The management of femoral bone loss is challenging during revision hip arthroplasty. In patients with Paprosky grade IIIB and IV defects, obtaining fixation and rotational stability using traditional surgical constructs is difficult. The use of a custom-made internal proximal femoral replacement prostheses has been proposed as a solution in patients, with severe femoral bone stock loss. However, there is a paucity in the literature on their use and long-term outcomes. We report on the clinical and radiological results of our cohort. We retrospectively reviewed all patients who underwent internal proximal femoral replacement for revision hip arthroplasty between April 1996 and April 2019. All patients had at least 2 years of follow-up time. 160 patients underwent limb salvage at our institution using internal proximal femoral replacement. The mean follow-up was 79.7 months (S.D 41.3). Indications for revision included periprosthetic fractures, aseptic loosening, and deep infection. The mean Oxford hip score increased from 13.8 (0–22) to 31.5 (18–43) (paired t-test, p < 0.001). Kaplan-Meier prosthesis survival analysis with revision as the endpoint was 87% at 5 years. None required revision of the femoral stem. There were four dislocations (5%) and there was failure to eradicate the deep infection in four. This technique allows instant distal fixation, allowing for early mobilisation. Long-term clinical and radiological outcomes are encouraging and the complication rates are acceptable for this patient group.
A growing number of fractures progress to delayed or nonunion, causing significant morbidity and socioeconomic impact. Localized delivery of stem cells and subcutaneous parathyroid hormone (PTH) has been shown individually to accelerate bony regeneration. This study aimed to combine the therapies with the aim of upregulating fracture healing. A 1.5 mm femoral osteotomy (delayed union model) was created in 48 female juvenile Wistar rats, aged six to nine months, and stabilized using an external fixator. At day 0, animals were treated with intrafracture injections of 1 × 106 cells/kg bone marrow mesenchymal stem cells (MSCs) suspended in fibrin, daily subcutaneous injections of high (100 μg/kg) or low (25 μg/kg) dose PTH 1-34, or a combination of PTH and MSCs. A group with an empty gap served as a control. Five weeks post-surgery, the femur was excised for radiological, histomorphometric, micro-CT, and mechanical analysis.Aims
Methods
Mesenchymal stem cells (MSCs) are of growing interest in terms of bone regeneration. Most preclinical trials utilize bone-marrow-derived mesenchymal stem cells (bMSCs), although this is not without isolation and expansion difficulties. The aim of this study was: to compare the characteristics of bMSCs and adipose-derived mesenchymal stem cells (AdMSCs) from juvenile, adult, and ovarectomized (OVX) rats; and to assess the effect of human parathyroid hormone (hPTH) 1-34 on their osteogenic potential and migration to stromal cell-derived factor-1 (SDF-1). Cells were isolated from the adipose and bone marrow of juvenile, adult, and previously OVX Wistar rats, and were characterized with flow cytometry, proliferation assays, osteogenic and adipogenic differentiation, and migration to SDF-1. Experiments were repeated with and without intermittent hPTH 1-34.Objectives
Methods
Massive endoprostheses rely on extra-cortical bone bridging (ECBB)
to enhance fixation. The aim of this study was to investigate the
role of selective laser sintered (SLS) porous collars in augmenting
the osseointegration of these prostheses. The two novel designs of porous SLS collars, one with small pores
(Ø700 μm, SP) and one with large pores (Ø1500 μm, LP), were compared
in an ovine tibial diaphyseal model. Osseointegration of these collars
was compared with that of a clinically used solid, grooved design
(G). At six months post-operatively, the ovine tibias were retrieved and
underwent radiological and histological analysis.Aims
Materials and Methods
Intermittent parathyroid hormone 1–34 (teriparatide) is the N-fragment terminal of the intact hormone, currently in clinical use to treat osteoporosis. Unlike anti-catabolic agents such as bisphosphonates, PTH 1–34 not only affects the osteoclast, but also up regulates bone formation via both modelling and remodelling mechanisms. The actions of iPTH on mesenchymal stem cell differentiation (MSCs) may underpin a further method in the treatment of osteoporosis specifically, and for fracture healing in general. Stem cells from older female osteoporotic animals have reduced activity and poorer osteogenic potential; additionally, their migration to and retention at sites of increased bone turnover are reduced in comparison to cells from younger animals. The aim of this study was to isolate bone marrow derived MSCs from both young Wild Type (WT) and ovarectomized senile (OVX) rats, then to investigate and compare the effect of pulsatile and continuous PTH administration on migration to SDF-1, proliferation and osteogenic differentiation. MSCs were harvested from the femora of 6–9week Wistar rats, and from 10–13month ovarectomized rats with established osteopenia. Cells were cultured with 25, 50 and 100nmMol of PTH 1–34 added to osteogenic media either continuously or in a pulsatile fashion for 6 hours in every 72hour cycle. ALP and Alizarin Red were used to assess the optimal concentration of PTH for osteogenic differentiation. Subsequently, proliferation was assessed with Alamar Blue and cells were seeded in a Boyden chamber to quantify the migration to SDF-1. As the data was parametric a student t-test was used to analyse results, and a p value < 0.05 was considered significant. ALP and Alizarin Red parameters were significantly increased for both WT and OVX groups at 50nmMol of pulsatile PTH in comparison to groups cultured in 25 or 100nmMol. Continuous administration at all concentrations led to reduced calcium phosphate deposition by day 21 in all groups. Interestingly, in comparison to cells cultured in osteogenic media, 50nmMol of pulsatile PTH lead to statistically significant higher ALP and Alizarin Red measurements up to day 10 and 14 respectively in WT cells, and days 10 and 21 in OVX cells. The proliferation rate normalised against DNA was similar for both OVX and WT rats at all-time points. PTH administration did not effect cell proliferation in any group. WT MSCs not only had improved osteogenic differentiation, but also showed increased migration to SDF-1 in comparison to OVX groups. Pulsatile PTH led to further increases in migration of both OVX and WT cells. Intermittent PTH increases the osteogenic diffrentiation and migration of MSCs from both young and ovarectomised rats, though importantly this effect is not dose dependent. Ultimately, the role of PTH 1–34 on MSCs may lead to improved bone formation and cell homing capacity-particularly in the context of osteoporosis.
Osteoporosis is characterised by an uncoupling of bone formation and resorption resulting in a net reduction in bone density. Stem cells derived from bone marrow in osteoporotic patients typically contain more adipocytes,. Intermittent Parathyroid hormone (iPTH), has been shown to cause the preferential differentiation of mesenchymal stem cells (MSCs) to osteoblasts. We isolated rat bone marrow derived MSCs, investigating the effect of iPTH on adipocyte differentiation. MSCs were harvested from the femora of 6–10week oldWT rats and cultured to induce adipogenesis for 21 days. Subsequently, cells were continually cultured in adipogenic media, osteogenic media or in osteogenic media supplemented with PTH 1–34 either continuously or intermittently for 6hours in every 72hour cycle. ALP and Alizarin Red assessed osteogenic differentiation, and Oil Red O used to assess intracellular microdroplet formation. A student t-test was used to analyse results, and a p value<0.05 considered significant. Quantitatively measurements of Alizarin Red staining significantly increased in all adipocytes grown in osteogenic media compared to the cells continually cultured in adipogenic media. Calcium phosphate deposition continued to increase significantly in these groups up to day 14. At day 14, Alizarin Red staining from cells cultured in iPTH were significantly higher than osteogenic media alone. ALP expression was significantly higher for cells cultured in osteogenic media and iPTH compared to adipogenic media at days 3–14. Expression peaked at day 7, at this timepoint cells cultured in iPTH expressed significantly more ALP than other groups. Oil Red O measurements were significantly reduced from days 7–14 for all osteogenic groups, this significance was greatest for the iPTH group at day 7. iPTH increased the transdifferentiation of adipocytes derived from MSCs into osteoblasts, this effect was most significant after 7 days. Ultimately, the role of iPTH on adipocytes may lead to improved bone formation with many orthopaedic applications.
Intermittently administered parathyroid hormone (PTH 1-34) has been shown to promote bone formation in both human and animal studies. The hormone and its analogues stimulate both bone formation and resorption, and as such at low doses are now in clinical use for the treatment of severe osteoporosis. By varying the duration of exposure, parathyroid hormone can modulate genes leading to increased bone formation within a so-called ‘anabolic window’. The osteogenic mechanisms involved are multiple, affecting the stimulation of osteoprogenitor cells, osteoblasts, osteocytes and the stem cell niche, and ultimately leading to increased osteoblast activation, reduced osteoblast apoptosis, upregulation of Wnt/β-catenin signalling, increased stem cell mobilisation, and mediation of the RANKL/OPG pathway. Ongoing investigation into their effect on bone formation through ‘coupled’ and ‘uncoupled’ mechanisms further underlines the impact of intermittent PTH on both cortical and cancellous bone. Given the principally catabolic actions of continuous PTH, this article reviews the skeletal actions of intermittent PTH 1-34 and the mechanisms underlying its effect.
Photodynamic therapy (PDT) requires a photosensitiser, a light source of an appropriate wavelength, and the presence of molecular oxygen. Once stimulated to its excited phase by the light, the photosensitiser reacts with oxygen to form free radicals of ‘singlet oxygen’ which is cytotoxic to microorganisms. We aim to demonstrate the effectiveness of PDT as an A PDT treatment protocol was devised using lawns of bacteria on agar plates. PDT was targeted towards the bacteria and the remaining microorganisms were quantified using a serial dilution technique. In order to assess the ability of photodynamic therapy to target biofilms on metallic implants, biofilms were cultured on polished titanium and hydroxyapatite-coated titanium discs and subjected to PDT.Aim
Method
Osteoporosis is characterised by an uncoupling of bone formation and resorption resulting in net resorption. Stem cells derived from bone marrow in osteoporotic patients typically contain more adipocytes. Intermittent Parathyroid hormone (iPTH), has been shown to cause the preferential differentiation of mesenchymal stem cells (MSCs) to osteoblasts. We isolated rat bone marrow derived MSCs, investigating the effect of iPTH on adipocyte differentiation. MSCs were harvested from the femora of 6–10week oldWT rats and cultured to induce adipogenesis for 21 days. Subsequently, cells were continually cultured in adipogenic media, osteogenic media or in osteogenic media supplemented with PTH 1–34 either continuously or intermittently for 6hours in every 72hour cycle. ALP and Alizarin Red assessed osteogenic differentiation, and Oil Red O used to assess intracellular microdroplet formation. A student t-test was used to analyse results, and a p value<0.05 considered significant. Quantitatively measurements of Alizarin Red staining significantly increased in all adipocytes grown in osteogenic media compared to the cells continually cultured in adipogenic media. Calcium phosphate deposition continued to increase significantly in these groups up to day 14. At day 14, Alizarin Red staining from cells cultured in iPTH were significantly higher than osteogenic media alone. ALP expression was significantly higher for cells cultured in osteogenic media and iPTH compared to adipogenic media at days 3–14. Expression peaked at day 7, at this timepoint cells cultured in iPTH expressed significantly more ALP than other groups (Figure 2). Oil Red O measurements were significantly reduced from days 7–14 for all osteogenic groups, this significance was greatest for the iPTH group at day 7. iPTH increased the transdifferentiation of adipocytes derived from MSCs into osteoblasts, this effect was most significant after 7 days. Ultimately, the role of iPTH on adipocytes may lead to improved bone formation with many orthopaedic applications.
Intermittent parathyroid hormone (iPTH 1–34) increases bone formation via modelling and remodelling mechanisms and as such is used to treat osteoporosis. The actions of iPTH on mesenchymal stem cell (MSCs) may underpin a further treatment option. We isolated bone marrow derived MSCs from young (WT) and ovarectomized senile (OVX) rats, investigating the effect of intermittent and continuous PTH administration on migration to SDF-1, proliferation and osteogenic differentiation. MSCs were harvested from the femora of 6–10week old WT rats and 10–13month old OVX rats. Cells were cultured with 25,50 and 100nmMol of PTH 1–34 added to osteogenic media either continuously or intermittently for 6hours in every 72hour cycle. ALP and Alizarin Red assessed osteogenic differentiation, and Alamar Blue- proliferation. Cells were seeded in a Boyden chamber to quantify SDF-1 migration. A student t-test was used to analyse results, and a p value<0.05 considered significant. ALP and Alizarin Red were significantly increased for WT and OVX groups at 50nmMol of iPTH. Continuous administration at all concentrations reduced calcium phosphate deposition by day 21 in all groups. In comparison to cells cultured in osteogenic media, 50nmMol of iPTH led to significantly higher ALP and Alizarin Red measurements up to days 10 and 7 respectively (figure 1). There was no change in proliferation between the groups, and PTH had no effect (figure 2.) WT MSCs not only had improved osteogenic differentiation, but also showed increased migration to SDF-1 in comparison to OVX groups. iPTH led to further increases in migration of both OVX and WT cells. iPTH increases the osteogenic differentiation and migration of MSCs from both young and ovarectomised rats, though this effect is not dose dependent. Ultimately, the role of iPTH on MSCs may lead to improved bone formation and cell homing capacity-particularly in the context of osteoporosis.
THR is one of the most frequently performed operations nationally. A large number of prostheses are available, and the procedure is therefore associated with variation in practice and outcomes. NICE guidelines aim to standardise best practice, and are informed by separate, independent bodies, such as the NJR and ODEP, which monitor data about the implants used and their performance. This study aims to determine whether clinical practice and component use has changed since the publication of NJR data. NJR reports from 2006–2014 were analysed, with record made of the different prostheses used in THR, noting ODEP ratings of components used. Analysis was also performed by component type (i.e. cemented and cementless stems and cups), and combinations of components, according to their frequency of use in a given year. The Kruksal-Wallis test was used for statistical analysis.Introduction
Methods
Patients who have limb amputation for musculoskeletal
tumours are a rare group of cancer survivors. This was a prospective
cross-sectional survey of patients from five specialist centres
for sarcoma surgery in England. Physical function, pain and quality
of life (QOL) outcomes were collected after lower extremity amputation
for bone or soft-tissue tumours to evaluate the survivorship experience
and inform service provision. Of 250 patients, 105 (42%) responded between September 2012 and
June 2013. From these, completed questionnaires were received from
100 patients with a mean age of 53.6 years (19 to 91). In total
60 (62%) were male and 37 (38%) were female (three not specified).
The diagnosis was primary bone sarcoma in 63 and soft-tissue tumour
in 37. A total of 20 tumours were located in the hip or pelvis,
31 above the knee, 32 between the knee and ankle and 17 in the ankle
or foot. In total 22 had hemipelvectomy, nine hip disarticulation,
35 transfemoral amputation, one knee disarticulation, 30 transtibial
amputation, two toe amputations and one rotationplasty. The Toronto
Extremity Salvage Score (TESS) differed by amputation level, with
poorer scores at higher levels (p <
0.001). Many reported significant
pain. In addition, TESS was negatively associated with increasing
age, and pain interference scores. QOL for Cancer Survivors was
significantly correlated with TESS (p <
0.001). This relationship appeared
driven by pain interference scores. This unprecedented national survey confirms amputation level
is linked to physical function, but not QOL or pain measures. Pain
and physical function significantly impact on QOL. These results
are helpful in managing the expectations of patients about treatment
and addressing their complex needs. Cite this article:
Congenital insensitivity to pain is a rare autosomal recessive condition that leads to varying degrees of sensory and autonomic neuropathy. The aim of the study was to explore the common orthopaedic presentations of congenital insensitivity to pain and provide guidance on their treatment and complications. This study presents the results of fifteen patients with congenital insensitivity to pain, which were referred and treated at our supra-regional referral centre. Intradermal histamine tests and quantitative sweat tests were performed on all fifteen patients.Purpose.
Methods.
Pigmented Villonodular Synovitis (PVNS) is a rare inflammatory disorder of the synovium, bursa and tendon sheath. The objective of this study was to evaluate the long-term outcomes and morbidity associated with operative management of PVNS of the hand. Histological databases were retrospectively interrogated. All patients between 2003–2008 with confirmed PVNS of the hand were included in the study.Introduction:
Methods:
Endoprosthetic replacement of the proximal femur is common in the management of bone tumours and failed revision arthroplasty. This study seeks to compare those patients undergoing acetabular resurfacing at the time of femoral replacement with those patients where the native acetabulum was preserved. All proximal femoral replacements from 2004 to 2009 with a five year follow up were included. Case files were interrogated to identify those that had either revision surgery or dislocation of the hip.Introduction:
Methods:
Distal femoral replacement is recognised as the optimum treatment for malignant distal femoral tumours. Aseptic loosening is known to be a major cause for failure in these implants. Studies have indicated that the HA coated collar promotes osteointegration and bony in growth. This study compares long term aseptic loosening in implants with HA coated collars to those without in the immature skeleton. To assess the effect of HA coated collars on aseptic loosening in extendable distal femoral replacement prosthesis in the immature skeleton.Introduction:
Objectives:
Local recurrence of tumours along the biopsy tract is a known complication of percutaneous closed needle biopsy. Correct surgical management requires preoperative identification and excision of the biopsy tract at time of surgery. These tracts become increasingly difficult to identify with time, leading to risk of inadequate excision of the biopsy tract and recurrence of the tumour at the biopsy site. In a prospective study conducted at our institution, 22 of the 45 patients with musculoskeletal tumours (49%) had unidentifiable biopsy sites, with a mean duration between biopsy and definite surgery being 98 days (range 13–164 days). We concluded that identification of the biopsy site was more difficult after 50 days. Radiotherapy related scar formation and the longer time duration between biopsy and definite surgery in patients requiring neoadjuvant therapy made identification more unlikely. Consequently, all patients received India ink skin tattoo to mark the biopsy site at the time of the needle biopsy. 56 patients were then prospectively reviewed on the day of surgery to identify the biopsy site.Introduction
Materials/Methods
Osteoarthritis is associated with changes to the matrix composition of subchondral bone. Raman spectroscopy has the potential to detect in vivo the molecular changes in osteoarthritic subchondral bone. The objectives were to determine the levels of mineralisation, carbonate accumulation and bone remodelling in osteoarthritic subchondral bone, which we defined as within 3mm of articular cartilage. This was compared to the proximal-compartment (10mm distal to articular cartilage) and the head-neck junction. Five osteoarthritic (average age: 76 years) and five normal cadaveric femoral heads (average age: 72 years) were scanned using peripheral quantitative computed tomography and then sectioned coronally. Raman spectroscopy was then used to scan the femoral heads. All scans were done in the plane of the longitudinal axis of the diaphysis. Cores were subsequently extracted and sodium dodecyl sulphate polyacrylamide gel electrophoresis performed to determine the levels of homotrimeric collagen. The phosphate-to-amide I ratio, from the Raman spectra, in osteoarthritic subchondral bone was significantly greater than controls (p=0.023). Within osteoarthritic specimens, the phosphate-to-amide I ratio increased proximally. The density in osteoarthritic subchondral bone was 89mg/cm3 higher than controls (p=0.022), and 494mg/cm3 higher than the osteoarthritic proximal-compartment (p<0.001). Moreover, carbonate substitution into the apatite crystals decreased in osteoarthritic specimens. The carbonate-to-amide I ratio was highest in osteoarthritic subchondral bone. Furthermore, the median α1-to-α2-chain ratio in osteoarthritic specimens was 2:1. The changes found in subchondral bone are important in the pathogenesis of osteoarthritis. This study shows that Raman spectroscopy can detect differences between osteoarthritic specimens and controls, further supporting its potential use in diagnosing bone disorders.
Osteoarthritis (OA) is a common, debilitating joint disease involving degeneration of cartilage and bone. It has been suggested that subtle changes in the molecular structure of subchondral bone may precede cartilaginous changes in the osteoarthritic joint. To explore these changes Raman spectroscopy was employed as a diagnostic tool. Raman spectroscopy measures inelastic scattered laser light produced when photons interact with chemical materials. Resultant changes in wavelength form spectra relative to the chemical composition of the given sample: with bone this includes the mineral and matrix components, unlike conventional X-rays. The aim of our study is to explore the hypothesis: Changes in matrix composition of osteoarthritic subchondral bone can be detected with Raman spectroscopy. pQCT and Raman spectroscopy were employed to determine the bone mineral density (BMD) and bone quality, respectively. Ten medial compartment OA and five control (non-OA) tibial plateaus were interrogated and analysis performed to compare OA to control, and medial to lateral compartments. The subchondral bone of the medial OA compartments had higher BMD (p=0.05) and thickness compared to lateral and control samples. Spectral analysis revealed there is no difference between the medial and lateral compartments within either cohort. However, there is a statistically significant (p=0.02) spectral difference between the OA and control specimens. The detection of bone matrix changes in osteoarthritis using Raman spectroscopy contributes to the understanding of the biochemical signature of subchondral bone across diseased and control tibial plateaus. This technique has potential to shed light on the role of bone in osteoarthritis.
