receiving an intramedullary nail for a tibial or femoral shaft fracture, were enrolled in a randomized controlled trial comparing vitamin D3 supplementation to placebo. Serum C-terminal telopeptide of type I collagen (CTX; bone resorption marker) and N-terminal propeptide of type I procollagen (P1NP; bone formation marker) were measured at baseline, six weeks, and 12 weeks post-injury. Clinical and radiological fracture healing was assessed at three months.Aims
Methods
In this study, we aimed to explore surgical variations in the Femoral Neck System (FNS) used for stable fixation of Pauwels type III femoral neck fractures. Finite element models were established with surgical variations in the distance between the implant tip and subchondral bone, the gap between the plate and lateral femoral cortex, and inferior implant positioning. The models were subjected to physiological load.Aims
Methods
With the ageing population, fragility fractures have become one of the most common conditions. The objective of this study was to investigate whether microbiological outcomes and fracture-healing in osteoporotic bone is worse than normal bone with fracture-related infection (FRI). A total of 120 six-month-old Sprague-Dawley (SD) rats were randomized to six groups: Sham, sham + infection (Sham-Inf), sham with infection + antibiotics (Sham-Inf-A), ovariectomized (OVX), OVX + infection (OVX-Inf), and OVX + infection + antibiotics (OVX-Inf-A). Open femoral diaphysis fractures with Kirschner wire fixation were performed. Aims
Methods
Exosomes derived from bone marrow mesenchymal stem cells (BMSCs) have been reported to be a promising cellular therapeutic approach for various human diseases. The current study aimed to investigate the mechanism of BMSC-derived exosomes carrying microRNA (miR)-136-5p in fracture healing. A mouse fracture model was initially established by surgical means. Exosomes were isolated from BMSCs from mice. The endocytosis of the mouse osteoblast MC3T3-E1 cell line was analyzed. CCK-8 and disodium phenyl phosphate microplate methods were employed to detect cell proliferation and alkaline phosphatase (ALP) activity, respectively. The binding of miR-136-5p to low-density lipoprotein receptor related protein 4 (LRP4) was analyzed by dual luciferase reporter gene assay. HE staining, tartrate-resistant acid phosphatase (TRAP) staining, and immunohistochemistry were performed to evaluate the healing of the bone tissue ends, the positive number of osteoclasts, and the positive expression of β-catenin protein, respectively.Aims
Methods
Objectives. The monitoring of fracture healing is a complex process. Typically, successive radiographs are performed and an emerging calcification of the fracture area is evaluated. The aim of this study was to investigate whether different bone healing patterns can be distinguished using a telemetric instrumented femoral internal plate fixator. Materials and Methods. An electronic telemetric system was developed to assess bone healing mechanically. The system consists of a telemetry module which is applied to an internal locking plate fixator, an external reader device, a sensor for measuring externally applied load and a laptop computer with processing software. By correlation between externally applied load and load measured in the implant, the elasticity of the osteosynthesis is calculated. The elasticity decreases with ongoing consolidation of a fracture or nonunion and is an appropriate parameter for the course of bone healing. At our centre, clinical application has been performed in 56 patients suffering nonunion or
Objectives. Intramedullary fixation is considered the most stable treatment for pertrochanteric
Fractures of the proximal femur are one of the
greatest challenges facing the medical community, constituting a
heavy socioeconomic burden worldwide. The National Hip Fracture
Audit currently provides a framework for service evaluation. This
evaluation is based upon the assessment of process rather than assessment
of patient-centred outcome and therefore it fails to provide meaningful
data regarding the clinical effectiveness of treatments. This study
aims to capture data from the cohort of patients who present with
a
A balanced inflammatory response is important for successful fracture healing. The response of osteoporotic fracture healing is deranged and an altered inflammatory response can be one underlying cause. The objectives of this review were to compare the inflammatory responses between normal and osteoporotic fractures and to examine the potential effects on different healing outcomes. A systematic literature search was conducted with relevant keywords in PubMed, Embase, and Web of Science independently. Original preclinical studies and clinical studies involving the investigation of inflammatory response in fracture healing in ovariectomized (OVX) animals or osteoporotic/elderly patients with available full text and written in English were included. In total, 14 articles were selected. Various inflammatory factors were reported; of those tumour necrosis factor-α (TNF-α) and interleukin (IL)-6 are two commonly studied markers. Preclinical studies showed that OVX animals generally demonstrated higher systemic inflammatory response and poorer healing outcomes compared to normal controls (SHAM). However, it is inconclusive if the local inflammatory response is higher or lower in OVX animals. As for clinical studies, they mainly examine the temporal changes of the inflammatory stage or perform comparison between osteoporotic/fragility fracture patients and normal subjects without fracture. Our review of these studies emphasizes the lack of understanding that inflammation plays in the altered fracture healing response of osteoporotic/elderly patients. Taken together, it is clear that additional studies, preclinical and clinical, are required to dissect the regulatory role of inflammatory response in osteoporotic fracture healing. Cite this article:
For cementless implants, stability is initially attained by an interference fit into the bone and osteo-integration may be encouraged by coating the implant with bioactive substances. Blood based autologous glue provides an easy, cost-effective way of obtaining high concentrations of growth factors for tissue healing and regeneration with the intention of spraying it onto the implant surface during surgery. The aim of this study was to incorporate nucleated cells from autologous bone marrow (BM) aspirate into gels made from the patient’s own blood, and to investigate the effects of incorporating three different concentrations of platelet rich plasma (PRP) on the proliferation and viability of the cells in the gel. The autologous blood glue (ABG) that constituted 1.25, 2.5, and 5 times concentration PRP were made with and without equal volumes of BM nucleated cells. Proliferation, morphology, and viability of the cells in the glue was measured at days 7 and 14 and compared to cells seeded in fibrin glue.Aims
Methods
The purpose of this study was to determine whether intracellular After stabilizing with Kirschner wire, we created a midshaft femur fracture in Sprague-Dawley rats and infected the wound with green fluorescent protein (GFP)-tagged Aims
Methods
Diabetes mellitus (DM) is known to impair fracture healing. Increasing evidence suggests that some microRNA (miRNA) is involved in the pathophysiology of diabetes and its complications. We hypothesized that the functions of miRNA and changes to their patterns of expression may be implicated in the pathogenesis of impaired fracture healing in DM. Closed transverse fractures were created in the femurs of 116 rats, with half assigned to the DM group and half assigned to the control group. Rats with DM were induced by a single intraperitoneal injection of streptozotocin. At post-fracture days five, seven, 11, 14, 21, and 28, miRNA was extracted from the newly generated tissue at the fracture site. Microarray analysis was performed with miRNA samples from each group on post-fracture days five and 11. For further analysis, real-time polymerase chain reaction (PCR) analysis was performed at each timepoint.Objectives
Methods
Despite its intrinsic ability to regenerate form and function after injury, bone tissue can be challenged by a multitude of pathological conditions. While innovative approaches have helped to unravel the cascades of bone healing, this knowledge has so far not improved the clinical outcomes of bone defect treatment. Recent findings have allowed us to gain in-depth knowledge about the physiological conditions and biological principles of bone regeneration. Now it is time to transfer the lessons learned from bone healing to the challenging scenarios in defects and employ innovative technologies to enable biomaterial-based strategies for bone defect healing. This review aims to provide an overview on endogenous cascades of bone material formation and how these are transferred to new perspectives in biomaterial-driven approaches in bone regeneration. Cite this article: T. Winkler, F. A. Sass, G. N. Duda, K. Schmidt-Bleek. A review of biomaterials in bone defect healing, remaining shortcomings and future opportunities for bone tissue engineering: The unsolved challenge.
This study aimed to investigate the functional effects of microRNA (miR)-214-5p on osteoblastic cells, which might provide a potential role of miR-214-5p in bone fracture healing. Blood samples were obtained from patients with hand fracture or intra-articular calcaneal fracture and from healthy controls (HCs). Expression of miR-214-5p was monitored by qRT-PCR at day 7, 14 and 21 post-surgery. Mouse osteoblastic MC3T3-E1 cells were transfected with antisense oligonucleotides (ASO)-miR-214-5p, collagen type IV alpha 1 (COL4A1) vector or their controls; thereafter, cell viability, apoptotic rate, and the expression of collagen type I alpha 1 (COL1A1), type II collagen (COL-II), and type X collagen (COL-X) were determined. Luciferase reporter assay, qRT-PCR, and Western blot were performed to ascertain whether COL4A1 was a target of miR-214-5p.Objectives
Methods
Cellular movement and relocalisation are important for many physiologic properties. Local mesenchymal stem cells (MSCs) from injured tissues and circulating MSCs aid in fracture healing. Cytokines and chemokines such as Stromal cell-derived factor 1(SDF-1) and its receptor chemokine receptor type 4 (CXCR4) play important roles in maintaining mobilisation, trafficking and homing of stem cells from bone marrow to the site of injury. We investigated the differences in migration of MSCs from the femurs of young, adult and ovariectomised (OVX) rats and the effect of CXCR4 over-expression on their migration. MSCs from young, adult and OVX rats were put in a Boyden chamber to establish their migration towards SDF-1. This was compared with MSCs transfected with CXCR4, as well as MSCs differentiated to osteoblasts.Objectives
Methods
Approximately half of all hip fractures are displaced intracapsular fractures. The standard treatment for these fractures is either hemiarthroplasty or total hip arthroplasty. The recent National Institute for Health and Care Excellence (NICE) guidance on hip fracture management recommends the use of ‘proven’ cemented stem arthroplasty with an Orthopaedic Device Evaluation Panel (ODEP) rating of at least 3B (97% survival at three years). The Thompsons prosthesis is currently lacking an ODEP rating despite over 50 years of clinical use, likely due to the paucity of implant survival data. Nationally, adherence to these guidelines is varied as there is debate as to which prosthesis optimises patient outcomes. This study design is a multi-centre, multi-surgeon, parallel, two arm, standard-of-care pragmatic randomised controlled trial. It will be embedded within the WHiTE Comprehensive Cohort Study (ISRCTN63982700). The main analysis is a two-way equivalence comparison between Hemi-Thompson and Hemi-Exeter polished taper with Unitrax head. Secondary outcomes will include radiological leg length discrepancy measured as per Bidwai and Willett, mortality, re-operation rate and indication for re-operation, length of index hospital stay and revision at four months. This study will be supplemented by the NHFD (National Hip Fracture Database) dataset.Background
Design
Fractures of the proximal femur are one of the
greatest challenges facing the medical community, constituting a
heavy socioeconomic burden worldwide. Controversy exists regarding
the optimal treatment for independent patients with displaced intracapsular fractures
of the proximal femur. The recognised alternatives are hemiarthroplasty
and total hip replacement. At present there is no established standard
of care, with both types of arthroplasty being used in many centres.
The principal advantages of total hip replacement are a functional
benefit over hemiarthroplasty and a reduced risk of revision surgery.
The principal criticism is the increased risk of dislocation. We
believe that an alternative acetabular component may reduce the
risk of dislocation but still provide the functional benefit of
total hip replacement in these patients. We therefore propose to
investigate the dislocation risk of a dual-mobility acetabular component
compared with standard polyethylene component in total hip replacement
for independent patients with displaced intracapsular fractures
of the proximal femur within the framework of the larger WHiTE (Warwick
Hip Trauma Evaluation) Comprehensive Cohort Study. Cite this article:
Fractures of the proximal femur are one of the
greatest challenges facing the medical community, constituting a
heavy socioeconomic burden worldwide. Controversy exists regarding
the optimal treatment for patients with unstable trochanteric proximal
femoral fractures. The recognised treatment alternatives are extramedullary
fixation usually with a sliding hip screw and intramedullary fixation
with a cephalomedullary nail. Current evidence suggests that best
results and lowest complication rates occur using a sliding hip screw.
Complications in these difficult fractures are relatively common
regardless of type of treatment. We believe that a novel device,
the X-Bolt dynamic plating system, may offer superior fixation over
a sliding hip screw with lower reoperation risk and better function.
We therefore propose to investigate the clinical effectiveness of
the X-bolt dynamic plating system compared with standard sliding
hip screw fixation within the framework of a the larger WHiTE (Warwick
Hip Trauma Evaluation) Comprehensive Cohort Study. Cite this article:
One commonly used rat fracture model for bone and mineral research
is a closed mid-shaft femur fracture as described by Bonnarens in
1984. Initially, this model was believed to create very reproducible
fractures. However, there have been frequent reports of comminution
and varying rates of complication. Given the importance of precise
anticipation of those characteristics in laboratory research, we
aimed to precisely estimate the rate of comminution, its importance and
its effect on the amount of soft callus created. Furthermore, we
aimed to precisely report the rate of complications such as death
and infection. We tested a rat model of femoral fracture on 84 rats based on
Bonnarens’ original description. We used a proximal approach with
trochanterotomy to insert the pin, a drop tower to create the fracture
and a high-resolution fluoroscopic imager to detect the comminution.
We weighed the soft callus on day seven and compared the soft callus
parameters with the comminution status.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
To study the measurement properties of a joint specific patient
reported outcome measure, a measure of capability and a general
health-related quality of life (HRQOL) tool in a large cohort of
patients with a hip fracture. Responsiveness and associations between the Oxford Hip Score
(a hip specific measure: OHS), ICEpop CAPability (a measure of capability
in older people: ICECAP-O) and EuroQol EQ-5D (general health-related
quality of life measure: EQ-5D) were assessed using data available
from two large prospective studies. The three outcome measures were assessed
concurrently at a number of fixed follow-up time-points in a consecutive
sequence of patients, allowing direct assessment of change from
baseline, inter-measure associations and validity using a range
of statistical methods.Objectives
Methods
The Oxford hip score (OHS) is a 12-item questionnaire designed
and developed to assess function and pain from the perspective of
patients who are undergoing total hip replacement (THR). The OHS
has been shown to be consistent, reliable, valid and sensitive to
clinical change following THR. It has been translated into different
languages, but no adequately translated, adapted and validated Danish
language version exists. The OHS was translated and cross-culturally adapted into Danish
from the original English version, using methods based on best-practice
guidelines. The translation was tested for psychometric quality
in patients drawn from a cohort from the Danish Hip Arthroplasty
Register (DHR).Objectives
Methods
