Aims. Patients receiving cemented hemiarthroplasties after hip fracture have a significant risk of deep surgical site infection (SSI). Standard UK practice to minimize the risk of SSI includes the use of antibiotic-loaded bone cement with no consensus regarding type, dose, or antibiotic content of the cement. This is the protocol for a randomized clinical trial to investigate the clinical and cost-effectiveness of high dose dual antibiotic-loaded cement in comparison to low dose single antibiotic-loaded cement in patients 60 years and over receiving a cemented hemiarthroplasty for an intracapsular hip fracture. Methods. The WHiTE 8 Copal Or Palacos Antibiotic Loaded bone cement trial (WHiTE 8 COPAL) is a multicentre, multi-surgeon, parallel, two-arm, randomized clinical trial. The pragmatic study will be embedded in the World Hip Trauma Evaluation (WHiTE) (ISRCTN 63982700). Participants, including those that lack capacity, will be allocated on a 1:1 basis stratified by recruitment centre to either a low dose single antibiotic-loaded bone cement or a high dose dual antibiotic-loaded bone cement. The primary analysis will compare the differences in deep SSI rate as defined by the Centers for Disease Control and Prevention within 90 days of surgery via medical record review and patient self-reported questionnaires. Secondary outcomes include UK Core Outcome Set for hip fractures, complications, rate of antibiotic prescription, resistance patterns of deep SSI, and resource use (more specifically, cost-effectiveness) up to four months post-randomization. A minimum of 4,920 patients will be recruited to obtain 90% power to detect an absolute difference of 1.5% in the rate of deep SSI at 90 days for the expected 3% deep SSI rate in the control group. Conclusion. The results of this trial will provide evidence regarding clinical and cost-effectiveness between low dose single and high dose dual antibiotic-loaded bone cement, which will inform policy and practice guidelines such as the National Institute for Health and Care Excellence guidance on management of hip fractures. Cite this article: Bone Jt Open 2021;2(2):72–78

Two-stage exchange revision is the gold standard in treating an infected total hip arthroplasty. The new emerging gold standard appears to be using an antibiotic impregnated spacer made from polymethylmeta-crylate (PMMA) bone cement between two stages. However, a consensus has not been reached on the antibiotic to use in the cement and its dose. Vancomycin an aminoglycoside is widely used for this purpose in the PMMA cement in doses such as 3 to 9 gr per 40 gr polymer powder. The purpose of this study was to see if Vancomycin is as effective in safer low doses of 1 gr per 40 gr polymer powder.Between 1997 and 2002, twenty-six patients were treated for an infected hip arthroplasty with a two-stage exchange arthroplasty using a Vancomycin impregnated polymethylmetacrylate (PMMA) bone cement spacer. During the first stage all prosthetic material was removed and after debridement, irrigation an articulating spacer was made from PMMA cement (Surgical Simplex, Howmedica, Rutherford, NJ, USA). One gram of Vancomycin HCl (Vancomycin, Eli Lilly, USA) powder was added to each 40 gr polymer powder prior to curing the cement. After the first stage parenteral antibiotics were administered for six weeks. When erythrocyte sedimentation rate and the CRP returned to a normal level, the patient underwent the second stage were a cementless prosthesis was inserted. Intra-operative cultures and frozen sections obtained during the second stage were negative in all patients indicating successful treatment of the infection. Mean follow up after the second stage was 36 (range 24 to 74) months. Two patients had a reinfection after four months. These two patients were infected with gram-negative micro-organisms. This gave us a 92 percent infection eradication rate at 3 years. None of the patients suffered from Vancomycin related side effects.In this study we used a lower dose (1 gr per 40 gr polymer powder) of Vancomycin in the PMMA spacer instead of the commonly used 3 to 9 gr per 40 gr polymer powder. The reason for this was our concerns for nephrotoxicity and allergic reactions frequently associated with use of Vancomycin. Antibiotics are used in cement spacers as a disinfecting agent and sterilizer of dead spaces. As Vancomycin is highly effective when used in PMMA due to its elution dynamics and thermostability we believed it would be effective even in low doses. In all patients the infection appeared to be cured after the first stage. This was demonstrated with negative intraoperative cultures and frozen sections. However, we had two reinfections in patients that initially were infected with gram-negative organism, which Vancomycin is not as effective. Despite this we were able to sterilize the infected hip with a low dose approach in the first stage. Vancomycin is effective in low dose when used in PMMA cement spacers for infected total hip arthroplasties. This approach will decrease potential serious side effects of Vancomycin

Bone tissue engineering constructs (BTEC) combining natural resorbable osteoconductive scaffolds and mesenchymal stem cells (MSCs) have given promising results to repair critical size bone defect. Yet, results remain inconsistent. Adjonction of an osteoinductive factor to these BTEC, such as rh-BMP-2, to improve bone healing, seems to be a relevant strategy. However, currently supraphysiological dose of this protein are used and can lead to adverse effects such as inflammation, ectopic bone and/or bone cyst formation. Interestingly, in a preliminary study conducted in ectopic site in a murine model, a synergistic effect on bone formation was observed only when a low dose of rh-BMP-2 was associated with MSCs-seeded coral scaffolds but not with a high dose. The objective of the study was then to evaluate a BTEC combining coral scaffold, MSCs and a low dose of rh-BMP-2 in a large animal model of clinical relevance. Sixteen sheep were used for this study. MSCs were isolated from an aspirate of bone marrow harvested from the iliac crest of each sheep receiving BTEC with MSCs, cultivated and seeded on Acroporacoral scaffolds one week before implantation. Rh-BMP-2, used at two different doses (low dose: 68μg/defect and high dose: 680μg/defect), was diluted and absorbed on Acroporacoral scaffold one day before implantation. Metatarsal segmental bone defects (25 mm) were made in the left metatarsal bone of the sheep, stabilized by plate fixation, and filled with Acroporacoral scaffolds loaded with either (i) MSCs and a low dose of rh-BMP-2 (Group 1;n=6), (ii) a low dose of rh-BMP-2 (Group 2;n=5), (iii) a high dose of rh-BMP-2 (Group 3;n=5). Standard radiographs were taken after each surgery and each month until sheep sacrifice, 4 months postoperatively. Bone healing and scaffold resorption were assessed by micro-computed-tomography (μCT) and histomorphometry. Results were compared to a historical control group in which coral scaffolds were loaded with MSCs. Bone volumes (BV) evaluated by μCT and bone surfaces (BS) evaluated by histomorphometry did not differ between groups (BV: 1914±870, 1737±841, 1894±1028 and 1835±1342 mm. 3. ; BS: 25,41±14,25, 19,85±8,31, 25,54±16,98 and 26,08±22,52 %; groups 1, 2, 3 and control respectively); however, an higher bone union was observed in group 1 compared to the others (3, 1, 2 and 2 sheep with bone union in groups 1, 2, 3 and control respectively). No histological abnormalities were observed in any group. Coral resorption was almost complete in all specimens. No significant difference in coral volumes and coral surfaces was observed between groups. A trend towards a higher variability in coral resorption was noted in group 1 compared to the others. There seems to be a benefit to associate low dose of rh-BMP-2 with MSCs-seeded coral scaffolds as this strategy allowed an increase of bone unions in our model. Yet, results remain inconsistent. Although, defective coupling between scaffold resorption and bone formation impaired bone healing in some animals, adjunction of rh-BMP-2 (even at low dose) to CSMs loaded construct is a promising strategy for bone tissue engineering

Introduction: We believe the information given by a new 2D/3D low dose radiation system is useful to the spinal surgeon. Method: This commercially developed system was evaluated over the past three years. We evaluated 150 patients, with normal controls, using two prototypes. We compared it with a CT scan for accuracy in 2D and 3D reconstruction and for radiation doses. Results: We found various advantages of this system over CT scanning:. Reductions in radiation exposure of x8 to x10 fold in 2D, and x800 to x1000 in 3D. It gives data from standing imaging compared with supine in a CT scanner. It allows imaging of the skeleton from head to foot, which in CT imaging demands excessive radiation. It allows surface reconstruction from head to foot. It can be used with a force plate to indicate gravity forces. It, uniquely, can give a view of the skeleton from the top. It can measure thoracic cage volume. It can assess the effects of bracing. When combined with other non-invasive methods of measurement, can help to define operative procedures. Overall it provides a new approach to assessing spinal deformity both in the horizontal plane and in volumetric measurement. Conclusion: his innovative method is clearly a help for both patients and surgeons

Introduction. For preoperative planning of Total Hip Arthroplasty (THA) it is paramount to choose the correct implant size to avoid subsidence with too small a component or fracture with too large a component. This planning can be done either in 2D or 3D. 2D templating from X-rays frontal images remains the gold standard technique in THA preoperative planning despite the lower accuracy with uncemented components. 3D planning techniques require a CT-Scan examination overexposing patients to radiation. Biplanar EOS. ®. radiographs are an alternative to obtain bone 3D reconstructions with a very low dose of radiation. The objective of this study was to evaluate the accuracy and reproducibility a novel 3D technique for THA preoperative planning based on biplanar low-dose radiographs. Materials and methods. 31 patients (20 women, 11 men, average age 66.1 y/o) who underwent a primary THA (Hardinge anterolateral approach) were included. Two senior orthopedic surgeons (Op_1 and Op_2) performed the pre-operative planning: (1) In 2D superimposing templates of the cup and the stem on CR radiographs. The CR images had a magnification coefficient of 1.15. (2) In 3D using dedicated hipEOS (EOS Imaging, France) software. 2D planning was performed once by each operator, 3D planning twice. 3D planning with hipEOS [Figure 1] was performed by importing 3D models of the stem and cup and superimposing them on frontal-lateral EOS. ®. radiographs. This software proposes an initial estimate of the components size and position. If necessary, the user can correct the size of the stem and perform translations and rotations of the 3D models in order to correct the position, while clinical parameters such as the cup anteversion and inclination, as well as the femoral offset and leg length are automatically recalculated. To evaluate the accuracy, we have compared the 2D and 3D planning with respect to the actual size implanted during the surgery. To evaluate reproducibility we have calculated the Intra-class Correlation Coefficient (ICC) of both techniques. Results. In 2D, the stem size was planned in 69% of cases within ± 1 size with respect to the actual size, compared to 83% in 3D [Table 1]. The ICC [table 2] for stem planning was 0.91 in 2D, and 0.88 in 3D. In 2D, the cup size was planned in 87% of cases within ± 1 size, compared to 92% in 3D. The ICC for cup planning was 0.71 in 2D, and 0.84 in 3D. Discussion. The 3D planning technique proposed is accurate and reproducible. 3D planning based on biplanar EOS. ®. radiographs can become an alternative to 2D techniques which require calibration devices. The method proposed is a novel concept of 3D THA planning with a very low radiation dose, if compared to CR and CT [Delin, Eur J Radiol 2013; Deschênes, Spine 2010]. Conclusion. The 3D preoperative planning of THA based on EOS. ®. biplanar radiographs proved to be accurate and reproducible if compared to the ‘gold standard’ technique. A prospective study to evaluate clinically relevant parameters of THA surgeries such as the leg length and the femoral offset with hipEOS is in progress

Two-staged exchange arthroplasty with an antibiotic-impregnated PMMA cement spacer in-between two stages has a success rate of 85% to 95% in eradication of infection. Use of vancomycine in high doses has a high potential for complications due to nephrotoxicity. The aim of this study was to evaluate the results of two-staged exchange arthroplasty in infected hip arthroplasty using low-dose vancomycine-impregnated PMMA cement as an interim spacer between stages. Thirty-five (20 females, 15 males, average age: 60) patients with a confirmed infected total hip arthroplasty who were treated between 1999 and 2005 were the subjects of the study. In the first stage after removal of the prosthesis and debridement, a spacer made of 40 grams of PMMA cement impregnated with 1 gr vancomycine was placed in the infected joint space. Postoperatively, patients were treated with 6 weeks of intravenous antibiotics in consultation with an infectious disease consultant. When CRP and ESR returned to normal levels, revision surgery with cementless components was performed. The average follow-up after the second stage was 4 years. The ESR and CRP decreased significantly before the second stage with this treatment protocol (from 81.28 to 17.54 mm/h p< 0.001 and 10.05 to 0.64 mg/dl respectively, p< 0.001). The mean interval between the two stages was 193.3 days. A second debridement was needed in 4 patients (10.8 %) because they did not respond to treatment. Two patients (5.4 %) had recurrent infections after reimplantation and underwent a resection arthroplasty. None of the patients suffered from antibiotic toxicity. Two-stage exchange arthroplasty using a low dose vancomycine-impregnated cement spacer was an effective method in treating infected hip replacements. With using a lower dose than previously reported, we were able to avoid antibiotic toxicity while effectively treating our patients with the same success rate

As patients live longer following treatment for soft tissue sarcomas, complications from treatment will continue to emerge. Predicting which patients are at risk allows for improved preoperative planning, treatment, and surveillance. The data presented here suggests that females greater than fifty-five years of age treated with high dose, postoperative radiotherapy in combination with limb salvage surgery for soft tissue sarcomas are at an increased risk of post irradiation fractures. Unlike previous reports, a significantly higher rate of fracture occurred in patients who received higher doses (60 or 66Gy) of radiation versus lower doses (50 Gy). This retrospective study was performed to determine if the timing and dosage of radiotherapy are related to the risk of post radiation pathologic fracture following combined therapy for lower extremity soft tissue sarcomas. Three hundred sixty-four patients with sarcomas treated with external beam radiation therapy and limb salvage surgery were evaluated. High dose radiation was defined as 60 Gy or 66 Gy; low dose as 50Gy. Radiation timing schedules were preoperative, postoperative, or preoperative with a postoperative boost. Univariate and multivariate analysis was used to determine which factors were associated with fracture risk. Twenty- seven pathologic fractures occurred in twenty-three patients. Twenty- four fractures occurred in twenty patients who were treated with high dose radiation. Sixteen of these patients had postoperative radiation (fourteen patients received 66Gy, two received 60Gy), and four had pre-operative radiation with a postoperative boost (total dose = 66Gy). Three fractures occurred in three patients who received low dose preoperative radiation (50Gy). Both high dose radiation (versus low dose) (p=.001) and preoperative radiation (versus postoperative) (p =0.002) were associated with a risk of fracture. Findings in this study were consistent with previous reports in that females over fifty-five years of age who undergo removal of a thigh sarcoma combined with radiation therapy are at a higher risk of a pathologic fracture, and differs in that there was a significantly higher rate of fracture in patients who received higher doses (60 or 66Gy) of radiation versus lower doses (50 Gy), and when radiation therapy was given postoperatively versus preoperatively

Introduction. The gold standard for knee surgery is the restoration of the so-called «neutral mechanical alignment ». Recent literature as pointed out the patients with «constitutional varus »; in these cases, restoring neutral alignment could be abnormal and even undesirable. The same situation can be observed in patients with «constitutional valgus alignment ». To date, these outliers cases have only been explored focusing on the lower limb; the influence of the pelvic morphotype has not been studied. Intuitively, the pelvic width could be a significant factor. The EOS low dose imaging technique provides full body standing X-rays to evaluate the global anatomy of the patient. This work explores the influence of the pelvic parameters on the frontal knee alignment. Material and methods. – We included 170 patients (340 lower extremities). 2 operators performed measurements once per patient on AP X-rays. The classical anatomical parameters were:. –. Femoral mechanical angle (FMA). –. Tibial mechanical angle (TMA). –. Hip knee shaft angle (HKS). –. Hip knee ankle angle (HKA). –. Femoral and tibial lengths. The morphotype was evaluated by:. –. the distances between the center of two femoral heads (FHD), between knees (KD) and between ankles (AD). –. the medial neck-shaft angle (MNSA). –. the femoral offset. The horizontal distance between the limb mechanical axis (line passing from center of the femoral head to the center of the ankle) and the center of the knee was called the intrinsic mechanical axis deviation (IMAD) (fig 1). The horizontal distance between the pelvic mechanical axis (line from the center of the sacral plate to the center of the ankle) and the center of the knee was called the global mechanical axis deviation (GMAD) (fig 2). Inter-Operator Reliability was calculated with Intra-class Correlation Coefficient (ICC) and Inter-Reader Agreement was assessed with Bland-Altman test. A relationship between IMAD and GMAD to the other parameters was assessed using Pearson's correlation coefficient. Results. Inter-Operator Reliability was high for femoral offset, TMA and MSNA (ICC > 0,88) and very high for the other parameters (ICC > 0,93). These values are given in table 1 and all the 2D parameters are given in the table 2. IMAD was significantly correlated with HKA (r = 0,99), FMA (r = −0,58), TMA (r = −0,61) and KD (r = 0,72). GMAD was significantly correlated with HKA (r = 0,94), FMA (r = −0,53), TMA (r = −0,60) and KD (r = 0,67). Two groups were identified according to pelvic width (FHD):. Group 1 (standard patients): Pelvic width < 18 cm (164 lower extremities). Group 2 (wide pelvis): Pelvic width ≥ 18 cm (176 lower extremities). For standard patients the FHD is a significant parameter, whereas the proximal femoral anatomy (offset and MNSA) are more relevant for wide pelvis. Conclusion. Accurate analysis of the morphotype of the lower limbs is essential for planning femoral or tibial osteotomy and knee prostheses. Taking into account pelvic morphotype can provide additional informations for the axes restoration and the detection of outliers patients

Accurately planning the intervention and precisely measuring outcome in computer assisted orthopaedic surgery (CAOS) is essential for it permits robust analysis of the efficacy of these systems. We demonstrate the use of low dose computer tomography (CT) radiation for both the planning and outcome measurement of robotic and conventionally performed knee arthroplasty. Studies were initially performed on a human phantom pelvis and lower limb. The mAs (milliampere seconds) were varied from 120 to 75 at the pelvis and from 100 to 45 for both the knee and ankle whilst keeping the kV (kilovolt) between 120 and 140. Image quality was evaluated at the different doses. The volumes scanned were defined on the scout film; they included the whole femoral head (0.5cm above and below the head), 20cm at the knee (10cm on either side of the joint line) and 5cm at the ankle (the distal tibia and the talus). Effective dose (mSv) was calculated using two commercially available software packages. This protocol was subsequently used to image patients in our prospective double-blind randomised controlled study of our active constraint robotic system ACRO-BOT. With the reduction in the mA and scanned volume the effective dose was reduced to 0.761 mSv in females and 0.497 mSv in males whilst maintaining a sufficient image resolution for our purposes. We found that a mAs of 80 for the hip joint, 100 for the knee and 45 for the ankle was sufficient for imaging in both pre-op planning and pos-operative assessment in knee arthroplasty. This contributed on an average effective dose to the hip of 0.61 mSv, the knee 0.120 mSv and to the ankle 0.0046 mSv. The results of our study show that we have considerably reduced the effective dose (0.8 mSv) to one third of the Perth Protocol (2.5mSv) by reducing the areas of the body scanned and adjusting the mA for the various parts of the body whist maintaining the x, y and z axis throughout the scan. The areas between the knee, hip and ankle that were not exposed to radiation are not strictly necessary for the planning of knee arthroplasty, but it is essential that the leg does not move during the scanning process. In order to prevent this leg was placed in a radiolucent splint. For post op three dimensional (3D) assessments only the knee component of the protocol is necessary

Whilst computer assistance enables more accurate arthroplasty to be performed, demonstrating this is difficult. The superior results of CAOS systems have not been widely appreciated because accurate determination of the position of the implants is impossible with conventional radiographs for they give very little information outside their plane of view. We report on the use of low dose (approximately a quarter of a conventional pelvic scan), low cost CT to robustly measure and demonstrate the efficacy of computer assisted hip resurfacing. In this study we demonstrate 3 methods of using 3D CT to measure the difference between the planned and achieved positions in both conventional and navigated hip resurfacing. The initial part of this study was performed by imaging a standard radiological, tissue equivalent phantom pelvis. The 3D surface models extracted from the CT scan were co-registered with a further scan of the same phantom. Subsequently both the femoral and acetabular components were scanned encased in a large block of ice to simulate the equivalent Hounsfield value of human tissue. The CT images of the metal components were then co-registered with their digital images provided by the implant manufactures. The accuracy of the co-registration algorithm developed here was shown to be within 0.5mm. This technique was subsequently used to evaluate the accuracy of component placement in our patients who were all pre-operatively CT scanned. Their surgery was digitally planned by first defining the anterior pelvic plane (APP), which is then used as the frame of reference to accurately position and size the wire frame models of the implant. This plan greatly aids the surgeon in both groups and in the computer assisted arm the Acrobot Wayfinder uses this pre-operative plan to guide the surgeon. Following surgery all patients, in both groups were further CT scanned to evaluate the achieved accuracy. This post-operative CT scan is co-registered to the pre-operative CT based plan. The difference between the planned and achieved implant positions is accurately computed in all three planes, giving 3 angular and 3 translational numerical values for each component. Further analysis of the CT generated results is used to measure the implant intersection volume between the pre-operatively planned and achieved positions. This gives a single numerical value of placement error for each component. These 3D CT datasets have also been used to quantify the volume of bone resected in both groups of patients comparing the simulated resection of the planned position of the implant to that measured on the post-operative CT. This study uses 3D CT as a surrogate outcome measure to demonstrate the efficacy of CAOS systems

Introduction

Venous thromboembolism (VTE), defined as either pulmonary embolism (PE) or deep venous thrombosis (DVT), is a rare, but serious complication following total hip arthroplasty (THA). Current VTE guidelines recommend pharmacologic agents with or without intermittent pneumatic compression devices (IPCDs). At our institution, both 81mg aspirin (ASA) twice a day (BID) and portable IPCDs were prescribed to THA patients at standard risk for VTE. The aim of this study is to determine if discontinuing the use of portable outpatient IPCDs is safe and does not increase the rate of VTE in patients undergoing THA.

The Pulmonary Embolism Prevention (PEP) Trial was designed to assess the effects of a 35 day course of aspirin (160 mg daily) on the risks of thromboembolic events, other cardiovascular outcomes and bleeding among individuals undergoing surgery for hip fracture or joint replacement. From 1992 to 1998, 148 hospitals in Australia, New Zealand, South Africa, Sweden and the United Kingdom randomised 13,356 hip fracture patients, and 22 hospitals in New Zealand randomised 4,088 elective arthroplasty patients. Among hip fracture patients, aspirin produced proportional reductions in PE of 43% (95% confidence interval [CI] 18% to 60%; 2P=0.002) and symptomatic DVT of 29% (95% CI 3% to 48%; 2P=0.03). PE or DVT was confirmed in 105 (1.6%) of 6679 patients allocated aspirin versus 165 (2.5%) of 6677 allocated placebo, representing an absolute reduction of 9±2 per 1000 and a proportional reduction of 36% (95% CI 19% to 50%; 2P=0.0003). Aspirin prevented 4±1 fatal pulmonary emboli per 1000 treated (18 aspirin vs 43 placebo deaths), representing a proportional reduction of 58% (95% CI 27% to 76%; 2P=0.002), with no apparent effect on deaths from other vascular (hazard ratio 1.04; 95% CI 0.86 to 1.26) or non-vascular cause (1.01; 95% CI 0.84 to 1.23). Deaths due to bleeding were rare (13 aspirin vs 15 placebo), but there was an excess of 6±3 post-operative transfused bleeds per 1000 allocated aspirin (2P=0.04). Among elective arthroplasty patients, venous thromboembolism rates were lower but the proportional effects of aspirin appeared similar to those among hip fracture patients.

We present the 12 month data on the relatively novel drug Dabigatran Etexilate (Pradaxa), a new oral anticoagulant which was introduced to combat the risk of post operative venous-thromboembolic disease (VTED) in orthopaedic surgery. This drug was introduced at our hospital in March 2010 and we present our modified protocol of: using 5000u subcutaneous Dalteparin whilst in hospital and giving Dabigatran only on discharge, and at a lower dose (150mg compared to 220mg).

We carried out a retrospective analysis of the notes and imaging of every patient who underwent elective hip and knee arthroplasty over 12 months since the drug was introduced. We evaluated the rate of VTED complications and the rate of transfusion and bleeding post operatively.

The case series of 370 patients showed a 1% risk of deep vein thrombosis with no pulmonary emboli and 1 death due to an unrelated cause. There was a transfusion rate of 11% with 0.5% patients taken back to theatre for evacuation of haematomas. There were no reported adverse effects of Dabigatran.

We argue that our modified protocol for this novel drug should be followed as it is both safe and effective for postoperative anticoagulation.

We have evaluated the effect of the short-term administration of low therapeutic doses of modern COX-2 inhibitors on the healing of fractures. A total of 40 adult male New Zealand rabbits were divided into five groups. A mid-diaphyseal osteotomy of the right ulna was performed and either normal saline, prednisolone, indometacin, meloxicam or rofecoxib was administered for five days. Radiological, biomechanical and histomorphometric evaluation was performed at six weeks. In the group in which the highly selective anti-COX-2 agent, rofecoxib, was used the incidence of radiologically-incomplete union was similar to that in the control group. All the biomechanical parameters were statistically significantly lower in both the prednisolone and indometacin (p = 0.01) and in the meloxicam (p = 0.04) groups compared with the control group. Only the fracture load values were found to be statistically significantly lower (p = 0.05) in the rofecoxib group. Histomorphometric parameters were adversely affected in all groups with the specimens of the rofecoxib group showing the least negative effect. Our findings indicated that the short-term administration of low therapeutic doses of a highly selective COX-2 inhibitor had a minor negative effect on bone healing

Aims

To evaluate whether an ultra-low-dose CT protocol can diagnose selected limb fractures as well as conventional CT (C-CT).

Our previous rat study demonstrated an ex vivo-created “Biomimetic Hematoma” (BH) that mimics the intrinsic structural properties of normal fracture hematoma, consistently and efficiently enhanced the healing of large bone defects at extremely low doses of rhBMP-2 (0.33 μg). The aim of this study was to determine if an extremely low dose of rhBMP-2 delivered within BH can efficiently heal large bone defects in goats. Goat 2.5 cm tibial defects were stabilized with circular fixators, and divided into groups (n=2-3): 2.1 mg rhBMP-2 delivered on an absorbable collagen sponge (ACS); 52.5 μg rhBMP-2 delivered within BH; and an empty group. BH was created using autologous blood with a mixture of calcium and thrombin at specific concentrations. Healing was monitored with X-rays. After 8 weeks, femurs were assessed using microCT. Using 2.1 mg on ACS was sufficient to heal 2.5 cm bone defects. Empty defects resulted in a nonunion after 8 weeks. Radiographic evaluation showed earlier and more robust callus formation with 97.5 % (52.5 μg) less of rhBMP-2 delivered within the BH, and all tibias were fully bridged at 3 weeks. The bone mineral density was significantly higher in defects treated with BH than with ACS. Defects in the BH group had smaller amounts of intramedullary and cortical trabeculation compared to the ACS group, indicating advanced remodeling. The results confirm that the delivery of rhBMP-2 within the BH was much more efficient than on an ACS. Not only did the large bone defects heal consistently with a 40x lower dose of rhBMP-2, but the quality of the defect regeneration was also superior in the BH group. These findings should significantly influence how rhBMP-2 is delivered clinically to maximize the regenerative capacity of bone healing while minimizing the dose required, thereby reducing the risk of adverse effects

Aims. Acridine orange (AO) demonstrates several biological activities. When exposed to low doses of X-ray radiation, AO increases the production of reactive radicals (radiodynamic therapy (AO-RDT)). We elucidated the efficacy of AO-RDT in breast and prostate cancer cell lines, which are likely to develop bone metastases. Methods. We used the mouse osteosarcoma cell line LM8, the human breast cancer cell line MDA-MB-231, and the human prostate cancer cell line PC-3. Cultured cells were exposed to AO and radiation at various concentrations followed by various doses of irradiation. The cell viability was then measured. In vivo, each cell was inoculated subcutaneously into the backs of mice. In the AO-RDT group, AO (1.0 μg) was locally administered subcutaneously around the tumour followed by 5 Gy of irradiation. In the radiation group, 5 Gy of irradiation alone was administered after macroscopic tumour formation. The mice were killed on the 14th day after treatment. The change in tumour volume by AO-RDT was primarily evaluated. Results. The viability of LM8, MDA-MB-231, and PC-3 cells strongly decreased at AO concentration of 1.0 μg/ml and a radiation dose of 5 Gy. In xenograft mouse model, the AO-RDT also showed a strong cytocidal effect on tumour at the backside in osteosarcoma, breast cancer, and prostate cancer. AO-RDT treatment was more effective for tumour control than radiotherapy in breast cancer. Conclusion. AO-RDT was effective in preventing the proliferation of osteosarcoma, breast cancer, and prostate cancer cell lines in vitro. The reduction in tumour volume by AO-RDT was also confirmed in vivo. Cite this article: Bone Joint Res 2022;11(10):715–722

Radiological investigations are essential in the work-up of patients presenting with non-arthritic hip pain, to allow close review of the complex anatomy around the hip and proximal femur. The aim of this study is to quantify the radiation exposure associated with common radiological investigations performed in assessing young adult patients presenting with non-arthritic hip pain. A retrospective review of our UK tertiary hip preservation centre institutional imaging database was performed. Data was obtained for antero-posterior, cross-table lateral and frog-lateral radiographs, along with data for the low dose CT hip protocol and the Mako CT Hip protocol. The radiation dose of each imaging technique was measured in terms of dose-area product (DAP) with units of mGycm2, and the effective doses (ED, mSv) calculated. The mean effective radiation dose for hip radiographs was in the range 0.03 to 0.83mSv (mean DLP 126.7–156.2 mGycm2). The mean effective dose associated with the low-dose CT hip protocol was 3.04mSv (416.8 mGycm2) and for the Stryker Mako CT Hip protocol was 8.4mSv (1061 mGycm2). The radiation dose associated with use of CT imaging was significantly greater than plain radiographs (p<0.005). Investigation of non-arthritic hip pain can lead to significant ionising radiation exposure for patients. In our institution, the routine protocol is to obtain an anteroposterior radiograph and then a specific hip sequence 3 Tesla MRI including anteversion views. This provides the necessary information in the majority of cases, with CT scanning reserved for more complex cases where we feel there is a specific indication. We would encourage the hip preservation community to carefully consider and review the use of ionising radiation investigations

Background. Bone Morphogenetic Protein (BMP) has been used in clinical practice to stimulate fracture healing and spinal arthrodesis. Difficulty in localising and maintaining BMP at the target site has resulted in the use of large doses of BMP, and has been associated with significant adverse effects. We have previously shown clay hydrogels can bind growth factors for localised efficacy. We hypothesised that localisation of BMP within clay gels would reduce the dose required to mediate bone formation. Methods. 2×10-4mg and 1×10-5 mg BMP were mixed in Laponite and applied to collagen sponge. 3 sponges containing high dose, and 3 containing low dose BMP were implanted subcutaneously in a mouse. This process was repeated in 8 mice, for controls, alginate hydrogel was used in a further 8 mice, and 1 mouse received 6 blank collagen scaffolds. Micro Computed Tomography was used to assess bone formation fortnightly; at 8 weeks the mice were culled and underwent histological analysis. Results. Mean Bone Volume formed within collagen per μg BMP was significantly greater with Laponite and low dose BMP compared to Alginate and Laponite with high dose BMP (p<0.0001). No bone formation was observed with Alginate and low dose BMP. Conclusions. We have demonstrated that Laponite is able to reduce, by several orders, the effective dose of BMP required to mediate ectopic bone formation compared to current gold standard methods of BMP delivery. Clinical translation of this finding offers, potentially, great significance to orthopaedic surgery. Level of Evidence. In vivo study. Approval. Our study received ethical approval complied with Home Office licensing. Acknowledgments. Funded by grants from EU(FP7) Biodesign, Rosetrees Trust, BBSRC and EPSRC

Objectives. This study was conducted to evaluate the cytokine-release kinetics of platelet-rich plasma (PRP) according to different activation protocols. Methods. Two manual preparation procedures (single-spin (SS) at 900 g for five minutes; double-spin (DS) at 900 g for five minutes and then 1500 g for 15 minutes) were performed for each of 14 healthy subjects. Both preparations were tested for platelet activation by one of three activation protocols: no activation, activation with calcium (Ca) only, or calcium with a low dose (50 IU per 1 ml PRP) of thrombin. Each preparation was divided into four aliquots and incubated for one hour, 24 hours, 72 hours, and seven days. The cytokine-release kinetics were evaluated by assessing PDGF, TGF, VEGF, FGF, IL-1, and MMP-9 concentrations with bead-based sandwich immunoassay. Results. The concentration of cytokine released from PRP varied over time and was influenced by various activation protocols. Ca-only activation had a significant effect on the DS PRPs (where the VEGF, FGF, and IL-1 concentrations were sustained) while Ca/thrombin activation had effects on both SS and DS PRPs (where the PDGF and VEGF concentrations were sustained and the TGF and FGF concentrations were short). The IL-1 content showed a significant increase with Ca-only or Ca/thrombin activation while these activations did not increase the MMP-9 concentration. Conclusion. The SS and DS methods differed in their effect on cytokine release, and this effect varied among the cytokines analysed. In addition, low dose of thrombin/calcium activation increased the overall cytokine release of the PRP preparations over seven days, relative to that with a calcium-only supplement or non-activation. Cite this article: Professor J. H. Oh. Cytokine-release kinetics of platelet-rich plasma according to various activation protocols. Bone Joint Res 2016;5:37–45. doi: 10.1302/2046-3758.52.2000540