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. Anterior cruciate ligament (ACL) rupture commonly leads to post-traumatic osteoarthritis, regardless of surgical reconstruction. This study uses standing MRI to investigate changes in contact area, contact centroid location, and tibiofemoral alignment between ACL-injured knees and healthy controls, to examine the effect of ACL reconstruction on these parameters. Methods. An upright, open MRI was used to directly measure tibiofemoral contact area, centroid location, and alignment in 18 individuals with unilateral ACL rupture within the last five years. Eight participants had been treated nonoperatively and ten had ACL reconstruction performed within one year of injury. All participants were high-functioning and had returned to sport or recreational activities. Healthy contralateral knees served as controls. Participants were imaged in a standing posture with knees fully extended. Results. Participants’ mean age was 28.4 years (SD 7.3), the mean time since injury was 2.7 years (SD 1.6), and the mean International Knee Documentation Subjective Knee Form score was 84.4 (SD 13.5). ACL injury was associated with a 10% increase (p = 0.001) in contact area, controlling for compartment, sex, posture, age, body mass, and time since injury. ACL injury was associated with a 5.2% more posteriorly translated medial centroid (p = 0.001), equivalent to a 2.6 mm posterior translation on a representative tibia with mean posteroanterior width of 49.4 mm. Relative to the femur, the tibiae of ACL ruptured knees were 2.3 mm more anteriorly translated (p = 0.003) and 2.6° less externally rotated (p = 0.010) than healthy controls. ACL reconstruction was not associated with an improvement in any measure. Conclusion. ACL rupture was associated with an increased contact area, posteriorly translated medial centroid, anterior tibial translation, and reduced tibial external rotation in full extension. These changes were present 2.7 years post-injury regardless of ACL reconstruction status. Cite this article: Bone Joint J 2021;103-B(9):1505–1513

Aims. The modified Radiological Union Scale for Tibia (mRUST) fractures score was developed in order to assess progress to union and define a numerical assessment of fracture healing of metadiaphyseal fractures. This score has been shown to be valuable in predicting radiological union; however, there is no information on the sensitivity, specificity, and accuracy of this index for various cut-off scores. The aim of this study is to evaluate sensitivity, specificity, accuracy, and cut-off points of the mRUST score for the diagnosis of metadiaphyseal fractures healing. Methods. A cohort of 146 distal femur fractures were retrospectively identified at our institution. After excluding AO/OTA type B fractures, nonunions, follow-up less than 12 weeks, and patients aged less than 16 years, 104 sets of radiographs were included for analysis. Anteroposterior and lateral femur radiographs at six weeks, 12 weeks, 24 weeks, and final follow-up were separately scored by three surgeons using the mRUST score. The sensitivity and specificity of mean mRUST score were calculated using clinical and further radiological findings as a gold standard for ultimate fracture healing. A receiver operating characteristic curve was also performed to determine the cut-off points at each time point. Results. The mean mRUST score of ten at 24 weeks revealed a 91.9% sensitivity, 100% specificity, and 92.6% accuracy of predicting ultimate fracture healing. A cut-off point of 13 points revealed 41.9% sensitivity, 100% specificity, and 46.9% accuracy at the same time point. Conclusion. The mRUST score of ten points at 24 weeks can be used as a viable screening method with the highest sensitivity, specificity, and accuracy for healing of metadiaphyseal femur fractures. However, the cut-off point of 13 increases the specificity to 100%, but decreases sensitivity. Furthermore, the mRUST score should not be used at six weeks, as results show an inability to accurately predict eventual fracture healing at this time point. Cite this article: Bone Jt Open 2021;2(10):796–805

Aims. Femoral revision component subsidence has been identified as predicting early failure in revision hip surgery. This comparative cohort study assessed the potential risk factors of subsidence in two commonly used femoral implant designs. Methods. A comparative cohort study was undertaken, analyzing a consecutive series of patients following revision total hip arthroplasties using either a tapered-modular (TM) fluted titanium or a porous-coated cylindrical modular (PCM) titanium femoral component, between April 2006 and May 2018. Clinical and radiological assessment was compared for both treatment cohorts. Risk factors for subsidence were assessed and compared. Results. In total, 65 TM and 35 PCM cases were included. At mean follow-up of seven years (1 to 13), subsidence was noted in both cohorts during the initial three months postoperatively (p < 0.001) then implants stabilized. Subsidence noted in 58.7% (38/65 cases) of the TM cohort (mean 2.3 mm, SD 3.5 mm) compared to 48.8% (17/35) of PCM cohort (mean 1.9 mm, SD 2.6 mm; p = 0.344). Subsidence of PCM cohort were significantly associated with extended trochanteric osteotomy (ETO) (p < 0.041). Although the ETO was used less frequently in PCM stem cohort (7/35), subsidence was noted in 85% (6/7) of them. Significant improvement of the final mean Oxford Hip Score (OHS) was reported in both treatment groups (p < 0.001). Conclusion. Both modular TM and PCM revision femoral components subsided within the femur. TM implants subsided more frequently than PCM components if the femur was intact but with no difference in clinical outcomes. However, if an ETO is performed then a PCM component will subside significantly more and suggests the use of a TM implant may be advisable. Cite this article: Bone Joint J 2020;102-B(6):709–715

Aims. Surgeons commonly resect additional distal femur during primary total knee arthroplasty (TKA) to correct a flexion contracture, which leads to femoral joint line elevation. There is a paucity of data describing the effect of joint line elevation on mid-flexion stability and knee kinematics. Thus, the goal of this study was to quantify the effect of joint line elevation on mid-flexion laxity. Methods. Six computational knee models with cadaver-specific capsular and collateral ligament properties were implanted with a posterior-stabilized (PS) TKA. A 10° flexion contracture was created in each model to simulate a capsular contracture. Distal femoral resections of + 2 mm and + 4 mm were then simulated for each knee. The knee models were then extended under a standard moment. Subsequently, varus and valgus moments of 10 Nm were applied as the knee was flexed from 0° to 90° at baseline and repeated after each of the two distal resections. Coronal laxity (the sum of varus and valgus angulation with respective maximum moments) was measured throughout flexion. Results. With + 2 mm resection at 30° and 45° of flexion, mean coronal laxity increased by a mean of 3.1° (SD 0.18°) (p < 0.001) and 2.7° (SD 0.30°) (p < 0.001), respectively. With + 4 mm resection at 30° and 45° of flexion, mean coronal laxity increased by 6.5° (SD 0.56°) (p < 0.001) and 5.5° (SD 0.72°) (p < 0.001), respectively. Maximum increased coronal laxity for a + 4 mm resection occurred at a mean 15.7° (11° to 33°) of flexion with a mean increase of 7.8° (SD 0.2°) from baseline. Conclusion. With joint line elevation in primary PS TKA, coronal laxity peaks early (about 16°) with a maximum laxity of 8°. Surgeons should restore the joint line if possible; however, if joint line elevation is necessary, we recommend assessment of coronal laxity at 15° to 30° of knee flexion to assess for mid-flexion instability. Further in vivo studies are warranted to understand if this mid-flexion coronal laxity has negative clinical implications. Cite this article: Bone Joint J 2021;103-B(6 Supple A):87–93

Aims. To clarify the effectiveness of the induced membrane technique (IMT) using beta-tricalcium phosphate (β-TCP) for reconstruction of segmental bone defects by evaluating clinical and radiological outcomes, and the effect of defect size and operated site on surgical outcomes. Methods. A review of the medical records was conducted of consecutive 35 lower limbs (30 males and five females; median age 46 years (interquartile range (IQR) 40 to 61)) treated with IMT using β-TCP between 2014 and 2018. Lower Extremity Functional Score (LEFS) was examined preoperatively and at final follow-up to clarify patient-centered outcomes. Bone healing was assessed radiologically, and time from the second stage to bone healing was also evaluated. Patients were divided into ≥ 50 mm and < 50 mm defect groups and into femoral reconstruction, tibial reconstruction, and ankle arthrodesis groups. Results. There were ten and 25 defects in the femur and tibia, respectively. Median LEFS improved significantly from 8 (IQR 1.5 to 19.3) preoperatively to 63.5 (IQR 57 to 73.3) at final follow-up (p < 0.001). Bone healing was achieved in all limbs, and median time from the second stage to bone healing was six months (IQR 5 to 10). Median time to bone healing, preoperative LEFS, or postoperative LEFS did not differ significantly between the defect size groups or among the treatment groups. Conclusion. IMT using β-TCP provided satisfactory clinical and radiological outcomes for segmental bone defects in the lower limbs; surgical outcomes were not influenced by bone defect size or operated part. Cite this article: Bone Joint J 2021;103-B(3):456–461

Aims. The diversity of femoral morphology renders femoral component sizing in total hip arthroplasty (THA) challenging. We aimed to determine whether femoral morphology and femoral component filling influence early clinical and radiological outcomes following THA using fully hydroxyapatite (HA)-coated femoral components. Methods. We retrospectively reviewed records of 183 primary uncemented THAs. Femoral morphology, including Dorr classification, canal bone ratio (CBR), canal flare index (CFI), and canal-calcar ratio (CCR), were calculated on preoperative radiographs. The canal fill ratio (CFR) was calculated at different levels relative to the lesser trochanter (LT) using immediate postoperative radiographs: P1, 2 cm above LT; P2, at LT; P3, 2 cm below LT; and D1, 7 cm below LT. At two years, radiological femoral component osseointegration was evaluated using the Engh score, and hip function using the Postel Merle d’Aubigné (PMA) and Oxford Hip Score (OHS). Results. CFR was moderately correlated with CCR at P1 (r = 0.44; p < 0.001), P2 (r = 0.53; p < 0.001), and CFI at P1 (r = − 0.56; p < 0.001). Absence of spot welds (n = 3, 2%) was associated with lower CCR (p = 0.049), greater CFI (p = 0.017), and lower CFR at P3 (p = 0.015). Migration (n = 9, 7%) was associated with lower CFR at P2 (p = 0.028) and P3 (p = 0.007). Varus malalignment (n = 7, 5%), predominantly in Dorr A femurs (p = 0.028), was associated with lower CFR at all levels (p < 0.05). Absence of spot welds was associated with lower PMA gait (p = 0.012) and migration with worse OHS (p = 0.032). Conclusion. This study revealed that femurs with insufficient proximal filling tend to have less favourable radiological outcomes following uncemented THA using a fully HA-coated double-tapered femoral component. Cite this article: Bone Joint Res. 2020;9(4):182–191

Objectives. MicroRNAs (miRNAs) have been reported as key regulators of bone formation, signalling, and repair. Fracture healing is a proliferative physiological process where the body facilitates the repair of a bone fracture. The aim of our study was to explore the effects of microRNA-186 (miR-186) on fracture healing through the bone morphogenetic protein (BMP) signalling pathway by binding to Smad family member 6 (SMAD6) in a mouse model of femoral fracture. Methods. Microarray analysis was adopted to identify the regulatory miR of SMAD6. 3D micro-CT was performed to assess the bone volume (BV), bone volume fraction (BVF, BV/TV), and bone mineral density (BMD), followed by a biomechanical test for maximum load, maximum radial degrees, elastic radial degrees, and rigidity of the femur. The positive expression of SMAD6 in fracture tissues was measured. Moreover, the miR-186 level, messenger RNA (mRNA) level, and protein levels of SMAD6, BMP-2, and BMP-7 were examined. Results. MicroRNA-186 was predicted to regulate SMAD6. Furthermore, SMAD6 was verified as a target gene of miR-186. Overexpressed miR-186 and SMAD6 silencing resulted in increased callus formation, BMD and BV/TV, as well as maximum load, maximum radial degrees, elastic radial degrees, and rigidity of the femur. In addition, the mRNA and protein levels of SMAD6 were decreased, while BMP-2 and BMP-7 levels were elevated in response to upregulated miR-186 and SMAD6 silencing. Conclusion. In conclusion, the study indicated that miR-186 could activate the BMP signalling pathway to promote fracture healing by inhibiting SMAD6 in a mouse model of femoral fracture. Cite this article: Bone Joint Res 2019;8:550–562

Objectives. In total hip arthroplasty (THA), the cementless, tapered-wedge stem design contributes to achieving initial stability and providing optimal load transfer in the proximal femur. However, loading conditions on the femur following THA are also influenced by femoral structure. Therefore, we determined the effects of tapered-wedge stems on the load distribution of the femur using subject-specific finite element models of femurs with various canal shapes. Patients and Methods. We studied 20 femurs, including seven champagne flute-type femurs, five stovepipe-type femurs, and eight intermediate-type femurs, in patients who had undergone cementless THA using the Accolade TMZF stem at our institution. Subject–specific finite element (FE) models of pre- and post-operative femurs with stems were constructed and used to perform FE analyses (FEAs) to simulate single-leg stance. FEA predictions were compared with changes in bone mineral density (BMD) measured for each patient during the first post-operative year. Results. Stovepipe models implanted with large-size stems had significantly lower equivalent stress on the proximal-medial area of the femur compared with champagne-flute and intermediate models, with a significant loss of BMD in the corresponding area at one year post-operatively. Conclusions. The stovepipe femurs required a large-size stem to obtain an optimal fit of the stem. The FEA result and post-operative BMD change of the femur suggest that the combination of a large-size Accolade TMZF stem and stovepipe femur may be associated with proximal stress shielding. Cite this article: M. Oba, Y. Inaba, N. Kobayashi, H. Ike, T. Tezuka, T. Saito. Effect of femoral canal shape on mechanical stress distribution and adaptive bone remodelling around a cementless tapered-wedge stem. Bone Joint Res 2016;5:362–369. DOI: 10.1302/2046-3758.59.2000525

Aims. In patients where the proximal femur shows gross deformity due to degenerative changes or fracture, the contralateral femur is often used to perform preoperative templating for hip arthroplasty. However, femurs may not be symmetrical: the aim of this study was to determine the degree of variation between hips in healthy individuals and to determine whether it is affected by demographic parameters. Materials and Methods. CT-scan based modelling was used to examine the pelvis and bilateral femurs of 345 patients (211 males, 134 women; mean age 62 years (standard deviation (. sd). 17), mean body mass index 27 kg/m. 2. (. sd. 5)) representing a range of ethnicities. The femoral neck-shaft angle (NSA), femoral offset (FO), femoral neck version (FNV), femoral length (FL), femoral canal flare index (fCFI), and femoral head radius (FHr) were then determined for each patient. All measurements were constructed using algorithm-calculated landmarks, resulting in reproducible and consistent constructs for each specimen. We then analyzed femoral symmetry based on absolute differences (AD) and percentage asymmetry (%AS) following a previously validated method. Results. We found an asymmetry > 2% for NSA (mean AD 2.9°, mean %AS 2.3; p = 0.03), FO (AD 3.8 mm, %AS 9.1 ; p = 0.01), FNV (AD 5.1°, %AS 46.7 ; p = 0.001) and fCFI (AD 0.2 mm, %AS 5.4 ; p = 0.7). Significant relationships were found for AD regarding NSA and ethnicity (p = 0.037), FL and height (R. 2.  = 0.22), and fCFI and gender (R. 2.  = 0.34). Conclusion. Our data confirm the presence of asymmetry of proximal femurs, which is mostly independent of demographic parameters. In cases where contralateral templating is used, such asymmetry may lead to inaccurate anatomical restoration of the hip if the templated sizes are routinely implanted. However, the clinical impact cannot be determined from our investigation. Cite this article: Bone Joint J 2018;100-B:839–44

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This study intended to investigate the effect of vericiguat (VIT) on titanium rod osseointegration in aged rats with iron overload, and also explore the role of VIT in osteoblast and osteoclast differentiation.

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The aim of this study was to compare a bicruciate-retaining (BCR) total knee arthroplasty (TKA) with a posterior cruciate-retaining (CR) TKA design in terms of kinematics, measured using fluoroscopy and stability as micromotion using radiostereometric analysis (RSA).

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This study aimed to investigate the optimal sagittal positioning of the uncemented femoral component in total knee arthroplasty to minimize the risk of aseptic loosening and periprosthetic fracture.

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The aim of this study was to describe the incidence of refractures among children, following fractures of all long bones, and to identify when the risk of refracture decreases.

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This study aimed to evaluate if total knee arthroplasty (TKA) femoral components aligned in either mechanical alignment (MA) or kinematic alignment (KA) are more biomimetic concerning trochlear sulcus orientation and restoration of trochlear height.

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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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Given the possible radiation damage and inaccuracy of radiological investigations, particularly in children, ultrasound and superb microvascular imaging (SMI) may offer alternative methods of evaluating new bone formation when limb lengthening is undertaken in paediatric patients. The aim of this study was to assess the use of ultrasound combined with SMI in monitoring new bone formation during limb lengthening in children.

Aims. Restoration of proximal medial femoral support is the keystone in the treatment of intertrochanteric fractures. None of the available implants are effective in constructing the medial femoral support. Medial sustainable nail (MSN-II) is a novel cephalomedullary nail designed for this. In this study, biomechanical difference between MSN-II and proximal femoral nail anti-rotation (PFNA-II) was compared to determine whether or not MSN-II can effectively reconstruct the medial femoral support. Methods. A total of 36 synthetic femur models with simulated intertrochanteric fractures without medial support (AO/OTA 31-A2.3) were assigned to two groups with 18 specimens each for stabilization with MSN-II or PFNA-II. Each group was further divided into three subgroups of six specimens according to different experimental conditions respectively as follows: axial loading test; static torsional test; and cyclic loading test. Results. The mean axial stiffness, vertical displacement, and maximum failure load of MSN-II were 258.47 N/mm (SD 42.27), 2.99 mm (SD 0.56), and 4,886 N (SD 525.31), respectively, while those of PFNA-II were 170.28 N/mm (SD 64.63), 4.86 mm (SD 1.66), and 3,870.87 N (SD 552.21), respectively. The mean torsional stiffness and failure torque of MSN-II were 1.72 N m/° (SD 0.61) and 16.54 N m (SD 7.06), respectively, while those of PFNA-II were 0.61 N m/° (SD 0.39) and 6.6 N m (SD 6.65), respectively. The displacement of MSN-II in each cycle point was less than that of PFNA-II in cyclic loading test. Significantly higher stiffness and less displacement were detected in the MSN-II group (p < 0.05). Conclusion. The biomechanical performance of MSN-II was better than that of PFNA-II, suggesting that MSN-II may provide more effective mechanical support in the treatment of unstable intertrochanteric fractures. Cite this article: Bone Joint Res 2020;9(12):840–847

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This study aimed to analyze the accuracy and errors associated with 3D-printed, patient-specific resection guides (3DP-PSRGs) used for bone tumour resection.

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To systematically review the predominant complication rates and changes to patient-reported outcome measures (PROMs) following osteochondral allograft (OCA) transplantation for shoulder instability.