Aims

The modified Glasgow Prognostic Score (mGPS) uses preoperative CRP and albumin to calculate a score from 0 to 2 (2 being associated with poor outcomes). mGPS is validated in multiple carcinomas. To date, its use in soft-tissue sarcoma (STS) is limited, with only small cohorts reporting that increased mGPS scores correlates with decreased survival in STS patients.

Thrombin has many biological properties similar to those of growth factors. In a previous study, we showed that thrombin improves healing of the rat tendo Achillis. Low molecular weight heparin (LMWH) inhibits the activity and the generation of thrombin. We therefore considered that LMWH at a thromboprophylactic dose might inhibit tendon repair. Transection of the tendo Achillis was carried out in 86 rats and the healing tested mechanically. Low molecular weight heparin (dalateparin) was either injected a few minutes before the operation and then given continuously with an osmotic mini pump for seven days, or given as one injection before the operation. In another experiment ,we gave LMWH or a placebo by injection twice daily. The anti-factor Xa activity was analysed. Continuous treatment with LMWH impaired tendon healing. After seven days, this treatment caused a 33% reduction in force at failure, a 20% reduction in stiffness and a 67% reduction in energy uptake. However, if injected twice daily, LMWH had no effect on tendon healing. Anti-factor Xa activity was increased by LMWH treatment, but was normal between intermittent injections. Low molecular weight heparin delays tendon repair if given continuously, but not if injected intermittently, probably because the anti-factor Xa activity between injections returns to normal, allowing sufficient thrombin stimulation for repair. These findings indicate the need for caution in the assessment of long-acting thrombin and factor Xa inhibitors

Aims

LY3023414 is a novel oral phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) dual inhibitor designed for advanced cancers, for which a phase II clinical study was completed in March 2020; however, little is known about its effect on bone modelling/remodelling. In this study, we aimed to explore the function of LY3023414 in bone modelling/remodelling.

Proximal femoral varus osteotomy improves the biomechanics of the hip and can stimulate normal acetabular development in a dysplastic hip. Medial closing wedge osteotomy remains the most popular technique, but is associated with shortening of the ipsilateral femur. We produced a trigonometric formula which may be used pre-operatively to predict the resultant leg length discrepancy (LLD). We retrospectively examined the influence of the choice of angle in a closing wedge femoral osteotomy on LLD in 120 patients (135 osteotomies, 53% male, mean age six years, (3 to 21), 96% caucasian) over a 15-year period (1998 to 2013). A total of 16 of these patients were excluded due to under or over varus correction. The patients were divided into three age groups: paediatric (< 10 years), adolescent (10 to 16 years) and adult (> 16 years). When using the same saw blades as in this series, the results indicated that for each 10° of angle of resection the resultant LLD equates approximately to multiples of 4 mm, 8 mm and 12 mm in the three age groups, respectively. Statistical testing of the 59 patients who had a complete set of pre- and post-operative standing long leg radiographs, revealed a Pearson’s correlation coefficient for predicted versus radiologically observed shortening when using a wedge of either 10° or 20° of 0.93 (p <  0.001). The 95% limits of agreement from the Bland–Altman analysis for this subgroup were –3.5 mm to +3.3 mm. It has been accepted that a 10 mm discrepancy is clinically acceptable. This study identified a geometric model that provided satisfactory accuracy when using specific saw blades of known thicknesses for this formula to be used in clinical practice. Cite this article: Bone Joint J 2014;96-B:1124–9

We analysed the effects of commonly used medications on human osteoblastic cell activity in vitro, specifically proliferation and tissue mineralisation. A list of medications was retrieved from the records of patients aged > 65 years filed in the database of the largest health maintenance organisation in our country (> two million members). Proliferation and mineralisation assays were performed on the following drugs: rosuvastatin (statin), metformin (antidiabetic), metoprolol (β-blocker), citalopram (selective serotonin reuptake inhibitor [SSRI]), and omeprazole (proton pump inhibitor (PPI)). All tested drugs significantly stimulated DNA synthesis to varying degrees, with rosuvastatin 5 µg/ml being the most effective among them (mean 225% (. sd. 20)), compared with metformin 10 µg/ml (185% (. sd.  10)), metoprolol 0.25 µg/ml (190% (. sd. 20)), citalopram 0.05 µg/ml (150% (. sd. 10)) and omeprazole 0.001 µg/ml (145% (. sd. 5)). Metformin and metoprolol (to a small extent) and rosuvastatin (to a much higher extent) inhibited cell mineralisation (85% (. sd. 5)). Our results indicate the need to evaluate the medications prescribed to patients in terms of their potential action on osteoblasts. Appropriate evaluation and prophylactic treatment (when necessary) might lower the incidence and costs associated with potential medication-induced osteoporosis. Cite this article: Bone Joint J 2013;95-B:1575–80

Puppies in the second half of their growing period have been observed for one and a half to four and a half months after creation of a superficial femoral arteriovenous fistula on the right side. From measurements of the whole bone and from microradiographic and tetracycline-fluorophore studies of the diaphysial bone, it is believed that the following statistically significant phenomena may be attributed to the influence of the arteriovenous fistula. 1. All bones distal to the fistula are influenced in their growth. The tibia and metatarsals become heavier and larger, but retain normal shape. Although stimulation of longitudinal growth is small, it is significant for the tibiae and nearly significant for the femora in these short-term experiments. 2. The histological structure of the bones remains normal but quantitative changes are induced. The compact bone is more porous because of an increased number of osteones. Haversian turnover itself is affected in that the individual formation time of osteones tends to become longer, especially in the metatarsals. 3. Periosteal new bone formation is immediately stimulated, producing a flare of new bone. This accounts for the increase in diaphysial weight in the tibia but not in the metatarsals, where the same effect results from decreased resorption of old bone. 4. Endosteal new bone formation is depressed, especially in the metatarsals, resulting in an enlarged medullary cavity

Aims

Rheumatoid arthritis (RA), which mainly results from fibroblast-like synoviocyte (FLS) dysfunction, is related to oxidative stress. Advanced oxidation protein products (AOPPs), which are proinflammatory mediators and a novel biomarker of oxidative stress, have been observed to accumulate significantly in the serum of RA patients. Here, we present the first investigation of the effects of AOPPs on RA-FLSs and the signalling pathway involved in AOPP-induced inflammatory responses and invasive behaviour.

Congenital pseudarthrosis of the tibia is an uncommon manifestation of neurofibromatosis type 1 (NF1), but one that remains difficult to treat due to anabolic deficiency and catabolic excess. Bone grafting and more recently recombinant human bone morphogenetic proteins (rhBMPs) have been identified as pro-anabolic stimuli with the potential to improve the outcome after surgery. As an additional pharmaceutical intervention, we describe the combined use of rhBMP-2 and the bisphosphonate zoledronic acid in a mouse model of NF1-deficient fracture repair. Fractures were generated in the distal tibiae of neurofibromatosis type 1-deficient (Nf1. +/−. ) mice and control mice. Fractures were open and featured periosteal stripping. All mice received 10 μg rhBMP-2 delivered in a carboxymethylcellulose carrier around the fracture as an anabolic stimulus. Bisphosphonate-treated mice also received five doses of 0.02 mg/kg zoledronic acid given by intraperitoneal injection. When only rhBMP but no zoledronic acid was used to promote repair, 75% of fractures in Nf1. +/−. mice remained ununited at three weeks compared with 7% of controls (p < 0.001). Systemic post-operative administration of zoledronic acid halved the rate of ununited fractures to 37.5% (p < 0.07). These data support the concept that preventing bone loss in combination with anabolic stimulation may improve the outcome following surgical treatment for children with congenital pseudarthoris of the tibia and NF1

Two types of fracture, early and late, have been reported following limb lengthening in patients with achondroplasia (ACH) and hypochondroplasia (HCH). . We reviewed 25 patients with these conditions who underwent 72 segmental limb lengthening procedures involving the femur and/or tibia, between 2003 and 2011. Gender, age at surgery, lengthened segment, body mass index, the shape of the callus, the amount and percentage of lengthening and the healing index were evaluated to determine predictive factors for the occurrence of early (within three weeks after removal of the fixation pins) and late fracture (> three weeks after removal of the pins). The Mann‑Whitney U test and Pearson’s chi-squared test for univariate analysis and stepwise regression model for multivariate analysis were used to identify the predictive factor for each fracture. Only one patient (two tibiae) was excluded from the analysis due to excessively slow formation of the regenerate, which required supplementary measures. A total of 24 patients with 70 limbs were included in the study. There were 11 early fractures in eight patients. The shape of the callus (lateral or central callus) was the only statistical variable related to the occurrence of early fracture in univariate and multivariate analyses. Late fracture was observed in six limbs and the mean time between removal of the fixation pins and fracture was 18.3 weeks (3.3 to 38.4). Lengthening of the tibia, larger healing index, and lateral or central callus were related to the occurrence of a late fracture in univariate analysis. A multivariate analysis demonstrated that the shape of the callus was the strongest predictor for late fracture (odds ratio: 19.3, 95% confidence interval: 2.91 to 128). Lateral or central callus had a significantly larger risk of fracture than fusiform, cylindrical, or concave callus. Radiological monitoring of the shape of the callus during distraction is important to prevent early and late fracture of lengthened limbs in patients with ACH or HCH. In patients with thin callus formation, some measures to stimulate bone formation should be considered as early as possible. Cite this article: Bone Joint J 2014;96-B:1269–73

Aims

Perthes’ disease (PD) often results in femoral head deformity and leg length discrepancy (LLD). Our objective was to analyze femoral morphology in PD patients at skeletal maturity to assess where the LLD originates, and evaluate the effect of contralateral epiphysiodesis for length equalization on proximal and subtrochanteric femoral lengths.

Aims

Spinal deformity surgery carries the risk of neurological injury. Neurophysiological monitoring allows early identification of intraoperative cord injury which enables early intervention resulting in a better prognosis. Although multimodal monitoring is the ideal, resource constraints make surgeon-directed intraoperative transcranial motor evoked potential (TcMEP) monitoring a useful compromise. Our experience using surgeon-directed TcMEP is presented in terms of viability, safety, and efficacy.

Bone growth into cementless prosthetic components is compromised by osteoporosis, by any gap between the implant and the bone, by micromotion, and after the revision of failed prostheses. Recombinant human transforming growth factor-β1 (rhTGF-β1) has recently been shown to be a potent stimulator of bone healing and bone formation in various models in vivo. We have investigated the potential of rhTGF-β1, adsorbed on to weight-loaded tricalcium phosphate (TCP) coated implants, to enhance bone ongrowth and mechanical fixation. We inserted cylindrical grit-blasted titanium alloy implants bilaterally into the weight-bearing part of the medial femoral condyles of ten skeletally mature dogs. The implants were mounted on special devices which ensured stable weight-loading during each gait cycle. All implants were initially surrounded by a 0.75 mm gap and were coated with TCP ceramic. Each animal received two implants, one with 0.3 μg rhTGF-β1 adsorbed on the ceramic surface and the other without growth factor. Histological analysis showed that bone ongrowth was significantly increased from 22 ± 5.6% bone-implant contact in the control group to 36 ± 2.9% in the rhTGF-β stimulated group, an increase of 59%. The volume of bone in the gap was increased by 16% in rhTGF-β1-stimulated TCP-coated implants, but this difference was not significant. Mechanical push-out tests showed no difference in fixation of the implant between the two groups. Our study suggests that rhTGF-β1 adsorbed on TCP-ceramic-coated implants can enhance bone ongrowth

Aims

Despite the interest in the association of gut microbiota with bone health, limited population-based studies of gut microbiota and bone mineral density (BMD) have been made. Our aim is to explore the possible association between gut microbiota and BMD.

The purpose of this paper has been to stimulate interest in amputation surgery, prosthetics and orthotics, and to illustrate the excellent work done in only some of the centres within the British Isles and to enlist the assistance of all orthopaedic surgeons in improving the orthotic equipment of their patients. We also need the interest and the practical involvement of one orthopaedic surgeon in amputation work and prosthetics in almost every large hospital, particularly in the centres where it is to be expected that limb-fitting units will be installed and fully integrated within the hospital service. It is necessary to say "almost every large hospital", because in some the vascular surgeon will lead the amputation and prosthetic team. This is a worthwhile special interest for the orthopaedic surgeon. The need presents itself not only for the geriatric patient with limb ischaemia and for those who lose a limb from trauma, but also for the quite considerable number of children who are congenitally without a limb or part of a limb. Orthopaedic surgery embraces a wide field, and in the larger centres the best work will result from a voluntary restriction in the field of operation of individual surgeons, many being involved in trauma and fractures, all being involved in adult orthopaedic surgery, some with a special interest and considerable time in children's orthopaedic surgery, or hand surgery, or the surgery of rheumatoid arthritis patient; and to this list one would hope might be added amputation surgery and the prosthetic rehabilitation of these patients. I will be well satisfied if I have succeeded in stimulating a renewed interest in this oldest branch of orthopaedic surgery

Aims

To determine the relationship between articular cartilage status and clinical outcomes after medial opening-wedge high tibial osteotomy (MOHTO) for medial compartmental knee osteoarthritis at intermediate follow-up.

The use of journal clubs and, more recently, case-based discussions in order to stimulate debate among orthopaedic surgeons lies at the heart of orthopaedic training and education. A virtual learning environment can be used as a platform to host virtual journal clubs and case-based discussions. This has many advantages in the current climate of constrained time and diminishing trainee and consultant participation in such activities. The virtual environment model opens up participation and improves access to journal clubs and case-based discussions, provides reusable educational content, establishes an electronic record of participation for individuals, makes use of multimedia material (including clinical imaging and photographs) for discussion, and finally, allows participants to link case-based discussions with relevant papers in the journal club. The Leicester experience highlights the many advantages and some of the potential difficulties in setting up such a virtual system and provides useful guidance for those considering such a system in their own training programme. As a result of the virtual learning environment, trainee participation has increased and there is a trend for increased consultant input in the virtual journal club and case-based discussions. It is likely that the use of virtual environments will expand to encompass newer technological approaches to personal learning and professional development

An increasing number of patients are treated by autologous chondrocyte implantation (ACI). This study tests the hypothesis that culture within a defined chondrogenic medium containing TGF-β enhances the reexpression of a chondrocytic phenotype and the subsequent production of cartilaginous extracellular matrix by human chondrocytes used in ACI. Chondrocytes surplus to clinical requirements for ACI from 24 patients were pelleted and cultured in either DMEM (Dulbecco’s modified eagles medium)/ITS+Premix/TGF-β1 or DMEM/10%FCS (fetal calf serum) and were subsequently analysed biochemically and morphologically. Pellets cultured in DMEM/ITS+/TGF-β1 stained positively for type-II collagen, while those maintained in DMEM/10%FCS expressed type-I collagen. The pellets cultured in DMEM/ITS+/TGF-β1 were larger and contained significantly greater amounts of DNA and glycosaminoglycans. This study suggests that the use of a defined medium containing TGF-β is necessary to induce the re-expression of a differentiated chondrocytic phenotype and the subsequent stimulation of glycosaminoglycan and type-II collagen production by human monolayer expanded chondrocytes

Aims

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.