Aims

Bone turnover markers (BTMs) follow distinct trends after fractures and limited evidence suggests differential levels in BTMs in patients with delayed healing. The effect of vitamin D, and other factors that influence BTMs and fracture healing, is important to elucidate the use of BTMs as surrogates of fracture healing. We sought to determine whether BTMs can be used as early markers of delayed fracture healing, and the effect of vitamin D on BTM response after fracture.

Aims. Unicompartmental and total knee arthroplasty (UKA and TKA) are successful treatments for osteoarthritis, but the solid metal implants disrupt the natural distribution of stress and strain which can lead to bone loss over time. This generates problems if the implant needs to be revised. This study investigates whether titanium lattice UKA and TKA implants can maintain natural load transfer in the proximal tibia. Methods. In a cadaveric model, UKA and TKA procedures were performed on eight fresh-frozen knee specimens, using conventional (solid) and titanium lattice tibial implants. Stress at the bone-implant interfaces were measured and compared to the native knee. Results. Titanium lattice implants were able to restore the mechanical environment of the native tibia for both UKA and TKA designs. Maximum stress at the bone-implant interface ranged from 1.2 MPa to 3.3 MPa compared with 1.3 MPa to 2.7 MPa for the native tibia. The conventional solid UKA and TKA implants reduced the maximum stress in the bone by a factor of 10 and caused > 70% of bone surface area to be underloaded compared to the native tibia. Conclusion. Titanium lattice implants maintained the natural mechanical loading in the proximal tibia after UKA and TKA, but conventional solid implants did not. This is an exciting first step towards implants that maintain bone health, but such implants also have to meet fatigue and micromotion criteria to be clinically viable. Cite this article: Bone Joint Res 2022;11(2):91–101

Aims. This study aimed to identify the effect of anatomical tibial component (ATC) design on load distribution in the periprosthetic tibial bone of Koreans using finite element analysis (FEA). Methods. 3D finite element models of 30 tibiae in Korean women were created. A symmetric tibial component (STC, NexGen LPS-Flex) and an ATC (Persona) were used in surgical simulation. We compared the FEA measurements (von Mises stress and principal strains) around the stem tip and in the medial half of the proximal tibial bone, as well as the distance from the distal stem tip to the shortest anteromedial cortical bone. Correlations between this distance and FEA measurements were then analyzed. Results. The distance from the distal stem tip to the shortest cortical bone showed no statistically significant difference between implants. However, the peak von Mises stress around the distal stem tip was higher with STC than with ATC. In the medial half of the proximal tibial bone: 1) the mean von Mises stress, maximum principal strain, and minimum principal strain were higher with ATC; 2) ATC showed a positive correlation between the distance and mean von Mises stress; 3) ATC showed a negative correlation between the distance and mean minimum principal strain; and 4) STC showed no correlation between the distance and mean measurements. Conclusion. Implant design affects the load distribution on the periprosthetic tibial bone, and ATC can be more advantageous in preventing stress-shielding than STC. However, under certain circumstances with short distances, the advantage of ATC may be offset. Cite this article: Bone Joint Res 2022;11(5):252–259

Aims. The association of auraptene (AUR), a 7-geranyloxycoumarin, on osteoporosis and its potential pathway was predicted by network pharmacology and confirmed in experimental osteoporotic mice. Methods. The network of AUR was constructed and a potential pathway predicted by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) terms enrichment. Female ovariectomized (OVX) Institute of Cancer Research mice were intraperitoneally injected with 0.01, 0.1, and 1 mM AUR for four weeks. The bone mineral density (BMD) level was measured by dual-energy X-ray absorptiometry. The bone microstructure was determined by histomorphological changes in the femora. In addition, biochemical analysis of the serum and assessment of the messenger RNA (mRNA) levels of osteoclastic markers were performed. Results. In total, 65.93% of the genes of the AUR network matched with osteoporosis-related genes. Osteoclast differentiation was predicted to be a potential pathway of AUR in osteoporosis. Based on the network pharmacology, the BMD and bone mineral content levels were significantly (p < 0.05) increased in the whole body, femur, tibia, and lumbar spine by AUR. AUR normalized the bone microstructure and the serum alkaline phosphatase (ALP), bone-specific alkaline phosphatase (bALP), osteocalcin, and calcium in comparison with the OVX group. In addition, AUR treatment reduced TRAP-positive osteoclasts and receptor activator of nuclear factor kappa-B ligand (RANKL). +. nuclear factor of activated T cells 1 (NFATc1). +. expression in the femoral body. Moreover, the expressions of initiators for osteoclastic resorption and bone matrix degradation were significantly (p < 0.05) regulated by AUR in the lumbar spine of the osteoporotic mice. Conclusion. AUR ameliorated bone loss by downregulating the RANKL/NFATc1 pathway, resulting in improvement of osteoporosis. In conclusion, AUR might be an ameliorative cure that alleviates bone loss in osteoporosis via inhibition of osteoclastic activity. Cite this article: Bone Joint Res 2022;11(5):304–316

Aims. One of the main causes of tibial revision surgery for total knee arthroplasty is aseptic loosening. Therefore, stable fixation between the tibial component and the cement, and between the tibial component and the bone, is essential. A factor that could influence the implant stability is the implant design, with its different variations. In an existing implant system, the tibial component was modified by adding cement pockets. The aim of this experimental in vitro study was to investigate whether additional cement pockets on the underside of the tibial component could improve implant stability. The relative motion between implant and bone, the maximum pull-out force, the tibial cement mantle, and a possible path from the bone marrow to the metal-cement interface were determined. Methods. A tibial component with (group S: Attune S+) and without (group A: Attune) additional cement pockets was implanted in 15 fresh-frozen human leg pairs. The relative motion was determined under dynamic loading (extension-flexion 20° to 50°, load-level 1,200 to 2,100 N) with subsequent determination of the maximum pull-out force. In addition, the cement mantle was analyzed radiologically for possible defects, the tibia base cement adhesion, and preoperative bone mineral density (BMD). Results. The BMD showed no statistically significant difference between both groups. Group A showed for all load levels significantly higher maximum relative motion compared to group S for 20° and 50° flexion. Group S improved the maximum failure load significantly compared to group A without additional cement pockets. Group S showed a significantly increased cement adhesion compared to group A. The cement penetration and cement mantle defect analysis showed no significant differences between both groups. Conclusion. From a biomechanical point of view, the additional cement pockets of the component have improved the fixation performance of the implant. Cite this article: Bone Joint Res 2022;11(4):229–238

Aims. Accumulated evidence indicates that local cell origins may ingrain differences in the phenotypic activity of human osteoblasts. We hypothesized that these differences may also exist in osteoblasts harvested from the same bone type at periarticular sites, including those adjacent to the fixation sites for total joint implant components. Methods. Human osteoblasts were obtained from the acetabulum and femoral neck of seven patients undergoing total hip arthroplasty (THA) and from the femoral and tibial cuts of six patients undergoing total knee arthroplasty (TKA). Osteoblasts were extracted from the usually discarded bone via enzyme digestion, characterized by flow cytometry, and cultured to passage three before measurement of metabolic activity, collagen production, alkaline phosphatase (ALP) expression, and mineralization. Results. Osteoblasts from the acetabulum showed lower proliferation (p = 0.034), cumulative collagen release (p < 0.001), and ALP expression (p = 0.009), and produced less mineral (p = 0.006) than those from the femoral neck. Osteoblasts from the tibia produced significantly less collagen (p = 0.021) and showed lower ALP expression than those from the distal femur. Conclusion. We have demonstrated for the first time an anatomical regional variation in the biological behaviours of osteoblasts on either side of the hip and knee joint. The lower osteoblast proliferation, matrix production, and mineralization from the acetabulum compared to those from the proximal femur may be reflected in differences in bone formation and implant fixation at these sites. Cite this article: Bone Joint Res 2021;10(9):611–618

Objectives. This study aims to evaluate if micro-CT can work as a method for the 3D assessment and analysis of cancellous bone by comparing micro-CT with undecalcified histological sections in OVX rats. Methods. The mandible and tibia of sham, ovariectomised (OVX) and zoledronate-injected ovariectomised (OVX-ZOL) rats were assessed morphometrically. Specimens were scanned by micro-CT. Undecalcified histological sections were manufactured from the specimen scanned by micro-CT and stained with haematoxylin and eosin. Bivariate linear regressions and one-way analysis of variance were undertaken for statistics using SPSS 16.0.1 software. Results. There were highly significant correlations between undecalcified histological sections and micro-CT for all parameters (bone volume density (BV/TV), bone surface density (BS/BV), trabecular thickness (Tb.Th), trabecular number (Tb.N), and trabecular separation (Tb.Sp))in the mandible and tibia. Bone histomorphometric parameters analysed by both methods exhibited significant differences among sham, OVX, and OVX-ZOL groups. There were significant correlations between mandible and tibia in BV/TV, BS/BV, and Tb.Sp. Conclusions. Micro-CT is a complementary tool to histological sections in basic research that could improve our understanding of bone histomorphometry. The mandible can be used as an effective site to assess bone morphometry of OVX or metabolic bone disease rat models. Cite this article: H. Liu, W. Li, Y. S. Liu, Y. S. Zhou. Bone micro-architectural analysis of mandible and tibia in ovariectomised rats: A quantitative structural comparison between undecalcified histological sections and micro-CT. Bone Joint Res 2016;5:253–262

Objectives. Little biomechanical information is available about kinematically aligned (KA) total knee arthroplasty (TKA). The purpose of this study was to simulate the kinematics and kinetics after KA TKA and mechanically aligned (MA) TKA with four different limb alignments. Materials and Methods. Bone models were constructed from one volunteer (normal) and three patients with three different knee deformities (slight, moderate and severe varus). A dynamic musculoskeletal modelling system was used to analyse the kinematics and the tibiofemoral contact force. The contact stress on the tibial insert, and the stress to the resection surface and medial tibial cortex were examined by using finite element analysis. Results. In all bone models, posterior translation on the lateral side and external rotation in the KA TKA models were greater than in the MA TKA models. The tibiofemoral force at the medial side was increased in the moderate and severe varus models with KA TKA. In the severe varus model with KA TKA, the contact stress on the tibial insert and the stress to the resection surface and to the medial tibial cortex were increased by 41.5%, 32.2% and 53.7%, respectively, compared with MA TKA, and the bone strain at the medial side was highest among all models. Conclusion. Near normal kinematics was observed in KA TKA. However, KA TKA increased the contact force, stress and bone strain at the medial side for moderate and severe varus knee models. The application of KA TKA for severe varus knees may be inadequate. Cite this article: S. Nakamura, Y. Tian, Y. Tanaka, S. Kuriyama, H. Ito, M. Furu, S. Matsuda. The effects of kinematically aligned total knee arthroplasty on stress at the medial tibia: A case study for varus knee. Bone Joint Res 2017;6:43–51. DOI: 10.1302/2046-3758.61.BJR-2016-0090.R1

Aims

Prompt and sufficient broad-spectrum empirical antibiotic treatment is key to preventing infection following open tibial fractures. Succeeding co-administration, we dynamically assessed the time for which vancomycin and meropenem concentrations were above relevant epidemiological cut-off (ECOFF) minimal inhibitory concentrations (T > MIC) in tibial compartments for the bacteria most frequently encountered in open fractures. Low and high MIC targets were applied: 1 and 4 µg/ml for vancomycin, and 0.125 and 2 µg/ml for meropenem.

Objectives

The purpose of this study was to compare the results and complications of tibial lengthening over an intramedullary nail with treatment using the traditional Ilizarov method.

Aims. The aim of this study was to determine the risk of tibial eminence avulsion intraoperatively for bi-unicondylar knee arthroplasty (Bi-UKA), with consideration of the effect of implant positioning, overstuffing, and sex, compared to the risk for isolated medial unicondylar knee arthroplasty (UKA-M) and bicruciate-retaining total knee arthroplasty (BCR-TKA). Methods. Two experimentally validated finite element models of tibia were implanted with UKA-M, Bi-UKA, and BCR-TKA. Intraoperative loads were applied through the condyles, anterior cruciate ligament (ACL), medial collateral ligament (MCL), and lateral collateral ligament (LCL), and the risk of fracture (ROF) was evaluated in the spine as the ratio of the 95. th. percentile maximum principal elastic strains over the tensile yield strain of proximal tibial bone. Results. Peak tensile strains occurred on the anterior portion of the medial sagittal cut in all simulations. Lateral translation of the medial implant in Bi-UKA had the largest increase in ROF of any of the implant positions (43%). Overstuffing the joint by 2 mm had a much larger effect, resulting in a six-fold increase in ROF. Bi-UKA had ~10% increased ROF compared to UKA-M for both the male and female models, although the smaller, less dense female model had a 1.4 times greater ROF compared to the male model. Removal of anterior bone akin to BCR-TKA doubled ROF compared to Bi-UKA. Conclusion. Tibial eminence avulsion fracture has a similar risk associated with Bi-UKA to UKA-M. The risk is higher for smaller and less dense tibiae. To minimize risk, it is most important to avoid overstuffing the joint, followed by correctly positioning the medial implant, taking care not to narrow the bone island anteriorly. Cite this article: Bone Joint Res 2022;11(8):575–584

Aims. The main objective of this study is to analyze the penetration of bone cement in four different full cementation techniques of the tibial tray. Methods. In order to determine the best tibial tray cementation technique, we applied cement to 40 cryopreserved donor tibiae by four different techniques: 1) double-layer cementation of the tibial component and tibial bone with bone restrictor; 2) metallic cementation of the tibial component without bone restrictor; 3) bone cementation of the tibia with bone restrictor; and 4) superficial bone cementation of the tibia and metallic keel cementation of the tibial component without bone restrictor. We performed CT exams of all 40 subjects, and measured cement layer thickness at both levels of the resected surface of the epiphysis and the endomedular metaphyseal level. Results. At the epiphyseal level, Technique 2 gave the greatest depth compared to the other investigated techniques. At the endomedular metaphyseal level, Technique 1 showed greater cement penetration than the other techniques. Conclusion. The best metaphyseal cementation technique of the tibial component is bone cementation with cement restrictor. Additionally, if full tibial component cementation is to be done, the cement volume used should be about 40 g of cement, and not the usual 20 g. Cite this article: Bone Joint Res 2021;10(8):467–473

Aims. A number of anti-retroviral therapies (ART) have been implicated in potentially contributing to HIV-associated bone disease. The aim of this study was to evaluate the effect of combination ART on the fracture healing process. Methods. A total of 16 adult male Wistar rats were randomly divided into two groups (n = eight each): Group 1 was given a combination of Tenfovir 30 mg, Lamivudine 30 mg, and Efavirenz 60 mg per day orally, whereas Group 2 was used as a control. After one week of medication preload, all rats underwent a standardized surgical procedure of mid-shaft tibial osteotomy fixed by intramedullary nail with no gap at the fracture site. Progress in fracture healing was monitored regularly for eight weeks. Further evaluations were carried out after euthanasia by micro-CT, mechanically and histologically. Two blinded orthopaedic surgeons used the Radiological Union Scoring system for the Tibia (RUST) to determine fracture healing. Results. The fracture healing process was different between the two groups at week 4 after surgery; only two out of eight rats showed full healing in Group 1 (ART-treated), while seven out of eight rats had bone union in Group 2 (control) (p = 0.040). However, at week eight postoperatively, there was no statistical difference in bone healing; seven out of eight progressed to full union in both groups. Conclusion. This study demonstrated that combination ART resulted in delayed fracture healing at week 4 after surgery in rats, but did not result in the development of nonunion. Cite this article: Bone Joint Res 2022;11(8):585–593

Aims. This study investigated the effects of β-caryophyllene (BCP) on protecting bone from vitamin D deficiency in mice fed on a diet either lacking (D-) or containing (D+) vitamin D. Methods. A total of 40 female mice were assigned to four treatment groups (n = 10/group): D+ diet with propylene glycol control, D+ diet with BCP, D-deficient diet with control, and D-deficient diet with BCP. The D+ diet is a commercial basal diet, while the D-deficient diet contains 0.47% calcium, 0.3% phosphorus, and no vitamin D. All the mice were housed in conditions without ultraviolet light. Bone properties were evaluated by X-ray micro-CT. Serum levels of klotho were measured by enzyme-linked immunosorbent assay. Results. Under these conditions, the D-deficient diet enhanced the length of femur and tibia bones (p < 0.050), and increased bone volume (BV; p < 0.010) and trabecular bone volume fraction (BV/TV; p < 0.010) compared to D+ diet. With a diet containing BCP, the mice exhibited higher BV and bone mineral density (BMD; p < 0.050) than control group. The trabecular and cortical bone were also affected by vitamin D and BCP. In addition, inclusion of dietary BCP improved the serum concentrations of klotho (p < 0.050). In mice, klotho regulates the expression level of cannabinoid type 2 receptor (Cnr2) and fibroblast growth factor 23 (Fgf23) through CD300a. In humans, data suggest that klotho is connected to BMD. The expression of klotho is also associated with bone markers. Conclusion. These data indicate that BCP enhances the serum level of klotho, leading to improved bone properties and mineralization in an experimental mouse model. Cite this article: Bone Joint Res 2022;11(8):528–540

Aims. In recent conflicts, most injuries to the limbs are due to blasts resulting in a large number of lower limb amputations. These lead to heterotopic ossification (HO), phantom limb pain (PLP), and functional deficit. The mechanism of blast loading produces a combined fracture and amputation. Therefore, to study these conditions, in vivo models that replicate this combined effect are required. The aim of this study is to develop a preclinical model of blast-induced lower limb amputation. Methods. Cadaveric Sprague-Dawley rats’ left hindlimbs were exposed to blast waves of 7 to 13 bar burst pressures and 7.76 ms to 12.68 ms positive duration using a shock tube. Radiographs and dissection were used to identify the injuries. Results. Higher burst pressures of 13 and 12 bar caused multiple fractures at the hip, and the right and left limbs. Lowering the pressure to 10 bar eliminated hip fractures; however, the remaining fractures were not isolated to the left limb. Further reducing the pressure to 9 bar resulted in the desired isolated fracture of the left tibia with a dramatic reduction in the fractures to other sites. Conclusion. In this paper, a rodent blast injury model has been developed in the hindlimb of cadaveric rats that combines the blast and fracture in one insult, necessitating amputation. Experimental setup with 9 bar burst pressure and 9.13 ms positive duration created a fracture at the tibia with total reduction in non-targeted fractures, rendering 9 bar burst pressure suitable for translation to a survivable model to investigate blast injury-associated diseases. Cite this article: Bone Joint Res 2021;10(3):166–173

Aims. The mobile bearing Oxford unicompartmental knee arthroplasty (OUKA) is recommended to be performed with the leg in the hanging leg (HL) position, and the thigh placed in a stirrup. This comparative cadaveric study assesses implant positioning and intraoperative kinematics of OUKA implanted either in the HL position or in the supine leg (SL) position. Methods. A total of 16 fresh-frozen knees in eight human cadavers, without macroscopic anatomical defects, were selected. The knees from each cadaver were randomized to have the OUKA implanted in the HL or SL position. Results. Tibial base plate rotation was significantly more variable in the SL group with 75% of tibiae mal-rotated. Multivariate analysis of navigation data found no difference based on all kinematic parameters across the range of motion (ROM). However, area under the curve analysis showed that knees placed in the HL position had much smaller differences between the pre- and post-surgery conditions for kinematics mean values across the entire ROM. Conclusion. The sagittal tibia cut, not dependent on standard instrumentation, determines the tibial component rotation. The HL position improves accuracy of this step compared to the SL position, probably due to better visuospatial orientation of the hip and knee to the surgeon. The HL position is better for replicating native kinematics of the knee as shown by the area under the curve analysis. In the supine knee position, care must be taken during the sagittal tibia cut, while checking flexion balance and when sizing the tibial component

Aims. Tibial plateau fractures (TPFs) are complex injuries around the knee caused by high- or low-energy trauma. In the present study, we aimed to define the distribution and frequency of TPF lines using a 3D mapping technique and analyze the rationalization of divisions employed by frequently used classifications. Methods. In total, 759 adult patients with 766 affected knees were retrospectively reviewed. The TPF fragments on CT were multiplanar reconstructed, and virtually reduced to match a 3D model of the proximal tibia. 3D heat mapping was subsequently created by graphically superimposing all fracture lines onto a tibia template. Results. The cohort included 405 (53.4%) cases with left knee injuries, 347 (45.7%) cases with right knee injuries, and seven (0.9%) cases with bilateral injuries. On mapping, the hot zones of the fracture lines were mainly concentrated around the anterior cruciate ligament insertion, posterior cruciate ligament insertion, and the inner part of the lateral condyle that extended to the junctional zone between Gerdy’s tubercle and the tibial tubercle. Moreover, the cold zones were scattered in the posteromedial fragment, superior tibiofibular syndesmosis, Gerdy’s tubercle, and tibial tubercle. TPFs with different Orthopaedic Trauma Association/AO Foundation (OTA/AO) subtypes showed peculiar characteristics. Conclusion. TPFs occurred more frequently in the lateral and intermedial column than in the medial column. Fracture lines of tibial plateau occur frequently in the transition zone with marked changes in cortical thickness. According to 3D mapping, the four-column and nine-segment classification had a high degree of matching as compared to the frequently used classifications. Cite this article: Bone Joint Res 2020;9(6):258–267

Aims. A growing number of fractures progress to delayed or nonunion, causing significant morbidity and socioeconomic impact. Localized delivery of stem cells and subcutaneous parathyroid hormone (PTH) has been shown individually to accelerate bony regeneration. This study aimed to combine the therapies with the aim of upregulating fracture healing. Methods. A 1.5 mm femoral osteotomy (delayed union model) was created in 48 female juvenile Wistar rats, aged six to nine months, and stabilized using an external fixator. At day 0, animals were treated with intrafracture injections of 1 × 10. 6. cells/kg bone marrow mesenchymal stem cells (MSCs) suspended in fibrin, daily subcutaneous injections of high (100 μg/kg) or low (25 μg/kg) dose PTH 1-34, or a combination of PTH and MSCs. A group with an empty gap served as a control. Five weeks post-surgery, the femur was excised for radiological, histomorphometric, micro-CT, and mechanical analysis. Results. Combination therapy treatment led to increased callus formation compared to controls. In the high-dose combination group there was significantly greater mineralized tissue volume and trabecular parameters compared to controls (p = 0.039). This translated to significantly improved stiffness (and ultimate load to failure (p = 0.049). The high-dose combination therapy group had the most significant improvement in mean modified Radiographic Union Score for Tibia fractures (RUST) compared to controls (13.8 (SD 1.3) vs 5.8 (SD 0.5)). All groups demonstrated significant increases in the radiological scores – RUST and Allen score – histologically compared to controls. Conclusion. We demonstrate the beneficial effect of localized MSC injections on fracture healing combined with low- or high-dose teriparatide, with efficacy dependent on PTH dose. Cite this article: Bone Joint Res 2021;10(10):659–667

Aims. Bone metastasis ultimately occurs due to a complex multistep process, during which the interactions between cancer cells and bone microenvironment play important roles. Prior to colonization of the bone, cancer cells must succeed through a series of steps that will allow them to gain migratory and invasive properties; epithelial-to-mesenchymal transition (EMT) is known to be integral here. The aim of this study was to determine the effects of G protein subunit alpha Q (GNAQ) on the mechanisms underlying bone metastasis through EMT pathway. Methods. A total of 80 tissue samples from patients who were surgically treated during January 2012 to December 2014 were used in the present study. Comparative gene analysis revealed that the GNAQ was more frequently altered in metastatic bone lesions than in primary tumour sites in lung cancer patients. We investigated the effects of GNAQ on cell proliferation, migration, EMT, and stem cell transformation using lung cancer cells with GNAQ-knockdown. A xenograft mouse model tested the effect of GNAQ using micro-CT analyses and histological analyses. Results. GNAQ-knockdown showed down-regulation of tumour growth through mitogen-activated protein kinase (MAPK) signalling in lung cancer cells, but not increased apoptosis. We found that GNAQ-knockdown induced EMT and promoted invasiveness. GNAQ-knockdown cells injected into the bone marrow of murine tibia induced tumour growth and bone-to-lung metastasis, whereas it did not in control mice. Moreover, the knockdown of GNAQ enhanced cancer stem cell-like properties in lung cancer cells, which resulted in the development of resistance to chemotherapy. Conclusion. The present study reveals that the GNAQ-knockdown induced cancer stem cell-like properties. Cite this article: Bone Joint Res 2021;10(5):310–320

Objectives. Opening wedge high tibial osteotomy (HTO) is an established surgical procedure for the treatment of early-stage knee arthritis. Other than infection, the majority of complications are related to mechanical factors – in particular, stimulation of healing at the osteotomy site. This study used finite element (FE) analysis to investigate the effect of plate design and bridging span on interfragmentary movement (IFM) and the influence of fracture healing on plate stress and potential failure. Materials and Methods. A 10° opening wedge HTO was created in a composite tibia. Imaging and strain gauge data were used to create and validate FE models. Models of an intact tibia and a tibia implanted with a custom HTO plate using two different bridging spans were validated against experimental data. Physiological muscle forces and different stages of osteotomy gap healing simulating up to six weeks postoperatively were then incorporated. Predictions of plate stress and IFM for the custom plate were compared against predictions for an industry standard plate (TomoFix). Results. For both plate types, long spans increased IFM but did not substantially alter peak plate stress. The custom plate increased axial and shear IFM values by up to 24% and 47%, respectively, compared with the TomoFix. In all cases, a callus stiffness of 528 MPa was required to reduce plate stress below the fatigue strength of titanium alloy. Conclusion. We demonstrate that larger bridging spans in opening wedge HTO increase IFM without substantially increasing plate stress. The results indicate, however, that callus healing is required to prevent fatigue failure. Cite this article: A. R. MacLeod, G. Serrancoli, B. J. Fregly, A. D. Toms, H. S. Gill. The effect of plate design, bridging span, and fracture healing on the performance of high tibial osteotomy plates: An experimental and finite element study. Bone Joint Res 2018;7:639–649. DOI: 10.1302/2046-3758.712.BJR-2018-0035.R1

Objectives. Experimental studies indicate that non-steroidal anti-inflammatory drugs (NSAIDs) may have negative effects on fracture healing. This study aimed to assess the effect of immediate and delayed short-term administration of clinically relevant parecoxib doses and timing on fracture healing using an established animal fracture model. Methods. A standardized closed tibia shaft fracture was induced and stabilized by reamed intramedullary nailing in 66 Wistar rats. A ‘parecoxib immediate’ (Pi) group received parecoxib (3.2 mg/kg bodyweight twice per day) on days 0, 1, and 2. A ‘parecoxib delayed’ (Pd) group received the same dose of parecoxib on days 3, 4, and 5. A control group received saline only. Fracture healing was evaluated by biomechanical tests, histomorphometry, and dual-energy x-ray absorptiometry (DXA) at four weeks. Results. For ultimate bending moment, the median ratio between fractured and non-fractured tibia was 0.61 (interquartile range (IQR) 0.45 to 0.82) in the Pi group, 0.44 (IQR 0.42 to 0.52) in the Pd group, and 0.50 (IQR 0.41 to 0.75) in the control group (n = 44; p = 0.068). There were no differences between the groups for stiffness, energy, deflection, callus diameter, DXA measurements (n = 64), histomorphometrically osteoid/bone ratio, or callus area (n = 20). Conclusion. This study demonstrates no negative effect of immediate or delayed short-term administration of parecoxib on diaphyseal fracture healing in rats. Cite this article: G. A. Hjorthaug, E. Søreide, L. Nordsletten, J. E. Madsen, F. P. Reinholt, S. Niratisairak, S. Dimmen. Short-term perioperative parecoxib is not detrimental to shaft fracture healing in a rat model. Bone Joint Res 2019;8:472–480. DOI: 10.1302/2046-3758.810.BJR-2018-0341.R1

Objectives. Elevated proximal tibial bone strain may cause unexplained pain, an important cause of unicompartmental knee arthroplasty (UKA) revision. This study investigates the effect of tibial component alignment in metal-backed (MB) and all-polyethylene (AP) fixed-bearing medial UKAs on bone strain, using an experimentally validated finite element model (FEM). Methods. A previously experimentally validated FEM of a composite tibia implanted with a cemented fixed-bearing UKA (MB and AP) was used. Standard alignment (medial proximal tibial angle 90°, 6° posterior slope), coronal malalignment (3°, 5°, 10° varus; 3°, 5° valgus), and sagittal malalignment (0°, 3°, 6°, 9°, 12°) were analyzed. The primary outcome measure was the volume of compressively overstrained cancellous bone (VOCB) < -3000 µε. The secondary outcome measure was maximum von Mises stress in cortical bone (MSCB) over a medial region of interest. Results. Varus malalignment decreased VOCB but increased MSCB in both implants, more so in the AP implant. Varus malalignment of 10° reduced the VOCB by 10% and 3% in AP and MB implants but increased the MSCB by 14% and 13%, respectively. Valgus malalignment of 5° increased the VOCB by 8% and 4% in AP and MB implants, with reductions in MSCB of 7% and 10%, respectively. Sagittal malalignment displayed negligible effects. Well-aligned AP implants displayed greater VOCB than malaligned MB implants. Conclusion. All-polyethylene implants are more sensitive to coronal plane malalignments than MB implants are; varus malalignment reduced cancellous bone strain but increased anteromedial cortical bone stress. Sagittal plane malalignment has a negligible effect on bone strain. Cite this article: I. Danese, P. Pankaj, C. E. H. Scott. The effect of malalignment on proximal tibial strain in fixed-bearing unicompartmental knee arthroplasty: A comparison between metal-backed and all-polyethylene components using a validated finite element model. Bone Joint Res 2019;8:55–64. DOI: 10.1302/2046-3758.82.BJR-2018-0186.R2

Aims

Micromotion of the polyethylene (PE) inlay may contribute to backside PE wear in addition to articulate wear of total knee arthroplasty (TKA). Using radiostereometric analysis (RSA) with tantalum beads in the PE inlay, we evaluated PE micromotion and its relationship to PE wear.

Aims

This study aimed to analyze kinematics and kinetics of the tibiofemoral joint in healthy subjects with valgus, neutral, and varus limb alignment throughout multiple gait activities using dynamic videofluoroscopy.

Aims. CERAMENT|G is an absorbable gentamicin-loaded biocomposite used as an on-site vehicle of antimicrobials for the treatment of chronic osteomyelitis. The purpose of the present study was to investigate the sole effect of CERAMENT|G, i.e. without additional systemic antimicrobial therapy, in relation to a limited or extensive debridement of osteomyelitis lesions in a porcine model. Methods. Osteomyelitis was induced in nine pigs by inoculation of 10. 4. colony-forming units (CFUs) of Staphylococcus aureus into a drill hole in the right tibia. After one week, the pigs were allocated into three groups. Group A (n = 3) received no treatment during the study period (19 days). Groups B (n = 3) and C (n = 3) received limited or extensive debridement seven days postinoculation, respectively, followed by injection of CERAMENT|G into the bone voids. The pigs were euthanized ten (Group C) and 12 (Group B) days after the intervention. Results. All animals presented confirmatory signs of bone infection post-mortem. The estimated amount of inflammation was substantially greater in Groups A and B compared to Group C. In both Groups B and C, peptide nucleic acid fluorescence in situ hybridization (PNA FISH) of CERAMENT|G and surrounding bone tissue revealed bacteria embedded in an opaque matrix, i.e. within biofilm. In addition, in Group C, the maximal measured post-mortem gentamicin concentrations in CERAMENT|G and surrounding bone tissue samples were 16.6 μg/ml and 6.2 μg/ml, respectively. Conclusion. The present study demonstrates that CERAMENT|G cannot be used as a standalone alternative to extensive debridement or be used without the addition of systemic antimicrobials. Cite this article: Bone Joint Res 2020;9(7):394–401

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As has been shown in larger animal models, knee immobilization can lead to arthrofibrotic phenotypes. Our study included 168 C57BL/6J female mice, with 24 serving as controls, and 144 undergoing a knee procedure to induce a contracture without osteoarthritis (OA).

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This study aimed to demonstrate the promoting effect of elastic fixation on fracture, and further explore its mechanism at the gene and protein expression levels.

Aims. Metaphyseal tritanium cones can be used to manage the tibial bone loss commonly encountered at revision total knee arthroplasty (rTKA). Tibial stems provide additional fixation and are generally used in combination with cones. The aim of this study was to examine the role of the stems in the overall stability of tibial implants when metaphyseal cones are used for rTKA. Methods. This computational study investigates whether stems are required to augment metaphyseal cones at rTKA. Three cemented stem scenarios (no stem, 50 mm stem, and 100 mm stem) were investigated with 10 mm-deep uncontained posterior and medial tibial defects using four loading scenarios designed to mimic activities of daily living. Results. Small micromotions (mean < 12 µm) were found to occur at the bone-implant interface for all loading cases with or without a stem. Stem inclusion was associated with lower micromotion, however these reductions were too small to have any clinical significance. Peak interface micromotion, even when the cone is used without a stem, was too small to effect osseointegration. The maximum difference occurred with stair descent loading. Stress concentrations in the bone occurred around the inferior aspect of each implant, with the largest occurring at the end of the long stem; these may lead to end-of-stem pain. Stem use is also found to result in stress shielding in the bone along the stem. Conclusion. When a metaphyseal cone is used at rTKA to manage uncontained posterior or medial defects of up to 10 mm depth, stem use may not be necessary. Cite this article:Bone Joint Res. 2020;9(4):162–172

Objectives. Unicompartmental knee arthroplasty (UKA) is one surgical option for treating symptomatic medial osteoarthritis. Clinical studies have shown the functional benefits of UKA; however, the optimal alignment of the tibial component is still debated. The purpose of this study was to evaluate the effects of tibial coronal and sagittal plane alignment in UKA on knee kinematics and cruciate ligament tension, using a musculoskeletal computer simulation. Methods. The tibial component was first aligned perpendicular to the mechanical axis of the tibia, with a 7° posterior slope (basic model). Subsequently, coronal and sagittal plane alignments were changed in a simulation programme. Kinematics and cruciate ligament tensions were simulated during weight-bearing deep knee bend and gait motions. Translation was defined as the distance between the most medial and the most lateral femoral positions throughout the cycle. Results. The femur was positioned more medially relative to the tibia, with increasing varus alignment of the tibial component. Medial/lateral (ML) translation was smallest in the 2° varus model. A greater posterior slope posteriorized the medial condyle and increased anterior cruciate ligament (ACL) tension. ML translation was increased in the > 7° posterior slope model and the 0° model. Conclusion. The current study suggests that the preferred tibial component alignment is between neutral and 2° varus in the coronal plane, and between 3° and 7° posterior slope in the sagittal plane. Varus > 4° or valgus alignment and excessive posterior slope caused excessive ML translation, which could be related to feelings of instability and could potentially have negative effects on clinical outcomes and implant durability. Cite this article: K. Sekiguchi, S. Nakamura, S. Kuriyama, K. Nishitani, H. Ito, Y. Tanaka, M. Watanabe, S. Matsuda. Bone Joint Res 2019;8:126–135. DOI: 10.1302/2046-3758.83.BJR-2018-0208.R2

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This study was designed to characterize the recurrence incidence and risk factors of antibiotic-loaded cement spacer (ALCS) for definitive bone defect treatment in limb osteomyelitis.

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The goal was to evaluate tibiofemoral knee joint kinematics during stair descent, by simulating the full stair descent motion in vitro. The knee joint kinematics were evaluated for two types of knee implants: bi-cruciate retaining and bi-cruciate stabilized. It was hypothesized that the bi-cruciate retaining implant better approximates native kinematics.

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Focal knee arthroplasty is an attractive alternative to knee arthroplasty for young patients because it allows preservation of a large amount of bone for potential revisions. However, the mechanical behaviour of cartilage has not yet been investigated because it is challenging to evaluate in vivo contact areas, pressure, and deformations from metal implants. Therefore, this study aimed to determine the contact pressure in the tibiofemoral joint with a focal knee arthroplasty using a finite element model.

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The aim of this study was to investigate the global and local impact of fat on bone in obesity by using the diet-induced obese (DIO) mouse model.

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cAMP response element binding protein (CREB1) is involved in the progression of osteoarthritis (OA). However, available findings about the role of CREB1 in OA are inconsistent. 666-15 is a potent and selective CREB1 inhibitor, but its role in OA is unclear. This study aimed to investigate the precise role of CREB1 in OA, and whether 666-15 exerts an anti-OA effect.

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Adenosine, lidocaine, and Mg²⁺ (ALM) therapy exerts differential immuno-inflammatory responses in males and females early after anterior cruciate ligament (ACL) reconstruction (ACLR). Our aim was to investigate sex-specific effects of ALM therapy on joint tissue repair and recovery 28 days after surgery.

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Dead-space management, following dead bone resection, is an important element of successful chronic osteomyelitis treatment. This study compared two different biodegradable antibiotic carriers used for dead-space management, and reviewed clinical and radiological outcomes. All cases underwent single-stage surgery and had a minimum one-year follow-up.

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Biofilm-related infection is a major complication that occurs in orthopaedic surgery. Various treatments are available but efficacy to eradicate infections varies significantly. A systematic review was performed to evaluate therapeutic interventions combating biofilm-related infections on in vivo animal models.

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The aim of this systematic review and meta-analysis was to gather epidemiological information on selected musculoskeletal injuries and to provide pooled injury-specific incidence rates.

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We aimed to assess the reliability and validity of OpenPose, a posture estimation algorithm, for measurement of knee range of motion after total knee arthroplasty (TKA), in comparison to radiography and goniometry.

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The present study investigated receptor activator of nuclear factor kappa-Β ligand (RANKL), osteoprotegerin (OPG), and Runt-related transcription factor 2 (RUNX2) gene expressions in giant cell tumour of bone (GCTB) patients in relationship with tumour recurrence. We also aimed to investigate the influence of CpG methylation on the transcriptional levels of RANKL and OPG.

Aims. To determine whether half-threaded screw holes in a new titanium locking plate design can substantially decrease the notch effects of the threads and increase the plate fatigue life. Methods. Three types (I to III) of titanium locking plates were fabricated to simulate plates used in the femur, tibia, and forearm. Two copies of each were fabricated using full- and half-threaded screw holes (called A and B, respectively). The mechanical strengths of the plates were evaluated according to the American Society for Testing and Materials (ASTM) F382-14, and the screw stability was assessed by measuring the screw removal torque and bending strength. Results. The B plates had fatigue lives 11- to 16-times higher than those of the A plates. Before cyclic loading, the screw removal torques were all higher than the insertion torques. However, after cyclic loading, the removal torques were similar to or slightly lower than the insertion torques (0% to 17.3%), although those of the B plates were higher than those of the A plates for all except the type III plates (101%, 109.8%, and 93.8% for types I, II, and III, respectively). The bending strengths of the screws were not significantly different between the A and B plates for any of the types. Conclusion. Removing half of the threads from the screw holes markedly increased the fatigue life of the locking plates while preserving the tightness of the screw heads and the bending strength of the locking screws. However, future work is necessary to determine the relationship between the notch sensitivity properties and titanium plate design. Cite this article: Bone Joint Res 2020;9(10):645–652

Objectives. We studied subchondral intraosseous pressure (IOP) in an animal model during loading, and with vascular occlusion. We explored bone compartmentalization by saline injection. Materials and Methods. Needles were placed in the femoral condyle and proximal tibia of five anaesthetized rabbits and connected to pressure recorders. The limb was loaded with and without proximal vascular occlusion. An additional subject had simultaneous triple recordings at the femoral head, femoral condyle and proximal tibia. In a further subject, saline injections at three sites were carried out in turn. Results. Loading alone caused a rise in subchondral IOP from 11.7 mmHg (. sd. 7.1) to 17.9 mmHg (. sd. 8.1; p < 0.0002). During arterial occlusion, IOP fell to 5.3 mmHg (. sd. 4.1), then with loading there was a small rise to 7.6 mmHg (. sd. 4.5; p < 0.002). During venous occlusion, IOP rose to 20.2 mmHg (. sd. 5.8), and with loading there was a further rise to 26.3 mmHg (. sd. 6.3; p < 0.003). The effects were present at three different sites along the limb simultaneously. Saline injections showed pressure transmitted throughout the length of the femur but not across the knee joint. Conclusion. This is the first study to report changes in IOP in vivo during loading and with combinations of vascular occlusion and loading. Intraosseous pressure is not a constant. It is reduced during proximal arterial occlusion and increased with proximal venous occlusion. Whatever the perfusion state, in vivo load is transferred partly by hydraulic pressure. We propose that joints act as hydraulic pressure barriers. An understanding of subchondral physiology may be important in understanding osteoarthritis and other bone diseases. Cite this article: M. Beverly, S. Mellon, J. A. Kennedy, D. W. Murray. Intraosseous pressure during loading and with vascular occlusion in an animal model. Bone Joint Res 2018;7:511–516. DOI: 10.1302/2046-3758.78.BJR-2017-0343.R2

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This study aimed to evaluate the effectiveness of the induced membrane technique for treating infected bone defects, and to explore the factors that might affect patient outcomes.

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The effects of remnant preservation on the anterior cruciate ligament (ACL) and its relationship with the tendon graft remain unclear. We hypothesized that the co-culture of remnant cells and bone marrow stromal cells (BMSCs) decreases apoptosis and enhances the activity of the hamstring tendons and tenocytes, thus aiding ACL reconstruction.

Objectives. Because there have been no standard methods to determine pre-operatively the thickness of resection of the proximal tibia in unicompartmental knee arthroplasty (UKA), information about the relationship between the change of limb alignment and the joint line elevation would be useful for pre-operative planning. The purpose of this study was to clarify the correlation between the change of limb alignment and the change of joint line height at the medial compartment after UKA. Methods. A consecutive series of 42 medial UKAs was reviewed retrospectively. These patients were assessed radiographically both pre- and post-operatively with standing anteroposterior radiographs. The thickness of bone resection at the proximal tibia and the distal femur was measured radiographically. The relationship between the change of femorotibial angle (δFTA) and the change of joint line height, was analysed. Results. The mean pre- and post-operative FTA was 180.5° (172.2° to 184.8°) and 175.0° (168.5° to 178.9°), respectively. The mean δFTA was 5.5° (2.3° to 10.1°). The joint line elevation of the tibia (JLET) was 4.4 mm (2.1 to 7.8). The δFTA was correlated with the JLET (correlation coefficient 0.494, p = 0.0009). Conclusions. This study indicated that there is a significant correlation between the change of limb alignment and joint line elevation. This observation suggests that it is possible to know the requirement of elevation of the joint line to obtain the desired correction of limb alignment, and to predict the requirement of bone resection of the proximal tibia pre-operatively. Cite this article: Bone Joint Res 2015;4:128–133

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The optimum type of antibiotics and their administration route for treating Gram-negative (GN) periprosthetic joint infection (PJI) remain controversial. This study aimed to determine the GN bacterial species and antibacterial resistance rates related to clinical GN-PJI, and to determine the efficacy and safety of intra-articular (IA) antibiotic injection after one-stage revision in a GN pathogen-induced PJI rat model of total knee arthroplasty.

Aim. It has been suggested that the use of a pilot-hole may reduce the risk of fracture to the lateral cortex. Therefore the purpose of this study was to determine the effect of a pilot hole on the strains and occurrence of fractures at the lateral cortex during the opening of a high tibial osteotomy (HTO) and post-surgery loading. Materials and Methods. A total of 14 cadaveric tibias were randomized to either a pilot hole (n = 7) or a no-hole (n = 7) condition. Lateral cortex strains were measured while the osteotomy was opened 9 mm and secured in place with a locking plate. The tibias were then subjected to an initial 800 N load that increased by 200 N every 5000 cycles, until failure or a maximum load of 2500 N. Results. There was no significant difference in the strains on the lateral cortex during HTO opening between the pilot hole and no-hole conditions. Similarly, the lateral cortex and fixation plate strains were not significantly different during cyclic loading between the two conditions. Using a pilot hole did not significantly decrease the strains experienced at the lateral cortex, nor did it reduce the risk of fracture. Conclusions. The nonsignificant differences found here most likely occurred because the pilot hole merely translated the stress concentration laterally to a parallel point on the surface of the hole. Cite this article: K. Bujnowski, A. Getgood, K. Leitch, J. Farr, C. Dunning, T. A. Burkhart. A pilot hole does not reduce the strains or risk of fracture to the lateral cortex during and following a medial opening wedge high tibial osteotomy in cadaveric specimens. Bone Joint Res 2018;7:166–172. DOI: 10.1302/2046-3758.72.BJR-2017-0337.R1

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Therapeutic agents that prevent chondrocyte loss, extracellular matrix (ECM) degradation, and osteoarthritis (OA) progression are required. The expression level of epidermal growth factor (EGF)-like repeats and discoidin I-like domains-containing protein 3 (EDIL3) in damaged human cartilage is significantly higher than in undamaged cartilage. However, the effect of EDIL3 on cartilage is still unknown.

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The involvement of cyclin D1 in the proliferation of microglia, and the generation and maintenance of bone cancer pain (BCP), have not yet been clarified. We investigated the expression of microglia and cyclin D1, and the influences of cyclin D1 on pain threshold.