Aims. Osteosarcoma is the most common primary bone malignancy among children and adolescents. We investigated whether benzamil, an amiloride analogue and sodium-calcium exchange blocker, may exhibit therapeutic potential for osteosarcoma in vitro. Methods. MG63 and U2OS cells were treated with benzamil for 24 hours. Cell viability was evaluated with the MTS/PMS assay, colony formation assay, and flow cytometry (forward/side scatter). Chromosome condensation, the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay, cleavage of poly-ADP ribose polymerase (PARP) and caspase-7, and FITC annexin V/PI double staining were monitored as indicators of apoptosis. Intracellular calcium was detected by flow cytometry with Fluo-4 AM. The phosphorylation and activation of focal adhesion kinase (FAK) and signal transducer and activator of transcription 3 (STAT3) were measured by western blot. The expression levels of X-linked inhibitor of apoptosis protein (XIAP), B-cell lymphoma 2 (Bcl-2), B-cell lymphoma-extra large (Bcl-xL), SOD1, and SOD2 were also assessed by western blot. Mitochondrial status was assessed with tetramethylrhodamine, ethyl ester (TMRE), and intracellular adenosine triphosphate (ATP) was measured with BioTracker ATP-Red Live Cell Dye. Total cellular integrin levels were evaluated by western blot, and the expression of cell surface integrins was assessed using fluorescent-labelled antibodies and flow cytometry. Results. Benzamil suppressed growth of osteosarcoma cells by inducing apoptosis. Benzamil reduced the expression of cell surface integrins α5, αV, and β1 in MG63 cells, while it only reduced the expression of αV in U2OS cells. Benzamil suppressed the phosphorylation and activation of FAK and STAT3. In addition, mitochondrial function and ATP production were compromised by benzamil. The levels of anti-apoptotic proteins XIAP, Bcl-2, and Bcl-xL were reduced by benzamil. Correspondingly, benzamil potentiated cisplatin- and methotrexate-induced apoptosis in osteosarcoma cells. Conclusion. Benzamil exerts anti-osteosarcoma activity by inducing apoptosis. In terms of mechanism, benzamil appears to inhibit integrin/FAK/STAT3 signalling, which triggers mitochondrial dysfunction and ATP depletion. Cite this article: Bone Joint Res 2024;13(4):157–168

Aims. Autologous chondrocyte implantation (ACI) is a promising treatment for articular cartilage degeneration and injury; however, it requires a large number of human hyaline chondrocytes, which often undergo dedifferentiation during in vitro expansion. This study aimed to investigate the effect of suramin on chondrocyte differentiation and its underlying mechanism. Methods. Porcine chondrocytes were treated with vehicle or various doses of suramin. The expression of collagen, type II, alpha 1 (COL2A1), aggrecan (ACAN); COL1A1; COL10A1; SRY-box transcription factor 9 (SOX9); nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX); interleukin (IL)-1β; tumour necrosis factor alpha (TNFα); IL-8; and matrix metallopeptidase 13 (MMP-13) in chondrocytes at both messenger RNA (mRNA) and protein levels was determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blot. In addition, the supplementation of suramin to redifferentiation medium for the culture of expanded chondrocytes in 3D pellets was evaluated. Glycosaminoglycan (GAG) and collagen production were evaluated by biochemical analyses and immunofluorescence, as well as by immunohistochemistry. The expression of reactive oxygen species (ROS) and NOX activity were assessed by luciferase reporter gene assay, immunofluorescence analysis, and flow cytometry. Mutagenesis analysis, Alcian blue staining, reverse transcriptase polymerase chain reaction (RT-PCR), and western blot assay were used to determine whether p67. phox. was involved in suramin-enhanced chondrocyte phenotype maintenance. Results. Suramin enhanced the COL2A1 and ACAN expression and lowered COL1A1 synthesis. Also, in 3D pellet culture GAG and COL2A1 production was significantly higher in pellets consisting of chondrocytes expanded with suramin compared to controls. Surprisingly, suramin also increased ROS generation, which is largely caused by enhanced NOX (p67. phox. ) activity and membrane translocation. Overexpression of p67. phox. but not p67. phox. AD (deleting amino acid (a.a) 199 to 212) mutant, which does not support ROS production in chondrocytes, significantly enhanced chondrocyte phenotype maintenance, SOX9 expression, and AKT (S473) phosphorylation. Knockdown of p67. phox. with its specific short hairpin (sh) RNA (shRNA) abolished the suramin-induced effects. Moreover, when these cells were treated with the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) inhibitor LY294002 or shRNA of AKT1, p67. phox. -induced COL2A1 and ACAN expression was significantly inhibited. Conclusion. Suramin could redifferentiate dedifferentiated chondrocytes dependent on p67. phox. activation, which is mediated by the PI3K/AKT/SOX9 signalling pathway. Cite this article: Bone Joint Res 2022;11(10):723–738

Aims. This study aims to assess the relationship between history of pseudotumour formation secondary to metal-on-metal (MoM) implants and periprosthetic joint infection (PJI) rate, as well as establish ESR and CRP thresholds that are suggestive of infection in these patients. We hypothesized that patients with a pseudotumour were at increased risk of infection. Methods. A total of 1,171 total hip arthroplasty (THA) patients with MoM articulations from August 2000 to March 2014 were retrospectively identified. Of those, 328 patients underwent metal artefact reduction sequence MRI and had minimum two years’ clinical follow-up, and met our inclusion criteria. Data collected included demographic details, surgical indication, laterality, implants used, history of pseudotumour, and their corresponding preoperative ESR (mm/hr) and CRP (mg/dl) levels. Multivariate logistic regression modelling was used to evaluate PJI and history of pseudotumour, and receiver operating characteristic curves were created to assess the diagnostic capabilities of ESR and CRP to determine the presence of infection in patients undergoing revision surgery. Results. The rate of PJI for all identified MoM THAs was 3.5% (41/1,171), with a mean follow-up of 10.9 years (2.0 to 20.4). Of the patients included in the final cohort, 8.2% (27/328) had PJI, with a mean follow-up of 12.2 years (2.3 to 20.4). Among this cohort, 31.1% (102/328) had a history of pseudotumour. The rate of PJI in these patients was 14.7% (15/102), which was greater than those without pseudotumour, 5.3% (12/226) (p = 0.008). Additionally, logistic regression analysis showed an association between history of pseudotumour and PJI (odds ratio 4.36 (95% confidence interval 1.77 to 11.3); p = 0.002). Optimal diagnostic cutoffs for PJI in patients with history of pseudotumour versus those without were 33.1 mm/hr and 24.5 mm/hr for ESR and 7.37 mg/dl and 1.88 mg/dl for CRP, respectively. Conclusion. Patients with history of pseudotumour secondary to MoM THA had a higher likelihood of infection than those without. While suspicion of infection should be high for these patients, ESR and CRP cutoffs published by the European Bone and Joint Infection Society may not be appropriate for patients with a history of pseudotumour, as ESR and CRP levels suggestive of PJI are likely to be higher than for those without a pseudotumour. Additional investigation, such as aspiration, is highly recommended for these patients unless clinical suspicion and laboratory markers are low. Cite this article: Bone Joint J 2024;106-B(6):555–564

Aims. Periprosthetic joint infection (PJI) in total hip arthroplasty in the elderly may occur but has been subject to limited investigation. This study analyzed infection characteristics, surgical outcomes, and perioperative complications of octogenarians undergoing treatment for PJI in a single university-based institution. Methods. We identified 33 patients who underwent treatment for PJIs of the hip between January 2010 and December 2019 using our institutional joint registry. Mean age was 82 years (80 to 90), with 19 females (57%) and a mean BMI of 26 kg/m. 2. (17 to 41). Mean American Society of Anesthesiologists (ASA) grade was 3 (1 to 4) and mean Charlson Comorbidity Index was 6 (4 to 10). Leading pathogens included coagulase-negative Staphylococci (45%) and Enterococcus faecalis (9%). Two-stage exchange was performed in 30 joints and permanent resection arthroplasty in three. Kaplan-Meier survivorship analyses were performed. Mean follow-up was five years (3 to 7). Results. The two-year survivorship free of any recurrent PJI was 72% (95% confidence interval (CI) 56 to 89; 18 patients at risk). There were a total of nine recurrent PJIs at a mean of one year (16 days to eight years), one for the same pathogen as at index infection. One additional surgical site infection was noted at two weeks, resulting in a 69% (95% CI 52 to 86; 17 patients at risk) survivorship free of any infection at two years. There were two additional revisions for dislocations at one month each. As such, the two-year survivorship free of any revision was 61% (95% CI 42 to 80; 12 patients at risk). In addition to the aforementioned revisions, there was one additional skin grafting for a decubitus ulcer, resulting in a survivorship free of any reoperation of 54% (95% CI 35 to 73; ten patients at risk) at two years. Mean Clavien-Dindo score of perioperative complications was two out of five, with one case of perioperative death noted at six days. Conclusion. Octogenarians undergoing surgery for PJI of the hip are at low risk of acute mortality, but are at moderate risk of other perioperative complications. One in two patients will undergo a reoperation within two years, with 70% attributable to recurrent infections. Cite this article: Bone Joint J 2023;105-B(2):135–139

Aims. Postoperative malalignment of the femur is one of the main complications in distal femur fractures. Few papers have investigated the impact of intraoperative malalignment on postoperative function and bone healing outcomes. The aim of this study was to investigate how intraoperative fracture malalignment affects postoperative bone healing and functional outcomes. Methods. In total, 140 patients were retrospectively identified from data obtained from a database of hospitals participating in a trauma research group. We divided them into two groups according to coronal plane malalignment of more than 5°: 108 had satisfactory fracture alignment (< 5°, group S), and 32 had unsatisfactory alignment (> 5°, group U). Patient characteristics and injury-related factors were recorded. We compared the rates of nonunion, implant failure, and reoperation as healing outcomes and Knee Society Score (KSS) at three, six, and 12 months as functional outcomes. We also performed a sub-analysis to assess the effect of fracture malalignment by plates and nails on postoperative outcomes. Results. The rates of nonunion and reoperation in group U were worse than those in group S (25.0% vs 14.3%; 15.6% vs 5.6%), but the differences were not significant (p = 0.180 and p = 0.126, respectively). Mean KSS in group U at all follow-up periods was significantly worse that in group S (75.7 (SD 18.8) vs 86.0 (SD 8.7); p < 0.001; 78.9 (SD 17.2) vs 89.1 (SD 9.8); p < 0.001; 85.0 (SD 11.9) vs 91.1 (SD 7.2); p = 0.002, respectively). In the sub-analysis of plates, mean KSS was significantly worse in group U at three and six months. In the sub-analysis of nails, the rate of reoperation was significantly higher in group U (28.6% vs 5.8%; p = 0.025), and mean KSS at six and 12 months was significantly worse in Group U. Conclusion. To obtain good postoperative functional results, intraoperative alignment of the coronal plane should be accurately restored to less than 5°. Cite this article: Bone Jt Open 2022;3(2):165–172

Aims. The aim of this study was to investigate whether the type of cervical disc herniation influences the severity of symptoms at the time of presentation, and the outcome after surgical treatment. Methods. The type and extent of disc herniation at the time of presentation in 108 patients who underwent anterior discectomy for cervical radiculopathy were analyzed on MRI, using a four-point scale. These were dichotomized into disc bulge and disc herniation groups. Clinical outcomes were evaluated using the Neck Disability Index (NDI), 36-Item Short Form Survey (SF-36), and a visual analogue scale (VAS) for pain in the neck and arm at baseline and two years postoperatively. The perceived recovery was also assessed at this time. Results. At baseline, 46 patients had a disc bulge and 62 had a herniation. There was no significant difference in the mean NDI and SF-36 between the two groups at baseline. Those in the disc bulge group had a mean NDI of 44.6 (SD 15.2) compared with 43.8 (SD 16.0) in the herniation group (p = 0.799), and a mean SF-36 of 59.2 (SD 6.9) compared with 59.4 (SD 7.7) (p = 0.895). Likewise, there was no significant difference in the incidence of disabling arm pain in the disc bulge and herniation groups (84% vs 73%; p = 0.163), and no significant difference in the incidence of disabling neck pain in the two groups (70.5% (n = 31) vs 63% (n = 39); p = 0.491). At two years after surgery, no significant difference was found in any of the clinical parameters between the two groups. Conclusion. In patients with cervical radiculopathy, the type and extent of disc herniation measured on MRI prior to surgery correlated neither to the severity of the symptoms at presentation, nor to clinical outcomes at two years postoperatively. Cite this article: Bone Joint J 2022;104-B(11):1242–1248

Aims. This study aimed to investigate the estimated change in primary and revision arthroplasty rate in the Netherlands and Denmark for hips, knees, and shoulders during the COVID-19 pandemic in 2020 (COVID-period). Additional points of focus included the comparison of patient characteristics and hospital type (2019 vs COVID-period), and the estimated loss of quality-adjusted life years (QALYs) and impact on waiting lists. Methods. All hip, knee, and shoulder arthroplasties (2014 to 2020) from the Dutch Arthroplasty Register, and hip and knee arthroplasties from the Danish Hip and Knee Arthroplasty Registries, were included. The expected number of arthroplasties per month in 2020 was estimated using Poisson regression, taking into account changes in age and sex distribution of the general Dutch/Danish population over time, calculating observed/expected (O/E) ratios. Country-specific proportions of patient characteristics and hospital type were calculated per indication category (osteoarthritis/other elective/acute). Waiting list outcomes including QALYs were estimated by modelling virtual waiting lists including 0%, 5% and 10% extra capacity. Results. During COVID-period, fewer arthroplasties were performed than expected (Netherlands: 20%; Denmark: 5%), with the lowest O/E in April. In the Netherlands, more acute indications were prioritized, resulting in more American Society of Anesthesiologists grade III to IV patients receiving surgery. In both countries, no other patient prioritization was present. Relatively more arthroplasties were performed in private hospitals. There were no clinically relevant differences in revision arthroplasties between pre-COVID and COVID-period. Estimated total health loss depending on extra capacity ranged from: 19,800 to 29,400 QALYs (Netherlands): 1,700 to 2,400 QALYs (Denmark). With no extra capacity it will take > 30 years to deplete the waiting lists. Conclusion. The COVID-19 pandemic had an enormous negative effect on arthroplasty rates, but more in the Netherlands than Denmark. In the Netherlands, hip and shoulder patients with acute indications were prioritized. Private hospitals filled in part of the capacity gap. QALY loss due to postponed arthroplasty surgeries is considerable. Cite this article: Bone Jt Open 2022;3(12):977–990

Aims. Children with spinal dysraphism can develop various musculoskeletal deformities, necessitating a range of orthopaedic interventions, causing significant morbidity, and making considerable demands on resources. This systematic review aimed to identify what outcome measures have been reported in the literature for children with spinal dysraphism who undergo orthopaedic interventions involving the lower limbs. Methods. A PROSPERO-registered systematic literature review was performed following PRISMA guidelines. All relevant studies published until January 2023 were identified. Individual outcomes and outcome measurement tools were extracted verbatim. The measurement tools were assessed for reliability and validity, and all outcomes were grouped according to the Outcome Measures Recommended for use in Randomized Clinical Trials (OMERACT) filters. Results. From 91 eligible studies, 27 individual outcomes were identified, including those related to clinical assessment (n = 12), mobility (n = 4), adverse events (n = 6), investigations (n = 4), and miscellaneous (n = 1). Ten outcome measurement tools were identified, of which Hoffer’s Functional Ambulation Scale was the most commonly used. Several studies used unvalidated measurement tools originally developed for other conditions, and 26 studies developed new measurement tools. On the OMERACT filter, most outcomes reported pathophysiology and/or the impact on life. There were only six patient- or parent-reported outcomes, and none assessed the quality of life. Conclusion. The outcomes that were reported were heterogenous, lack validation and failed to incorporate patient or family perceptions. Until outcomes can be reported unequivocally, research in this area will remain limited. Our findings should guide the development of a core outcome set, which will allow consistency in the reporting of outcomes for this condition. Cite this article: Bone Joint J 2024;106-B(3):277–285

Aims. Oxidized zirconium (OxZi) and highly cross-linked polyethylene (HXLPE) were developed to minimize wear and risk of osteolysis in total hip arthroplasty (THA). However, retrieval studies have shown that scratched femoral heads may lead to runaway wear, and few reports of long-term results have been published. The purpose of this investigation is to report minimum ten-year wear rates and clinical outcomes of THA with OxZi femoral heads on HXLPE, and to compare them with a retrospective control group of cobalt chrome (CoCr) or ceramic heads on HXLPE. Methods. From 2003 to 2006, 108 THAs were performed on 96 patients using an OxZi head with a HXLPE liner with minimum ten-year follow-up. Harris Hip Scores (HHS) were collected preoperatively and at the most recent follow-up (mean 13.3 years). Linear and volumetric liner wear was measured on radiographs of 85 hips with a minimum ten-year follow-up (mean 14.5 years). This was compared to a retrospective control group of 45 THAs using ceramic or CoCr heads from October 1999 to February 2005, with a minimum of ten years’ follow-up. Results. Average HHS improved from 50.8 to 91.9 and 51.0 to 89.8 in the OxZi group and control group, respectively (p = 0.644), with no osteolysis in either group. Linear and volumetric wear rates in the OxZi group averaged 0.03 mm/year and 3.46 mm. 3. /year, respectively. There was no statistically significant difference in HHS scores, nor in linear or volumetric wear rate between the groups, and no revision for any indication. Conclusion. The radiological and clinical outcomes, and survivorship of THA with OxZi femoral heads and HXLPE liners, were excellent, and comparable to CoCr or ceramic heads at minimum ten-year follow-up. Wear rates are below what would be expected for development of osteolysis. OxZi-HXLPE is a durable bearing couple with excellent long-term outcomes. Cite this article: Bone Joint J 2024;106-B(3 Supple A):38–43

Aims. Early detection of developmental dysplasia of the hip (DDH) is associated with improved outcomes of conservative treatment. Therefore, we aimed to evaluate a novel screening programme that included both the primary risk factors of breech presentation and family history, and the secondary risk factors of oligohydramnios and foot deformities. Methods. A five-year prospective registry study investigating every live birth in the study’s catchment area (n = 27,731), all of whom underwent screening for risk factors and examination at the newborn and six- to eight-week neonatal examination and review. DDH was diagnosed using ultrasonography and the Graf classification system, defined as grade IIb or above or rapidly regressing IIa disease (≥4. o. at four weeks follow-up). Multivariate odds ratios were calculated to establish significant association, and risk differences were calculated to provide quantifiable risk increase with DDH, positive predictive value was used as a measure of predictive efficacy. The cost-effectiveness of using these risk factors to predict DDH was evaluated using NHS tariffs (January 2021). Results. The prevalence of DDH that required treatment within our population was 5/1,000 live births. The rate of missed presentation of DDH was 0.43/1000 live births. Breech position, family history, oligohydramnios, and foot deformities demonstrated significant association with DDH (p < 0.0001). The presence of breech presentation increased the risk of DDH by 1.69% (95% confidence interval (CI) 0.93% to 2.45%), family history by 3.57% (95% CI 2.06% to 5.09%), foot deformities by 8.95% (95% CI 4.81% to 13.1%), and oligohydramnios nby 11.6% (95 % CI 3.0% to 19.0%). Primary risk factors family history and breech presentation demonstrated an estimated cost-per-case detection of £6,276 and £11,409, respectively. Oligohydramnios and foot deformities demonstrated a cost-per-case detected less than the cost of primary risk factors of £2,260 and £2,670, respectively. Conclusion. The inclusion of secondary risk factors within a national screening programme was clinically successful as they were more cost and resource-efficient predictors of DDH than primary risk factors, suggesting they should be considered in the national guidance. Cite this article: Bone Jt Open 2023;4(4):234–240

Aims. Chronic osteomyelitis (COM) of the lower limb in adults can be surgically managed by either limb reconstruction or amputation. This scoping review aims to map the outcomes used in studies surgically managing COM in order to aid future development of a core outcome set. Methods. A total of 11 databases were searched. A subset of studies published between 1 October 2020 and 1 January 2011 from a larger review mapping research on limb reconstruction and limb amputation for the management of lower limb COM were eligible. All outcomes were extracted and recorded verbatim. Outcomes were grouped and categorized as per the revised Williamson and Clarke taxonomy. Results. A total of 3,303 records were screened, of which 99 studies were included. Most studies were case series (77/99; 78%) and assessed one method of reconstruction (68/99; 69%). A total of 511 outcomes were reported, which were grouped into 58 distinct outcomes. Overall, 143/511 of all outcomes (28%) were provided with a clear, in-text definition, and 231 outcomes (45%) had details reported of how and when they were measured. The most commonly reported outcome was ‘recurrence of osteomyelitis’ (62; 12%). The single-most patient-reported outcome measure was ‘pain’. Conclusion. This study has highlighted significant inconsistencies in the defining, reporting, and measuring of outcomes across studies investigating surgical management for chronic osteomyelitis of the lower limb in adults. Future studies should clearly report complete details of how outcomes are defined and measured, including timing. The development of a standardized core outcome set would be of significant benefit in order to allow evidence synthesis and comparison across studies. Cite this article: Bone Jt Open 2023;4(3):146–157

Aims. The prevalence of scoliosis is not known in patients with idiopathic short stature, and the impact of treatment with recombinant human growth hormone on those with scoliosis remains controversial. We investigated the prevalence of scoliosis radiologically in children with idiopathic short stature, and the impact of treatment with growth hormone in a cross-sectional and retrospective cohort study. Methods. A total of 2,053 children with idiopathic short stature and 4,106 age- and sex-matched (1:2) children without short stature with available whole-spine radiographs were enrolled in the cross-sectional study. Among them, 1,056 with idiopathic short stature and 790 controls who had radiographs more than twice were recruited to assess the development and progression of scoliosis, and the need for bracing and surgery. Results. In the cross-sectional study, there was an unexpectedly higher prevalence of scoliosis (33.1% (681/2,053) vs 8.52% (350/4,106)) in children with idiopathic short stature compared with controls (odds ratio 3.722; p < 0.001), although most cases were mild. In the longitudinal study, children with idiopathic short stature had a higher risk of the development and progression of scoliosis than the controls. Among children with idiopathic short stature without scoliosis at baseline, treatment with growth hormone significantly increased the risk of developing scoliosis (p = 0.015) and the need for bracing (p < 0.001). Among those with idiopathic short stature and scoliosis at baseline, treatment with growth hormone did not increase the risk of progression of the scoliosis, the need for bracing, or surgery. Conclusion. The impact of treatment with growth hormone on scoliosis in children with idiopathic short stature was considered controllable. However, physicians should pay close attention to the assessment of spinal curves in these children. Cite this article: Bone Joint J 2023;105-B(4):439–448

Aims. Femoral component anteversion is an important factor in the success of total hip arthroplasty (THA). This retrospective study aimed to investigate the accuracy of femoral component anteversion with the Mako THA system and software using the Exeter cemented femoral component, compared to the Accolade II cementless femoral component. Methods. We reviewed the data of 30 hips from 24 patients who underwent THA using the posterior approach with Exeter femoral components, and 30 hips from 24 patients with Accolade II components. Both groups did not differ significantly in age, sex, BMI, bone quality, or disease. Two weeks postoperatively, CT images were obtained to measure acetabular and femoral component anteversion. Results. The mean difference in femoral component anteversion between intraoperative and postoperative CT measurements (system accuracy of component anteversion) was 0.8° (SD 1.8°) in the Exeter group and 2.1° (SD 2.3°) in the Accolade II group, respectively (p = 0.020). The mean difference in anteversion between the plan and the postoperative CT measurements (clinical accuracy of femoral component anteversion) was 1.2° (SD 3.6°) in the Exeter group, and 4.2° (SD 3.9°) in the Accolade II group (p = 0.003). No significant differences were found in acetabular component inclination and anteversion; however, the clinical accuracy of combined anteversion was significantly better in the Exeter group (0.6° (SD 3.9°)) than the Accolade II group (3.6° (SD 4.1°)). Conclusion. The Mako THA system and software helps surgeons control the femoral component anteversion to achieve the target angle of insertion. The Exeter femoral component, inserted using Mako THA system, showed greater precision for femoral component and combined component anteversion than the Accolade II component. Cite this article: Bone Joint J 2024;106-B(3 Supple A):104–109

Aims. There is an increasing concern of osteoporotic fractures in the ageing population. Low-magnitude high-frequency vibration (LMHFV) was shown to significantly enhance osteoporotic fracture healing through alteration of osteocyte lacuno-canalicular network (LCN). Dentin matrix protein 1 (DMP1) in osteocytes is known to be responsible for maintaining the LCN and mineralization. This study aimed to investigate the role of osteocyte-specific DMP1 during osteoporotic fracture healing augmented by LMHFV. Methods. A metaphyseal fracture was created in the distal femur of ovariectomy-induced osteoporotic Sprague Dawley rats. Rats were randomized to five different groups: 1) DMP1 knockdown (KD), 2) DMP1 KD + vibration (VT), 3) Scramble + VT, 4) VT, and 5) control (CT), where KD was performed by injection of short hairpin RNA (shRNA) into marrow cavity; vibration treatment was conducted at 35 Hz, 0.3 g; 20 minutes/day, five days/week). Assessments included radiography, micro-CT, dynamic histomorphometry and immunohistochemistry on DMP1, sclerostin, E11, and fibroblast growth factor 23 (FGF23). In vitro, murine long bone osteocyte-Y4 (MLO-Y4) osteocyte-like cells were randomized as in vivo groupings. DMP1 KD was performed by transfecting cells with shRNA plasmid. Assessments included immunocytochemistry on osteocyte-specific markers as above, and mineralized nodule staining. Results. Healing capacities in DMP1 KD groups were impaired. Results showed that DMP1 KD significantly abolished vibration-enhanced fracture healing at week 6. DMP1 KD significantly altered the expression of osteocyte-specific markers. The lower mineralization rate in DMP1 KD groups indicated that DMP1 knockdown was associated with poor fracture healing process. Conclusion. The blockage of DMP1 would impair healing outcomes and negate LMHFV-induced enhancement on fracture healing. These findings reveal the importance of DMP1 in response to the mechanical signal during osteoporotic fracture healing. Cite this article: Bone Joint Res 2022;11(7):465–476

Aims. The aim of this study was to describe the pattern of revision indications for unicompartmental knee arthroplasty (UKA) and total knee arthroplasty (TKA) and any change to this pattern for UKA patients over the last 20 years, and to investigate potential associations to changes in surgical practice over time. Methods. All primary knee arthroplasty surgeries performed due to primary osteoarthritis and their revisions reported to the Danish Knee Arthroplasty Register from 1997 to 2017 were included. Complex surgeries were excluded. The data was linked to the National Patient Register and the Civil Registration System for comorbidity, mortality, and emigration status. TKAs were propensity score matched 4:1 to UKAs. Revision risks were compared using competing risk Cox proportional hazard regression with a shared γ frailty component. Results. Aseptic loosening (loosening) was the most common revision indication for both UKA (26.7%) and TKA (29.5%). Pain and disease progression accounted for 54.6% of the remaining UKA revisions. Infections and instability accounted for 56.1% of the remaining TKA revision. The incidence of revision due to loosening or pain decreased over the last decade, being the second and third least common indications in 2017. There was a decrease associated with fixation method for pain (hazard ratio (HR) 0.40; 95% confidence interval (CI) 0.17 to 0.94) and loosening (HR 0.29; 95% CI 0.10 to 0.81) for cementless compared to cemented, and units UKA usage for pain (HR 0.67, 95% CI 0.50 to 0.91), and loosening (HR 0.51; 95% CI 0.37 to 0.70) for high usage. Conclusion. The overall revision patterns for UKA and TKA for the last 20 years are comparable to previous published patterns. We found large changes to UKA revision patterns in the last decade, and with the current surgical practice, revision due to pain or loosening are significantly less likely. Cite this article: Bone Jt Open 2023;4(12):923–931

Aims. Total hip arthroplasty (THA) is a common procedure to address pain and enhance function in hip disorders such as osteoarthritis. Despite its success, postoperative patient recovery exhibits considerable heterogeneity. This study aimed to investigate whether patients follow distinct pain trajectories following THA and identify the patient characteristics linked to suboptimal trajectories. Methods. This retrospective cohort study analyzed THA patients at a large academic centre (NYU Langone Orthopedic Hospital, New York, USA) from January 2018 to January 2023, who completed the Patient-Reported Outcomes Measurement Information System (PROMIS) pain intensity questionnaires, collected preoperatively at one-, three-, six-, 12-, and 24-month follow-up times. Growth mixture modelling (GMM) was used to model the trajectories. Optimal model fit was determined by Bayesian information criterion (BIC), Vuong-Lo-Mendell-Rubin likelihood ratio test (VLMR-LRT), posterior probabilities, and entropy values. Association between trajectory groups and patient characteristics were measured by multinomial logistic regression using the three-step approach. Results. Among the 1,249 patients, a piecewise GMM model revealed three distinct pain trajectory groups: 56 patients (4.5%) in group 1; 1,144 patients (91.6%) in group 2; and 49 patients (3.9%) in group 3. Patients in group 2 experienced swift recovery post-THA and minimal preoperative pain. In contrast, groups 1 and 3 initiated with pronounced preoperative pain; however, only group 3 exhibited persistent long-term pain. Multinomial regression indicated African Americans were exceedingly likely to follow trajectory groups 1 (odds ratio (OR) 2.73) and 3 (OR 3.18). Additionally, odds of membership to group 3 increased by 12% for each BMI unit rise, by 19% for each added postoperative day, and by over four if discharged to rehabilitation services (OR 4.07). Conclusion. This study identified three distinct pain trajectories following THA, highlighting the role of individual patient factors in postoperative recovery. This emphasizes the importance of preoperatively addressing modifiable risk factors associated with suboptimal pain trajectories, particularly in at-risk patients. Cite this article: Bone Jt Open 2024;5(3):174–183

Aims. Custom triflange acetabular components (CTACs) play an important role in reconstructive orthopaedic surgery, particularly in revision total hip arthroplasty (rTHA) and pelvic tumour resection procedures. Accurate CTAC positioning is essential to successful surgical outcomes. While prior studies have explored CTAC positioning in rTHA, research focusing on tumour cases and implant flange positioning precision remains limited. Additionally, the impact of intraoperative navigation on positioning accuracy warrants further investigation. This study assesses CTAC positioning accuracy in tumour resection and rTHA cases, focusing on the differences between preoperative planning and postoperative implant positions. Methods. A multicentre observational cohort study in Australia between February 2017 and March 2021 included consecutive patients undergoing acetabular reconstruction with CTACs in rTHA (Paprosky 3A/3B defects) or tumour resection (including Enneking P2 peri-acetabular area). Of 103 eligible patients (104 hips), 34 patients (35 hips) were analyzed. Results. CTAC positioning was generally accurate, with minor deviations in cup inclination (mean 2.7°; SD 2.84°), anteversion (mean 3.6°; SD 5.04°), and rotation (mean 2.1°; SD 2.47°). Deviation of the hip centre of rotation (COR) showed a mean vector length of 5.9 mm (SD 7.24). Flange positions showed small deviations, with the ischial flange exhibiting the largest deviation (mean vector length of 7.0 mm; SD 8.65). Overall, 83% of the implants were accurately positioned, with 17% exceeding malpositioning thresholds. CTACs used in tumour resections exhibited higher positioning accuracy than rTHA cases, with significant differences in inclination (1.5° for tumour vs 3.4° for rTHA) and rotation (1.3° for tumour vs 2.4° for rTHA). The use of intraoperative navigation appeared to enhance positioning accuracy, but this did not reach statistical significance. Conclusion. This study demonstrates favourable CTAC positioning accuracy, with potential for improved accuracy through intraoperative navigation. Further research is needed to understand the implications of positioning accuracy on implant performance and long-term survival. Cite this article: Bone Jt Open 2024;5(4):260–268

Aims. Frozen shoulder is a common, painful condition that results in impairment of function. Corticosteroid injections are commonly used for frozen shoulder and can be given as glenohumeral joint (GHJ) injection or suprascapular nerve block (SSNB). Both injection types have been shown to significantly improve shoulder pain and range of motion. It is not currently known which is superior in terms of relieving patients’ symptoms. This is the protocol for a randomized clinical trial to investigate the clinical effectiveness of corticosteroid injection given as either a GHJ injection or SSNB. Methods. The Therapeutic Injections For Frozen Shoulder (TIFFS) study is a single centre, parallel, two-arm, randomized clinical trial. Participants will be allocated on a 1:1 basis to either a GHJ corticosteroid injection or SSNB. Participants in both trial arms will then receive physiotherapy as normal for frozen shoulder. The primary analysis will compare the Oxford Shoulder Score (OSS) at three months after injection. Secondary outcomes include OSS at six and 12 months, range of shoulder movement at three months, and Numeric Pain Rating Scale, abbreviated Disabilities of Arm, Shoulder and Hand score, and EuroQol five-level five-dimension health index at three months, six months, and one year after injection. A minimum of 40 patients will be recruited to obtain 80% power to detect a minimally important difference of ten points on the OSS between the groups at three months after injection. The study is registered under ClinicalTrials.gov with the identifier NCT04965376. Conclusion. The results of this trial will demonstrate if there is a difference in shoulder pain and function after GHJ injection or SSNB in patients with frozen shoulder. This will help provide effective treatment to patients with frozen shoulder. Cite this article: Bone Jt Open 2023;4(3):205–209

Aims. The objectives of this study were to investigate the patient characteristics and mortality of Vancouver type B periprosthetic femoral fractures (PFF) subgroups divided into two groups according to femoral component stability and to compare postoperative clinical outcomes according to treatment in Vancouver type B2 and B3 fractures. Methods. A total of 126 Vancouver type B fractures were analyzed from 2010 to 2019 in 11 associated centres' database (named TRON). We divided the patients into two Vancouver type B subtypes according to implant stability. Patient demographics and functional scores were assessed in the Vancouver type B subtypes. We estimated the mortality according to various patient characteristics and clinical outcomes between the open reduction internal fixation (ORIF) and revision arthroplasty (revision) groups in patients with unstable subtype. Results. The one-year mortality rate of the stable and unstable subtype of Vancouver type B was 9.4% and 16.4%. Patient demographic factors, including residential status and pre-injury mobility were associated with mortality. There was no significant difference in mortality between patients treated with ORIF and Revision in either Vancouver B subtype. Patients treated with revision had significantly higher Parker Mobility Score (PMS) values (5.48 vs 3.43; p = 0.00461) and a significantly lower visual analogue scale (VAS) values (1.06 vs 1.94; p = 0.0399) for pain than ORIF in the unstable subtype. Conclusion. Among patients with Vancouver type B fractures, frail patients, such as those with worse scores for residential status and pre-injury mobility, had a high mortality rate. There was no significant difference in mortality between patients treated with ORIF and those treated with revision. However, in the unstable subtype, the PMS and VAS values at the final follow-up examination were significantly better in patients who received revision. Based on postoperative activities of daily life, we therefore recommend evision in instances when either treatment option is feasible. Cite this article: Bone Jt Open 2023;4(1):38–46

Aims. The aim of this study was to understand the experience of mature patients who undergo a periacetabular osteotomy (PAO), a major hip-preserving surgical procedure that treats symptomatic hip dysplasia by realigning the acetabulum. Our aim was to improve our understanding of how the operation affected the lives of patients and their families, with a long-term goal of improving their experience. Methods. We used a phenomenological approach with in-depth, semi-structured interviews to investigate the experience of seven female patients, aged between 25 and 40 years, who underwent a PAO. A modified homogeneity sampling approach coupled with criterion sampling was used. Inclusion criteria involved having at least one child at home and being in a committed relationship with a spouse or partner. Results. Analysis of interview transcripts revealed five major themes: feelings of frustration before having a treatment plan; fear of the operation; the importance of understanding the procedure in order to feel in control of their care; feelings of helplessness, dependence, and depression during recovery; and the need for support during recovery. Conclusion. Our findings suggest that both the physical and psychosocial burdens of undergoing a PAO are great, with a major impact on the patient and their family. Many important issues lie outside the scope of what healthcare teams currently address. Cite this article: Bone Joint J 2022;104-B(7):781–785