Introduction. Within the reconstruction of unicondylar femoral bone defects with morselized bone grafts in revision total knee arthroplasty (TKA), a stem extension appears to be critical to obtain adequate mechanical stability. Whether the stability is still secured by this reconstruction technique in bicondylar defects has not been assessed. Long, rigid stem extensions have been advocated to maximize the stability in revision TKAs. The disadvantage of relatively stiff stem extensions is that bone resorption is promoted due to stress shielding. Therefore, we developed a relatively thin intramedullary stem which allowed for axial sliding movements of the articulating part relative to the intramedullary stem. The hypothesis behind the design is that compressive contact forces are directly transmitted to the distal femoral bone, whereas adequate stability is provided by the sliding intramedullary stem. A prototype was made of this new knee revision design and applied to the reconstruction of uncontained bicondylar femoral bone defects. Materials and Methods. Five synthetic distal femora with a bicondylar defect were reconstructed with impacted bone grafting (IBG) and this new knee revision design. A custom-made screw connection between the stem and the intercondylar box was designed to lock or initiate the sliding mechanism, another screw (dis)connected the stem. A cyclically axial load of 500 N was applied to the prosthetic condyles to assess the stability of the reconstruction. Radiostereometry was used to determine the migrations of the femoral component with a rigidly connected stem, a sliding stem and no stem extension. Results. We found a stable reconstruction of the bicondylar femoral defects with IBG in case of a rigidly connected stem. After disconnecting the stem, the femoral component showed substantially more migrations. With a sliding stem rotational migrations were similar to those of a rigidly connected stem. However, the sliding stem allowed proximal migration of the condylar component, thereby compressing the IBG. Discussion. A stable reconstruction of uncontained bicondylar femoral defects could be created with IBG and a TKA with a thin stem extension. It appeared that the presence of a functional stem extension was important for the stability of the bicondylar reconstruction. In an effort to reduce stress shielding, we developed a sliding stem mechanism. This sliding stem provided adequate stability, while compressive contact forces are still transmitted to the distal femoral bone. Clinical studies have to confirm that our sliding stem mechanism leads to long term bone maintenance after revision TKAs

Primary total hip replacement (THR) in patients with abnormal/altered proximal femoral anatomy/narrow canals presents a technical challenge. There are only limited standard prosthetic stems available to deal with narrow canals or abnormal morphology. Many prefer to use expensive custom implants which often have a lag time to manufacture and do not always have long term published outcomes.

We present results of the Asian C-stem (which is a standard implant available on the shelf) used in patients predominantly of Caucasian origin with abnormal proximal femoral anatomy.

We retrospectively reviewed clinic-radiological results of 131 patients (131 stems) who underwent primary THR using Asian C-stem at Wrightington Hospital till their latest follow up. Revision for any reason was considered as primary end point.

Mean age at surgery was 50.8 years (16 – 80). The 2 commonest indications were primary osteoarthritis (66 patients) and hip dysplasia (54 patients). Mean follow up was 43.5 months with a minimum follow up of 12 months and maximum follow up of 97 months. There were 2 recurrent dislocations and 1 hip subluxed twice. One dislocation needed revision surgery. 1 patient underwent acetabular revision for loosening. There was no stem failure, obvious loosening or loss of fixation in any patients in our series with regards to the Asian C-stem. There were no infections and intra-operative perforations or fractures.

C-stem Asian is a reliable implant for patients undergoing THR with abnormal proximal femoral anatomy or narrow canals. Long term follow up is essential.

Aims. Double-level lengthening, bone transport, and bifocal compression-distraction are commonly undertaken using Ilizarov or other fixators. We performed double-level fixator-assisted nailing, mainly for the correction of deformity and lengthening in the same segment, using a straight intramedullary nail to reduce the time in a fixator. Patients and Methods. A total of 23 patients underwent this surgery, involving 27 segments (23 femora and four tibiae), over a period of ten years. The most common indication was polio in ten segments and rickets in eight; 20 nails were inserted retrograde and seven antegrade. A total of 15 lengthenings were performed in 11 femora and four tibiae, and 12 double-level corrections of deformity without lengthening were performed in the femur. The mean follow-up was 4.9 years (1.1 to 11.4). Four patients with polio had tibial lengthening with arthrodesis of the ankle. We compared the length of time in a fixator and the external fixation index (EFI) with a control group of 27 patients (27 segments) who had double-level procedures with external fixation. The groups were matched for the gain in length, age, and level of difficulty score. Results. The mean gain in length was statistically similar in the two groups: 3.9 cm (1.5 to 9.0) in the study group and 4.2 cm (3.4 to 5.0) in the control group (p = 0.350). The mean time in a fixator was significantly less in the study group compared with the control group: 8.6 weeks (2.0 to 22.8) versus 30.2 weeks (25.0 to 35.4; p < 0.001). The mean EFI was significantly lower in the study group compared with the control group: 17.7 days/cm (10.6 to 35.6) versus 73.4 days/cm (44.5 to 102.3; p < 0.001). The ASAMI (Association for the Study and Application of the Method of Ilizarov) bone score was excellent in 22, good in four, and fair in one. The ASAMI functional score was excellent in 20 and good in seven. There were no infections, superficial or deep. Conclusion. Double-level osteotomies or two procedures using a custom-made straight nail and external fixation can be used to correct deformities or to treat nonunion or malunion and may be combined with arthrodesis of the ankle with lengthening. It is a reasonably safe procedure that allows accurate and cost-effective treatment with a relatively short time in a fixator

Introduction. Metabolic bone disease encompasses disorders of bone mineralization, abnormal matrix formation or deposition and alteration in osteoblastic and osteoclastic activity. In the paediatric cohort, patients with metabolic bone disease present with pain, fractures and deformities. The aim was to evaluate the use of lateral entry rigid intramedullary nailing in lower limbs in children and adolescents. Materials and Methods. Retrospective review was performed for an 11-year period. Lower limb rigid intramedullary nailing was performed in 27 patients with a total of 63 segments (57 femora, 6 tibiae). Majority of patients had underlying diagnoses of osteogenesis imperfecta or fibrous dysplasia (including McCune Albright disease). Mean age at surgery was 14 years. Indications for surgery included acute fractures, prophylactic stabilisation, previous nonunion and malunion, deformity correction and lengthening via distraction osteogenesis. Results. All fractures healed. Correction of deformity was successfully achieved in all segments. Delayed union occurred in 4 segments in 1 patient and was successfully treated with nail dynamization. Other complications included prominence, cortical penetrance and loosening of locking screws. One patient who had lengthening performed had nonunion and was managed with exchange nailing and adjunctive measures. Conclusions. Rigid intramedullary nailing is very effective in stabilisation and deformity correction of long bones in adolescent patients with pathological bone disease. The technique has low complication rates. We recommend the use of this technique in paediatric units with experience in managing metabolic bone conditions

Porous surfaces on orthopaedic implants have been shown to promote tissue ingrowth. This study evaluated biological fixation of novel additively manufactured porous implants with and without hydroxyapatite coatings in a canine transcortical model. Laser rapid manufacturing (LRM) Ti6Al4V cylindrical implants were built with a random interconnected architecture mimicking cancellous bone (5.2 mm diameter, 10mm length, 50–60% porous, mean pore size 450μm). Three groups were investigated in this study: as-built with no coating (LRM), as-built coated with solution precipitated hydroxyapatite (LRM-PA), and as-built coated with a plasma sprayed hydroxyapatite (LRM-PSHA). Implants were press-fit into a 5mm unicortical, perpendicular drill hole in the femoral diaphysis of the left and right femurs in 12 canines. Right femora were harvested for histology (SEM, bone ingrowth into implant within cortical region) and left femora for mechanical push-out testing (shear strength of bone-implant interface) at 4 and 12 weeks (N=6, un-paired Student's t-test, p=0.05). For mean bone ingrowth, there was no significant difference between groups at 4 weeks (LRM, LRM-PA, LRM-PSHA: 41.5+8.6%, 51+5.5% and 53.2+11%, respectively) or 12 weeks (LRM, LRM-PA, LRM-PSHA: 64.4+2.8%, 59.9+7.6%, 64.9+6.4%, respectively). LRM and LRM-PA implants had more bone ingrowth at 12 weeks than 4 weeks (p < 0 .05). Mean shear strength of all implants at 12 weeks (LRM, LRM-PA, LRM-PSHA: 39.9+3.6MPa, 33.7+4.6MPa, 36+4.1MPa respectively) were greater than at 4 weeks (LRM, LRM-PA, LRM-PSHA: 21.6+2.8MPa, 20.7+1.1MPa, 20.2+2.5MPa respectively) (p < 0 .05). No significant difference was observed between all groups at 4 or 12 weeks. Overall, this canine study confirmed the suitability of this novel additive manufacturing porous material for biological fixation by bone ingrowth. All implants exhibited high bone ingrowth and mechanical shear strength in this canine model. No difference was observed between uncoated and hydroxyapatite coated implants

Previously, we reported impaired biomechanical bone properties and inferior bone matrix quality in tachykinin1 (Tac1)-deficient mice lacking the sensory neuropeptide substance P (SP). Additionally, fracture callus development is affected by the absence of SP indicating a critical effect of sensory nerve fibers on bone health and regeneration. For α-calcitonin gene-related peptide (α-CGRP)-deficient mice, a profound distortion of bone microarchitecture has also been described. We hypothesize that SP and α-CGRP modulate inflammatory as well as pain-related processes and positively affect bone regeneration during impaired fracture healing under osteoporotic conditions. Therefore, this study investigates the effects of SP and α-CGRP on fracture healing and fracture-related pain processes under conditions of experimental osteoporosis using SP- and α-CGRP-deficient mice and WT controls. We ovariectomized female WT, Tac1−/− and α-CGRP−/− mice (age 10 weeks, all strains on C57Bl/6J background) and set intramedullary fixed femoral fractures in the left femora 28 days later. We analyzed pain threshold (Dynamic Plantar Aesthesiometer Test) and locomotion (recorded at day and night, each for 1 hour, EthoVision®XT, Noldus) at 5, 9, 13, 16 and 21 days after fracture. At each time point, fractured femora were prepared for histochemical analysis of callus tissue composition (alcian blue/sirius red staining). Pain threshold is significantly higher in Tac1−/− mice 13 days after fracture and tends to be higher after 21 days compared to WT controls. In contrast, touch sensibility was similar in α-CGRP−/− mice and WT controls but compared to Tac1−/− mice pain threshold was significantly lower in α-CGRP−/− mice 13 and 16 days and tends to be lower 21 days after fracture. Locomotion of Tac1−/− mice during daylight was by trend higher 9 days after fracture and significantly higher 16 days after fracture whereas nightly locomotion is reduced compared to WT mice. Analysis of locomotion during daylight or night revealed no differences between α-CGRP−/− and WT mice. During early fracture healing phase, 5 and 9 days after fracture, transition of mesenchymal to cartilaginous callus tissue tends to be faster in Tac1−/− mice compared to WT controls whereas no difference was observed during late stage of fracture healing, 13, 16 and 21 days after fracture. In contrast, callus tissue maturation seems to be similar in α-CGRP−/− and WT mice. Our data indicate different effects of SP and α-CGRP on fracture healing under conditions of experimental osteoporosis as a model for impaired bone tissue. Lack of α-CGRP seems to have no effects, but loss of SP affects locomotion throughout osteoporotic fracture healing and fracture-related pain processes during late phases of osteoporotic fracture healing. This indicates a modified role of SP during fracture healing under impaired versus healthy conditions, where SP changed early fracture-related pain processes and had no influence on callus tissue composition

Introduction. The Exeter cemented polished tapered stem design was introduced into clinical practice in the early 1970's. [i] Design and cement visco-elastic properties define clinical results [ii]; a recent study by Carrington et al. reported the Exeter stem has 100% survivorship at 7 years. [iii] Exeter stems with offsets 37.5–56 mm have length 150 mm (shoulder to tip). Shorter stems, lengths 95–125 mm, exist in offsets 30–35.5 mm. The Australian National Joint Replacement Registry recently published that at 7 years the shorter stems are performing as well as longer stems on the registry [iv]. Clinical observation indicates in some cases of shorter, narrower femora that fully seating a 150 mm stem's rasp in the canal can be difficult, which may affect procedural efficiency. This study investigates the comparative risk of rasp distal contact for the Exeter 150 mm stem or a 125 mm stem. Materials and Methods. Rasps for 37.5, 44, 50 mm offset, No.1, 150 mm length stems (Exeter, Stryker Orthopaedics, Mahwah NJ) were compared with shortened length models using SOMA™ (Stryker Orthopaedics Modeling and Analytics technology). 637 patients' CT scanned femora were filtered for appropriate offset and size by measuring femoral-head to femoral-axis distance and midsection cancellous bone width (AP view). These femora were analyzed for distal contact (rasp to cortices) for 150 mm and 125 mm models (Figure 1). The widths of the rasp's distal tip and the cancellous bone boundary were compared to assess contact for each femur in the AP and ML views; the rasp was aligned along an ideal axis and flexed in order to pass through the femoral neck (ML view only). Results. The sample size of appropriate patients totaled 238 femora. In the AP view, the rasp exhibited contact in 43 cases for a 150 mm stem but in 0 cases for a 125 mm stem; 95% of bones with contact were Champagne Fluted. In the ML view, rasp distal contact occurred in 52 femora for a 150 mm stem and in 1 femur for a 125 mm stem (Table 1). The difference was significant in both views with p < 0.001. Discussion. This study shows that a shortened stem design's rasp avoids distal contact. Shorter stem rasps resolved all cases where there was a risk of contact with a 150 mm rasp and reduced the likelihood of contact (one case compared to 52), AP and ML views respectively. These results indicate that shorter stems may address patients with champagne-fluted and/or excessively bowed femora, commonly found in the Asian population[v]. Contact avoidance may improve rasp seating height (AP view) and alignment with the femoral axis (ML view), thereby increasing procedural efficiency and producing an optimal cement mantle distally.[vi] The data shows that a total 29% of appropriate model patients would benefit from a shorter stem. Shorter cemented stems may effectively address the global population's needs in THR

The Lubinus SP2 femoral stem has a 10 year survivorship of 96%. Curiosity lies in that force-closed stem designs such as the Exeter appear to be more superior to that of the composite-beam like the Lubinus which performs best compared with all other stem types. Biomechanical comparisons of the stress distributions between native and implanted human femora with a cemented Lubinus stem simulating an everyday clinical activity were made. Rosette strain gauges were placed onto fourth generation composite cortical sawbone femora and placed within a hemipelvis rig simulating the dynamic position of the femur during single-legged stance. The femora were then implanted with the Lubinus and principal strain measurements calculated for both intact and implanted femora. These values correlate directly with stress. Statistical calculations were carried out including a two-way ANOVA and Student's unpaired t-test so as to ascertain any relationship between the intact and implanted femora strain values. There were significant decreases (p<0.05) in principal tensile and principal compressive strains upon implantation in the proximal and distal areas of the femur. However, there were insignificant changes (p>0.05) in principal tensile strains at the mid-stem and insignificant changes (p>0.05) in principal compressive strains at both the mid-stem and distal areas. This is the largest biomechanical study to be carried out on this stem and the first in the English language. Changes in principal stresses were not significant in all aspects of the femur upon implantation which appears to give some biomechanical explanation to its clinical success

Femoral lengthening using the Intramedullary Skeletal Kinetic Distractor is a new technique. However, with intramedullary distraction the surgeon has less control over the lengthening process. Therefore, 33 femora lengthened with this device were assessed to evaluate the effect of operative variables under the surgeon’s control on the course of lengthening. The desired lengthening was achieved in 32 of 33 limbs. Problems encountered included difficulty in achieving length in eight femora (24%) and uncontrolled lengthening in seven (21%). Uncontrolled lengthening was more likely if the osteotomy was placed with less than 80 mm of the thick portion of the nail in the distal fragment (p = 0.052), and a failure to lengthen was more likely if there was over 125 mm in the distal fragment (p = 0.008). The latter problem was reduced with over-reaming by 2.5 mm to 3 mm. Previous intramedullary nailing also predisposed to uncontrolled lengthening (p = 0.042), and these patients required less reaming. Using the Intramedullary Skeletal Kinetic Distractor, good outcomes were obtained; problems were minimised by optimising the position of the osteotomy and the amount of over-reaming performed

Introduction. Femoro-acetabular impingement (FAI) is a common source of impaired motion of the hip, often attributed to the presence of an aspherical femoral head. However, other types of femoral deformity, including posterior slip, retroversion, and neck enlargement, can also limit hip motion. This study was performed to establish whether the “cam” impinging femur has a single deformity of the head/neck junction or multiple abnormalities. Materials and Methods. Computer models of 71 femora (28 normal and 43 “cam” impinging) were prepared from CT scans. Morphologic parameters describing the dimensions of the head, neck, and medullary canal were calculated for each specimen. The anteversion angle, alpha angle of Notzli, beta angle of Beaulé, and normalized anterior heads offset were also calculated. Average dimensions were compared between the normal and impinging femora. Results. Compared to the normal controls, the impinging femora had wider necks (AP: 15.2 vs 13.3 mm, p<0.0001), larger heads (diameter: 48.3mm vs 46.0mm, p=0.032) and decreased head/neck ratios (1.60 vs 1.74, p=0.0002). However, there was no difference in neck/shaft angle (125.7° vs 126.5°, p=0.582) or anteversion angle (8.70 vs 8.44°, p=0.866). Most significantly, 53% of impinging femora also had a significant posterior slip (>2mm), compared to only 14% of normal controls. Average head displacements for the two groups were: FAI: 1.93mm vs Normals: 0.78mm (p<0.0001). Conclusions. The CAM impinging femur has many abnormalities apart from the “bump” at the head/neck junction. These femora have increased neck width and head/neck ratio, a smaller spherical bearing surface, and reduced neck offset from the medullary canal. Therefore, surgical treatment limited to localized re-contouring of the head–neck profile may fail to address significant components of the underlying abnormality

Clinical and radiological results of total hip arthroplasty (THA) using proximally coated single wedge (PSW) cementless stems are generally excellent. The geometry of cementless stems and the morphology of proximal femurs (Dorr types) provide optimal fit for primary stability and secondary biologic fixation. Because the geometry of PSW shape is designed to be engaged at the metaphysis, cementless PSW stem is not traditionally recommended to Dorr type C femurs with concerns of inadequate implant-host bone contact and the risk of femoral fracture. Nevertheless, previous studies on PSW cementless stems have not examined long-term survivorship according to Dorr types of femur. Paucity of a long-term comparative study makes it difficult to know whether the PSW stem plays a role in Dorr type C femurs or not. We postulated that the PSW stem could achieve stable fixation without increased risk of femoral fracture even in Dorr type C femurs, and demonstrate acceptable long-term results. The aim of this study was to investigate differences of clinical and radiological outcomes of THA using PSW stem according to proximal femoral geometry (Dorr types) in more than a 10-year follow-up. Three hundred and seven primary THA in 247 patients, which was performed with use of a single-designed PSW stem from 1997 to 2003 and was followed up for over 10 years, were included in this retrospective study. According to Dorr's criteria, 89 femora were classified as Type A, 156 as Type B, and 62 as Type C. The patients' mean age at operation was 43.2 years (range, 18.4 – 69.6 years). They were followed-up for an average of 13.2 years (the range, 10.0 – 17.3 years). All of the hips were evaluated clinically and radiologically with special attention to the occurrence of implant loosening and periprosthetic femoral fracture. The mean preoperative Harris hip score (50.4±20.6 points) improved significantly to 95.6±9.0 points at the final follow-ups. The improvements were observed regardless of Dorr types (p<0.001 in all 3 groups). The incidence of thigh pain (p=0.704) was not significantly different among groups. Implant survivorship was 100% in all 3 groups. None of the stems were loosened or revised. No significant differences were observed in osteolysis (p=0.492), pedestal formation (p=0.323), or cortical hypertrophy (p=0.169) among the groups [Fig. 1]. Radiolucent lines less than 2mm in thickness in Gruen zone 4 were observed more in Dorr type C femora than in Dorr type A or B (p=0.003) [Fig. 2]. Spot weld (p<0.001) and stress shielding (p=0.010) of proximal femur were more pronounced in Dorr C type femora than in type A or B [Fig. 3]. The prevalence of intraoperative (p=0.550) or postoperative (p=0.600) femoral fractures were not significantly different among the groups. From over a 10-year follow-up, the PSW stem provided excellent stem survivorship regardless of Dorr type with satisfactory outcomes. The remodeling process around the stem was more pronounced in Dorr type C femur. The present study shows that the PSW stem is a recommendable option for Dorr type C femur. For any figures or tables, please contact authors directly (see Info & Metrics tab above).

INTRODUCTION. During total knee arthroplasty (TKA), the pursuit of accurate alignment, proper bone cuts, and good soft tissue balancing sometimes can result in the overhang of the femoral component, especially in smaller-sized Asian knees. As size and shape of the distal femur are highly variable, component designs that offer increased shape and size offerings may be desirable to fit the distal femur. This study tested the hypothesis that increased shape and size offerings in TKA femoral designs may improve their fit to the Japanese femur compared to designs that offer only one shape and limited sizes. METHODS. Five contemporary femoral component designs were evaluated (Designs A-E). Design A has multiple mediolateral (ML) size offerings for a specific component anteroposterior (AP) size, and the finest increment (2mm) in AP sizes among all the designs. Designs B-E have single ML offerings across component AP sizes. For each design, virtual TKA resections were performed on the digital surfaces of 82 Japanese distal femora, each sized by selecting the component AP size that most closely matched but did not exceed the femoral AP dimension (Fig 1A,B). The aspect ratio (ML/AP) of the resected femora was regressed against the aspect ratio of their properly sized components per design. The closeness of each design to the perfect shape match was evaluated by the root-mean-square deviation (RMSD) of the deviations between the femoral bone and components. Differences in ML dimensions (overhang/underhang) between component and resected femora were calculated (Fig1C,D). The incidence of clinically significant femoral overhang (>3mm), in which component downsizing is required, were analyzed. RESULTS. Design A captured the shape variability in the resected femur, with component aspect ratios being the closest to the anatomy of the resected femur among the five designs (RMSD=0.04) (Fig 2). In contrast, Designs B-E had greater deviation from the shape of the resected femur (RMSD=0.08–0.12), indicating higher incidence of shape mismatch that may lead to surgical compromise. Designs C and E had the highest incidence and severity for clinically significant overhang, followed by Designs B and D (Fig 3A). Design A exhibited the lowest incidence and severity of clinically significant overhang and had the least variability in ML width differences (standard deviation=2.4mm) compared to the other designs (Designs B-E, standard deviation=4.0–4.9mm). In all the designs investigated, the percentage of bones that required downsizing was the highest in Designs C (48%) and E (39%), followed by Designs B and D (17% and 22%). In contrast, minimal downsizing was required in Design A (4%). The highest incidences of downsizing were generally observed in mid-sized components (Fig 3B). DISCUSSION. The design family with multiple ML offerings per AP size (Design A) provides the closest match to the shape of the distal femur compared to those with single ML offerings (Designs B-E). Additionally, increased AP size offerings in Design A (12 sizes) further improve component fit compared to Designs B-E (7–9 sizes). Among all five design families investigated, Design A exhibited minimal incidence of downsizing due to clinically significant overhang in the Japanese patients

INTRODUCTION. Loosening is a major cause for revision in uncemented hip prostheses due to insufficient primary stability. Primary stability after surgery is achieved through press-fit in an undersized cavity. Cavity preparation is performed either by extraction (removing bone) or compaction (crushing bone) broaching. Densification of trabecular bone has been shown to enhance primary stability in human femora; however, the effect of clinically used compaction and extraction broaches on human bone with varying bone mineral density (BMD) has not yet been quantified. The purpose of this study was to determine the influence of the broach design and BMD on the level of densification at the bone-cavity interface, stem seating, the bone-implant contact area and the press-fit achieved. METHODS. Paired human femora (m/f=11/12, age=60±18 y) were scanned with quantitative computed tomography (QCT, Philips Brilliance 16) before broaching, with the final broach, after its removal and after stem implantation. Compaction broaching (n=4) was compared in an in situ (cadaver) study against extraction broaching with blunt tooth types (n=3); in an ex situ (excised femora) study, compaction broaching was compared against extraction broaching with sharp tooth types (n=8 each). QCT data were resampled to voxel sizes of 1×1×1 mm (in situ) and 0.5×0.5×1 mm (ex situ). Mean trabecular BMD of the proximal femur was determined. The cavity volumes were segmented in the post-broach images (threshold: −250 mgHA/cm3, Avizo 9.2) and a volume of interest (VOI) of one-voxel thickness was added around the cavity to capture the interfacial bone. VOIs were transferred to the pre-broach image and bone densification was calculated within each VOI as the increase from pre- to post-broach image (MATLAB). Detailed surface data sets of broaches and stems were collected with a 3D laser-scanner (Creaform Handyscan 700) and aligned with the segmented components in the CT scans (Fig. 1). Stem seating was defined as the difference between the top edge of the stem coating and the final broach. Distance maps between the stem and cavity surface were generated to determine the bone-implant contact area and press-fit. All parameters were analysed between 5 mm distal to the coating and 1 cm distal to the lesser trochanter and analysed with related-samples Wilcoxon signed rank and Spearman's correlation tests (IBM SPSS Statistics 22). RESULTS. Trabecular BMD ranged from 81 to 221 mgHA/cm3. Densification was higher with compaction compared to sharp (p=0.034), but not blunt extraction broaching (p=1.000). Proximal bone-implant contact area, press-fit and stem seating did not differ between broaching methods. Bone-implant contact area and bone densification increased with trabecular BMD (rs=0.658, p=0.001 and rs=0.443, p=0.034), press-fit with stem seating (rs=0.746, p<0.001) and contact area with bone densification (rs=0.432, p=0.039). DISCUSSION. Sharp extraction broaching reduces densification at the bone-cavity interface, but does not affect the press-fit or contact area. Trabecular BMD was positively associated with contact area, and stem seating with press-fit. Future studies will aim to link these findings to primary stability and influence on periprosthetic fractures. For any figures or tables, please contact authors directly

Bone regeneration includes a well-orchestrated series of biological events of bone induction and conduction. Among them, the Wnt/β-catenin signaling pathway is critical for bone regeneration. Being involved in several developmental processes, Wnt/β-catenin signaling must be safely targeted. There are currently only few specific therapeutic agents which are FDA-approved and already entered clinical trials. A published work has shown that Tideglusib, a selective and irreversible small molecule non-ATP-competitive glycogen synthase kinase 3-β(GSK-3β) inhibitor currently in trial for Alzheimer's patients, can promote tooth growth and repair cavities. [1]Despite some differences, they are some similarities between bone and tooth formation and we hypothesise that this new drug could represent a new avenue to stimulate bone healing. In this work, we locally delivered Tideglusib (GSK3β inhibitor) in the repair of femoral cortical window defects and investigated bone regeneration. A biodegradable FDA-approved collagen sponge was soaked in GSK-3βinhibitor solution or vehicle only (DMSO) and was implanted in 1 × 2 mm unicortical defects created in femora of 35 adult wild-type male mice. Bone defect repair on control and experimental (GSK-3βinhibitor) groups was assessed after 1 week (n=22), 2 weeks (n=24) and 4 weeks (n=24) with microCT and histological analysis foralkaline phosphatase (ALP, osteoblast activity), tartrate resistant acid phosphatase (TRAP, osteoclasts), and immunohistochemistry to confirm the activation of the Wnt/β-catenin pathway. Our results showed that Tideglusib significantly enhanced cortical bone bridging (20.6 ±2.3) when compared with the control (12.7 ±1.9, p=0.001). Activity of GSK-3β was effectively downregulated at day 7 and 14 resulting in a higher accumulation of active β-catenin at day 14 in experimental group (2.5±0.3) compared to the control (1.1±0.2, p=0.03). Furthermore, the onset of ALP activity appears earlier in the experimental group (day 14, 1.79±0.28), a level of activity never reached at any end-point by the control defects. At 4 weeks treatment, we observed a significant drop in ALP in the experimental group (0.47±0.05) compared to the control (1.01±0.19, p=0.02) and a decrease in osteoclast (experimental=1.32±0.36, control=2.23±0.67, p=0.04). Local downregulation of GSK-3β by tideglusib during bone defect repair resulted in significant increase in amount of new bone formation. The early upregulation of osteoblast activity is one explanation of bone healing augmentation. This is likely the effect of upregulation of β-catenin following pharmaceutical inhibition of GSK-3β since β-catenin activation is known to positively regulate osteoblasts, once committed to the osteoblast lineage. As a GSK-3β inhibitor, Tideglusib demonstrates a different mechanism of action compared with other GSK-3β antagonists as treatment was started immediately upon injury and did not interfere with precursor cells recruitment and commitment. This indicates that tideglusib could be used at the fracture site during the initial intraoperative internal fixation without the need for further surgery. This safe and FDA-approved drug could be used in prevention of non-union in patients presenting with high risk for fracture-healing complications

Mesenchymal stem cells (MSCs) are capable of forming bone, cartilage and other mesenchymal tissues but are also important modulators of innate and adaptive immune responses. We have capitalized on these important functions to mitigate adverse responses when bone is exposed to pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), or prolonged pro-inflammatory cytokines. Our goal was to optimize osteogenesis and mitigate persistent undesired inflammation by: 1. preconditioning MSCs by short term exposure to lipopolysaccharide (LPS) and Tumor Necrosis Factor alpha (TNF-α), 2. genetic modification of MSCs to overexpress Interleukin 4 (IL-4) either constitutively, or as NFκB-responsive IL-4 over-expression cells, and 3. training the MSCs (innate immune memory) by repeated stimulation with LPS. In the first experiment, bone marrow MSCs and macrophages were isolated from femurs and tibias of C57BL/6 mice. MSCs (1×104 cells) were seeded in 24-well transwell plates in the bottom chamber with MSC growth medium. MSCs were treated with 20 ng/ml TNF-α and 1–20 μg/ml LPS for three days. Primary macrophages (2 × 103 cells) were seeded to the insert of a separate transwell plate and polarized into the M1 phenotype. At day four, MSCs and macrophages were washed and the inserts with M1 macrophages were moved to the plates containing preconditioned MSCs at the bottom of the well. Co-culture was carried out in MSC growth medium for 24h. In the second experiment, bone marrow derived macrophages and MSCs were isolated from femora and tibiae of Balb/c male mice. 5×104 macrophages and 1×104 MSCs were seeded in the bottom well of the 24-well transwell plate. The upper chambers were seeded with unmodified MSCs, MSCs preconditioned with 20 ng/ml TNF-α and 20 mg/ml LPS for 3 days, NFκB-IL4 secreting MSCs (all 5×104 cells), or controls without MSCs. Co-culture was carried out in mixed osteogenic-macrophage media with clinically relevant polyethylene or titanium alloy particles. In the third experiment, bone marrow MSCs and macrophages were collected from femurs and tibias of C57BL/6 male mice. The MSCs were stimulated by LPS, washed out for five days, and re-stimulated by LPS in co-culture with macrophages. First, preconditioned MSCs enhanced anti-inflammatory M2 macrophage (Arginase 1 and CD206) expression, decreased pro-inflammatory M1 macrophage (TNF-α/IL-1Ra ratio) expression, and increased osteogenic markers (alkaline phosphatase expression and matrix mineralization) in co-culture. Second, NFκB-IL4 secreting MSCs decreased pro-inflammatory M1 (TNF-α), increased anti-inflammatory M2 (Arg1, IL-1ra) expression, and enhanced the expression of osteogenic factors Runx2 and alkaline phosphatase, in the presence of particles, compared to other groups. Third, LPS-trained MSCs increased anti-inflammatory (Arginase1 and CD206), and decreased the proinflammatory (TNF-α, IL1b, iNOS, and IL6) marker expression in MSC/macrophage co-culture. Transforming MSCs via the techniques of preconditioning, genetic modification, or training (innate immune memory) can modulate/convert a potentially injurious microenvironment to an anti-inflammatory pro-reconstructive milieu. These effects are highly relevant for bone healing in the presence of adverse stimuli. These concepts using transformed MSCs could also be extended to other organ systems subjected to potentially damaging agents

Background. The accurate positioning of the total knee arthroplasty affects the survival of the implants(1). Alignment of the femoral component in relation to the native knee is best determined using pre- and post-operative 3D-CT reconstruction(2). Currently, the scans are visualised on separate displays. There is a high inter- and intra-observer variability in measurements of implant rotation and translation(3). Correct alignment is required to allow a direct comparison of the pre- and post-operative surfaces. This is prevented by the presence of the prostheses, the bone shape alteration around the implant, associated metal artefacts, and possibly a segmentation noise. Aim. Create a novel method to automatically register pre- and post-operative femora for the direct comparison of the implant and the native bone. Methods. The concept is to use post-operative femoral shaft segments free of metal noise and of surgical alteration for alignment with the pre-operative scan. It involves three steps. Firstly, using principal component analysis, the femoral shafts are re-oriented to match the X axis. Secondly, variants of the post-operative scan are created by subtracting 1mm increments from the distal femoral end (Fig1). Thirdly, an iterative closest point algorithm is applied to align the variants with the pre-operative scan. For exploratory validation, this algorithm was applied to a mesh representing the distal half of a 3D scanned femur. The mesh of a prosthesis was blended with the femur to create a post-operative model. To simulate a realistic environment, segmentation and metal artefact noise were added. For segmentation noise, each femoral vertex was translated randomly within +−1mm,+−2mm,+−3mm along its normal vector. To create metal artefact random noise was added within 50 mm of the implant points in the planes orthogonal to the shaft. The alignment error was considered as the average distance between corresponding points which are identical in pre- and post-operative femora. Results. Figure 2 shows, that when the implant zone is completely ignored, the error reaches a minimum plateau to below 1mm level. Different levels of segmentation noise had low impact on error value. Conclusions. These preliminary results obtained within a simulated environment show that by using only the native parts of the femur, the algorithm was able to automatically register the pre- and post-operative scans even in presence of the implant. Its application will allow visualisation of the scans on the same display for the direct comparison of the perioperative scans. This method requires further validation with more realistic noise models and with patient data. Future studies will have to determine if correct alignment has any effect on inter- and intra-observer variability. For figures, please contact authors directly.

Introduction. Revision of total knee endoprostheses (TKA) is increasing in number and causes rising healthcare costs. For constrained prostheses, the use of intramedullar femoral stems is standard. However, there is a big variety of available stem types with regard to length, type of fixation (cemented vs. hybrid) and fixation area (diaphyseal vs. metaphyseal). The aim of this biomechanical study was to investigate the primary stability of revision TKA with different stem types and different femoral bone defects, to find out whether smaller or shorter stems may achieve sufficient stability while preserving bone for re-revision. Methods. 30 right human femora were collected, fresh frozen and divided in six groups, matching for age, gender, height, weight and bone density. In group 1–3 a bone defect of AORI type F2a (15mm medial) and in group 4–6 a defect of AORI type F3 (25mm on both sides) was created. In all six groups the same modular femoral surface component (Endo-Model-W, Waldemar Link) was used, combined with different stem types (100/ 160 mm cemented / uncemented / standard/ anatomical with / without cone). Additionally, one trial was set up, omitting the modular stem. The correct fit of the implants was confirmed by fluoroscopy. After embedding, specimens were mechanically loaded 10mm medially and parallel to the mechanical femoral axis with an axial force of 2700N and a torsional moment of 5.6Nm at a flexion angle of 15° with respect to the coupled tibial plateau according to in-vivo gait load for 10,000 cycles (1Hz) in a servohydraulic testing machine (Bionix, MTS). The relative movement between implant, cement and distal femur was recorded using a stereo video system (Aramis3D,gom). An axial pull-out test at 1mm/min was performed after dynamic loading. Results. No clinical or radiological loosening of any configuration was observed. In all cases, relative movements were below 20µm and the differences between groups were very small. There were two cases, the trial without stem and one probe with short cemented stem with poor cementing technique (not included in the group result), which showed greatly increased relative movements. Pull-out test exhibited that forces of short stems with cones and uncemented anatomical cone stems with large defects (groups 4–6) were not significantly different to cemented stems in small defects. Discussion. Despite the high experimental load, even causing bone fracture in two cases, no difference between the investigated stem types concerning primary stability was found, partially probably due to the high inter-individual variations. Possible long-term differences cannot be assessed with in-vitro testing representing direct post-op situation, but the results might partially explain the controversial clinical observations and suggest further investigation on patient specific decisive parameters for implant choice. For any figures or tables, please contact authors directly

Self-locking button-like fixation devices for ACL reconstruction are attracting knee surgeons' attention due to promising technical advantages: complete filling of the tunnel with graft, anatomic reconstruction (AM portal), fixation achievement even when a short tunnel is reamed, opportunity of graft re-tensioning after tibial fixation and/or cyclic load. We compared two similar devices (TightRope vs ToggleLocZL). 20 fresh-frozen porcine femurs (mean age 2.1 years) were assigned to the two groups by randomization. Hamstrings with 9 mm of diameter were obtained using bovine tendons that show the same biomechanic behaviour of human hamstrings. Femoral tunnel was created by AM portal technique (anatomic position). Zwick-Roell z010 tension/compression device with bone and tendon clamps, was used for the study:. Cyclic test (1000 cycles, 0.5 Hz, 50–250 N/cycle, 50 cycles of preload at 10–80 N/cycle). Final pull-out test (1 mm/s). Failure analysis. CT scan and densitometry. Any implant didn't fail during cyclic test. The elongation average was 2.85±1.63 for ToggleLoc and 2.71±.85 for TightRope (P>0.05). Pull-out test showed different values in terms of Ultimate Strength Failure (USF), Stiffness at USF, and Stiffness:. The failure mode was:. The mean method of failure was the fracture of the cortical bone of the femoral condyle, for both groups. But if we extrapolate the USF the difference was favourable(P<0.05) for TightRope (707.83 N) than ToggleLoc (580.16). The mean bone density of porcine femora was comparable to young human femora (1.12±0.31 BMD). The reproducibility of surgical technique, the mechanical strength and endurance of the systems suggest two valid options for ACL reconstruction with hamstring. ToggleLoc showed worse results due to the sharp squared edges of the button

Anterior positioning of a cephomedullary nail in the distal femur occurs in up to 88% of cases. This is considered to occur because of a mismatch between the radius of curvature of the femur and that of available implants. The hypothesis for this study was that the relative thicknesses of the cortices of the femur (referenced off the linea aspera) change with age and determine the final position of intramedullary implants. This study used the data from CT scans undertaken as part of routine clinical practice in 919 patients with intact left femora (median age 66 years, 484 male and 435 female). The linea aspera and transverse intervals were plotted on a template femur between 25% – 60% femoral bone length (5% increments) and mapped automatically to all individual femora in the database with measurements taken in the plane of the linea aspera. The linea aspera was found to be internally rotated as compared to the sagittal plane referenced off the posterior femoral condyles. An age related change in the posterior/anterior cortical thickness ratio was demonstrated. The >80 year old cohort shows a significantly disproportional posterior/anterior ratio increase of 70.0% from 25–50% bone length as compared to 48.1% for the <40 year old cohort (p<0.05). This study has shown that assessment in the sagittal plane may be inaccurate because of rotational changes in the linea aspera. The centering influence of the corticies is lost with age with a relative thinning of the anterior cortex and thickening of the posterior cortex moving distally in the femur. This has a direct influence on the positioning of intramedullary implants explaining the preponderance of anterior malpositioning of intramedullary implants in the elderly

Transverse pin femoral fixation of bone-patella tendon-bone (BPTB) in ACL reconstruction has been widely applied during the last decades. Aim of our study is to confront two different system of transverse femoral fixation for BPTB graft: Transfix BTB (Arthrex) and BioTransfix T3 (Arthrex). The main differences between these two system are the diameter (3.0 mm Transfix BTB and 3.5 mm BioTransfix T3), and section (Transfix BTB is cannulated). Surgical technique adopts the same transverse vectorial guide but different guide sleeves. 30 fresh-frozen porcine knees (mean age 2.2 years) were assigned to the two groups randomisedly. the patellar bone block and tendon were harvested using the same size in all specimens (10mm × 25 mm, 10 mm). Zwick-Roell z010 tension/compression device with bone clamps, was used for the study:. Cyclic test (1000 cycles, 0.5 Hz, 50–250 N/cycle, 100 cycles of preload). Final pull-out test (1 mm/s). Failure analysis. CT scan and densitometry. Any implant didn't fail during cyclic test. The elongation average was 1.85±0.63 for Transfix BTB and 1.69±0.87 for BioTransfix T3. Pull-out test showed very similar values in terms of Ultimate Strength Failure (USF), Stiffness at USF, and Stiffness:. The failure mode was bone plug fracture (12 for Transfix BTB and 13 for BioTransfix T3) and tendon failure (3 for Transfix BTB and 2 for BioTransfix T3). The post-test CT scan showed any failure of the fixation devices and the correct position inside the femoral half-tunnel. The mean bone density of porcine femora was comparable to young human femora (1.12±0.31 BMD). Both systems showed a similar behaviour in terms of USF, Stiffness, Cyclic load, method of failure and other biomechanical parameters. The reproducibility of surgical technique, the mechanical strength and endurance of the systems suggest two valid options for ACL reconstruction with BPTB even if in-vivo studies are necessary to confirm the animal ex-vivo biomechanical data