Aims. Tuberculosis (TB) infection of bones and joints accounts for 6.7% of TB cases in England, and is associated with significant morbidity and disability. Public Health England reports that patients with TB experience delays in diagnosis and treatment. Our aims were to determine the demographics, presentation and investigation of patients with a TB infection of bones and joints, to help doctors assessing potential cases and to identify avoidable delays. Patients and Methods. This was a retrospective observational study of all adults with positive TB cultures on specimens taken at a tertiary orthopaedic centre between June 2012 and May 2014. A laboratory information system search identified the patients. The demographics, clinical presentation, radiology, histopathology and key clinical dates were obtained from medical records. Results. A total of 31 adult patients were identified. Their median age was 37 years (interquartile range (IQR): 29 to 53); 21 (68%) were male; 89% were migrants. The main sites affected were joints (10, 32%), the spine (8, 26%) and long bones (6, 19%); 8 (26%) had multifocal disease. The most common presenting symptoms were pain (29/31, 94%) and swelling (26/28, 93%). ‘Typical’ symptoms of TB, such as fever, sweats and weight loss, were uncommon. Patients waited a median of seven months (IQR 3 to 13.5) between the onset of symptoms and referral to the tertiary centre and 2.3 months (IQR 1.6 to 3.4.)) between referral and starting treatment. Radiology suggested TB in 26 (84%), but in seven patients (23%) the initial biopsy specimens were not sent for mycobacterial culture, necessitating a second biopsy. Rapid Polymerase Chain Reaction-based testing for TB using Xpert MTB/RIF was performed in five patients; 4 (80%) tested positive for TB. These patients had a reduced time between the diagnostic biopsy and starting treatment than those whose samples were not tested (median eight days versus 36 days, p = 0.016). Conclusion. Patients with bone and joint TB experience delays in diagnosis and treatment, some of which are avoidable. Maintaining a high index of clinical suspicion and sending specimens for mycobacterial culture are crucial to avoid missing cases. Rapid diagnostic tests reduce delays and should be performed on patients with radiological features of TB. Cite this article: Bone Joint J 2018;100-B:119–24

Aim. Aim of this monocentric, prospective study was to evaluate the safety, efficacy, clinical and radiographical results at 24-month follow-up (N = 6 patients) undergoing hip revision surgery with severe acetabular bone defects (Paprosky 2C-3A-3B) using a combination of a novel phase-pure betatricalciumphosphate - collagen 3D matrix with allograft bone chips. Method. Prospective follow-up of 6 consecutive patients, who underwent revision surgery of the acetabular component in presence of massive bone defects between April 2018 and July 2019. Indications for revision included mechanical loosening in 4 cases and history of hip infection in 2 cases. Acetabular deficiencies were evaluated radiographically and CT and classified according to the Paprosky classification. Initial diagnosis of the patients included osteoarthritis (N = 4), a traumatic fracture and a congenital hip dislocation. 5 patients underwent first revision surgery, 1 patient underwent a second revision surgery. Results. All patients were followed-up radiographically with a mean of 25,8 months. No complications were observed direct postoperatively. HHS improved significantly from 23.9 preoperatively to 81.5 at the last follow-up. 5 patients achieved a defined good result, and one patient achieved a fair result. No periprosthetic joint infection, no dislocations, no deep vein thrombosis, no vessel damage, and no complaint about limbs length discrepancy could be observed. Postoperative dysmetria was found to be + 0.2cm (0cm/+1.0cm) compared to the preoperative dysmetria of − 2.4 cm (+0.3cm/−5.7cm). Conclusions. Although used in severe acetabular bone defects, the novel phase-pure betatricalciumphosphate - collagen 3D matrixshowed complete resorption and replacement by newly formed bone, leading to a full implant integration at 24 months follow-up and thus represents a promising method with excellent bone regeneration capacities for complex cases, where synthetic bone grafting material is used in addition to autografts

Abstract. Background. The aim of the present experimental study was to analyse vancomycin elution kinetics of nine bone fillers used in orthopaedic and trauma surgery over 42 consecutive days. Methods. Two allograft bone chips (carriers 1 and 2), a calcium-sulfate matrix (carrier 3), a hydroxyapatite/calcium-sulphate composite (carrier 4), four bone cements (carriers 5-8) and a pure tricalcium phosphate matrix (carrier 9), either already contained vancomycin, or were mixed with it following manufacturer's recommendations. Over 42 days, half of elution medium was substituted by the same amount of PBS at 9 distinct time points. Vancomycin concentration in obtained samples were measured with a kinetic microparticle immunoassay, and masses consecutively calculated. To enhance comparability between carriers analysed, vancomycin mass released related to overall mass within each probe was determined. Notably, elution kinetics of carriers 1 to 4 have been published previously. Results. All carriers initially released high vancomycin masses, followed by constant reduction later into the experiment. Mean initial vancomycin masses released after 4 hours were highest for carriers 1 (337.7 ± 76.2 mg), 9 (68.4 ± 4.9 mg), and 2 (49.0 ± 54.6 mg). From prefinal (35 days) to last measurement (42 days) carriers 2 (8.6 ± 4.8 mg), 1 (2.4 ± 1.0 mg), and 5 (0.1 ± 0.1 mg) had released highest vancomycin masses. Notably, all five bone cements tested only released a small percental amount of their total mass up to the last measurement (42 days; 2.1% – 9.3%), whilst allografts and resorbable synthetic bone fillers discarded high percental values (22.5% – 79.2%). Conclusions. Elution kinetics differ between 9 antibiotic-loaded bone fillers, with high vancomycin masses released by allografts and resorbable bone fillers over time. Transferred to clinical practice, these may be favoured over bone cements in case prolonged and high antibiotic release is warranted rather than mechanical stability

INTRODUCTION. Deformation of modular acetabular press-fit shells is of much interest for surgeons and manufacturers. Initial fixation is achieved through press-fit between shell and acetabulum with the shell mechanically deforming upon insertion. Shell deformation may disrupt the assembly process of modular systems and may adversely affect integrity and durability of the components and tribology of the bearing. The aim of the study was to show shell deformation as a function of bone and shell stiffness. METHODS. The stiffness of the generic shells was determined using a uniaxial/ two point loading frame by applying different loads, and the change in dimension was measured by a coordinate measurement machine (CMM). Cadaver lab deformation measurements were done before and after insertion for 32 shells with 2 wall thicknesses and 11 shell sizes using the ATOS Triple Scan III (ATOS) optical system previously validated as a suitable measurement system to perform those measurements. Multiple deformation measurements per cadaver were performed by using both hip sides and stepwise increasing the reamed acetabulum by at least 1 mm, depending on sufficient residual bone stock. The under-reaming was varied between 0mm and 1mm, respectively. From the deformations, the resulting forces on the shells and bone stiffness were calculated assuming force equilibrium as well as linear-elastic material behaviour in each point at the rim of the shell. RESULTS. Radial stiffness for shells with 3 mm wall thickness ranged between 6257 N/mm and 2920 N/mm, with 4 mm wall thickness it ranged between 14341 N/mm and 6875 N/mm. The radial shell deformation ranged between 3 µm and 187 µm. The resulting maximum radial forces acting on the shells ranged between 26 N and 916 N. From these values, bone stiffness [N/mm] at the point of the maximum deformation has been calculated. Adding the bone stiffness and the shell stiffness using the equation for serial springs, one obtains a positive correlation between total stiffness and maximum deformation. DISCUSSION. The measured deformation values are within the same order of magnitude previously published [Lin 2006, Squire 2006]. The large variations of resulting maximum forces exhibit the need to further investigate shell deformation using commercial shell systems. The calculated bone stiffness at the point of the maximum deformation seems to be a valid predictor for expected shell deformation, but this also needs more data. A future goal is to determine expected shell deformation from bone data as a design rational

Aims. Disorders of bone integrity carry a high global disease burden, frequently requiring intervention, but there is a paucity of methods capable of noninvasive real-time assessment. Here we show that miniaturized handheld near-infrared spectroscopy (NIRS) scans, operated via a smartphone, can assess structural human bone properties in under three seconds. Methods. A hand-held NIR spectrometer was used to scan bone samples from 20 patients and predict: bone volume fraction (BV/TV); and trabecular (Tb) and cortical (Ct) thickness (Th), porosity (Po), and spacing (Sp). Results. NIRS scans on both the inner (trabecular) surface or outer (cortical) surface accurately identified variations in bone collagen, water, mineral, and fat content, which then accurately predicted bone volume fraction (BV/TV, inner R. 2. = 0.91, outer R. 2. = 0.83), thickness (Tb.Th, inner R. 2. = 0.9, outer R. 2. = 0.79), and cortical thickness (Ct.Th, inner and outer both R. 2. = 0.90). NIRS scans also had 100% classification accuracy in grading the quartile of bone thickness and quality. Conclusion. We believe this is a fundamental step forward in creating an instrument capable of intraoperative real-time use. Cite this article: Bone Jt Open 2023;4(4):250–261

Trabecular bone is a multiscale hierarchical composite material that is known to display time-dependant properties. However, most biomechanical models treat this material as time independent. Time-dependant properties, such as creep and relaxation, are thought to play an important role in many clinically relevant orthopaedic issues: implant loosening, vertebral collapse, and non-traumatic fractures. In this study compressive multiple-load-creep-unload-recovery (MLCUR) tests were applied to human trabecular bone specimens. 15 female femoral heads were harvested, with full ethical approval and patient consent, at the time of total hip replacement. Central cores were extracted and cut parallel under constant irrigation. Specimens were embedded in end caps using surgical cement, an epoxy tube was secured around the end caps and filled with phosphate buffered saline (PBS) to ensure the specimens remained hydrated throughout. Embedded samples were scanned by microCT (SkyScan 1172, Bruker) at a resolution of 17µm to determine microarchitecture. Bone volume fraction (BVF) was used to represent microarchitecture. Specimens had an effective length of 16.37mm (±1.90SD) with diameter of 8.08mm (±0.05SD), and BVF of 19.22% (±5.61SD). The compressive MLCUR tests were conducted at 5 strain levels, 2000µε, 4000µε, 6000µε, 8000µε and 10000µε. At each strain level, the load required to maintain each strain was held for 200s (creep) then unloaded to 1N for 600s (recovery). The instantaneous, creep, unloading and recovered strains can be easily obtained from the strain-time curves. Stress-strain plots revealed the Young's modulus. Data was modelled using line of best fit with appropriate curve fitting. R2 values were used to indicate association. Mechanical testing demonstrated the expected time independent relationship between BVF and stiffness: higher stiffness was found for specimen with higher BVF and this was consistent for all strain levels. Creep strain was found to depend on instantaneous strain and BVF. At low levels of instantaneous strain, there was a greater amount of creep strain in low BVF samples (R2 = 0.524). This relationship was no longer apparent at higher strain levels (R2 = 0.058). Residual strain also depended on the applied instantaneous strain and BVF: at low levels of strain, residual strain was similar with all BVF (R2 = 0.108) and at high levels of strain, residual strain was greater in low BVF samples (R2 = 0.319). The amount of instantaneous strain applied to each sample is constant, variations in stiffness result in different applied loads. In low BVF bone, the stiffness is also low, therefore the stress required to reach designed strain is also lower: yet, there is more creep and less recovery. We have demonstrated that even at loads below recognised yield levels, time-dependence affects the mechanical response and residual strain is present. In cases of low BVF, deflection due to creep, and increased irrecoverable strain could have clinically relevant consequences, such as implant loosening and vertebral collapse. The role of time-dependant properties of bone is seldom considered. This data could be developed into a constitutive model allowing these time-dependant behaviours to be incorporated in finite element modelling, leading to better predictions of implant loosening, especially for lower quality bone

Introduction. The reconstruction of segmental long bone defects remains one of the holy grails of orthopaedic surgery. The optimal treatment of which remains a topic of great debate. This study aimed to evaluate the outcomes following the management of critical-sized bone defects using a classification-based treatment algorithm. Materials & Methods. A retrospective review of all patients undergoing treatment for segmental diaphyseal defects of long bones at a tertiary-level limb reconstruction unit was performed. The management of the bone defect was standardised as per the classification by Ferreira and Tanwar (2020). Results. A total of 96 patients (mean age 39.8, SD 15.2) with a minimum six months follow-up were included. Most bone defects were the result of open fractures (75/96) with 67% associated with Gustilo-Anderson IIIB injuries. There was a statistical difference in the likelihood of union between treatment strategies with more than 90% of cases undergoing acute shortening and bone transport achieving union and only 72% of cases undergoing the induced membrane technique consolidating (p=0.049). Of those defects that consolidated, there was no difference in the time to bone union between strategies (p=0.308) with an overall median time to union 8.33 months (95% CI 7.4 — 9.2 months). The induced membrane technique was associated with a 40% risk of sepsis. Conclusions. This study reported the outcomes of a standardised approach to the management of critical-sized bone defects. Whilst overall results were supportive of this approach, the outcomes associated with the induced membrane technique require further refinement of its indications in the management of critical-sized bone defects

One out of nine Canadian males would suffer prostate cancer (PC) during his lifetime. Life expectancy of males with PC has increased with modern therapy and 90% live >10 years. However, 20% of PC-affected males would develop incurable metastatic diseases. Bone metastases (BM) are present in ~80% of metastatic PC patients, and are the most severe complication of PC, generating severe pain, fractures, spinal cord compression, and death. Interestingly, PC-BMs are mostly osteoblastic. However, the structure of this newly formed bone and how it relates to pain and fracture are unknown. Due to androgen antagonist treatment, different PC phenotypes develop with differential dependency on androgen receptor (AR) signaling: androgen-dependent (AR+), double negative (AR-) and neuroendocrine. How these phenotypes are related to changes in bone structure has not been studied. Here we show a state-of-the-art structural characterization of PCBM and how PC phenotypes are associated to abnormal bone formation in PCBM. Cadaveric samples (n=14) obtained from metastases of PC in thoracic or lumbar vertebrae (mean age 74yo) were used to analyze bone structure. We used micro-computed tomography (mCT) to analyze the three-dimensional structure of the bone samples. After imaging, the samples were sectioned and one 3mm thick section was embedded in epoxy-resin, ground and polished. Scanning electron microscopy (SEM)/energy-dispersive X-ray spectroscopy (EDS) and quantitative backscattering electron (qBSE) imaging were used to determine mineral morphology and composition. Another section was used for histological analysis of the PC-affected bone. Collagen structure, fibril orientation and extracellular matrix composition were characterized using histochemistry. Additionally, we obtained biopsies of 3 PCBM patients undergoing emergency decompression surgery following vertebral fracture and used them for immunohistological characterization. By using mCT, we observed three dysmorphic bone patterns: osteolytic pattern with thinned trabecula of otherwise well-organized structures, osteoblastic pattern defined as accumulation of disorganized matrix deposited on pre-existing trabecula, and osteoblastic pattern with minimum residual trabecula and bone space dominated by accumulation of disorganized mineralized matrix. Comparing mCT data with patho/clinical parameters revealed a trend for higher bone density in males with larger PSA increase. Through histological sections, we observed that PC-affected bone, lacks collagen alignment structure, have a higher number of lacunae and increased amount of proteoglycans as decorin. Immunohistochemistry of biopsies revealed that PC-cells inside bone organize into two manners: i) glandular-like structures where cells maintain their polarization in the expression of prostate markers, ii) diffuse infiltrate that spreads along bone surfaces, with loss of cell polarity. These cells take direct contact with osteoblasts in the surface of trabecula. We define that PCBM are mostly composed by AR+ with some double negative cells. We did not observe neuroendocrine phenotype cells. PCBMs generate predominantly osteoblastic lesions that are characterized by high lacunar density, lack of collagen organization and elevated proteoglycan content. These structural changes are associated with the infiltration of PC cells that are mostly androgen-dependent but have lost their polarization and contact directly with osteoblasts, perhaps altering their function. These changes could be associated with lower mechanical properties that led to fracture and weakness of the PCBM affected bone

Aims. The standard of wide tumour-like resection for chronic osteomyelitis (COM) has been challenged recently by adequate debridement. This paper reviews the evolution of surgical debridement for long bone COM, and presents the outcome of adequate debridement in a tertiary bone infection unit. Methods. We analyzed the retrospective record review from 2014 to 2020 of patients with long bone COM. All were managed by multidisciplinary infection team (MDT) protocol. Adequate debridement was employed for all cases, and no case of wide resection was included. Results. A total of 53 patients (54 bones) with median age of 45.5 years (interquartile range 31 to 55) and mean follow-up of 29 months (12 to 59) were included. In all, ten bones were Cierny-Mader type I, 39 were type III, and five were type IV. All patients were treated with single-staged management, except for one (planned two-stage stabilization). Positive microbial cultures grew in 75%. Overall, 46 cases (85%) had resolution of COM after index procedure, and 49 (90.7%) had resolution on last follow-up. Four patients (7%) underwent second surgical procedure and six patients (11%) had complications. Conclusion. We challenge the need for wide tumour-like resection in all cases of COM. Through detailed preoperative evaluation and planning with MDT approach, adequate debridement and local delivery of high concentration of antibiotic appears to provide comparable outcomes versus radical debridement. Cite this article: Bone Jt Open 2023;4(8):643–651

Revision surgeries for orthopaedic infections are done in two stages – one surgery to implant an antibiotic spacer to clear the infection and another to install a permanent implant. A permanent porous implant, that can be loaded with antibiotics and allow for single-stage revision surgery, will benefit patients and save healthcare resources. Gyroid structures can be constructed with high porosity, without stress concentrations that can develop in other period porous structures [1] [2]. The purpose of this research is to compare the resulting bone and prosthesis stress distributions when porous versus solid stems are implanted into three proximal humeri with varying bone densities, using finite element models (FEM). Porous humeral stems were constructed in a gyroid structure at porosities of 60%, 70%, and 80% using computer-aided design (CAD) software. These CAD models were analyzed using FEM (Abaqus) to look at the stress distributions within the proximal humerus and the stem components with loads and boundary conditions representing the arm actively maintained at 120˚ of flexion. The stem was assumed to be made of titanium (Ti6Al4V). Three different bone densities were investigated, representing a healthy, an osteopenic, and an osteoporotic humerus, with an average bone shape created using a statistical shape and density model (SSDM) based on 75 cadaveric shoulders (57 males and 18 females, 73 12 years) [3]. The Young's moduli (E) of the cortical and trabecular bones were defined on an element-by-element basis, with a minimum allowable E of 15 MPa. The Von Mises stress distributions in the bone and the stems were compared between different stem scenarios for each bone density model. A preliminary analysis shows an increase in stress values at the proximal-lateral region of the humerus when using the porous stems compared to the solid stem, which becomes more prominent as bone density decreases. With the exception of a few mesh dependent singularities, all three porous stems show stress distributions below the fatigue strength of Ti-6Al-4V (410 MPa) for this loading scenario when employed in the osteopenic and osteoporotic humeri [4]. The 80% porosity stem had a single strut exceeding the fatigue strength when employed in the healthy bone. The results of this study indicate that the more compliant nature of the porous stem geometries may allow for better load transmission through the proximal humeral bone, better matching the stress distributions of the intact bone and possibly mitigating stress-shielding effects. Importantly, this study also indicates that these porous stems have adequate strength for long-term use, as none were predicted to have catastrophic failure under the physiologically-relevant loads. Although these results are limited to a single boney geometry, it is based on the average shape of 75 shoulders and different bone densities are considered. Future work could leverage the shape model for probabilistic models that could explore the effect of stem porosity across a broader population. The development of these models are instrumental in determining if these structures are a viable solution to combatting orthopaedic implant infections

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

Primary hip and knee joint replacements in Canada have been estimated to cost over $1.4 billion dollars annually, with revision surgery costing $177 million. The most common cause of revision arthroplasty surgery in Canada is infection. Periprosthetic joint infections (PJIs) are a devastating though preventable complication following arthroplasty. Though variably used, antibiotic laden bone cement (ALBC) has been demonstrated to decrease PJIs following primary total knee arthroplasty (TKA). Unfortunately, ALBC is costlier than regular bone cement (RBC). Therefore, the aim of this study was to determine if the routine use of ALBC in primary TKA surgery is a cost-effective practice from the perspective of the Canadian healthcare system. A decision tree was constructed using a decision analysis software (TreeAge Software, Williamstown, Massachusetts) to a two-year time horizon comparing primary TKA with either ALBC or RBC from the perspective of a single-payer healthcare system. All costs were in 2020 Canadian dollars. Health utilities were in the form of quality adjusted life years (QALYs). Model inputs for cost were derived from regional and national databases. Health utilities and probability parameters were derived from the latest literature. One-way deterministic sensitivity analysis was performed on all model parameters. The primary outcome of this analysis was an incremental cost-effectiveness ratio (ICER) with a willingness-to-pay (WTP) threshold of $50,000 per QALY. Primary TKA with ALBC (TKA-ALBC) was found to be more cost-effective compared to primary TKA with RBC (TKA-RBC). More specifically, TKA-ALBC dominated TKA-RBC as it was less costly on the long term ($11,160 vs. $11,118), while providing the same QALY (1.66). The ICER of this cost-utility analysis (CUA) was $-11,049.72 per QALY, much less than the WTP threshold of $50,000 per QALY. The model was sensitive to costs of ALBC-TKA as well as the probability of PJI following ALBC-TKA and RBC-TKA. ALBC ceased to be cost effective once the cost of ALBC was greater than $223.08 CAD per bag of cement. The routine use of ALBC in primary TKA is a cost-effective practice in the context of the Canadian healthcare system as long as the cost of ALBC is maintained at a reasonable price and the published studies to-date keep supporting the efficacy of ALBC in decreasing PJI following primary TKA. Further, this analysis is very conservative, and ALBC is likely much more cost-effective than presented. This is due to this model's revision surgery cost parameter being based on the average cost of all revision TKA surgery in Canada, regardless of etiology. Considering many PJIs require two-stage revisions, the cost parameter used in this analysis for revision surgery is an underestimate of true cost. Ultimately, this is the first cost-effectiveness study evaluating this topic from the perspective of the Canadian healthcare system and can inform future national guidelines on the subject matter

Aim. Galleria mellonella larvae is a well-known insect infection model that has been used to test the virulence of bacterial and fungal strains as well as for the high throughput screening of antimicrobial compounds against infections. Recently, we have developed insect infection model G. mellonella larvae to study implant associated biofilm infections using small K-wire as implant material. Here, we aimed to further expand the use of G. mellonella to test other materials such as bone cement with combination of gentamicin to treat implant-associated infections. Method. The poly methyl methacrylate (PMMA) with and without gentamicin and liquid methyl methacrylate (MMA) were kindly provided by Heraeus Medical GmbH, Wehrheim. To make the bone cement implants as cubes, Teflon plate (Karl Lettenbauer, Erlangen) with specified well size was used. The Radiopaque polymer and monomer were mixed well in a bowl, applied over on to the Teflon plate and pressed with spatula to form fine and uniform cubes. After polymerization, the bone cement implants were taken out of the Teflon well plate with the help of pin. For the infection process, bone cement cubes were pre-incubated with S. aureus EDCC 5055 culture at 5×10. 6. CFU/ml for 30 min at 150 rpm shaking conditions. Later, these implants were washed with 10ml PBS and implanted in the larvae as mentioned. Survival of the larvae were observed at 37°C in an incubator. To analyze the susceptibility of the bacterial infections towards gentamicin, survival of the larvae compared with control group implanted only with bone cement. The effect of gentamicin was also measured in terms of S. aureus load in larvae on 2. nd. day. SEM analysis was performed to see the effect of gentamicin on biofilm formation on bone cement. Results. Our experiments established the G. mellonella as an excellent model to screen bone cement with antimicrobial compounds against bacterial infections. The gentamicin bone cement samples showed excellent S. aureus bacterial load reduction after the implantation in G. mellonella model. The bone cement with gentamicin showed better survival of larvae infected with S. aureus compared to control. Finally, the gentamicin also affected the biofilm formation on the bone cement surface with S. aureus. Conclusions. Thus, our work showed G. mellonella is a rapid, cheap economical pre-clinical model to study the bone cement associate bacterial infections as well as screening of the various antimicrobial compounds

The Cierny and Mader classification assists with decision-making in the management of osteomyelitis by strafying the host status and the pathoanatomy of disease. However the anatomical type IV represents a heterogenous group with regards to treatment requirements and outcomes. We propose that modification of the Cierny and Mader anatomical classification with an additional type V classifier (diffuse corticomedullary involvement with an associated critical bone defect) will allow more accurate stratification of patients and tailoring of treatment strategies. A retrospective review of 83 patients undergoing treatment for Cierny and Mader anatomical type IV osteomyelitis of the appendicular skeleton at a single centre was performed. Risk factors for the presence of a critical bone defect were female patients (OR 3.1 (95% CI 1.08– 8.92)) and requirement for soft tissue reconstruction (OR 3.35 (95% CI 1.35–8.31)); osteomyelitis of the femur was negatively associated with the presence of a critical bone defect (OR 0.13 (95% CI 0.03–0.66)). There was no statistical significant risk of adverse outcomes (failure to eradicate infection or achieve bone union) associated with the presence of a critical-sized bone defect. The median time to bone union was ten months (95% CI 7.9–12.1 months). There was a statistically significant difference in the median time to bone union between cases with a critical bone defect (12.0 months (95% 10.2–13.7 months)) and those without (6.0 months (95% CI 4.8–7.1 months)). This study provided evidence to support the introduction of a new subgroup of the Cierny and Mader anatomical classification (Type V). Using a standardised approach to management, comparable early outcomes can be achieved in patients with Cierny and Mader anatomical type V osteomyelitis. However, to achieve a successful outcome, there is a requirement for additional bone and soft tissue reconstruction procedures with an associated increase in treatment time

Introduction. The Cierny and Mader classification assists with decision-making by stratifying host status and the pathoanatomy of the disease. However, the anatomical type IV represents a heterogenous group with regards to treatment requirements and outcomes. We propose that modification of the Cierny and Mader anatomical classification with an additional type V classifier (diffuse corticomedullary involvement with an associated critical bone defect) will allow more accurate stratification of patients and tailoring of treatment strategies. Materials & Methods. A retrospective review of 83 patients undergoing treatment for Cierny and Mader anatomical type IV osteomyelitis of the appendicular skeleton at a single centre was performed. Results. Risk factors for the presence of a critical bone defect were female patients (OR 3.1 (95% CI 1.08–8.92)) and requirement for soft tissue reconstruction (OR 3.35 (95% CI 1.35–8.31)); osteomyelitis of the femur was negatively associated with the presence of a critical bone defect (OR 0.13 (95% CI 0.03–0.66)). There was no statistically significant risk of adverse outcomes (failure to eradicate infection or achieve bone union) associated with the presence of a critical-sized bone defect. The median time to bone union was ten months (95% CI 7.9–12.1 months). There was a statistically significant difference in the median time to bone union between cases with a critical bone defect (12.0 months (95% 10.2–13.7 months)) and those without (6.0 months (95% CI 4.8–7.1 months)). Conclusions. This study provided evidence to support the introduction of a new subgroup of the Cierny and Mader anatomical classification (Type V). Using a standardised approach to management, comparable early outcomes can be achieved in patients with Cierny and Mader anatomical type V osteomyelitis. However, to achieve a successful outcome, there is a requirement for additional bone and soft tissue reconstruction procedures with an associated increase in treatment time

Metastatic bone disease (MBD) is a significant contributor to diminished quality of life in cancer patients, often leading to pathologic fractures, hypercalcaemia, intractable bone pain, and reduced functional independence. Standard of care management for MBD patients undergoing orthopaedic surgery is multi-disciplinary, includes regular surgical follow-up, case by case assessment for use of bone protective medications, and post-operative radiation therapy to the operative site. The number of patients in southern Alberta receiving standard of care post-operative management is currently unclear. Our aim is to develop a database of all patients in southern Alberta undergoing orthopaedic surgery for MBD and to assess for deficiencies and opportunities to ensure standard of care for this complex patient population. Patients were identified for database inclusion by a search query of the Alberta Cancer Registry of all patients with a diagnosis of metastatic cancer who underwent surgery for an impending or pathologic fracture in the Calgary, South and Central Alberta Zones. Demographic information, primary cancer history, previous local and systemic treatments, anatomical location of MBD event(s), surgical fixation techniques, and post-operative care details were collected. The rate of standard of care post-operative treatment was evaluated. A comparison of outcomes between tertiary urban centres and rural centres was also completed. Survival was calculated from time of first operation to date of death. Univariate and multivariate analyses were performed to identify the impact of post-operative care variables on survival amongst patients surviving longer than one month. We identified 402 patients who have undergone surgical treatment for MBD in southern Alberta from 2006-2018. Median age at time of surgery was 66.3 years and 52.7% of patients were female. Breast, lung, prostate, renal cell and multiple myeloma were the most common primary malignancies (n=328, 81.6%). Median post-operative survival was 6.8 months (95%CI: 5.7-8.3). 203 patients (52.5%) were treated with post-operative radiotherapy and 159 patients (50.8%) had post-operative surgical follow-up. Only 39 patients (11.3%) received bone protective agents in the peri-operative period. On multivariate survival analysis, post-operative surgical follow-up was associated with improved survival (p<0.001). Patients were treated at nine hospitals across southern Alberta with most patients treated in an urban center (65.9%). Post-operative survival was significantly longer amongst patients treated in an urban center (9.0 months, 95%CI: 6.9-12.3 versus 4.3 months, 95%CI: 3.4-5.6, p<0.001). The burden of MBD is significant and increasing. With treatment occurring at multiple provincial sites, there is a need for standardized, primary disease-specific peri- and post-operative protocols to ensure quality and efficacious patient care. To provide evidence informed treatment recommendations, we have developed a database of all patients in southern Alberta undergoing orthopaedic surgery for MBD. Our results demonstrate that many patients were not treated according to post-operative standard of care recommendations. Notably, half of the included patients did not have documented surgical follow-up, post-operative radiation treatment was low and only 11% were actively treated with bone protective agents. This data justifies the need for established surgical MBD care pathways and provides reference data to benchmark prospective QA and QI outcomes in this patient population

Introduction. The presence of pluripotent mesenchymal cells in the periosteum along with the growth factors produced or released following injury provides this tissue with an important role in bone healing. Utilising this property, vascularised periosteal flaps may increase the union rates in recalcitrant atrophic long bone non-union. The novel chimeric fibula-periosteal flap utilises the periosteum raised on an independent periosteal vessel, thus allowing the periosteum to be inset freely around the osteotomy site, improving bone biology. Materials & Methods. Ten patients, with established non-union, underwent fibula-periosteal chimeric flaps (2016–2022) at the Canniesburn Plastic Surgery Unit, UK. Preoperative CT angiography was performed to identify the periosteal branches. A case-control approach was used. Patients acted as their own controls, which obviated patient specific risks for non-union. One osteotomy site was covered by the chimeric periosteal flap and one without. In two patients both the osteotomies were covered using a long periosteal flap. Results. Union rate of 100% (11/11) was noted with periosteal flap osteotomies, versus those without flaps at 28.6% (2/7) (p = 0.0025). Time to union was also reduced in the periosteal flaps at 8.5 months versus 16.75 months in the control group (p = 0.023). Survival curves with a hazard ratio of 4.1, equating to a 4 times higher chance of union with periosteal flaps (log-rank p = 0.0016) was observed. Conclusions. The chimeric fibula-periosteal flap provides an option for atrophic recalcitrant non-unions where use of vascularised fibula graft alone may not provide an adequate biological environment for consolidation

Paediatric bone and joint infections remain common in low- and middle-income countries (LMICs). We aimed to determine the complication rate and incidence of disseminated infection in paediatric bone and joint infections in an LMIC setting. Secondly, we aimed to elucidate factors associated with complications and disseminated disease. We retrospectively reviewed our database for children that presented with bone and joint infections between September 2015 and March 2019. Data were extracted to identify factors that were associated with development of complications and disseminated infection. We analysed 49 children. The median age at presentation was 6 years (range 1 month to 12 years). Locally advanced disease was present in 13 children (27%). The remaining 36 children were evenly divided (18/49 each, 37%) between isolated AHOM and SA, respectively. Disseminated disease was present in 16 children (33%) and was associated with locally advanced disease, an increase in number of surgeries and an increased length of stay. Twenty-six complications were documented in 22 (45%) children. Chronic osteomyelitis developed in 15/49 (31%) cases, growth arrest in 5/49 (10%), and pathological fracture, DVT and septic shock in 2/49 (4%) each. Complicated disease was associated with locally advanced disease, a higher number of surgeries, disseminated disease and an increased length of stay. Sixty five percent of cases cultured Staphylococcus aureus, while 25% (12/49) were culture negative. The median time from admission to surgery was one day, and the median time from onset of symptoms to surgery was seven days. We found a high complication rate. One third of patients had locally advanced disease, and this was associated with the development of complications and disseminated disease. Further studies are needed to be able to predict which children will have poor outcomes

Osteogenic augmentation is required in various orthopaedic conditions. Autograft is the gold standard but has limitations of increased morbidity and limited amount. Bone graft substitutes are costly and limited and don't integrate with host bone. Deep freezed allografts are a viable option, though not widely used in India and there are sparse reports in literature. This paper studies early efficacy of deep freezed bone allografts in treatment of fractures requiring bone graft. This is a prospective descriptive study. Strict inclusion and exclusion criteria as per standard guidelines were followed. We have a in-house facility of gamma irradiated deep freezed allografts available in hospital. 20 patients with comminuted fracture, delayed / malunion / nonunion, depressed intra articular fractures were operated during one year and followed up for at least 24 weeks. Sloof's Criteria was used for assessing osteointegration of grafts. Efficacy was authenticated by observing complications like serous discharge from surgical site, infection (superficial/deep), rejection of graft, clinical and radiological integration of graft, maintenance of articular reduction etc. Allografts have not only accepted well but fractures have healed and bone integration is at various stages. Only one patients got infected (5%). The overall success rate in terms of adequate osteointegration is 95 %. 19 out of 20 patients in our study group had either attained or at various stages of osteointegration and healing. We concluded that deep freezed bone allografts is a viable option in patients with fractures requiring bone grafts, thus give satisfactory surgical outcome, with no serious side effects

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