Abstract. Purpose. Intracanal rib head penetration is a well-known entity in dystrophic scoliotic curves in neurofibromatosis type 1. There is potential for spinal cord injury if this is not recognised and managed appropriately. No current CT-based classification system is currently in use to quantify rib head penetration. This study aims to propose and evaluate a novel CT-based classification for rib head penetration primarily for neurofibromatosis but which can also be utilised in other conditions of rib head penetration. Materials and methods. The grading was developed as four grades: normal rib head (RH) position—Grade 0, subluxed ext-racanal RH position—Grade 1, RH at pedicle—Grade 2, intracanal RH—Grade 3. Grade 3 was further classified depending on the head position in the canal divided into thirds. Rib head penetration into proximal third (from ipsilateral side)—Grade 3A, into the middle third—Grade 3B and into the distal third—Grade 3C. Seventy-five axial CT images of Neurofibromatosis Type 1 patients in the paediatric age group were reviewed by a radiologist and a spinal surgeon independently to assess interobserver and intraobserver agreement of the novel CT classification. Agreement analysis was performed using the weighted Kappa statistic. Results. There was substantial interobserver correlation with mean Kappa score (k = 0.8, 95% CI 0.7–0.9) and near perfect intraobserver Kappa of 1.0 (95% CI 0.9–1.0) and 0.9 (95% CI 0.9–1.0) for the two readers. Conclusion. The novel CT-based classification quantifies rib head penetration which aids in management planning

Aim. This study seeks to outline the clinical, laboratory, and imaging features of patients with pyogenic spondylitis. It aims to define a novel imaging sign that could indicate the severity of suppurative spondylitis, aiding in its early diagnosis and treatment. Method. This retrospective study included 137 patients from 2013 to 2023. Through the analysis and summary of imaging characteristics among all patients, we identified a distinct MRI sign known as ‘the Disc Penetration sign’ (DP). This sign is defined as an image finding on sagittal MRI depicting the anterior and posterior penetration of an abscess through the intervertebral disc space, affecting both the anterior margin of the vertebrae and the structures within the spinal canal. Observational parameters included WBC, ESR, CRP, hemoglobin, and albumin levels. Documentation of the study included location and segment of the lesion, presence or absence of spinal cord compression, and paravertebral abscesses. Results. 56 patients presented with the Disc Penetration sign(DP) and 81 did not. In both groups, there were no significant differences in gender ratio or age (P > 0.05). However, significant differences were observed in the presence of comorbid diabetes and chronic kidney disease (p < 0.05). The DP group had a significantly greater ESR level (74.30±33.79 mm/h vs. 51.46±30.46 mm/h, P < 0.001) and CRP level (47.28 mg/L vs. 26.18 mg/L, P = 0.003). Additionally, the DP group had a significantly lower Hb (100.66±19.82 g/L vs. 116.99±19.99g/L,P < 0.001) and the serum albumin level (28.81±6.59 g/L vs. 34.09±6.17 g/L,P < 0.001). Imaging results showed no significant differences in affected spinal segments or parts (p>0.05). Patients in the DP group showed a higher likelihood of developing paravertebral abscesses compared to those in the non-DP group (n = 54 [96.4%] vs. n = 33 [40.7%], P < 0.001), and also exhibited a higher incidence of spinal cord compression(n = 32 [57.1%] vs. n = 17 [21.0%], P < 0.001). Conclusions. The study suggests that the Disc Penetration sign in pyogenic spondylitis patients correlates with more severe inflammation and higher incidence of paraspinal abscess, pointing to worse stability of the spine, longer bone restructuring time, and potentially poorer prognosis. These findings enable clinicians to rapidly assess the severity of the disease and prognosticate outcomes more effectively We emphasize the need for early, pathogen-specific diagnosis and treatment, particularly considering surgical intervention for patients demonstrating substantial paraspinal abscesses or spinal instability

Highly cross-linked polyethylene (HXLPE) has decreased wear and revision rates in total hip replacement (THR) at a long-term. However, the effect of HXLPE manufacturing characteristics on femoral head penetration has not been clearly defined yet. We report this single-institution study to investigate the clinical and radiological results of different HXLPE liners in THR. In this retrospective cohort analysis of our prospective database, we identified 904 THRs performed between 2000 and 2013. Seven different HXLPE liner types were assessed: remelted (3), annealed (2), sequentially annealed (1) and vitamin E-infused (1). The linear femoral head penetration rate was measured at six weeks, one year, and annually thereafter, using the Roman Software v1.70 package. Thirty hips were revised for the following reasons: aseptic loosening (11), dislocation (12), periprosthetic femoral fracture (6), and infection (1). No hip was revised for wear or osteolysis. 741 THRs were evaluated for a mean follow-up of 15 years (range, 10 to 20). The mean total penetration 15 years after THR was 0.17 mm in the sequentially annealed, and 0.16 mm in the vitamin E-infused groups, whereas it was 0.26 mm in the melted 95 kGy, 0.27 mm in the melted 5 Mrad and 0.25 mm in the melted 100 kGy groups (p=0.001). From one to 15 years after surgery, the mean wear was 0.206 mm in cups with an acetabular inclination greater than 50º and 0.105 mm in those placed between 35º and 50º (p<0.001). Although HXLPE characteristics can result in a different wear performance in patients undergoing THR at a mean follow-up of 15 years, the clinical results are excellent. The position of the acetabular component can influence on the femoral head penetration of modern HXLPEs. Nevertheless, these patients should continue to be monitored to detect future problems

Aims. The primary outcome was investigating differences in wear, as measured by femoral head penetration, between cross-linked vitamin E-diffused polyethylene (vE-PE) and cross-linked polyethylene (XLPE) acetabular component liners and between 32 and 36 mm head sizes at the ten-year follow-up. Secondary outcomes included acetabular component migration and patient-reported outcome measures (PROMs) such as the EuroQol five-dimension questionnaire, 36-Item Short-Form Health Survey, Harris Hip Score, and University of California, Los Angeles Activity Scale (UCLA). Methods. A single-blinded, multi-arm, 2 × 2 factorial randomized controlled trial was undertaken. Patients were recruited between May 2009 and April 2011. Radiostereometric analyses (RSAs) were performed from baseline to ten years. Of the 220 eligible patients, 116 underwent randomization, and 82 remained at the ten-year follow-up. Eligible patients were randomized into one of four interventions: vE-PE acetabular liner with either 32 or 36 mm femoral head, and XLPE acetabular liner with either 32 or 36 mm femoral head. Parameters were otherwise identical except for acetabular liner material and femoral head size. Results. A total of 116 patients participated, of whom 77 were male. The median ages of the vE-PE 32 mm and 36 mm groups were 65 (interquartile range (IQR) 57 to 67) and 63 years (IQR 56 to 66), respectively, and of the XLPE 32 mm and 36 mm groups were 64 (IQR 58 to 66) and 61 years (IQR 54 to 66), respectively. Mean total head penetration was significantly lower into vE-PE acetabular liner groups than into XLPE acetabular liner groups (-0.219 mm (95% confidence interval -0.348 to -0.090); p = 0.001). There were no differences in wear according to head size, acetabular component migration, or PROMs, except for UCLA. There were no cases of aseptic loosening or failures requiring revision at long-term follow-up. Conclusion. Significantly lower wear was observed in vE-PE acetabular liners than in XLPE acetabular liners. No difference in wear was observed between different head size or PROMs except for the UCLA at ten years. Cite this article: Bone Joint J 2023;105-B(10):1052–1059

Aims. The most frequent indication for revision surgery in total hip arthroplasty (THA) is aseptic loosening. Aseptic loosening is associated with polyethylene liner wear, and wear may be reduced by using vitamin E-doped liners. The primary objective of this study was to compare proximal femoral head penetration into the liner between a) two cross-linked polyethylene (XLPE) liners (vitamin E-doped (vE-PE)) versus standard XLPE liners, and b) two modular femoral head diameters (32 mm and 36 mm). Methods. Patients scheduled for a THA were randomized to receive a vE-PE or XLPE liner with a 32 mm or 36 mm metal head (four intervention groups in a 2 × 2 factorial design). Head penetration and acetabular component migration were measured using radiostereometric analysis at baseline, three, 12, 24, and 60 months postoperatively. The Harris Hip Score, University of California, Los Angeles (UCLA) Activity Score, EuroQol five-dimension questionnaire (EQ-5D), and 36-Item Short-Form Health Survey questionnaire (SF-36) were assessed at baseline, three, 12, 36, and 60 months. Results. Of 220 screened patients, 127 were included in this study. In all, 116 received the allocated intervention, and 94 had their results analyzed at five years. Head penetration was similar between liner materials and head sizes at five years, vE-PE versus XLPE was -0.084 mm (95% confidence interval (CI) -0.173 to 0.005; p = 0.064), and 32 mm versus 36 mm was -0.020 mm (95% CI -0.110 to 0.071; p = 0.671), respectively. No differences were found in acetabular component migration or in the patient-reported outcome measures. Conclusion. No significant difference in head penetration was found at five years between vE-PE and XLPE liners, nor between 32 mm and 36 mm heads. Cite this article: Bone Joint J 2020;102-B(10):1303–1310

Aims. To characterize the intracellular penetration of osteoblasts and osteoclasts by methicillin-resistant Staphylococcus aureus (MRSA) and the antibiotic and detergent susceptibility of MRSA in bone. Methods. Time-lapse confocal microscopy was used to analyze the interaction of MRSA strain USA300 with primary murine osteoblasts and osteoclasts. The effects of early and delayed antibiotic treatments on intracellular and extracellular bacterial colony formation and cell death were quantified. We tested the effects of cefazolin, gentamicin, vancomycin, tetracycline, rifampicin, and ampicillin, as well as agents used in surgical preparation and irrigation. Results. MRSA infiltrated bone-resident cells within 15 to 30 minutes. Penetration was most effectively prevented with early (i.e. 30 minutes) antibiotic administration. The combined administration of rifampicin with other antibiotics potentiated their protective effects against MRSA-induced cytotoxicity and most significantly reduced extracellular bacterial bioburden. Gentamicin-containing compounds were most effective in reducing intracellular MRSA bioburden. Of the surgical preparation agents evaluated, betadine reduced in vitro MRSA growth to the greatest extent. Conclusion. The standard of care for open fractures involves debridement and antibiotics within the first six hours of injury but does not account for the window in which bacteria penetrate cells. Antibiotics must be administered as early as possible after injury or prior to incision to prevent intracellular infestation. Rifampicin can potentiate the capacity of antibiotic regimens to reduce MRSA-induced cytotoxicity. Cite this article:Bone Joint Res. 2020;9(2):49–59

Cryopreserving agents (CPAs) can cryopreserve articular cartilage (AC) but their use is limited due to cellular toxicity. This study examined the time-dependent penetration of multiple CPAs into intact porcine AC. Porcine AC was immersed in CPAs for various amounts of time at three temperatures (4°C, 22°C, and 37°C). The results demonstrated an initial sharp rise in CPA concentration within the matrix for dimethyl sulfoxide and propylene glycol with maximum concentration after three to six hours. The trehalose and glucose concentration increased minimally even after twenty-four hours of exposure. The information from this study provides insight into the penetration kinetics of cryoprotectant agents into AC. This study examined the time-dependent penetration of cryoprotectant agents (CPAs) [dimethyl sulfoxide (DMSO), propylene glycol (PG), trehalose and glucose] into intact porcine articular cartilage (AC). Penetration of DMSO and PG into AC was rapid but time and temperature dependent while trehalose and glucose had poor penetration. The information gathered from this study can determine concentrations of CPAs within the cartilage matrix to create cryopreservation/vitrification solutions while minimizing toxicity. The results demonstrated there was a sharp rise in the CPA concentration within 15–30min exposure to DMSO and PG and the concentration peaked after three to six hours exposure at a concentration approximately 90% of the original concentration (6.5 molar). This was temperature dependent with slower penetration at lower temperatures. The trehalose and glucose had very poor penetration into the matrix at all temperatures, with a maximum penetration of 2% of the original concentration. Dowels of porcine AC (10mm diameter) were immersed in high concentration of each CPA for various amounts of time (0min, 15min, 30min, 60min, 3hr, 6hr, and 24hr) at three temperatures (4°C, 22°C, and 37°C). The cartilage was excised and the amount of cryoprotectant within the matrix determined. Successful cryopreservation of AC could improve clinical results of osteochondral allografting and provide a useful treatment alternative for large cartilage defects. However, successful cartilage cryopreservation is limited by chondrocyte death and matrix disruption due to inadequate CPA penetration

3-D finite element model of a resurfaced femoral head was composed. Five configurations of cement layer were analyzed and the transient heat transfer analysis during cement polymerization was performed. Peak temperature at the bone-cement interface temperature was lower than 40 oC when there was no or 1.5 mm cement penetration but reached 54 oC and 74 oC with 6 mm penetration and 6 mm penetration plus a cement –filled cyst of 1 cm3, respectively. With deep cement penetration, and a large cement-filled cyst, the peak temperatures exceeded bone thermal osteonecrosis at 55 oC. To evaluate using a finite element analysis model, the possibility of bone thermal necrosis secondary to cement in resurfacing arthroplasty of the hip. With deep cement penetration, and the presence of a large cement-filled cyst, the peak temperatures were in the range of bone thermal osteonecrosis 55 oC. Cementing technique in resurfacing arthroplasty should strive to strike a balance between fixation and avoiding bone thermal necrosis by excessive cement penetration. This information could explain why femoral head cysts > 1cm are a risk factor for femoral loosening after resurfacing arthroplasty and excessive cement penetration could lead to femoral neck fracture. 3-D finite element model of a hemispherical resurfaced femoral head was composed of a metal shell with a diameter of 46 mm. Five configurations of cement layer were analyzed a) no penetration into the bone, b) 1.5 mm penetration, c) 6 mm penetration, d) 6 mm penetration and a 1 cm3 cement filled cyst, and e) 6 mm penetration and 2 cm3 cement-filled cyst. The transient heat transfer analysis during cement polymerization was performed in a series of time steps. The temperature within the bone and cement was lower than 40 oC when there was no or 1.5 mm cement penetration into the femoral head. In contrast, the peak temperature at the bone-cement interface reached 54 oC and 74 oC and 63 oC with 6 mm penetration and 6 mm penetration plus a cement –filled cyst of 1 cm3, respectively

Introduction. Dual-mobility (DM) articulations may be useful for patients at increased risk for instability in primary and revision THA. While DM articulations are becoming increasingly popular, its routine use in primary THA is more uncertain. Even less is known about femoral head penetration in DM designs manufactured with highly cross-linked polyethylene infused with Vitamin E (E-HXLPE). The purpose of this study was to evaluate the early clinical results and femoral head penetration rates of primary THA implanted with DM E-HXLPE. Methods. Between 2012 and 2017, 105 primary DM THAs were performed using a one-piece acetabular shell, 28mm ceramic head, coupled with an E-HXLPE outer bearing via a standard posterior approach. Three patients refused follow-up after six months. 102 hips (92 patients) were available for review. The diagnosis was 99% OA. Average age was 65.7 years (33–90 years). 56% of patients were female. The most common femoral head size was 50mm (range, 44–60mm). The average thickness of the E-HXLPE outer bearing was 22.7mm (range, 16–32mm). Patients were followed at two months (baseline radiograph), six months, one, three, five, and seven years. Harris hip scores (HHS), UCLA activity score, and femoral head penetration (Martell method) were obtained at each visit beyond two months. Follow-up averaged 3 years (range, 1–7 years). Results. Average HHS improved from 43 to 95 points (50–100) at final follow-up. Similarly, average Harris pain scores improved from 10 to 42 points (20–44) with 78% of patients pain free and one patient, each, reporting groin and thigh pain (1%). Average UCLA activity scores was 8.1 (range, 5–10). There were no dislocations, revisions, or loose cups. The average femoral head penetration (including bedding-in) was 0.25mm/yr (s.d. 0.2mm/yr) at seven years. Discussion/Conclusion. The theoretical benefits of DM designs in diminishing wear include a smaller inner head, lower frictional torque with motion, less micro-separation, and less wear with impingement. The early clinical results of primary DM THA are promising. Although the early femoral head penetration using DM E-HXLPE appears to be less than other DM designs, it was greater than that of conventional THA using HXLPE and E-HXLPE inserts. The additional outer bearing surface, while affording additional stability, may actually enhance polyethylene creep and wear. For any tables or figures, please contact the authors directly

Introduction. Failure of total knee replacements due to the generation of polyethylene wear debris remains a crucial issue in orthopedics. Unlike the hip, it is difficult to accurately determine knee implant wear rates from retrieved components. Several studies have relied on thickness measurements to estimate penetration, but the complicated geometry of contemporary tibial liners poses a challenge to accurately assess wear. In this study we address the question whether linear penetration can serve as a surrogate measure for volumetric material loss. Methods. Eighty-one retrieved UHMWPE NexGen cruciate-retaining tibial liners (Zimmer, Warsaw, IN) with an average time in situ of 5.27±2.89 years were included in the study. Metrology data for the surfaces of the tibial liners were obtained with a coordinate measuring machine (OGP, Rochester, NY). Using a laser scanner with two micrometer depth accuracy, at least 400,000 measurement points were taken by investigator #1. Areal thickness changes were mapped for the lateral and medial sides with the help of an autonomous mathematical reconstruction algorithm and volume loss was calculated based on wear scar area and local thickness change. Investigator #2, blinded from these results, measured the minimum thickness of the medial and lateral tibial plateau using a dial indicator with a spherical tip radius of 3mm. Twenty-three short term retrievals (3 to 4 per implant size), removed due to infection and without any signs of wear, served as “unused” reference. Linear penetration was then calculated by subtracting the minimum thickness of each plateau from the average thickness of the reference components. Results. The autonomous reconstruction algorithm delivered results for all investigated components and wear maps could be generated in 100% of the cases. There was a linear association between volume loss and time in situ for the medial and lateral tibial plateau, respectively (R2=0.23, p<0.001 and R2=0.32, p<0.001; Fig. 1). The calculated wear rates were 6.89±1.33 medially and 6.91±1.11 mm3/year laterally with an average total wear rate of 13.81±2.04 mm3/year. Also linear penetration correlated with time in situ (R2=0.19, p<0.001). The annual linear penetration was 0.03±0.01 mm/yr medially and 0.03±0.01 mm/yr laterally. Linear penetration and volumetric loss correlated significantly for both the medial and lateral sides (R2= 0.46 re. R2= 0.22; p <0.001); however, the specific uncertainty for each component was relatively high with ±60 mm3 medially and ±63 mm3 laterally as suggested by the 95% single point prediction interval of the correlation. Discussion. There is a reasonable global correlation between linear penetration and volume loss. However, the uncertainty in obtaining a wear volume from an individual penetration value is relatively high. For example a penetration of 0.5 mm on the medial side correlates to a wear volume of 40 to 160 mm3. The large uncertainty might be because the location of the thickness minimum after wear does no longer coincide with the manufactured minimum of this device (Fig. 2). In conclusion, the results suggest that penetration is not a good surrogate measure for estimating wear volume of individual TKR polyethylene components, but might be a useful surrogate for large cohort studies

Cephalasporin antibiotics have been commonly used for prophylaxis against surgical site infection. To prevent Clostridium difficile, the preferential use of agents such as flucloxacillin and gentamicin has been recommended. The aim of this study was to investigate the bone penetration of these antibiotics during hip and knee arthroplasty, and their efficacy against Staphylococcus aureus and S. epidermidis. Bone samples were collected from 21 patients undergoing total knee arthroplasty (TKA) and 18 patients undergoing total hip replacement (THA). The concentration of both antibiotics was analysed using high performance liquid chromatography. Penetration was expressed as a percentage of venous blood concentration. The efficacy against common infecting organisms was measured using the epidemiological cut-off value for resistance (ECOFF). The bone penetration of gentamicin was higher than flucloxacillin. The concentration of both antibiotics was higher in the acetabulum than the femoral head or neck (p=0.007 flucloxacillin; p=0.021 gentamicin). Flucloxacillin concentrations were effective against S. aureus and S. epidermis in all THAs and 20 (95%) TKAs. Gentamicin concentrations were effective against S.epidermis in all bone samples. Gentamicin was effective against S. aureus in 11 (89%) femoral samples. Effective concentrations of gentamicin against S. aureus were only achieved in 4 (19%) femoral and 6 (29%) tibial samples in TKA. Flucloxacillin and gentamicin was found to effectively penetrate bone during arthroplasty. Gentamicin was effective against S. epidermidis in both THA and TKA, while it was found to be less effective against S. aureus during TKA. Bone penetration of both antibiotics was less in TKA than THA

Introduction: One of the most common complications following total joint surgery is aseptic loosening. Improving the bone-cement interlock may increase implant longevity. An ideally prepared bony surface is dry; clean; free from marrow, fat and debris; free from active bleeding; and free from micro-organisms. Lavage removes debris, blood and fat from the interstices of the bone surface so as to allow optimal penetration of the cement. The hypothesis that we investigated in this study was that lavage with a detergent solution obtains a greater depth of cement penetration into bone compared with lavage using 0.9% saline, hydrogen peroxide or an alcohol solution. Methods: The cancellous bone of ovine femoral condyles were cut into 10×10×13mm blocks. Lavage solutions were delivered via a pulsatile system and directed towards one side of the bone block. All blocks were swabbed dry. A high viscosity cement was manually mixed and applied to the sandblasted surface of titanium alloy plate (10×10mm, weight 0.9g ±0.01g). The titanium plate and cement were placed on the irrigated bone block, and a known weight applied to achieve pressurisation. Time, temperature and method were controlled. The prosthesis-cement-bone composite was sectioned perpendicularly, and image analysis used to quantify penetration depths. 10 readings were recorded per block with 6 blocks per lavage group. Results: Cancellous bone porosity averaged 75.2% (±4.0) . The mean penetration depth in the saline group averaged 3.39mm (± 0.77); 3.04mm (± 0.59) using a 2% alcohol solution; 3.33mm (±0.79) using a 3% hydrogen peroxide solution; and 5.41mm (± 1.30) when using the detergent lavage. There was no significant difference in cement penetration depth between hydrogen peroxide and saline irrigation (p> 0.05), nor with hydrogen peroxide and alcohol irrigation (p> 0.05). Irrigation with saline however, afforded statistically superior cement penetration than that of alcohol lavage (p < 0.012). Irrigation with detergent solution demonstrated significantly greater depth of penetration than all three other lavage groups (saline p< 0.05; alcohol p< 0.05; hydrogen peroxide p< 0.05). Discussion: Detergents can physically remove particulate matter and emulsify and remove fats, thereby acting to maximise porosity of the cancellous bone network and optimise space for occupation by intruding cement. This study has proven the ability of a detergent solution to provide a clean, debris free cancellous network, which consequently provides a significantly greater depth of cement penetration than other commonly used irrigating agents. It was noted that cement penetration into cancellous bone followed the line and depth of cleaning from lavage. In conclusion, the hypothesis can be accepted, and lavage with a detergent solution affords a statistically greater depth of cement penetration into bone than that of the universally used 0.9% saline lavage

Purpose of study. To investigate the linear penetration rate of the polyethylene bearing in unicompartmental knee arthroplasty at twenty years. Introduction. The Phase 1 Oxford medial UKR was introduced in 1978 as a design against wear, with a fully congruous articulation. In 1987 the Phase 2 implant was introduced with new instrumentation and changes to the bearing shape. We have previously shown a linear penetration rate (LPR) of 0.02 mm/year at ten years in Phase 2, but that higher penetration rates can be seen with impingement. The aim of this study was to determine the 20 year in-vivo LPR of the Oxford UKR, using Roentgen Stereophotogrammetric Analysis (RSA). Patients and Methods. Six Phase 1 (5 patients, mean age 65.3 years) and seven Phase 2 (4 patients, mean age 63.5) Oxford UKR bearings, with an average time since surgery of 22.5 years and 19.5 years respectively, were assessed. Stereoradiographs were taken and penetration was calculated using a model-based RSA system. The penetration for each bearing was calculated by subtracting the measured thickness from the corrected nominal bearing thickness. Results. The measured LPR was 0.072 mm/year for Phase 1 (S.D. 0.028, range: 0.031 – 0.104 mm/year) and 0.028 mm/year for Phase 2 (S.D. 0.019, range: 0.014 – 0.07 mm/year). This difference in LPR for the two phases was statistically significant (p = 0.0028). Discussion. The results show that in the knees studied there was a significant difference between the LPR in Phase 1 and 2. This is probably due to the change in instrumentation and bearing shape between Phases. This study demonstrates that very low penetration rates can be maintained to the end of the second decade after implantation. This is of particular importance when the device is used in younger patients

Introduction: Prevalence of femoral neck fracture in resurfacing hip arthroplasty continues to question if failure is technique-related or due to the inherent bone quality. This study aimed to correlate cement penetration profile during resurfacing hip with inherent bone density. The hypothesis is that osteoporotic bone is unable to support the prosthesis leading to fatigue failure. Methods: Fifteen patients scheduled for total hip replacement (THR) were recruited to undergo resurfacing arthroplasty prior to THR. Each patient was implanted with a resurfacing femoral component (BHR, Smith & Nephew, Memphis, TN). Antibiotic simplex cement was inserted one minute after mixing at 18°C to fill 10% of the femoral component volume. The femoral head-implant section was removed and kept in buffered formalin. The patients then proceeded with standard THR. The femoral head-cement-prosthesis section was separated using electrical discharge (ED) machining technique and CT-scanned. The depth and volume of cement penetration were measured from the CT scans and correlated with femoral neck bone densities. Results: Cement penetration was compared for three groups of bone density: normal, osteopenic, osteoporotic. Average cement thickness were found to be 0.36 ± 0.16mm (proximal), 0.28 ± 0.11 mm (centre) and 0.12 ± 0.05 mm. During hip resurfacing, cement is forced into the porous structure, e.g. the trabeculae and airspaces when the femoral component is fixed onto the head of the femur. In normal bone, the trabeculae is dense and air spaces occupy a small volume of the bone. Greater cement penetration was expected in osteopenic and osteoporotic bones. However, no significant difference was found between cement thickness and volume against inherent patient bone density (p> 0.05). High viscosity of the cement may have prevented more cement to penetrate the bone. While the exterior cortex of the femoral head is strengthened by a cement layer, the interior structure of the femoral neck is still susceptible to fracture at high loads. In addition, increased bone necrosis due to the exothermic reaction during cement fixation may predispose patients to fracture. Discussion: Resurfacing hip replacement is a viable technique if the fracture risk can be reduced by gaining the best possible cement penetration. This would provide continuous cement stiffness with the bone

Aim. A reason for treatment failure, in cases of periprosthetic bone infections and osteomyelitis, may be incomplete or heterogeneous tissue distribution of antimicrobials to the affected bone. Decreased bioavailability has been demonstrated in healthy bones but never in pathological bone tissue. Therefore, the aim was to obtain pharmacokinetic parameters of cefuroxime in infected bone tissue by means of microdialysis in a porcine model of implant associated osteomyelitis. Method. An implant cavity of 4 mm in diameter was drilled 25 mm into the right tibial bone of ten pigs (30 kg/BW). Subsequently, a small steel implant (K-wire 2 × 2 mm) and 10. 4. CFU of Staphylococcus aureus was inserted and injected into the implant cavity. Five days after inoculation, two additional drill holes of 2 × 25 mm were drilled into the trabecular bone tissue adjacent to the implant cavity and into the left uninfected tibia. After intravenous administration of 1500 mg of cefuroxime, the concentration was measured in plasma and in the three tibial drill holes for 8 hours. All measurements were performed with microdialysis. Post mortem, the presence of bone infection was assessed by computed tomography (CT) scans and cultures of swabs. Results. Destruction of bone tissue was seen on CT scans around all implant cavities but not in the adjacent trabecular bone tissue of the right leg or in the left leg. All swabs from the implant cavity and 8/10 swabs from the adjacent trabecular tissue were positive for S. aureus. Conversely, all swabs from the left tibia were negative. The area under the concentration-time curves differed significantly, with the lowest found in the implant cavity (P<0.001). Although not significant, cefuroxime penetration into the adjacent bone tissue was incomplete. Conclusions. This is the first study to show, by microdialysis, that the destructive bone processes associated with implant associated osteomyelitis significantly impair cefuroxime penetration. Our results support the clinical conception of fast diagnosis and initiation of antibiotic treatment if surgery is to be avoided. It is of crucial importance to know the exact level of antibiotics, which actually reaches a pathological bone focus in order to obtain more targeted and effective antibiotic treatments of bone infections

Objectives. Meropenem may be an important drug in the treatment of open tibial fractures and chronic osteomyelitis. Therefore, the objective of this study was to describe meropenem pharmacokinetics in plasma, subcutaneous adipose tissue (SCT), and cancellous bone using microdialysis in a porcine model. Methods. Six female pigs were assigned to receive 1000 mg of meropenem intravenously over five minutes. Measurements of meropenem were obtained from plasma, SCT, and cancellous bone for eight hours thereafter. Microdialysis was applied for sampling in solid tissues. The meropenem concentrations were determined using ultra-high-performance liquid chromatography. Results. The penetration of meropenem into cancellous bone, expressed as the ratio of plasma to cancellous bone area under the concentration-curve from zero to the last measured value, was incomplete and delayed. The time with concentration above the minimal inhibitory concentration (T. >MIC. ), for an MIC of 0.5 μg/ml, was shorter for cancellous bone in comparison with both plasma and SCT. For MICs above 0.5 μg/ml, T. >MIC. in cancellous bone was only shorter than SCT. Considering an MIC of 4 μg/ml, no animals achieved the target of 40% T. >MIC. in plasma and cancellous bone, while less than 20% achieved it in SCT. Conclusion. The main finding of this study was short T. >MIC. in cancellous bone after intravenous administration of 1000 mg meropenem. Consequently, in order to achieve sufficient tissue concentration in the cases of open tibial fractures and chronic osteomyelitis, supplemental application of meropenem may be necessary. Cite this article: P. Hanberg, A. Lund, K. Søballe, M. Bue. Single-dose pharmacokinetics of meropenem in porcine cancellous bone determined by microdialysis: An animal study. Bone Joint Res 2019;8:342–348. DOI: 10.1302/2046-3758.87.BJR-2018-0308.R1

Introduction. Topical diclofenac has proven efficacy and safety in the management of osteoarthritic pain. Its therapeutic efficacy is dependent on its ability to deliver pharmacodynamically active concentrations to the underlying tissues in the affected joint. However, the disposition of topical diclofenac is not fully characterized, and no studies have been performed using diclofenac diethylamine 2.32% gel. Methods. This study investigated the penetration of topical diclofenac into knee synovial tissue and fluid and evaluated relative exposure in the knee versus plasma. In this phase 1, double-blind, placebo-controlled steady-state multicenter pharmacokinetic study, patients scheduled for arthroplasty to treat knee OA were randomly assigned 2:1 to 4 g diclofenac/placebo gel, applied to the affected knee every 12 hours for 7 days pre-surgery. Diclofenac concentrations were measured in synovial tissue, fluid, and plasma ≥12 hours after last application. Adverse events (AEs) were evaluated. Diclofenac concentrations were assayed by validated high-performance liquid chromatography and tandem mass spectrometry. Results. Samples were obtained from 45 (diclofenac n=29; placebo n=16) of 47 patients enrolled. Mean (SD) age was 71.2 (7.9) years with 52.2% women and mean (SD) BMI 30.7 (4.8) kg/m. 2. All diclofenac-treated participants had measurable diclofenac concentrations in synovial tissue (mean [95% CI]) 1.57 [1.12, 2.20] ng/g) and fluid 2.27 [1.87, 2.76] ng/mL ≥12 hours after the last dose. The mean (95% CI) ratio of diclofenac in synovial tissue:plasma was 0.32 (0.23, 0.45) and in synovial fluid:plasma was 0.46 (0.34, 0.54). AEs were similar for diclofenac (55.2%) and placebo (58.8%); none were treatment related. No correlation (r=−0.003) between BMI and synovial fluid concentration, and weak positive correlation (r=0.315) between BMI and synovial tissue concentration were observed. Conclusions. Topical diclofenac diethylamine 2.32% gel penetrated the knee and remained detectable at the end of the final 12-hour dosing cycle. BMI had no impact on diclofenac's penetration into the knee

There is continued concern over complication rates (20–30% of cases) in locked proximal humeral plating. The most common sequelae of this is screw penetration of the humeral head. This is associated with natural settling of the fracture, malreducition in varus, insufficent medial support of the fracture. The proximity of the screws to the articular surface can also be influential on outcome if collapse occurs. Our operative technique is to establish the rotation of the humeral head where the drill appears closest to the articular margin (by sequential xray screening) and subtract from this to avoid intra-articular penetration of the humeral head. 55 Consecutive patients of average age 56.4 years (14.7–86.1), 17 male and 38 females, who underwent PHILOS plating were identified using Bluespier database. Xrays were analysed for fracture pattern, restoration of neck-shaft angle, plate positioning, number and configuration of screws and presence of screw penetration both intra-operatively and at postoperative follow-up. There were 6.07 screws used per head (total 330). There was one intraoperative screw penetration and 3 patients had evidence of screw penetration at follow-up, which required implant removal (total screw penetration rate of 7%). There was one case of AVN. The mean neck shaft angle was 137 degrees (anatomical 135 degrees). Accurate reduction of fractures and placement of screws in the humeral head using image intensifier can act to minimise risk of screw penetration and make some of the complications of locked proximal humeral plating avoidable

Twelve patients undergoing total hip replacements were given 600mg linezolid as a 20min intravenous infusion along with conventional prophylaxis of 1gm cefamandole immediately before surgery. Routine total hip arthroplasty was performed and at timed intervals during surgery, samples of bone, fat, muscle and blood were collected for assay by HPLC analysis. Samples of haematoma fluid that formed around the operation site and further blood samples were also collected at timed intervals following the operation for assay. The penetration of linezolid into bone was rapid with mean levels of 9.1mg/L (95% CI: 7.7–10.6mg/L) achieved at 10min after the infusion, decreasing to 6.3mg/L (95% CI: 3.9–8.6mg/L) at 30min. Correcting for the simultaneous blood concentrations gave values for bone penetration of 51% at 10min, 60% at 20min and 47% at 30min. although the penetration of linezolid into fat was also rapid, mean levels and degree of penetration were approximately 60% of those seen in bone at 10min: 4.5mg/L (95%CI:3–6.1mg/L; penetration 27%) 20min: 5.2mg/L (95% CI:4–6.4mg/L; penetration 37%) and 30min:4.1mg/L (95% CI:3.3–4.8mg/L; penetration 31%). For muscle, the corresponding values were 10min: 10.4mg/L (95%CI:8.1–12.7mg/L; penetration 58%), 20min 13.4mg/L (95%:10.2–16.5mg/L; penetration 94%) and 30min 12mg/L (95% CI:9.2–14.8mg/L; penetration 93%). Mean concentration of linezolid in the haematoma around the operation site were 8.2mg/L at 6–8h and 5.6mg/L at 8–10h after the infusion and 7mg/L at 2–4h following a second 600mg infusion given 12h postoperatively. We conclude that linezolid exhibits rapid penetration in bone, fat and muscle of patients undergoing hip arthroplasty to achieve levels in excess of the MIC for sensitive organisms (MIC of < _ 4mg/L); with therapeutic levels maintained in the drainage which surrounds the operation site for more than 16h. This pharmaco-kinetic profile is similar to those of agents currently used for the treatment of bone and associated soft tissue infections and suggests a role for linezolid in the management of such patients

The adequacy of cement mantles around some impaction-grafting systems has been criticised yet good clinical results have been reported. This study investigates this contradiction by asking. Does cement mantle thickness affect cement penetration depth?. Does cement mantle thickness affect early mechanical stability?. Twelve artificial femora were prepared to simulate cavitary defects. Porcine cancellous bone was morselized. The defect was reconstructed by impaction grafting, using a size 0, 1 or 2 tamp. Bone cement was injected, and a size 0, 1 or 2 Exeter stem inserted. By using all nine tamp/prosthesis combinations, 0–4 mm thick cement mantles were produced. Femora were positioned in a testing machine and loaded with 2500 cycles of 2500 N. Prosthesis subsidence and retroversion were measured. Each femur was sliced transversely and the sections digitised. Solid cement mantle thickness and cement penetration depth were measured using image analysis. Correlation analysis was used to find if tamp/stem mismatch (nominal mantle thickness) influenced actual solid mantle thickness and cement penetration. We then analysed if tamp size, stem size, solid mantle thickness or cement penetration determined stem subsidence and retroversion. Cement mantles were produced with an average thickness of 1.7–2.2 mm, with largest variations proximally (1.5–2.8 mm). Average cement penetration was 0.3–2.0 mm, with largest variations proximally (0.4–3.5 mm). Thicker solid mantles gave less penetration (r=−0.62). Stem subsidence ranged from 0.4–2.5 mm and correlated significantly with tamp size (r=0.59, p< .05). Better correlations were found with solid mantle thickness (r=0.90, p< 0.05) and cement penetration depth (r=−0.81). Stem retroversion ranged from 0.1–2.0 degrees and correlated with stem size (r=−0.53) but not with tamp size. Tamp/stem mismatch determined the thickness of the solid cement mantle around impaction-grafted stems, and thinner mantles were associated with deeper cement penetration. Thinner mantles and deeper penetration were associated with reduced stem subsidence. Stem retroversion was associated with stem size only, and larger for thinner stems. Thinner cement mantles will therefore be associated with deeper penetration and reduced stem subsidence upon loading. This association may explain the good long-term results of impaction-grafted Exeter stems, despite deficient solid cement mantles