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

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

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.

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.

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. 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. 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. 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

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.

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Osteoporosis is characterized by decreased trabecular bone volume, and microarchitectural deterioration in the medullary cavity. Interleukin-19 (IL-19), a member of the IL-10 family, is an anti-inflammatory cytokine produced primarily by macrophages. The aim of our study was to investigate the effect of IL-19 on osteoporosis.

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To fully quantify the effect of posterior tibial slope (PTS) angles on joint kinematics and contact mechanics of intact and anterior cruciate ligament-deficient (ACLD) knees during the gait cycle.

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This study aimed to establish the optimal fixation methods for calcaneal tuberosity avulsion fractures with different fragment thicknesses in a porcine model.

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It has been established that mechanical stimulation benefits tendon-bone (T-B) healing, and macrophage phenotype can be regulated by mechanical cues; moreover, the interaction between macrophages and mesenchymal stem cells (MSCs) plays a fundamental role in tissue repair. This study aimed to investigate the role of macrophage-mediated MSC chondrogenesis in load-induced T-B healing in depth.

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Fracture-related infection (FRI) is commonly classified based on the time of onset of symptoms. Early infections (< two weeks) are treated with debridement, antibiotics, and implant retention (DAIR). For late infections (> ten weeks), guidelines recommend implant removal due to tolerant biofilms. For delayed infections (two to ten weeks), recommendations are unclear. In this study we compared infection clearance and bone healing in early and delayed FRI treated with DAIR in a rabbit model.

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This study aimed to explore the role of small colony variants (SCVs) of Staphylococcus aureus in intraosseous invasion and colonization in patients with periprosthetic joint infection (PJI).

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To explore the novel molecular mechanisms of histone deacetylase 4 (HDAC4) in chondrocytes via RNA sequencing (RNA-seq) analysis.

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Open lower limb fracture is life-changing, resulting in substantial morbidity and resource demand, while inconsistent outcome-reporting hampers systematic review and meta-analysis. A core outcome set establishes consensus among key stakeholders for the recommendation of a minimum set of outcomes. This study aims to define a core outcome set for adult open lower limb fracture.

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Pigment epithelium-derived factor (PEDF) is known to induce several types of tissue regeneration by activating tissue-specific stem cells. Here, we investigated the therapeutic potential of PEDF 29-mer peptide in the damaged articular cartilage (AC) in rat osteoarthritis (OA).

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To investigate the efficacy of ethylenediaminetetraacetic acid-normal saline (EDTA-NS) in dispersing biofilms and reducing bacterial infections.

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To verify whether secretory leucocyte protease inhibitor (SLPI) can promote early tendon-to-bone healing after anterior cruciate ligament (ACL) reconstruction.

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A functional anterior cruciate ligament (ACL) or posterior cruciate ligament (PCL) has been assumed to be required for patients undergoing unicompartmental knee arthroplasty (UKA). However, this assumption has not been thoroughly tested. Therefore, this study aimed to assess the biomechanical effects exerted by cruciate ligament-deficient knees with medial UKAs regarding different posterior tibial slopes.

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Insufficient treatment response in rheumatoid arthritis (RA) patients requires novel treatment strategies to halt disease progression. The potential benefit of combination of cytokine-inhibitors in RA is still unclear and needs further investigation. To explore the impact of combined deficiency of two major cytokines, namely interleukin (IL)-1 and IL-6, in this study double deficient mice for IL-1αβ and IL-6 were investigated in different tumour necrosis factor (TNF)-driven inflammatory bone disorders, namely peripheral arthritis and sacroiliitis, as well as systemic bone loss.

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Gap junction intercellular communication (GJIC) in osteocytes is impaired by oxidative stress, which is associated with age-related bone loss. Ageing is accompanied by the accumulation of advanced oxidation protein products (AOPPs). However, it is still unknown whether AOPP accumulation is involved in the impairment of osteocytes’ GJIC. This study aims to investigate the effect of AOPP accumulation on osteocytes’ GJIC in aged male mice and its mechanism.

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Treatment outcomes for methicillin-resistant Staphylococcus aureus (MRSA) periprosthetic joint infection (PJI) using systemic vancomycin and antibacterial cement spacers during two-stage revision arthroplasty remain unsatisfactory. This study explored the efficacy and safety of intra-articular vancomycin injections for PJI control after debridement and cement spacer implantation in a rat model.

Cite this article: Bone Joint Res 2022;11(8):514–517.

Objectives. The aim of this experimental study on New Zealand’s white rabbits was to investigate the transplantation of autogenous growth plate cells in order to treat the injured growth plate. They were assessed in terms of measurements of radiological tibial varus and histological characteristics. . Methods. An experimental model of plate growth medial partial resection of the tibia in 14 New Zealand white rabbits was created. During this surgical procedure the plate growth cells were collected and cultured. While the second surgery was being performed, the autologous cultured growth plate cells were grafted at the right tibia, whereas the left tibia was used as a control group. . Results. Histological examinations showed that the grafted right tibia presented the regular shape of the plate growth with hypertrophic maturation, chondrocyte columniation and endochondral calcification. Radiological study shows that the mean tibial deformity at the left angle was 20.29° (6.25 to 33) and 7.21° (5 to 10) in the right angle. . Conclusion. This study has demonstrated that grafting of autogenous cultured growth plate cells into a defect of the medial aspect of the proximal tibial physis can prevent bone bridge formation, growth arrest and the development of varus deformity. Cite this article: Bone Joint Res 2014;3:310–16

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Treatment for delayed wound healing resulting from peripheral vascular diseases and diabetic foot ulcers remains a challenge. A novel surgical technique named ‘tibial cortex transverse transport’ (TTT) has been developed for treating peripheral ischaemia, with encouraging clinical effects. However, its underlying mechanisms remain unclear. In the present study, we explored the potential biological mechanisms of TTT surgery using various techniques in a rat TTT animal model.

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Exosomes (exo) are involved in the progression of osteoarthritis (OA). This study aimed to investigate the function of dysfunctional chondrocyte-derived exo (DC-exo) on OA in rats and rat macrophages.

Objectives. Up to 40% of unicompartmental knee arthroplasty (UKA) revisions are performed for unexplained pain which may be caused by elevated proximal tibial bone strain. This study investigates the effect of tibial component metal backing and polyethylene thickness on bone strain in a cemented fixed-bearing medial UKA using a finite element model (FEM) validated experimentally by digital image correlation (DIC) and acoustic emission (AE). Materials and Methods. A total of ten composite tibias implanted with all-polyethylene (AP) and metal-backed (MB) tibial components were loaded to 2500 N. Cortical strain was measured using DIC and cancellous microdamage using AE. FEMs were created and validated and polyethylene thickness varied from 6 mm to 10 mm. The volume of cancellous bone exposed to < -3000 µε (pathological loading) and < -7000 µε (yield point) minimum principal (compressive) microstrain and > 3000 µε and > 7000 µε maximum principal (tensile) microstrain was computed. Results. Experimental AE data and the FEM volume of cancellous bone with compressive strain < -3000 µε correlated strongly: R = 0.947, R. 2. = 0.847, percentage error 12.5% (p < 0.001). DIC and FEM data correlated: R = 0.838, R. 2. = 0.702, percentage error 4.5% (p < 0.001). FEM strain patterns included MB lateral edge concentrations; AP concentrations at keel, peg and at the region of load application. Cancellous strains were higher in AP implants at all loads: 2.2- (10 mm) to 3.2-times (6 mm) the volume of cancellous bone compressively strained < -7000 µε. Conclusion. AP tibial components display greater volumes of pathologically overstrained cancellous bone than MB implants of the same geometry. Increasing AP thickness does not overcome these pathological forces and comes at the cost of greater bone resection. Cite this article: C. E. H. Scott, M. J. Eaton, R. W. Nutton, F. A. Wade, S. L. Evans, P. Pankaj. Metal-backed versus all-polyethylene unicompartmental knee arthroplasty: Proximal tibial strain in an experimentally validated finite element model. Bone Joint Res 2017;6:22–30. DOI:10.1302/2046-3758.61.BJR-2016-0142.R1

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Osteoarthritis (OA) is the most prevalent systemic musculoskeletal disorder, characterized by articular cartilage degeneration and subchondral bone (SCB) sclerosis. Here, we sought to examine the contribution of accelerated growth to OA development using a murine model of excessive longitudinal growth. Suppressor of cytokine signalling 2 (SOCS2) is a negative regulator of growth hormone (GH) signalling, thus mice deficient in SOCS2 (Socs2^-/-) display accelerated bone growth.

Objectives. Cortical and cancellous bone healing processes appear to be histologically different. They also respond differently to anti-inflammatory agents. We investigated whether the leucocyte composition on days 3 and 5 after cortical and cancellous injuries to bone was different, and compared changes over time using day 3 as the baseline. Methods. Ten-week-old male C56/Bl6J mice were randomized to either cancellous injury in the proximal tibia or cortical injury in the femoral diaphysis. Regenerating tissues were analyzed with flow cytometry at days 3 and 5, using panels with 15 antibodies for common macrophage and lymphocyte markers. The cellular response from day 3 to 5 was compared in order to identify differences in how cancellous and cortical bone healing develop. Results. Between day 3 and 5, the granulocytes increased in the cancellous model, whereas the lymphocytes (T cells, B cells, NK cells) and monocytes (CD11b+, F4/80+, CD206+, CD14+) increased in the cortical model. Conclusion. These results suggest an acute type of inflammation in cancellous bone healing, and a more chronic inflammation in cortical healing. This might explain, in part, why cancellous healing is faster and more resistant to anti-inflammatory drugs than are diaphyseal fractures. Cite this article: L. Tätting, O. Sandberg, M. Bernhardsson, J. Ernerudh, P. Aspenberg. Different composition of leucocytes in cortical and cancellous bone healing in a mouse model. Bone Joint Res 2018;7:620–628. DOI: 10.1302/2046-3758.712.BJR-2017-0366.R2

Osteoarthritis (OA) is a highly prevalent degenerative joint disorder characterized by joint pain and physical disability. Aberrant subchondral bone induces pathological changes and is a major source of pain in OA. In the subchondral bone, which is highly innervated, nerves have dual roles in pain sensation and bone homeostasis regulation. The interaction between peripheral nerves and target cells in the subchondral bone, and the interplay between the sensory and sympathetic nervous systems, allow peripheral nerves to regulate subchondral bone homeostasis. Alterations in peripheral innervation and local transmitters are closely related to changes in nociception and subchondral bone homeostasis, and affect the progression of OA. Recent literature has substantially expanded our understanding of the physiological and pathological distribution and function of specific subtypes of neurones in bone. This review summarizes the types and distribution of nerves detected in the tibial subchondral bone, their cellular and molecular interactions with bone cells that regulate subchondral bone homeostasis, and their role in OA pain. A comprehensive understanding and further investigation of the functions of peripheral innervation in the subchondral bone will help to develop novel therapeutic approaches to effectively prevent OA, and alleviate OA pain.

Cite this article: Bone Joint Res 2022;11(7):439–452.

Objectives. Unicompartmental knee arthroplasty (UKA) is an alternative to total knee arthroplasty for patients who require treatment of single-compartment osteoarthritis, especially for young patients. To satisfy this requirement, new patient-specific prosthetic designs have been introduced. The patient-specific UKA is designed on the basis of data from preoperative medical images. In general, knee implant design with increased conformity has been developed to provide lower contact stress and reduced wear on the tibial insert compared with flat knee designs. The different tibiofemoral conformity may provide designers the opportunity to address both wear and kinematic design goals simultaneously. The aim of this study was to evaluate wear prediction with respect to tibiofemoral conformity design in patient-specific UKA under gait loading conditions by using a previously validated computational wear method. Methods. Three designs with different conformities were developed with the same femoral component: a flat design normally used in fixed-bearing UKA, a tibia plateau anatomy mimetic (AM) design, and an increased conforming design. We investigated the kinematics, contact stress, contact area, wear rate, and volumetric wear of the three different tibial insert designs. Results. Conforming increased design showed a lower contact stress and increased contact area. In addition, increased conformity resulted in a reduction of the wear rate and volumetric wear. However, the increased conformity design showed limited kinematics. Conclusion. Our results indicated that increased conformity provided improvements in wear but resulted in limited kinematics. Therefore, increased conformity should be avoided in fixed-bearing patient-specific UKA design. We recommend a flat or plateau AM tibial insert design in patient-specific UKA. Cite this article: Y-G. Koh, K-M. Park, H-Y. Lee, K-T. Kang. Influence of tibiofemoral congruency design on the wear of patient-specific unicompartmental knee arthroplasty using finite element analysis. Bone Joint Res 2019;8:156–164. DOI: 10.1302/2046-3758.83.BJR-2018-0193.R1

Objectives. Overlap between the distal tibia and fibula has always been quoted to be positive. If the value is not positive then an injury to the syndesmosis is thought to exist. Our null hypothesis is that it is a normal variant in the adult population. Methods. We looked at axial CT scans of the ankle in 325 patients for the presence of overlap between the distal tibia and fibula. Where we thought this was possible we reconstructed the images to represent a plain film radiograph which we were able to rotate and view in multiple planes to confirm the assessment. . Results. The scans were taken for reasons other than pathology of the ankle. We found there was no overlap in four patients. These patients were then questioned about previous injury, trauma, surgery or pain, in order to exclude underlying pathology. Conclusion. We concluded that no overlap between the tibia and fibula may exist in the population, albeit in a very small proportion

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The aim of this study was to establish a reliable method for producing 3D reconstruction of sonographic callus.

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Outcomes of current operative treatments for arthrofibrosis after total knee arthroplasty (TKA) are not consistently positive or predictable. Pharmacological in vivo studies have focused mostly on prevention of arthrofibrosis. This study used a rabbit model to evaluate intra-articular (IA) effects of celecoxib in treating contracted knees alone, or in combination with capsular release.

Objectives. Bone fracture healing is regulated by a series of complex physicochemical and biochemical processes. One of these processes is bone mineralization, which is vital for normal bone development. Phosphatase, orphan 1 (PHOSPHO1), a skeletal tissue-specific phosphatase, has been shown to be involved in the mineralization of the extracellular matrix and to maintain the structural integrity of bone. In this study, we examined how PHOSPHO1 deficiency might affect the healing and quality of fracture callus in mice. Methods. Tibial fractures were created and then stabilized in control wild-type (WT) and Phospho1. -/-. mice (n = 16 for each group; mixed gender, each group carrying equal number of male and female mice) at eight weeks of age. Fractures were allowed to heal for four weeks and then the mice were euthanized and their tibias analyzed using radiographs, micro-CT (μCT), histology, histomorphometry and three-point bending tests. Results. The μCT and radiographic analyses revealed a mild reduction of bone volume in Phospho1. -/-. callus, although it was not statistically significant. An increase in trabecular number and a decrease in trabecular thickness and separation were observed in Phospho1. -/-. callus in comparison with the WT callus. Histomorphometric analyses showed that there was a marked increase of osteoid volume over bone volume in the Phospho1. -/-. callus. The three-point bending test showed that Phospho1. -/-. fractured bone had more of an elastic characteristic than the WT bone. Conclusion. Our work suggests that PHOSPHO1 plays an integral role during bone fracture repair and may be a therapeutic target to improve the fracture healing process. Cite this article: M. W. Morcos, H. Al-Jallad, J. Li, C. Farquharson, J. L. Millán, R. C. Hamdy, M. Murshed. PHOSPHO1 is essential for normal bone fracture healing: An Animal Study. Bone Joint Res 2018;7:397–405. DOI: 10.1302/2046-3758.76.BJR-2017-0140.R2

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To develop an early implant instability murine model and explore the use of intermittent parathyroid hormone (iPTH) treatment for initially unstable implants.

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Distraction osteogenesis (DO) is a useful orthopaedic procedure employed to lengthen and reshape bones by stimulating bone formation through controlled slow stretching force. Despite its promising applications, difficulties are still encountered. Our previous study demonstrated that pulsed electromagnetic field (PEMF) treatment significantly enhances bone mineralization and neovascularization, suggesting its potential application. The current study compared a new, high slew rate (HSR) PEMF signal, with different treatment durations, with the standard Food and Drug Administration (FDA)-approved signal, to determine if HSR PEMF is a better alternative for bone formation augmentation.

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Post-traumatic osteoarthritis (PTOA) is a subset of osteoarthritis (OA). The gut microbiome is shown to be involved in OA. However, the effect of exercise on gut microbiome in PTOA remains elusive.

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There are concerns regarding nail/medullary canal mismatch and initial stability after cephalomedullary nailing in unstable pertrochanteric fractures. This study aimed to investigate the effect of an additional anteroposterior blocking screw on fixation stability in unstable pertrochanteric fracture models with a nail/medullary canal mismatch after short cephalomedullary nail (CMN) fixation.

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Periprosthetic joint infections (PJIs) are rare, but represent a great burden for the patient. In addition, the incidence of methicillin-resistant Staphylococcus aureus (MRSA) is increasing. The aim of this rat experiment was therefore to compare the antibiotics commonly used in the treatment of PJIs caused by MRSA.

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The distal radius is a major site of osteoporotic bone loss resulting in a high risk of fragility fracture. This study evaluated the capability of a cortical index (CI) at the distal radius to predict the local bone mineral density (BMD).

Objectives. Distraction osteogenesis (DO) mobilises bone regenerative potential and avoids the complications of other treatments such as bone graft. The major disadvantage of DO is the length of time required for bone consolidation. Mesenchymal stem cells (MSCs) have been used to promote bone formation with some good results. Methods. We hereby review the published literature on the use of MSCs in promoting bone consolidation during DO. Results. Studies differed in animal type (mice, rabbit, dog, sheep), bone type (femur, tibia, skull), DO protocols and cell transplantation methods. Conclusion. The majority of studies reported that the transplantation of MSCs enhanced bone consolidation or formation in DO. Many questions relating to animal model, DO protocol and cell transplantation regime remain to be further investigated. Clinical trials are needed to test and confirm these findings from animal studies. Cite this article: Y. Yang, S. Lin, B. Wang, W. Gu, G. Li. Stem cell therapy for enhancement of bone consolidation in distraction osteogenesis: A contemporary review of experimental studies. Bone Joint Res 2017;6:385–390. DOI: 10.1302/2046-3758.66.BJR-2017-0023

Objectives. Static radiostereometric analysis (RSA) using implanted markers is considered the most accurate system for the evaluation of prosthesis migration. By using CT bone models instead of markers, combined with a dynamic RSA system, a non-invasive measurement of joint movement is enabled. This method is more accurate than current 3D skin marker-based tracking systems. The purpose of this study was to evaluate the accuracy of the CT model method for measuring knee joint kinematics in static and dynamic RSA using the marker method as the benchmark. Methods. Bone models were created from CT scans, and tantalum beads were implanted into the tibia and femur of eight human cadaver knees. Each specimen was secured in a fixture, static and dynamic stereoradiographs were recorded, and the bone models and marker models were fitted to the stereoradiographs. Results. Results showed a mean difference between the two methods in all six degrees of freedom for static RSA to be within -0.10 mm/° and 0.08 mm/° with a 95% limit of agreement (LoA) ranging from ± 0.49 to 1.26. Dynamic RSA had a slightly larger range in mean difference of -0.23 mm/° to 0.16 mm/° with LoA ranging from ± 0.75 to 1.50. Conclusions. In a laboratory-controlled setting, the CT model method combined with dynamic RSA may be an alternative to previous marker-based methods for kinematic analyses. Cite this article: K. Stentz-Olesen, E. T. Nielsen, S. De Raedt, P. B. Jørgensen, O. G. Sørensen, B. L. Kaptein, M. S. Andersen, M. Stilling. Validation of static and dynamic radiostereometric analysis of the knee joint using bone models from CT data. Bone Joint Res 2017;6:376–384. DOI: 10.1302/2046-3758.66.BJR-2016-0113.R3

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This study aims to enhance understanding of clinical and radiological consequences and involved mechanisms that led to corrosion of the Precice Stryde (Stryde) intramedullary lengthening nail in the post market surveillance era of the device. Between 2018 and 2021 more than 2,000 Stryde nails have been implanted worldwide. However, the outcome of treatment with the Stryde system is insufficiently reported.

Objectives. Unicompartmental knee arthroplasty (UKA) is a demanding procedure, with tibial component subsidence or pain from high tibial strain being potential causes of revision. The optimal position in terms of load transfer has not been documented for lateral UKA. Our aim was to determine the effect of tibial component position on proximal tibial strain. Methods. A total of 16 composite tibias were implanted with an Oxford Domed Lateral Partial Knee implant using cutting guides to define tibial slope and resection depth. Four implant positions were assessed: standard (5° posterior slope); 10° posterior slope; 5° reverse tibial slope; and 4 mm increased tibial resection. Using an electrodynamic axial-torsional materials testing machine (Instron 5565), a compressive load of 1.5 kN was applied at 60 N/s on a meniscal bearing via a matching femoral component. Tibial strain beneath the implant was measured using a calibrated Digital Image Correlation system. Results. A 5° increase in tibial component posterior slope resulted in a 53% increase in mean major principal strain in the posterior tibial zone adjacent to the implant (p = 0.003). The highest strains for all implant positions were recorded in the anterior cortex 2 cm to 3 cm distal to the implant. Posteriorly, strain tended to decrease with increasing distance from the implant. Lateral cortical strain showed no significant relationship with implant position. Conclusion. Relatively small changes in implant position and orientation may significantly affect tibial cortical strain. Avoidance of excessive posterior tibial slope may be advisable during lateral UKA. Cite this article: A. M. Ali, S. D. S. Newman, P. A. Hooper, C. M. Davies, J. P. Cobb. The effect of implant position on bone strain following lateral unicompartmental knee arthroplasty: A Biomechanical Model Using Digital Image Correlation. Bone Joint Res 2017;6:522–529. DOI: 10.1302/2046-3758.68.BJR-2017-0067.R1

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Osteoarthritis (OA) is prevalent among the elderly and incurable. Intra-articular parathyroid hormone (PTH) ameliorated OA in papain-induced and anterior cruciate ligament transection-induced OA models; therefore, we hypothesized that PTH improved OA in a preclinical age-related OA model.

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Exosomes derived from bone marrow mesenchymal stem cells (BMSCs) have been reported to be a promising cellular therapeutic approach for various human diseases. The current study aimed to investigate the mechanism of BMSC-derived exosomes carrying microRNA (miR)-136-5p in fracture healing.

Objectives. External fixators are the traditional fixation method of choice for contaminated open fractures. However, patient acceptance is low due to the high profile and therefore physical burden of the constructs. An externalised locking compression plate is a low profile alternative. However, the biomechanical differences have not been assessed. The objective of this study was to evaluate the axial and torsional stiffness of the externalised titanium locking compression plate (ET-LCP), the externalised stainless steel locking compression plate (ESS-LCP) and the unilateral external fixator (UEF). Methods. A fracture gap model was created to simulate comminuted mid-shaft tibia fractures using synthetic composite bones. Fifteen constructs were stabilised with ET-LCP, ESS-LCP or UEF (five constructs each). The constructs were loaded under both axial and torsional directions to determine construct stiffness. Results. The mean axial stiffness was very similar for UEF (528 N/mm) and ESS-LCP (525 N/mm), while it was slightly lower for ET-LCP (469 N/mm). One-way analysis of variance (ANOVA) testing in all three groups demonstrated no significant difference (F(2,12) = 2.057, p = 0.171). There was a significant difference in mean torsional stiffness between the UEF (0.512 Nm/degree), the ESS-LCP (0.686 Nm/degree) and the ET-LCP (0.639 Nm/degree), as determined by one-way ANOVA (F(2,12) = 6.204, p = 0.014). A Tukey post hoc test revealed that the torsional stiffness of the ESS-LCP was statistically higher than that of the UEF by 0.174 Nm/degree (p = 0.013). No catastrophic failures were observed. Conclusion. Using the LCP as an external fixator may provide a viable and attractive alternative to the traditional UEF as its lower profile makes it more acceptable to patients, while not compromising on axial and torsional stiffness. Cite this article: B. F. H. Ang, J. Y. Chen, A. K. S. Yew, S. K. Chua, S. M. Chou, S. L. Chia, J. S. B. Koh, T. S. Howe. Externalised locking compression plate as an alternative to the unilateral external fixator: a biomechanical comparative study of axial and torsional stiffness. Bone Joint Res 2017;6:216–223. DOI: 10.1302/2046-3758.64.2000470

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Tert-butylhydroquinone (tBHQ) has been identified as an inhibitor of oxidative stress-induced injury and apoptosis in human neural stem cells. However, the role of tBHQ in osteoarthritis (OA) is unclear. This study was carried out to investigate the role of tBHQ in OA.

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We aimed to evaluate the long-term impact of fracture-related infection (FRI) on patients’ physical health and psychological wellbeing. For this purpose, quality of life after successful surgical treatment of FRIs of long bones was assessed.

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To explore the clinical relevance of joint space width (JSW) narrowing on standardized-flexion (SF) radiographs in the assessment of cartilage degeneration in specific subregions seen on MRI sequences in knee osteoarthritis (OA) with neutral, valgus, and varus alignments, and potential planning of partial knee arthroplasty.

Objectives. Initial stability of tibial trays is crucial for long-term success of total knee arthroplasty (TKA) in both primary and revision settings. Rotating platform (RP) designs reduce torque transfer at the tibiofemoral interface. We asked if this reduced torque transfer in RP designs resulted in subsequently reduced micromotion at the cemented fixation interface between the prosthesis component and the adjacent bone. Methods. Composite tibias were implanted with fixed and RP primary and revision tibial trays and biomechanically tested under up to 2.5 kN of axial compression and 10° of external femoral component rotation. Relative micromotion between the implanted tibial tray and the neighbouring bone was quantified using high-precision digital image correlation techniques. Results. Rotational malalignment between femoral and tibial components generated 40% less overall tibial tray micromotion in RP designs than in standard fixed bearing tibial trays. RP trays reduced micromotion by up to 172 µm in axial compression and 84 µm in rotational malalignment models. Conclusions. Reduced torque transfer at the tibiofemoral interface in RP tibial trays reduces relative component micromotion and may aid long-term stability in cases of revision TKA or poor bone quality. Cite this article: Mr S. R. Small. Micromotion at the tibial plateau in primary and revision total knee arthroplasty: fixed versus rotating platform designs. Bone Joint Res 2016;5:122–129. DOI: 10.1302/2046-3758.54.2000481

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We wanted to evaluate the effects of a bone anabolic agent (bone morphogenetic protein 2 (BMP-2)) on an anti-catabolic background (systemic or local zoledronate) on fixation of allografted revision implants.

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In contrast to operations performed for other fractures, there is a high incidence rate of surgical site infection (SSI) post-open reduction and internal fixation (ORIF) done for tibial plateau fractures (TPFs). This study investigates the effect of induced membrane technique combined with internal fixation for managing SSI in TPF patients who underwent ORIF.

Objectives. The biomembrane (induced membrane) formed around polymethylmethacrylate (PMMA) spacers has value in clinical applications for bone defect reconstruction. Few studies have evaluated its cellular, molecular or stem cell features. Our objective was to characterise induced membrane morphology, molecular features and osteogenic stem cell characteristics. Methods. Following Institutional Review Board approval, biomembrane specimens were obtained from 12 patient surgeries for management of segmental bony defects (mean patient age 40.7 years, standard deviation 14.4). Biomembranes from nine tibias and three femurs were processed for morphologic, molecular or stem cell analyses. Gene expression was determined using the Affymetrix GeneChip Operating Software (GCOS). Molecular analyses compared biomembrane gene expression patterns with a mineralising osteoblast culture, and gene expression in specimens with longer spacer duration (> 12 weeks) with specimens with shorter durations. Statistical analyses used the unpaired student t-test (two tailed; p < 0.05 was considered significant). Results. Average PMMA spacer in vivo time was 11.9 weeks (six to 18). Trabecular bone was present in 33.3% of the biomembrane specimens; bone presence did not correlate with spacer duration. Biomembrane morphology showed high vascularity and collagen content and positive staining for the key bone forming regulators, bone morphogenetic protein 2 (BMP2) and runt-related transcription factor 2 (RUNX2). Positive differentiation of cultured biomembrane cells for osteogenesis was found in cells from patients with PMMA present for six to 17 weeks. Stem cell differentiation showed greater variability in pluripotency for osteogenic potential (70.0%) compared with chondrogenic or adipogenic potentials (100% and 90.0%, respectively). Significant upregulation of BMP2 and 6, numerous collagens, and bone gla protein was present in biomembrane compared with the cultured cell line. Biomembranes with longer resident PMMA spacer duration (vs those with shorter residence) showed significant upregulation of bone-related, stem cell, and vascular-related genes. Conclusion. The biomembrane technique is gaining favour in the management of complicated bone defects. Novel data on biological mechanisms provide improved understanding of the biomembrane’s osteogenic potential and molecular properties. Cite this article: Dr H. E. Gruber. Osteogenic, stem cell and molecular characterisation of the human induced membrane from extremity bone defects. Bone Joint Res 2016;5:106–115. DOI: 10.1302/2046-3758.54.2000483