The operative treatment of fractures of the proximal humerus can be complicated by poor bone quality. Our aim was to evaluate a new method which allows prediction of the bone quality of the proximal humerus from radiographs. Anteroposterior radiographs were taken of 19 human cadaver humeri. The cortical thickness was measured at two levels of the proximal humeral diaphysis. The bone mineral density (BMD) was determined for the humeral head (HH), the surgical neck (SN), the greater tuberosity (GT) and lesser tuberosity (LT) using dual-energy x-ray absorptiometry. The mean cortical thickness was 4.4 ± 1.0 mm. Specimens aged 70 years or less had a significantly higher cortical thickness than those aged over 70 years. A significant positive correlation was found between cortical thickness and the BMD for each region of interest. The cortical thickness of the proximal diaphysis is a reliable predictor of the bone quality of the proximal humerus

Recent researches indicate that both M1 and M2 macrophages play vital roles in tissue repair and foreign body reaction processes. In this study, we investigated the dynamics of M1 macrophages in the induced membrane using a mouse femur critical-sized bone defect model. The Masquelet method (M) and control (C) groups were established using C57BL/6J male mice (n=24). A 3mm-bone defect was created in the right femoral diaphysis followed by a Kirschner wire fixation, and a cement spacer was inserted into the defect in group M. In group C, the bone defect was left uninserted. Tissues around the defect were harvested at 1, 2, 4, and 6 weeks after surgery (n=3 in each group at each time point). Following Hematoxylin and eosin (HE) staining, immunohistochemical staining (IHC) was used to evaluate the CD68 expression as a marker of M1 macrophage. Iron staining was performed additionally to distinguish them from hemosiderin-phagocytosed macrophages. In group M, HE staining revealed a hematoma-like structure, and CD68-positive cells were observed between the spacer and fibroblast layer at 1 week. The number of CD68-positive cells decreased at 2 weeks, while they were observed around the new bone at 4 and 6 weeks. In group C, fibroblast infiltration and fewer CD68-positive cells were observed in the bone defect without hematoma-like structure until 2 weeks, and no CD68-positive cells were observed at 4 and 6 weeks. Iron staining showed hemosiderin deposition in the surrounding area of the new bone in both groups at 4 and 6 weeks. The location of hemosiderin deposition was different from that of macrophage aggregation. This study suggests that M1 macrophage aggregation is involved in the formation of induced membranes and osteogenesis and may be facilitated by the presence of spacers

Renal Osteodystrophy is a type of metabolic bone disease characterized by bone mineralization deficiency due to electrolyte and endocrine abnormalities. Patients with chronic kidney disease (CKD) are more likely to experience falls and fractures due to renal osteodystrophy and the high prevalence of risk factors for falls. Treatment involves medical management to resolve the etiology of the underlying renal condition, as well as management (and prevention) of pathological fractures. A 66-year-old female patient, with severe osteoporosis and chronic kidney disease undergoing haemodialysis, has presented with multiple fractures along the years. She was submitted to bilateral proximal femoral nailing as fracture treatment on the left and prophylactically due to pathological bone injury on the right, followed by revision of the left nail with a longer one after varus angulation and fracture distal to the nail extremity. Meanwhile, the patient suffered a pathological fracture of the radial and cubital diaphysis and was submitted to conservative treatment with cast, with consolidation of the fracture. Posteriorly, she re-fractured these bones after a fall and repeated the conservative treatment. Clinical management: There is a multidisciplinary approach to manage the chronic illness of the patient, including medical management to resolve the etiology and consequences of her chronic kidney disease, pain control, conservative or surgical fracture management and prevention of falls. The incidence of chronic renal disease is increasing and the patients with this condition live longer than previously and are more physically active. Thus, patients may experience trauma as a direct result of increased physical activity in a setting of weakened pathologic bone. Their quality of life is primarily limited by musculoskeletal problems, such as bone pain, muscle weakness, growth retardation, and skeletal deformity. A multidisciplinary approach is required to treat these patients, controlling their chronic diseases, managing fractures and preventing falls

Most of researches related to osteoporosis emphasized on trabecular bone loss. However, cortical bone has a prominent role on bone strength determined by bone quality, such as 2D or 3D geometry and microstructure of bone, not only density.[1] The focal thinning of cortical bone associated with aging in post-menopausal osteoporotic bone in the proximal femur may predispose a hip to fracture.[2, 3] As the trabecular bone is lost with progression of osteoporosis, the remaining cortical bone take more predominant role on bone strength.[4] To date, no effective osteoporotic agent was demonstrated to enhance both cortical geometric change and bone strength. Herein, we investigate the effect of Teriparatide (rhPTH(1–34)) on cortical bone at femoral diaphysis in OVX rat model. Twenty 12-week-old, female Sprague Dawley rats were used in this study. Bilateral ovariectomies were performed in 16 animals and randomly divided to three groups as control (N=6), OVX (N=6) and treatment group after OVX (OVX+F) by teriparatide (N=8). After twelve weeks of intervention, all rats were euthanized and right femurs and L5 vertebrae were extracted for further tests. All bone specimens were subjected to dual-energy X-ray absorptiometer (DXA) to evaluate areal bone mineral density (aBMD) of L5 vertebrae and femurs, micro-computed tomography (micro-CT) to analyze cortical bone parameters of femoral diaphysis, including cortical cross section area (CSA), cortical thickness and cross-sectional moment of inertia (CSMI). A three-point bending test was applied to determine fracture load of each femurs. Compare to OVX group, increase of aBMD by 14.6 % at L5 vertebrae and 13.3% at femoral diahpysis in treatment group. The cortical parameters of femoral diaphysis, CSA and cortical thickness, analyzed by micro-CT were significantly increased but the increasing tendency of CSMI did not have significant changes statistically after teriparatide intervention for 3 months duration. The increase of cortical bone strength (OVX vs OVX+F group, 120.72±2.72 vs 137.93±5.02, p < 0.05) at femoral diaphysis after treatment were also noticed. This study has point out a deeper look at geometric change of cortical bone after teriparatide treatment. This finding imply teirparatide has the ability to change the geometry of cortical bone and increase bone strength at femoral diaphysis

Abstract. Objectives. Stem malalignment in total hip arthroplasty (THA) has been associated with poor long-term outcomes and increased complications (e.g. periprosthetic femoral fractures). Our understanding of the biomechanical impact of stem alignment in cemented and uncemented THA is still limited. This study aimed to investigate the effect of stem fixation method, stem positioning, and compromised bone stock in THA. Methods. Validated FE models of cemented (C-stem – stainless steel) and uncemented (Corail – titanium) THA were developed to match corresponding experimental model datasets; concordance correlation agreement of 0.78 & 0.88 for cemented & uncemented respectively. Comparison of the aforementioned stems was carried out reflecting decisions made in the current clinical practice. FE models of the implant positioned in varus, valgus, and neutral alignment were then developed and altered to represent five different bone defects according to the Paprosky classification (Type I – Type IIIb). Strain was measured on the femur at 0mm (B1), 40mm (B2), and 80mm (B3) from the lesser trochanter. Results. Cemented constructs had lower strain on the implant neck, and higher overall stiffness and strain on bone compared to uncemented THA. Strain on the bone increased further down the shaft of the femoral diaphysis, and with progressing bone defect severity in all stem alignment cases. Highest strain on the femur was found at B2 in all stem alignment and bone defect models. Varus alignment showed higher overall femoral strain in both fixation methods. Interestingly, in uncemented models, highest strain was shown on femoral bone proximally (B1-B2) in varus alignment, but distally (B3) in neutral alignment. Conclusion. Varus stem alignment showed overall higher strain on femur compared to neutral and valgus. This highlights the crucial role of stem alignment in long term outcomes of THA. Differences between the two stem types should be taken in consideration when interpreting results from this study

Adrenomedullin is a peptide hormone that has attracted attention with its proliferative and anti-apoptotic effects on osteoblasts in recent years. We investigated the effect of adrenomedullin on healing of the segmental bone defect in a rat model. 36 Wistar rats were randomly divided in six groups based on follow-up periods and administered dose of adrenomedullin hormone. In each group, a 2 mm bone defect was created at the diaphysis of radius, bilaterally. NaCl solution was administered to sham groups three times a week for 4 and 8 weeks, intraperitoneally. Adrenomedullin was administered to study groups three times a week; 15 µg-4 weeks, 15 µg-8 weeks, 30 µg-4 weeks and 30 µg-8 weeks, respectively. After euthanasia, the segmental defects were evaluated by histomorphometric (new bone area (NBA)) and micro-tomographic (bone volume (BV), bone surface (BS), bone mineral density (BMD)) analysis. Although 4 and 8 weeks 15 μg administered study groups had higher NBA values than the other study and control groups, histomorphometric analysis did not reveal any statistical difference between the control and study groups in terms of new bone area (p > 0.05). In micro-tomographic analysis, BV was higher in 15 μg – 4 weeks group than 30 μg – 4 weeks group (296.9 vs 208.5, p = 0.003) and BS was lower in 30 μg – 4 weeks than 4 week - control group (695.5 vs 1334.7, p = 0.005) but in overall, no significant difference was found between the control and study groups (p > 0.05). Despite these minor differences in histomorphometric and micro-tomographic criteria indicating new bone formation, BMD values of 15 µg-4 and −8 weeks study groups showed significant increase comparing with the control group (p = 0.04, p = 0.001, respectively). Adrenomedullin seemed to have a positive effect on BMD at a certain dose (15 µg) but it alone is not considered sufficient for healing of the defect with new bone formation. Further studies are needed to assess its effects on bone tissue trauma. This study was funded by Hacettepe University Scientific Research Projects Coordination Unit

Objectives. We evaluated the accuracy of augmented reality (AR)-based navigation assistance through simulation of bone tumours in a pig femur model. Methods. We developed an AR-based navigation system for bone tumour resection, which could be used on a tablet PC. To simulate a bone tumour in the pig femur, a cortical window was made in the diaphysis and bone cement was inserted. A total of 133 pig femurs were used and tumour resection was simulated with AR-assisted resection (164 resection in 82 femurs, half by an orthropaedic oncology expert and half by an orthopaedic resident) and resection with the conventional method (82 resection in 41 femurs). In the conventional group, resection was performed after measuring the distance from the edge of the condyle to the expected resection margin with a ruler as per routine clinical practice. Results. The mean error of 164 resections in 82 femurs in the AR group was 1.71 mm (0 to 6). The mean error of 82 resections in 41 femurs in the conventional resection group was 2.64 mm (0 to 11) (p < 0.05, one-way analysis of variance). The probabilities of a surgeon obtaining a 10 mm surgical margin with a 3 mm tolerance were 90.2% in AR-assisted resections, and 70.7% in conventional resections. Conclusion. We demonstrated that the accuracy of tumour resection was satisfactory with the help of the AR navigation system, with the tumour shown as a virtual template. In addition, this concept made the navigation system simple and available without additional cost or time. Cite this article: H. S. Cho, Y. K. Park, S. Gupta, C. Yoon, I. Han, H-S. Kim, H. Choi, J. Hong. Augmented reality in bone tumour resection: An experimental study. Bone Joint Res 2017;6:137–143

Introduction. In recent years, there has been a growing interest, in many fields of medicine, in the use of bone adhesives that are biodegraded to non-toxic products and resorbed after fulfilling their function in contact with living tissue. Biomechanical properties of newly developed bone glue, such as adhesion to bone and elastic modulus were tested in our study. Material and methods. Newly developed injectable biodegradable “self-setting” bone adhesive prepared from inorganic tricalcium phosphate powder and aqueous solution of organic thermogelling polymers was used for ex-vivo fixing fractured pig femur. Ex-vivo biomechanical tests were performed on 45 fresh pig femurs. Control group consist of 10 healthy bones, tested group was created by 35 bones with artificial fractures in diaphysis – oblique (O) and bending wedge (BW) type of fracture. Tested group were divided to following 4 subgroups (sg); sg1 – O fracture (n=15) glued together with 3 different type of bone adhesives, sg2 BW fracture (n=5) glued together with bone adhesive (n=5); sg3 – BW fracture fixed with locking compression plate (LCP), n=5; sg4 – BW fracture fixed with LCP in combination with bone adhesive. Three-point bending force and shear compression tests were performed on linear electrodynamic test instrument (ElectroPuls E10000, Instron). Femurs from sg1, sg2 and sg4 were tested on Micro-CT before and after biomechanical testing. Results. Shear compression tests in sg1 without amino acids modification showed that it is needed force of 0.5 mPa to recreate fracture, however, modification with amino acids increased glue strength to 3 mPa. Three-point bending force test in sg2 showed reduced force of 250 N to recreate fracture, anyhow in sg4 force needed to initiate the fracture was increased up to 5000 N. Conclusion. Newly developed injectable biodegradable “self- setting” bone adhesive represents new possibility how to fix small bone fragments in comminuted fractures and simultaneous chance how to improve and accelerate bone healing process. Acknowledgement. Project no. AOTEU-R-2016-064 was supported by AOTRAUMA, Switzerland

We measured the insertion and extraction torque forces in a randomised study of 76 external fixation screws in 19 patients treated by hemicallotasis for osteoarthritis of the medial side of the knee. The patients were randomised to have either standard tapered screws (Orthofix 6/5 mm) or the same screws with hydroxyapatite (HA) coating. One patient had two standard and two HA-coated screws. All patients had an anterior external fixator (Orthofix T-garche), with two screws in the proximal tibial metaphysis parallel to and about 2 cm below the joint surface and two in the tibial diaphysis. The mean torque forces for insertion of the standard screws were 260 Ncm for the proximal to medial screw, 208 for the proximal to lateral screw and 498 and 546 Ncm for the diaphyseal pins. The corresponding forces for the HA-coated pins were not significantly different. The torque forces for the extraction of the standard pins were 2 Ncm for the proximal pins, 277 and 249 Ncm for the distal pins and 482, 478, 585 and 620 Ncm, respectively (p < 0.005) for the HA-coated pins. All 18 of the metaphyseal standard screws were loose at extraction (extraction force < 20 Ncm), but only one of the HA screws in the metaphysis was loose. In the diaphysis the standard screws lost about 40% of their fixation in contrast to the HA-coated screws which retained full fixation strength

MicroRNA´s are regulatory sequences which influence the posttranscriptional synthesis of about 70% of protein encoding genes. In different studies, MicroRNA-146a (miR-146a) was associated with inflammatory and autoimmunological processes. In vitro it was shown, that miR-146a influences the bone metabolism by regulating differentiation of mesenchymal stem cells. The miR-146a deficient mouse starts to develop lymphoproliferative and myeloproliferative disease by 6–8 months of age. In this study, we investigate the influence of miR-146a deficiency on bone structure and stability dependent on age and gender. Material and Methods. Male and female mice of wild type (WT) and miR-146a deficient (KO) animals at the age of 2–3 and 5–7 month were analyzed Femur, Tibia and lumbar vertebra (LWK4) were dissected and used für structural analyses by microcomputer tomography (µCT). Parameters like bone volume/tissue volume, trabecular bone volume, trabecular thickness, number and separation as well as cortical thickness were determined. Biomechanical stability as load to failure testing was determined using torsional testing for the long bones and axial compression testing for the vertebra body. Statistical analysis was performed using Graph Pad Prism (Mann-Whitney-U-Test, significance: p<0.05). Results. Structural analyses of the bone structure in the long bones (femur, tibia) revealed a significant higher bone volume/tissue volume (BV/TV) and trabecular bone mass in the elder (5–7 month) miR-146a deficient female mice compared to the male group or wild type animals of either age. In the diaphysis of the femur a BV/TV of 21% was determined for the elder miR-146a deficient females compared to 9% BV/TV in the age matching WT group. These changes were due to an increase in trabecular thickness and trabecular number in this area. In contrast to that, the cortical thickness of all bones analyzed was lowered in the miR-146a deficient animals (male and female) compared to wild type. Biomechanical stability of long bones as well as the vertebra body of the older, female KO group was significantly lower compared to wild type bones. Femurs showed a maximal torque of 20Nmm compared to 34Nmm in the wild type group. The vertebra of the KO mice showed a maximal force at failure of 22N compared to 40N in the wild type group. Male groups and younger females revealed values comparable to wild type animals. Conclusion. The deficiency of miR-146a leads to an increase of trabecular bone in the long bones of female 5–7 month old mice, but to lowered biomechanical bone stability. If this is due to alterations in differentiation or proliferation of mesenchymal stem cells remains unclear and will be analyzed further. Additionally, gender relation of our observations points to the influence of female specific regulatory mechanisms like the involvement of estrogen receptor related mechanisms

The study of the chondrocyte maturation cycle and endochondral ossification showed that the developing vascular supply has appeared to play a key role in determining the cortical or trabecular structure of the long bones. The chondrocyte maturation cycle and endochondral ossification were studied in human, foetal cartilage anlagen and in postnatal meta-epiphyses. The relationship between the lacunar area, the inter territorial fibril network variations and CaP nucleation in primary and secondary ossification centres were assessed using light microscopy and SEM morphometry. The anlage topographic, zonal classification derived from the anatomical nomenclature of the completely developed long bone (diaphysis, metaphyses and epiphyses) allowed to follow the development of long bones cartilage model. A significant increase in chondrocyte lacunar area (p<0.001) was documented from the anlage epiphyseal zone 4 and 3 to zone 2 (metaphysis) and zone 1 (diaphysis), with the highest variation from zone 2 to zone 1. An inverse reduction in the intercellular matrix area (p<0.001) and matrix interfibrillar empty space (p<0.001) was also documented. These findings are consistent with the osmotic passage of free cartilage water from the interfibrillar space into the swelling chondrocytes, raising ion concentrations up to the critical threshold for mineral precipitation in the matrix. The mineralised cartilage served as a scaffold for osteoblasts apposition both in primary and secondary ossification centres and in the metaphyseal growth plate cartilage, but at different periods of bone anlage development and with distinct patterns for each zone. They all shared a common initial pathway, but it progressed with different times, modes and organisation in diaphysis, metaphysis and epiphysis. In the ossification phase the developing vascular supply has appeared to play a key role in determining the cortical or trabecular structure of the long bones

Background. A large proportion of the expense incurred due to hip fractures arises due to secondary factors such as duration of hospital stay and additional theatre time due to surgical complications. Studies have shown that the use of intramedullary (IM) nail fixation presents a statistically higher risk of re-fracture than plating, which has been attributed to the stress riser at the end of the nail. It is not clear, however, if this situation also applies to unstable fractures, for which plating has a higher fixation failure rate. Moreover, biomechanical studies to date have not considered newer designs of IM nails which have been specifically designed to better distribute weight-bearing loads. This aim of this experimental study was to evaluate the re-fracture risk produced by a newer type of nailing system compared to an equivalent plate. Methods. Experimental testing was conducted using fourth generation Sawbones composite femurs and X-Bolt IM hip nail (n=4) and fracture plate (n=4) implants. An unstable pertrochanteric fracture pattern was used (AO classification: 31-A1 / 31-A2). Loading was applied along the peak loading vector experienced during walking, up to a maximum load of 500N. The risk of re-fracture was evaluated from equivalent strains measured using four rosette strain gauges on the surface of the bone at known stress riser locations. Results. Strain gauge readings determined that the equivalent strains in the femoral diaphysis were approximately 25% larger for the nail than the plate (p < 0.005). The strain levels at the location coinciding with the end of the plate were also larger for the nail, but not significantly (p > 0.26). Conclusions. Although the risk of re-fracture for displaced tronchantaric fractures was found to be larger for nailing than plating, measured strains were substantially lower than the failure strain of cortical bone (even when scaled for full weight-bearing loads of 1800N). This indicates that fracture risk is not present in either implant for bone of healthy quality, but may still become problematic in highly osteoporotic patients. Level of Evidence. IIb - Evidence from at least one well designed experimental trial

The management of displaced forearm diaphyseal fractures in adults is predominantly operative. Anatomical reduction is necessary to infer optimal motion and strength. The authors have observed an intraoperative technique where passive pronosupination is examined to assess quality of reduction as a surrogate marker for active movement. We aimed to assess the value of this technique, but intentionally malreducing a simulated diaphyseal fracture of a radius in a cadaveric model, and measuring the effect on pronosupination. A single cadaveric arm was prepared and pronation/supination was examined according to American Academy of Orthopaedic Surgeons guidance. A Henry approach was then performed and a transverse osteotomy achieved in the radial diaphysis. A volar locking plate was used to hold the radius in progressive amounts of translation and rotation, with pronosupaintion measured with a goniometer. The radius could be grossly malreduced with no effect on pronation and supination until the extremes of deformity. The forearm showed more tolerance with rotational malreduction than translation. Passive pronation was more sensitive for malreduction than supination. The use of passive pronosupination to assess quality of reduction is misleading

Osteoarthritis is associated with changes to the matrix composition of subchondral bone. Raman spectroscopy has the potential to detect in vivo the molecular changes in osteoarthritic subchondral bone. The objectives were to determine the levels of mineralisation, carbonate accumulation and bone remodelling in osteoarthritic subchondral bone, which we defined as within 3mm of articular cartilage. This was compared to the proximal-compartment (10mm distal to articular cartilage) and the head-neck junction. Five osteoarthritic (average age: 76 years) and five normal cadaveric femoral heads (average age: 72 years) were scanned using peripheral quantitative computed tomography and then sectioned coronally. Raman spectroscopy was then used to scan the femoral heads. All scans were done in the plane of the longitudinal axis of the diaphysis. Cores were subsequently extracted and sodium dodecyl sulphate polyacrylamide gel electrophoresis performed to determine the levels of homotrimeric collagen. The phosphate-to-amide I ratio, from the Raman spectra, in osteoarthritic subchondral bone was significantly greater than controls (p=0.023). Within osteoarthritic specimens, the phosphate-to-amide I ratio increased proximally. The density in osteoarthritic subchondral bone was 89mg/cm3 higher than controls (p=0.022), and 494mg/cm3 higher than the osteoarthritic proximal-compartment (p<0.001). Moreover, carbonate substitution into the apatite crystals decreased in osteoarthritic specimens. The carbonate-to-amide I ratio was highest in osteoarthritic subchondral bone. Furthermore, the median α1-to-α2-chain ratio in osteoarthritic specimens was 2:1. The changes found in subchondral bone are important in the pathogenesis of osteoarthritis. This study shows that Raman spectroscopy can detect differences between osteoarthritic specimens and controls, further supporting its potential use in diagnosing bone disorders

In uncemented total hip arthroplasty (THA), the optimal femoral component should allow both maximum cortical contact with proximal load transfer and accurate restoration of individual joint biomechanics. This is often compromised due to a high variability in proximal femoral anatomy. The aim of this on-going study is to assess the variation in proximal femoral canal shape and its association with geometric and anthropometric parameters in primary hip OA. In a retrospective cohort study, AP-pelvis radiographs of 98 consecutive patients (42 males, 56 females, mean age 61 (range:45-74) years, BMI 27.4 (range:20.3-44.6) kg/m2) who underwent THA for primary hip OA were reviewed. All radiographs were calibrated and femoral offset (FO) and neck-shaft-angle (NSA) were measured using a validated custom programme. Point-based active shape modelling (ASM) was performed to assess the shape of the inner cortex of the proximal femoral meta- and diaphysis. Independent shape modes were identified using principal component analysis (PCA). Hierarchical cluster analysis of the shape modes was performed to identify natural groupings of patients. Differences in geometric measures of the proximal femur (FO, NSA) and demographic parameters (age, height, weight, BMI) between the clusters were evaluated using Kruskal-Wallis one-way-ANOVA or Chi-square tests, as appropriate. In the entire cohort, mean FO was 39.0 mm, mean NSA was 131 degrees. PCA identified 10 independent shape modes accounting for over 90% of variation in proximal femoral canal shape within the dataset. Cluster Analysis revealed 6 shape clusters for which all 10 shape modes demonstrated a significantly different distribution (p-range:0.000-0.015). We observed significant differences in age (p=0.032), FO (p<0.001) and NSA (p<0.001) between the clusters. No significant differences with regard to gender or BMI were seen. Our preliminary analysis has identified 6 different patterns of proximal femoral canal shape which are associated with significant differences in femoral offset, neck-shaft-angle and age at time of surgery. We are currently evaluating the entire dataset of 345 patients which will allow a comprehensive classification of variation in proximal femoral shape and joint geometry. The present data may optimise preoperative planning and improve future implant design in THA

Summary Statement. A single, locally-delivered injection of a human placental product containing multipotent stromal cells reduced severity of infection in an immunosuppressed murine osteomyelitis model and eliminated infection in 25% of animals compared with 0% of controls without the use of antibiotics. Introduction. Implant–associated osteomyelitis is a serious orthopaedic condition and is particularly difficult to treat in immunosuppressed individuals. Despite great advancement in the field of biomaterials and pharmaceuticals, emerging patterns of antibiotic resistance, complex biofilm production and penetration of therapeutic concentrations of effective antibiotics into bone continue to represent unmet clinical challenges. The promise of adult multipotent stromal cells (MSCs) for tissue regeneration has been of intense interest in recent years. Among their many potential therapeutic uses, MSCs have also been shown to have direct antimicrobial properties. The objective of this study was to evaluate the efficacy of a locally–delivered human placental-based tissue product containing multipotent stromal cells (hAmSC) to reduce the severity of implant-associated Staphylococcus aureus osteomyelitis in an immunosuppressed murine model. We hypothesised that athymic mice with implant-associated osteomyelitis would have diminished infection following treatment with hAmSC as evidenced by decreased bioluminescence intensity and lower histologic scores for infection and bacterial load when compared to saline-treated controls. Methods. An athymic murine model of chronic implant-associated osteomyelitis was developed using luciferase-transfected Staphylococcus aureus to study the antimicrobial effects of a human placental-based product containing multi-potent stromal cells (hAmSC). Sixteen athymic mice had osteomyelitis established in the right femoral diaphysis. Fifteen days after inducing luc S. aureus osteomyelitis, the mice were randomised to receive a single 0.5 cc injection of hAmSC (n=8) or vehicle (0.9% saline) (n=8) into the soft tissues immediately adjacent to the infected bone. No antibiotics were administered throughout the duration of the study. Mice were imaged with an In Vivo Imaging System (IVIS 1000, PerkinElmer) twice weekly for 30 days to assess change in bioluminescence intensity from baseline immediately prior to treatment with either hAmSC or saline. Radiographs were obtained at days −10, 0, 10, 20 and 30 days post-injection and scored for bone changes secondary to osteomyelitis by a reviewer blinded to treatment group. Mice were sacrificed 30 days after treatment and femurs were examined histologically and scored for bacterial load and degree of inflammation by a pathologist blinded to treatment group. Results. Osteomyelitis was successfully established in all mice as evidenced by baseline bioluminescence imaging and radiographs. Mean bioluminescence intensity decreased from baseline in animals receiving hAmSC and remained below baseline for 28 days, whereas vehicle-treated animals showed an increase in mean bioluminescence intensity throughout the study period. Osteomyelitis resolved in 2/8 hAmSC-treated animals and 0/8 vehicle-treated animals as evidenced by bioluminescence imaging and histological examination for bacteria/inflammation at sacrifice. Radiograph scores for secondary bone changes were lower in mice treated with hAmSC than vehicle at 10, 20 and 30 days post injection. Median inflammatory score was lower in the hAmSC-treated mice than vehicle treated controls. Conclusions. A single injection of hAmSC was effective at reducing the severity of S. aureus infection without the use of antibiotics in this chronic implant associated osteomyelitis immunosuppressed murine model. In addition to reduced bioluminescence intensity below baseline for 28 days during the study period, infection was eliminated in 25% of animals in the hAmSC-treated group

Objectives

We studied subchondral intraosseous pressure (IOP) in an animal model during loading, and with vascular occlusion. We explored bone compartmentalization by saline injection.

Objectives

The treatment of osteoporotic fractures is a major challenge, and the enhancement of healing is critical as a major goal in modern fracture management. Most osteoporotic fractures occur at the metaphyseal bone region but few models exist and the healing is still poorly understood. A systematic review was conducted to identify and analyse the appropriateness of current osteoporotic metaphyseal fracture animal models.

Objectives

We investigated the effects on fracture healing of two up-regulators of inducible nitric oxide synthase (iNOS) in a rat model of an open femoral osteotomy: tadalafil, a phosphodiesterase inhibitor, and the recently reported nutraceutical, COMB-4 (consisting of L-citrulline, Paullinia cupana, ginger and muira puama), given orally for either 14 or 42 days.

Objectives

To explore the therapeutic potential of combining bone marrow-derived mesenchymal stem cells (BM-MSCs) and hydroxyapatite (HA) granules to treat nonunion of the long bone.