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