Introduction. Bone fracture toughness is an important parameter in resistance of bone to monotonic and fatigue failure. Earlier studies on bone fracture toughness were focused on either cortical or cancellous bone, separately [1, 2]. Reported fracture toughness values indicated that cortical bone is tougher to break as compared to cancellous bone. In order to understand complete fracture of a whole bone, the interface between cortical and cancellous bone (named as corticellous bone) might play a crucial role and is interesting topic of research. The goal of this study was to identify fracture toughness in terms of J integral and fracture mechanism of the corticellous bone. Material and Methods. Corticellous bone samples (single edge notch bend specimen or SENB) were prepared from bovine proximal femur according to ASTM E399-90 standard (Fig.1). For corticellous bone, samples were prepared in such way that approximately half of the sample width consist of cortical bone and another half is cancellous bone. Precaution was taken while giving notch and pre-crack to corticellous bone that pre-crack should not enter from cortical to cancellous portion. All specimens were tested using a universal testing machine (Tinius Olsen, ± 100 N) under displacement rate of 100 µm/min until well beyond yield point. The fracture toughness parameter in terms of critical stress intensity (K. IC. ) was calculated according to ASTM E399-90 as given by, . (1). K. IC. =. PS. /. BW. 1.5. *. f. (. a. /. W. ). …. Where, P = applied load in kN, S = loading span in cm, B = specimen thickness in cm, W = specimen width in cm, a = total crack length, f(a/W) = geometric function. After the fracture test the J integral of each specimen was calculated using following equation. [ASTM E1820]. . (2). J. total. =. J. el. +. J. pl. =. K. IC. 2. /. E. ′. +. 2. A. pl. /. Bb. 0. …. Where, J. el. is J integral of the elastic deformation, J. pl. is J integral of the plastic deformation, E′=E for plane stress condition and E′= E/(1−ν. 2. ) for plane strain condition (E is elastic modulus; ν is Poisson's ratio), b. o. = W−a. o. , height of the un-cracked ligament, and A. pl. is the area of the plastic deformation part in the load–displacement curve. Result and Discussion. The fracture toughness in terms of critical stress intensity (K. IC. ) of corticellous bone was found to be 2.45 MPa.m. 1/2. The plastic part of J integral, J. pl. value of corticellous specimen was 9310 Jm. −2. , and shown to be 27 times of the J. el. value, 341 Jm. −. 2. Total J integral of corticellous bone was found to be 9651 Jm. −2. When crack travels through cortical portion and reaches at the interface, crack branching occurred and further it slows down (Fig.2). Indeed, more energy is required in plastic than elastic deformation. Conclusion. J integral of corticellous bone is found to higher which is due to plastic deformation and crack branches at the interface between cortical and cancellous bone. For any figures or tables, please contact the authors directly

Aim. Pyogenic spondylodiscitis is associated with prolonged antimicrobial therapy and high relapse rates. Nevertheless, tissue pharmacokinetic studies of relevant antimicrobials in both prophylactic and therapeutic situations are still sparse. Previous approaches based on bone biopsy and discectomy exhibit important methodological limitations. The objective of this study was therefore to assess the concentration of cefuroxime in intervertebral disc (IVD), vertebral body cancellous bone, subcutaneous adipose tissue (SCT) and plasma pharmacokinetics after single dose administration by use of microdialysis (MD) in a large animal model. Method. Ten female pigs were assigned to receive 1,500 mg of cefuroxime intravenously over 15 min. Measurements of cefuroxime were obtained from plasma, SCT, the vertebral cancellous bone and the IVD for 8 hours thereafter. MD was applied for sampling in solid tissues. The cefuroxime concentration in both the MD and plasma samples was determined using ultra-high performance liquid chromatography. Results. For both the IVD and the vertebral cancellous bone, the area under the concentration-curve from zero to the last measured value was significantly lower than that of free plasma. Tissue penetration of cefuroxime was incomplete for the IVD, whereas for vertebral cancellous bone and SCT it was not. Furthermore, the penetration of cefuroxime from plasma to IVD was delayed. Additionally, a noticeable prolonged elimination rate of cefuroxime in the IVD was found. The maximal concentration and the elimination of cefuroxime were reduced in IVD compared to both SCT and vertebral cancellous bone. Due to this delay in elimination of cefuroxime, the time with concentrations above the minimal inhibitory concentration (T>MIC) was significantly higher in IVD than in SCT, vertebral cancellous bone and free plasma for MICs up to 6 μg/ml. Conclusions. MD was successfully applied for serial assessment of the concentration of cefuroxime in the IVD and the vertebral cancellous bone. Penetration of cefuroxime from plasma to IVD was found to be incomplete and delayed, but due to a prolonged elimination, the best results regarding T>MIC was found in IVD

Aim. Cefuroxime is a time-dependent antibiotic widely used as intravenous perioperative prophylaxis in spine surgery. A previous study has indicated that a single dose of cefuroxime provided insufficient spine tissue concentrations for spine procedures lasting more than 2–3 hours. Due to the fact that postoperative pyogenic spondylodiscitis is associated with prolonged antimicrobial therapy and high relapse rates, we aimed to evaluate if a twofold increase of standard dosage of 1.5g cefuroxime given as one double dose or two single doses with 4-hours intervals will lead to sufficient cefuroxime spine tissue concentrations throughout the dosing interval. Method. This is preliminary data for 8 out of 16 female pigs. Data from all 16 pigs will be included for the conference. Eight pigs were randomized into two groups: Group A received one double dose of cefuroxime (3g) as a bolus, and Group B received two single doses of cefuroxime (2×1.5g) with 4-hours intervals. Measurements were obtained from plasma, subcutaneous tissue (SCT), vertebral cancellous bone and the intervertebral disc (IVD) for 8-hours thereafter. Microdialysis was applied for sampling in solid tissues. The cefuroxime concentrations were determined using ultra-high performance liquid chromatography. Results. The time with concentrations above the minimal inhibitory concentration (T>MIC) for the clinical breakpoint MIC for Staphylococcus aureus of 4 μg/ml, was superior in all compartments when administering cefuroxime as two single doses with 4-hours intervals. For the target MIC of 4 μg/ml, the mean T>MIC in all compartments ranged between 53–73% and 85–95% for Group A and B, respectively. For both groups the area under the concentration-curve (AUC) was higher for plasma compared to the remaining compartments, and the lowest AUCs were found in the vertebral cancellous bone and the IVD. There were no differences in AUC between the two groups. Furthermore, the maximal concentrations were lower for both vertebral cancellous bone and IVD compared to both SCT and plasma. When comparing the two groups, higher maximal concentrations were found in all compartments for Group A. Tissue penetration was incomplete and delayed for all compartments and comparable between the two groups. Conclusions. Despite comparable pharmacokinetic results between the two groups, Group B exhibited superior T>MIC in all compartments for the clinical breakpoint MIC for Staphylococcus aureus of 4 μg/ml. As such administration of cefuroxime as two single doses with 4-hours intervals provided sufficient cefuroxime spine tissue concentrations for a minimum of 85% of an 8-hour dosing interval, which may be acceptable for most spine procedures

Collo MIS is a new short stem created to achieve minimal metaepiphyseal invasiveness, to respect the joint physiology, to get optimal primary stability and osteointegration. This stem needs a subcapital osteotomy to respect and preserve the physiologic anteversion of the femoral neck; the technique provide compactation of the cancellous bone of the greater trochanter using just compactors and not rasps during the femur preparation and the stem has to match the calcar curvature to get the right position. This stem has been designed with a lateral wedge to ensure a great primary stability in the femoral neck. Since November 2008 at Niguarda Hospital we have implanted 350 prosthesis in cooperation with Frankfurt Hospital. Patients age varies form 26 to 80 years old with a mean age of 61 y.o. This stem has to be implanted in patients with good bone quality to achieve the compactation of the cancellous bone. We have operated patients affected mostly by coaxrthrosis and just in few cases by dysplasia (Crowe 1); contraindications are represented by a CCD angle less than 120° and more than 140° because of the stem morphology, severe osteoporosis, dymorphism, and dysplasia (Crowe 2,3,4). We have evaluated the offset and CCD angle pre and post op that resulted mostly increased after surgery (average CCD angle +6,15°, offset + 5.95 mm). In the post-op we normally give partial weight bearing after 1 day and the full weight bearing after 20 days. The mean HSS score before surgery was of 57.5 points and after 1 year of 98 points. The complications we have found in these study were: 11 cases of dysmetrias less than 1 cm, 6 cases of neck fissuration. No infection, mobilization, neck impingemen, subsidence, radiolucency have been evaluated

Prosthetic joint infections are difficult to treat due to bacterial biofilm. Our group has developed a linezolid elution system by human cancellous bone delivering high concentrations the first 48 hours (Giannitsioti et al. 53rd ICAAC, 2013: A-1050). We tested the activity of this system to inhibit growth of one ica expressing isolate of Staphylococcus epidermidis (MRSE). At a first step, sterile mesh cylinders containing bone particles of the femoral head of healthy volunteers (MCB) were impregnated into 3mg/ml linezolid for 1, 24 and 48 hours. Then log-phase inocula of 103, 105 and 107cfu/ml were exposed to MCB at 370C for 8 days with regular readings of bacterial growth. MCB were transferred into fresh Muller-Hinton Broth (MHB) every 24h to avoid material corrosion. At a second step, to simulate the ability of the system against biofilm-coated MCB, MCB without linezolid were incubated with 103 and 105 cfu/ml for 1 and 24h. MCB were daily transferred into fresh MHB containing 100μg/ml on day 1, 15 μg/ml on day 2, 3 μg/ml on day 3 and 0.5 μg/ml on day 4. 24h linezolid impregnated MCB achieved rapid bacterial killing of the 105 cfu/ml bacterial suspension followed by re-growth (Figure, n= 5). Similar results were observed for 1h and 48h impregnation and for both tested inocula. When biofilm-coated MCB generated by 24h exposure to 105 cfu/ml were exposed to linezolid, rapid bacterial killing was achieved followed by re-growth. Linezolid local elution may inhibit biofilm-producing MRSE only when locally eluted concentrations exceed 10μg/ml

Background and aim. Implant-associated osteomyelitis is one of the most feared complications following orthopedic surgery. Although the risk is low it is crucial to achieve adequate antibiotic concentrations proximate to the implant for a sufficient amount of time to protect the implant surface and ensure tissue integration. The aim of this study was to assess steady-state piperacillin concentrations in the proximity of an orthopedic implant inserted in cancellous bone. Method. Six female pigs received an intravenous bolus infusion of 4 g/0.5 g piperacillin/tazobactam over 30 min every 6 h. Steady state was assumed achieved in the third dosing interval (12–18 h). Microdialysis catheters were placed in a cannulated screw in the proximal tibial cancellous bone, in cancellous bone next to the screw, and in cancellous bone on the contralateral tibia. Dialysates were collected from time 12 to 18 h and plasma samples were collected as reference. Results. Time above the minimal inhibitory concentration (fT>MIC) was evaluated for MIC of 8 (low target) and 16 μg/mL (high target). For the low piperacillin target (8 μg/mL), comparable mean fT>MIC across all the investigated compartments (mean range: 54–74%) was found. For the high target (16 μg/mL), fT>MIC was shorter inside the cannulated screw (mean: 16%) than in the cancellous bone next to the screw and plasma (mean range: 49–54%), and similar between the two cancellous bone compartments. Conclusions. To reach more aggressive piperacillin fT>MIC targets in relation to the implant, alternative dosing regimens such as continuous infusion may be considered

Aim. The β-lactam penicillin is often used in the treatment of soft tissue infections and osteomyelitis caused by penicillin susceptible Staphylococcus aureus. Oral antibiotic treatment has been shown to be non-inferior to intravenous (IV) therapy when used during the first 6 weeks in complex orthopedic infections (OVIVA trial). However, the use of oral β-lactams in osteomyelitis treatment remains a topic of debate due to low and variable bioavailability. The aim was to assess the time for which the unbound penicillin concentration exceeded targeted minimum inhibitory concentrations (fT>MIC) in cancellous bone and subcutaneous tissue after IV (penicillin G) and oral (penicillin V) treatment in a porcine microdialysis model. Method. 12 female pigs (75kg) were assigned to standard clinical regimens of either three doses of IV penicillin G (1.2g) or oral penicillin V (0.8g) every 6h over 18h. Microdialysis catheters were placed for sampling in tibial cancellous bone and adjacent subcutaneous tissue. Data was collected in the first dosing interval (0–6h; prophylactic situation) and the third dosing interval (12–18h; assumed steady state). Plasma samples were collected for reference. MIC targets of 0.125μg/mL (Staph. aureus breakpoint), 0.25μg/mL (Strep. Group A, B, C and G breakpoint) and 0.5μg/mL (4xMIC) were applied. Results. For all investigated MIC targets, IV penicillin G resulted in a longer mean fT>MIC in cancellous bone during the first dosing interval, and in both cancellous bone and subcutaneous tissue during the third dosing interval compared to oral penicillin V. Across compartments, mean fT>MIC for IV penicillin G (MIC: 0.125, 0.25 and 0.5μg/mL) were ≥97%, ≥84% and ≥75% during the first dosing interval, and 100%, ≥95% and ≥88%, during the third dosing interval. The mean fT>MIC for oral penicillin V were ≥40%, ≥24% and ≥7% during the first dosing interval, and ≥42%, ≥36% and ≥18% during the third dosing interval. Conclusions. The findings suggest that standard clinical dosing of IV penicillin G provides superior fT>MIC in cancellous bone and subcutaneous tissue compared to oral penicillin V, particularly in the third dosing interval. This emphasizes the importance of appropriate route of administration when applying penicillin treatment. Acknowledgements. Funding was received from The Kirsten and Freddy Johansen Foundation, The Novo Nordisk Foundation, The Beckett Foundation, The Hede Nielsen Family Foundation, King Christian the 10. th. Foundation, The A.P. Møller Foundation, The Dagmar Marshalls Foundation, and The Carl and Ellen Hertz Foundation

Background. Systemically administered vancomycin may provide insufficient target-site concentrations. Intraosseous vancomycin administration has the potential to overcome this concern by providing high target-site concentrations. Aim. To evaluate the local bone and tissue concentrations following tibial intraosseous vancomycin administration in a porcine model. Method. Eight female pigs were assigned to receive 500 mg diluted vancomycin (50 mg/mL) through an intraosseous cannula into the proximal tibial cancellous bone. Microdialysis was applied for sampling of vancomycin concentrations in tibial cancellous bone adjacent to the intraosseous cannula, in cortical bone, in the intramedullary canal of the diaphysis, in the synovial fluid of the knee joint, and in the subcutaneous tissue. Plasma samples were obtained. Samples were collected for 12 hours. Results. High vancomycin concentrations were found in the tibial cancellous bone with a mean peak drug concentration of 1,236 (range 28–5,295) µg/mL, which remained high throughout the sampling period with a mean end concentration of 278 (range 2.7–1,362.7) µg/mL after 690 min. The mean (standard derivation (SD)) peak drug concentration in plasma was 19 (2) µg/mL, which was obtained immediately after administration. For the intramedullary canal, in the synovial fluid of the knee joint, and subcutaneous tissue, comparable mean peak drug concentration and mean time to peak drug concentration were found in the range of 7.5–8.2 µg/mL and 45–70 min, respectively. Conclusions. Tibial intraosseous administration of vancomycin provided high mean concentrations in tibial cancellous bone throughout a 12-hour period, but with an immediate and high systemic absorption. The concentrations in cancellous bone had an unpredictable and wide range of peak concentration. Low mean concentrations were found in all the remaining compartments. Our findings suggest that intraosseous vancomycin administration in proximal tibial cancellous bone only is relevant as treatment in cases requiring high local concentrations nearby the intraosseous cannula

Aim. Tourniquet is widely used in extremity surgery. In order to prevent surgical site infection, correct timing of antimicrobial prophylaxis and tourniquet inflation is important. We aimed to evaluate the time for which the free drug concentration of cefuroxime is maintained above the minimal inhibitory concentration (T>MIC) in subcutaneous tissue and calcaneal cancellous bone during three clinically relevant tourniquet application scenarios. Method. Twenty-four female pigs were included. Microdialysis catheters were placed for sampling of cefuroxime concentrations bilaterally in calcaneal cancellous bone and subcutaneous tissue, and a tourniquet cuff was applied on a randomly picked leg of each pig. Subsequently, the pigs were randomized into three groups to receive 1.5 g of cefuroxime by intravenous injection 15 min prior to tourniquet inflation (Group A), 45 min prior to tourniquet inflation (Group B), and at the tourniquet release (Group C). The tourniquet duration was 90 min in all groups. Dialysates and venous blood samples were collected eight-hours postcefuroxime administration. Results. Cefuroxime concentrations were maintained above the clinical breakpoint MIC for Staphylococcus aureus (4 µg/mL) in calcaneal cancellous bone and subcutaneous tissue throughout the 90 min tourniquet duration in Group A and B. Cefuroxime administration at tourniquet release (Group C) resulted in concentrations above 4 µg/mL for a minimum of 3.5 hours in the tissues on the tourniquet side. There were no significant differences in the T>MIC (4 µg/mL) in subcutaneous tissue or calcaneal cancellous bone between the three groups. However, Group A tended toward shorter T>MIC in tourniquet calcaneal cancellous bone compared to Group C (p=0.08). Conclusions. Administration of cefuroxime (1.5 g) in the 15–45 min window prior to tourniquet inflation resulted in sufficient calcaneal cancellous bone and subcutaneous tissue concentrations throughout the 90 min tourniquet application. If the target is to maintain postoperative cefuroxime concentrations above relevant MIC values, our results suggest that a second dose of cefuroxime should be administered at tourniquet release

This study examined the regional variations of cortical and cancellous bone density present in superiorly eroded glenoids. It is hypothesized that eroded regions will contain denser bone in response to localized stress. The shift in natural joint articulation may also cause bone resorption in areas opposite the erosion site. Clinical CT scans were obtained for 32 shoulders (10m/22f, mean age 72.9yrs, 56–88yrs) classified as having E2-type glenoid erosion. The glenoid was divided into four measurement regions - anterior, inferior, posterior, and superior - as well as five depth regions. Depth regions were segmented in two-millimeter increments from zero to 10 millimeters, beginning at the center of the glenoid surface. A repeated-measures multiple analysis of variance (RM-MANOVA) was performed using SPSS statistical software to look for differences and interactions between mean densities in each depth, quadrant, and between genders. A second RM-MANOVA was performed to examine effects of gender and quadrant on cortical to cancellous bone volume ratios. Significance was set at p < 0 .05. Quadrant and depth variables showed significant multivariate main effects (p 0.147 respectively). Quadrant, depth, and their interaction showed significant univariate main effects for cortical bone (p≤0.001) and cancellous bone (p < 0 .001). The lowest bone density was found to be in the inferior quadrant for cancellous bone (307±50 HU, p < 0 .001). The superior quadrant contained the highest mean density for cortical bone (895±97 HU), however it was only significantly different than in the posterior quadrant (865±97 HU, p=0.022). As for depth, it was found that cortical bone is most dense at the glenoid surface (zero to two millimeters, 892±91 HU) when compared to bone at two to eight millimeters in depth (p < 0 .02). Cancellous bone was also most dense at the surface (352±51 HU), but only compared to the eight to 10 millimeters depth (p=0.005). Cancellous bone density was found to decrease with increasing depth. For cortical-to-cancellous bone volume ratios, the inferior quadrant (0.37±0.28) had a significantly lower ratio than all other quadrants (p < 0 .001). The superoposterior region of the glenoid was found to have denser cancellous bone and a high ratio of cortical to cancellous bone, likely due to decreased formation of cancellous bone and increased formation of cortical bone, in response to localized stresses. The inferior quadrant was found to have the least dense cortical and cancellous bone, and the lowest volume of cortical bone relative to cancellous bone. Once again, this is likely due to reduction in microstrain responsible for bone adaptation via Wolff's law. The density values found in this study generally agree with the range of values found in previous studies of normal and arthritic glenoids. An important limitation of this study is the sizing of measurement regions. For a patient with a smaller glenoid, a depth measurement of two millimeters may represent a larger portion of the overall glenoid vault. Segments could be scaled for each patient based on a percentage of each individual's glenoid size

Aim. Pyogenic spondylodiscitis remains a therapeutic challenge, as demonstrated by divergent treatment guidelines. The combination of moxifloxacin and rifampicin may be an attractive treatment option for cases caused by staphylococci; however, previous studies have reported a reduction in plasma concentrations of moxifloxacin when co-administered with rifampicin. The magnitude of this reduction in spinal tissues is not known. We aimed to investigate the interaction of rifampicin on moxifloxacin tissue concentrations in vertebral cancellous bone, intervertebral disc and subcutaneous adipose tissue in steady-state conditions using microdialysis in a porcine model. Method. Twenty female pigs were randomized into two groups of ten pigs: Group A received moxifloxacin 400 mg orally once daily for three days preoperatively. Group B received moxifloxacin 400 mg orally for three days preoperatively combined with rifampicin 450 mg twice daily for seven days preoperatively. Measurements were obtained from plasma, vertebral cancellous bone, intervertebral disc and subcutaneous adipose tissue for 24 h. Microdialysis was applied for sampling in solid tissues. Results. Co-administration of moxifloxacin and rifampicin demonstrated a reduction of free moxifloxacin concentrations in spinal tissues. The peak drug concentration (C. max. ) and the area under the concentration-time curve (AUC. 0–24. ) in all tissue compartments decreased in the range of 66–79% and 65–76%, respectively. Conclusions. Using microdialysis, we demonstrated a significant reduction of moxifloxacin C. max. and AUC. 0–24. in the spinal tissues when co-administered with rifampicin. Further studies are warranted to understand the clinical implications of this finding for the treatment of pyogenic spondylodiscitis

Conventional fracture courses utilise prefabricated sawbones that are not realistic or patient specific. The aim of this study is to determine the feasibility of creating 3D fracture models and utilising them in fracture courses to teach surgical technique. We selected an AO type 2R3C2 fracture that underwent open reduction internal fixation. De-identified CT scan images were converted to a stereolithography (STL) format. This was then processed using Computer Aided Design (CAD) to create a virtual 3D model. The model was 3D printed using a combination of standard thermoplastic polymer (STP) and a porous filler to create a realistic cortical and cancellous bone. A case-based sawbone workshop was organised for residents, unaccredited registrars, and orthopaedic trainees comparing the fracture model with a prefabricated T-split distal radius fracture. Pre-operative images aided discussion of fixation, and post-operative x-rays allowed comparison between the participants fixation. Participants were provided with identical reduction tools. We created a questionnaire for participants to rate their satisfaction and experience using a Likert scale. The 3D printed fracture model aided understanding and appreciation of the fracture pattern and key fragments amongst residents and unaccredited trainees. Real case-based models provided a superior learning experience and environment to aid teaching. The generic sawbone provided easier drilling and inserting of screws. Preliminary results show that the cost of 3D printing can be comparable to generic sawbones. It is feasible to create a fracture model with a real bone feel. Further research and development is required to determine the optimum material to use for a more realistic feel. The use of 3D printed fracture models is feasible and provides an alternative to generic sawbone fracture models in providing surgical training to residents

Introduction: The mechanobiology and response of bone formation to strain under physiological loading is well established, however investigation into exceedingly soft scaffolds relative to cancellous bone is limited. In this study we designed and 3D printed mechanically-optimised low-stiffness implants, targeting specific strain ranges inducing bone formation and assessed their biological performance in a pre-clinical in vivo load-bearing tibial tuberosity advancement (TTA) model. The TTA model provides an attractive pre-clinical framework to investigate implant osseointegration within an uneven loading environment due to the dominating patellar tendon force. A knee finite element model from ovine CT data was developed to determine physiological target strains from simulated TTA surgery. We 3D printed low-stiffness Ti wedge osteotomy implants with homogeneous stiffness of 0.8 GPa (Ti1), 0.6 GPa (Ti2) and a locally-optimised design with a 0.3 GPa cortex and soft 0.1 GPa core (Ti3), for implantation in a 12-week ovine tibial advancement osteotomy (9mm). We quantitatively assessed bone fusion, bone area, mineral apposition rate and bone formation rate. Optimised Ti3 implants exhibited evenly high strains throughout, despite uneven wedge osteotomy loading. We demonstrated that higher strains above 3.75%, led to greater bone formation. Histomorphometry showed uniform bone ingrowthin optimised Ti3 compared to homogeneous designs (Ti1 and Ti2), and greater bone-implant contact. The greatest bone formation scores were seen in Ti3, followed by Ti2 and Ti1. Results from our study indicate lower stiffness and higher strain ranges than normally achieved in Ti scaffolds stimulate early bone formation. By accounting for loading environments through rational design, implants can be optimised to improve uniform osseointegration. Design and 3D printing of exceedingly soft titanium orthopaedic implants enhance strain induced bone formation and have significant importance in future implant design for knee, hip arthroplasty and treatment of large load-bearing bone defects

Aim. Prompt and sufficient broad spectrum empirical antibiotic treatment is key to prevent infection following open tibial fractures. Succeeding co-administration, we dynamically assessed the time for which vancomycin and meropenem concentrations were above relevant epidemiological cut-off minimal inhibitory concentrations (T>MIC) in tibial compartments for the bacteria most frequently encountered in open fractures. Low and high MIC-targets were applied: 1 and 4 µg/mL for vancomycin and 0.125 and 2 µg/mL for meropenem. Materials and methods. 8 pigs received a single dose of 1000 mg vancomycin and 1000 mg meropenem simultaneously over 100 min and 10 min, respectively. Microdialysis catheters were placed for sampling over 8 h in tibial cancellous bone, cortical bone, and adjacent subcutaneous adipose tissue. Venous blood samples were collected as references. Results. Across the targeted epidemiological cut-off values, vancomycin displayed longer T>MIC in all the investigated compartments in comparison to meropenem. For both drugs, cortical bone exhibited the shortest T>MIC. For the low MIC targets and across compartments, T>MIC ranged between 208–499 min (46–100%) for vancomycin and 189–406 min (42–90%) for meropenem. For the high MIC targets, T>MIC ranged between 30–446 min (7–99%) for vancomycin and 45–181 min (10–40%) for meropenem. Conclusion. The differences in the T>MIC between the low and high targets illustrates how the interpretation of these results is highly susceptible to the defined MIC target. To encompass any trauma, contaminating or individual tissue differences, a more aggressive dosing approach may be considered to achieve longer T>MIC in all the exposed tissues and thereby lowering the risk of acquiring an infection after open tibial fractures

Aim. Prosthetic joint infections (PJI) are a common reason for revisions in patients that underwent total arthroplasty of the hip (THA) or knee (TKA). Extensive antibiotic treatment follows while a clear understanding of target site concentrations is lacking. The aim is to investigate the target site concentrations, like bone and synovial tissue concentrations, which consequently may lead to an optimisation of the dosing regiments of cefuroxime of PJI patients suffering from pain and immobility. Dosing optimisation may lead to a reduced risk of (re-)infection and adverse effects like renal-insufficiency and therefore lower health-care costs. Method. Patients (n=26) with PJI of hip or knee undergoing a one- or two-stage revision treated with cefuroxime were included as part of the ASTERICS study. During implant removal two samples were collected 15-30 and 60-120 minutes after IV infusion of plasma, bone tissue and synovial tissue and one synovial fluid sample. Samples were analysed using a UltraPerformance Convergence Chromotography – quadruple mass spectrometry system (UPC. 2. -MS/MS). Bone tissue and synovial tissue were pulverized before analysis acquiring for bone tissue a homogenate of cortical and cancellous bone. Using nonlinear mixed effect modelling (NONMEM) a base model was developed to analyse the bone to plasma ratio of cefuroxime in osteomyelitis patients. Results. Mean bone concentrations (mg/L) of cefuroxime at 30-60 min after IV administration in the knee and hip are 21.29 (SD:11.86) and 19.06 (SD: 11.79) respectively and 8.23 (SD:4.90) and 9.67 (SD:9.75) respectively at 90-120 min after IV administration. The penetration of cefuroxime described by the bone:plasma ratio into knee and hip affected by osteomyelitis is 0.3 and 0.4 respectively within 1 hour and 0.1 for both joints within 2 hours. The results mentioned here were collected during knee operations without blood void conditions. Concentration data was used to develop a base pharmacokinetic model using NONMEM and was best described by a two-compartment model. Conclusions. Cefuroxime penetrates osteomyelitis affected bone tissue within the hour proving the usefulness of cefuroxime as prophylaxis of orthopaedic surgery and as treatment option for PJI. However, PK modelling and further simulations need to prove whether repeated cefuroxime dosing in this population is required to reach minimal inhibitory concentrations in target tissue

Aim. Deadspace is the tissue and bony defect in a surgical wound after closure. This space is presumably poorly perfused favouring bacterial proliferation and biofilm formation. In arthroplasty surgery, an obligate deadspace surrounding the prosthesis is introduced and deadspace management, in combination with obtaining therapeutic prophylactic antibiotic concentrations, is important for limiting the risk of acquiring a periprosthetic joint infection (PJI). This study aimed to investigate cefuroxime distribution to an orthopaedic surgical deadspace in comparison with plasma and bone concentrations during two dosing intervals (8 h × 2). Method. In a setup imitating shoulder arthroplasty surgery, but without insertion of a prosthesis, microdialysis catheters were placed for cefuroxime sampling in a deadspace in the glenohumeral joint and in cancellous bone of the scapular neck in eighteen pigs. Blood samples were collected from a central venous catheter as a reference. Cefuroxime was administered according to weight (20 mg/kg). The primary endpoint was time above the cefuroxime minimal inhibitory concentration of the free fraction of cefuroxime for Staphylococcus aureus (fT > MIC (4 µg/mL)). Results. During the two dosing intervals, mean fT > MIC (4 µg/mL) was significantly longer in deadspace (605 min) compared with plasma (284 min) and bone (334 min). For deadspace, the mean time to reach 4 µg/mL was prolonged from the first dosing interval (8 min) to the second dosing interval (21 min), while the peak drug concentration was lower and half-life was longer in the second dosing interval. Conclusions. In conclusion, weight-adjusted cefuroxime fT > MIC (4 µg/mL) and elimination from the deadspace was longer in comparison to plasma and bone. Our results suggest a deadspace consolidation and a longer diffusions distance, resulting in a low cefuroxime turn-over. Based on theoretical targets, cefuroxime appears to be an appropriate prophylactic drug for the prevention of PJI. Acknowledgments. We would like to thank Department of Clinical Medicine, the surgical research laboratories, Aarhus University Hospital and Department of Clinical Biochemistry, Lillebaelt Hospital, Vejle, Denmark, for supporting this study. This research was funded by Novo Nordisk Foundation, grant number [NNF20OC0062032, 2020]

The first rule in properly cementing a femoral component is obtaining adequate exposure of the proximal femur. This is achieved reproducibly in anterior approach surgery with anterior and superior capsulotomy, combined with release of the conjoined tendon from the inner trochanter and piriformis tendon retraction, or flip behind the trochanter. This will be demonstrated. The steps of cementation are well established, and not specific to one approach. They involve entry to the proximal femur in a lateral and posterior position, achieving central alignment within the proximal femur with the broach, application of a cement restrictor to a point 1.5 to 2cm distal to the proposed tip of the implant, appropriate preparation of the cancellous bone to receive the cement, applying cement in a sufficiently doughy state to be able to achieve penetration into the cancellous bone, and mechanical pressurization into that cancellous bone. We routinely apply cement directly to the proximal aspect of the femoral component as the cement sticks to the metal, preventing marrow contents generated during the insertion from contacting the metal. In discussing the factors contributing to a dry surgical field, the importance of relative hypotension achieved from regional anesthesia cannot be overstated

Aim. To describe the histopathology of the first and last debrided bone tissue in chronic osteomyelitis and answer the following research question; is the last debrided bone tissue viable and without signs of inflammation?. Method. In total, 15 patients with chronic osteomyelitis were allocated to surgical treatment using a one stage protocol including extensive debridement. Suspected infected bone tissue eradicated early in the debridement procedure was collected as a clearly infected sample (S1). Likewise, the last eradicated bone tissue was collected as a suspected non-infected sample (S2), representing the status of the bone void. In all cases, the surgeon debrided the bone until visual confirmation of healthy bleeding bone. The samples were processed for histology, i.e. decalcification and paraffin embedding, followed by cutting and staining with Haematoxylin and Eosin. Immunohistochemistry with MAC-387 antibodies towards the calprotectin of neutrophil granulocytes (NGs) was also performed and used for estimation of a neutrophil granulocyte (NG) score (0, 1, 2 or 3), by the method described for fracture related infections (1). Results. For the S1 samples the median NG score was 3 which is considered confirmatory for infection. However, following debridement the median NG score was significantly (p = 0.032) reduced to 2. Often NGs were seen as single cells, but in seven S1 samples and in one S2 sample massive NG accumulations were observed. The S1 samples showed a mix of granulation tissue, fibrosis, viable bone, and bone necrosis. The S2 samples contained viable bone tissue and occasionally (10/15) small fragments of necrotic bone or bone debris were seen. Furthermore, a large number of erythrocytes were observed in most S2 samples. Conclusions. The present study shows that the inflammatory response still existents after debridement, although the response fades from the center of infection. Therefore, sampling of debrided bone tissue for histology must be performed initially during surgery, to avoid underestimation of the inflammatory response, i.e. the NG score. The last debrided bone tissue cannot by definition be considered completely viable and caution should be made to remove blood (rinse) before intraoperative evaluation of the viability of debrided cancellous bone. Remnant necrotic bone fragments or debris could represent low-vascular hiding places for leftover bacteria. Application of local antibiotics might have a central role in clearing of these small non-viable bone pieces at the bone void interface

Aim. This study investigated if co-administration of rifampicin with moxifloxacin led to a decrease in moxifloxacin concentrations in relevant tissues in a porcine model of implant-associated osteomyelitis caused S. aureus. Pharmacokinetics were measured using microdialysis and treatment effect was measured by quantifying bacterial load from implant and periprosthetic bone following a 1-stage revision and antibiotics. Method. 15 female pigs received a stainless-steel implant in the right proximal tibia and were randomized into two groups. Infection was introduced by inoculating the implant with Staphylococcus aureus as previously described. 1. On day 7 post surgery, all pigs were revised with implant removal, debridement of implant cavity and insertion of a sterile implant. 7 days of treatment was then initiated with either moxifloxacin 400 mg iv q.d. (M) or moxifloxacin and rifampicin 450 mg iv b.i.d. (RM). At day 14, animals were sedated and microdialysis was applied for continuous sampling of moxifloxacin concentrations during 8 h in five compartments: the implant cavity, cancellous bone in both the infected and non-infected proximal tibia, and adjacent subcutaneous tissue on both the infected and non-infected side using a previously described setup. 2. Venous blood samples were collected. Implant and adjacent bone were removed for analysis. Results. Comparable cure rates (sterilization of both implant and bone) were observed with 5/8 pigs in the RM group compared to 3/7 in the M group, p= 0.62 (Fisher's exact test). Due to the small number of samples with growth, median log CFU/ml was 0 for implant and bones in both groups. AUC. 0-last. was significantly smaller in plasma for the RM group, 407; 315 – 499 min µg/mL vs 625; 536 – 724 min µg/mL (mean;95% CI), p= 0.002 (Student's t-test). For the implant cavity, there was a trend toward a lower AUC. 0-last. 425; 327 – 524 min µg/ml vs 297; 205 – 389 min µg/ml in the RM group compared to M, yet this difference was not statistically different, p = 0.06. For the other compartments for other parameters (C. max. and T. max. ) across all compartments, there was no difference. Conclusions. While the AUC. 0-last. was lower in plasma for animals treated with RM, both the concentrations at the site of infection and treatment outcomes were comparable between groups

Introduction. The success of cementless total hip arthroplasty (THA) depends on the primary stability of the components. One of the biomechanical factors that comes into play is the mechanical quality of the bone. To our knowledge, there are no reported studies in the literature analyzing the impact of the preoperative bone mineral density on the outcomes of cementless THA. The goal of the study was to analyze the clinical results at 2 year follow-up according to the preoperative cancellous bone mineral density (BD). Our hypothesis was that the clinical outcomes were correlated to the BD. Material and methods. From January to June 2013, a prospective study included patients who underwent a cementless THA using a proximally shortly fixed anatomic stem. A 3D preoperative CTscan-based planning was performed according to the routine protocol using the Hip-Plan software in order to determine the hip reconstruction goals as well as the implants size and position. The Hounsfield bone density (BD) of the metaphyseal cancellous bone was computed in a volume (of 1 mm thick and of 1cm² surface) at the level of the calcar 10 mm above the top of the lesser trochanter and laterally to the medial cortical (Figure 1). Intra-and inter-observer repeatability measurements were performed. Patients were clinically assessed at 2 years follow-up using self-administered auto-questionnaires corresponding to the Harris and the Oxford scores. A Multivariate statistical analysis assessed correlations between clinical scores, age, gender, body mass index, and BD. Results. 50 patients were included consisting of 29 men and 21 women, with an average age of 62 ± 12 years and an average BMI of 25.8. The average preoperative BD was 69.4 ± 54 HU. At 2 years follow-up, the hip function scores were significantly correlated with the preoperative BD (0.42, p = 0.002) and the age (0.39, p = 0.005). However, there was no significant correlation between BD and BMI. Discussion Bone density appears to be an important parameter to consider when planning THA. This highlights also the importance of preoperative image calibration. Conclusion. The functional outcomes after cementless THA are correlated with preoperative cancellous bone density. Bone density needs to be integrated into THA 3D planning