Aims. The most important complication of treatment of developmental dysplasia of the hip (DDH) is avascular necrosis (AVN) of the femoral head, which can result in proximal femoral growth disturbances leading to pain, dysfunction, and eventually to early onset osteoarthritis. In this study, we aimed to identify morphological variants in hip joint development that are predictive of a poor outcome. Methods. We retrospectively reviewed all patients who developed AVN after DDH treatment, either by closed and/or open reduction, at a single institution between 1984 and 2007 with a minimal follow-up of eight years. Standard pelvis radiographs obtained at ages one, two, three, five, and eight years, and at latest follow-up were retrieved. The Bucholz-Ogden classification was used to determine the type of AVN on all radiographs. Poor outcome was defined by Severin classification grade 3 or above on the latest follow-up radiographs and/or the need for secondary surgery. With statistical shape modelling, we identified the different shape variants of the hip at each age. Logistic regression analysis was used to associate the different modes or shape variants with poor outcome. Results. In all, 135 patients with AVN were identified, with a minimum of eight years of follow-up. Mean age at time of surgery was 7.0 months (SD 0.45), and mean follow-up was 13.3 years (SD 3.7). Overall, 46% had AVN type 1 while 54% type 2 or higher. More than half of the patients (52.6%) had a poor outcome. We found 11 shape variants that were significantly associated with a poor outcome. These shape variants were predominantly linked to AVN type 2 or higher. Conclusion. Specific morphological characteristics on pelvis radiographs of AVN hips were predictive for poor outcome, at a very young age. There was an overall stronger association to Bucholz-Ogden types 2-3-4 with the exception of two modes at age two and five years, linked to AVN type 1. Cite this article: Bone Joint J 2021;103-B(5):999–1004

Aims. Although lumbosacral transitional vertebrae (LSTV) are well-documented, few large-scale studies have investigated thoracolumbar transitional vertebrae (TLTV) and spinal numerical variants. This study sought to establish the prevalence of numerical variants and to evaluate their relationship with clinical problems. Methods. A total of 1,179 patients who had undergone thoracic, abdominal, and pelvic CT scanning were divided into groups according to the number of thoracic and lumbar vertebrae, and the presence or absence of TLTV or LSTV. The prevalence of spinal anomalies was noted. The relationship of spinal anomalies to clinical symptoms (low back pain, Japanese Orthopaedic Association score, Roland-Morris Disability Questionnaire) and degenerative spondylolisthesis (DS) was also investigated. Results. Normal vertebral morphology (12 thoracic and five lumbar vertebrae without TLTV and LSTV) was present in 531 male (76.7%) and 369 female patients (75.8%). Thoracolumbar transitional vertebrae were present in 15.8% of males and 16.0% of females. LSTV were present in 7.1% of males and 9.0% of females. The prevalence of the anomaly of 16 presacral mobile vertebrae (total number of thoracolumbar vertebrae and TLTV) without LSTV was 1.0% in males and 4.1% in females, and that of the anomaly of 18 vertebrae without LSTV was 5.3% in males and 1.2% in females. The prevalence of DS was significantly higher in females with a total of 16 vertebrae than in those with normal morphology. There was no significant correlation between a spinal anomaly and clinical symptoms. Conclusion. Overall, 24% of subjects had anomalies in the thoracolumbar region: the type of anomaly differed between males and females, which could have significant implications for spinal surgery. A decreased number of vertebrae was associated with DS: numerical variants may potentially be a clinical problem. Cite this article: Bone Joint J 2021;103-B(7):1301–1308

Aims. This study aimed to explore the role of small colony variants (SCVs) of Staphylococcus aureus in intraosseous invasion and colonization in patients with periprosthetic joint infection (PJI). Methods. A PJI diagnosis was made according to the MusculoSkeletal Infection Society (MSIS) for PJI. Bone and tissue samples were collected intraoperatively and the intracellular invasion and intraosseous colonization were detected. Transcriptomics of PJI samples were analyzed and verified by polymerase chain reaction (PCR). Results. SCVs can be isolated from samples collected from chronic PJIs intraoperatively. Transmission electron microscopy (TEM) and immunofluorescence (IF) showed that there was more S. aureus in bone samples collected from chronic PJIs, but much less in bone samples from acute PJIs, providing a potential mechanism of PJI. Immunofluorescence results showed that SCVs of S. aureus were more likely to invade osteoblasts in vitro. Furthermore, TEM and IF also demonstrated that SCVs of S. aureus were more likely to invade and colonize in vivo. Cluster analysis and principal component analysis (PCA) showed that there were substantial differences in gene expression profiles between chronic and acute PJI. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that these differentially expressed genes were enriched to chemokine-related signal pathways. PCR also verified these results. Conclusion. Our study has shown that the S. aureus SCVs have a greater ability to invade and colonize in bone, resulting in S. aureus remaining in bone tissues long-term, thus explaining the pathogenesis of chronic PJI. Cite this article: Bone Joint Res 2022;11(12):843–853

Aims. Knee arthroplasty surgery is a highly effective treatment for arthritis and disorders of the knee. There are a wide variety of implant brands and types of knee arthroplasty available to surgeons. As a result of a number of highly publicized failures, arthroplasty surgery is highly regulated in the UK and many other countries through national registries, introduced to monitor implant performance, surgeons, and hospitals. With time, the options available within many brand portfolios have grown, with alternative tibial or femoral components, tibial insert materials, or shapes and patella resurfacings. In this study we have investigated the effect of the expansion of implant brand portfolios and where there may be a lack of transparency around a brand name. We also aimed to establish the potential numbers of compatible implant construct combinations. Methods. Hypothetical implant brand portfolios were proposed, and the number of compatible implant construct combinations was calculated. Results. A simple knee portfolio with cemented cruciate-retaining (CR) and posterior-stabilized (PS) components, with and without a patella, has four combinations. If there are two options available for each component, the numbers double for each option, resulting in 32 combinations. The effect of adding a third option multiplies the number by 1.3. Introducing compatible uncemented options, with the effect of hybrids, multiplies the number by 4. An implant portfolio with two femoral components (both in CR and PS), with two insert options and a patella, all in cemented and uncemented versions leads to 192 possible compatible implant construct combinations. There are implant brands available to surgeons with many more than two options. Conclusion. This study demonstrates that the addition of multiple variants within a knee brand portfolio leads to a large number (many hundreds) of compatible implant construct combinations. Revision rates of implant combinations are not currently reviewed at this level of granularity, leading to the risk of camouflage of true outcomes. Cite this article: Bone Joint J 2021;103-B(10):1555–1560

We describe a rare variant of mirror hand in a 20-year-old man who presented with multiple fingers. Radiographs revealed two ulnae (one vestigial) and a radius. There was duplication of the humeral head. The unique features of this case are the age of patient before the start of treatment and extension of the duplication proximal to the elbow

Periprosthetic joint infection (PJI) is a difficult complication requiring a comprehensive eradication protocol. Cure rates have essentially stalled in the last two decades, using methods of antimicrobial cement joint spacers and parenteral antimicrobial agents. Functional spacers with higher-dose antimicrobial-loaded cement and antimicrobial-loaded calcium sulphate beads have emphasized local antimicrobial delivery on the premise that high-dose local antimicrobial delivery will enhance eradication. However, with increasing antimicrobial pressures, microbiota have responded with adaptive mechanisms beyond traditional antimicrobial resistance genes. In this review we describe adaptive resistance mechanisms that are relevant to the treatment of PJI. Some mechanisms are well known, but others are new. The objective of this review is to inform clinicians of the known adaptive resistance mechanisms of microbes relevant to PJI. We also discuss the implications of these adaptive mechanisms in the future treatment of PJI.

Cite this article: Bone Joint J 2022;104-B(5):575–580.

Seventeen patients with congenital spondylo-epiphysial dysplasia from six centres in Britain have been investigated and two variants delineated. There is wide clinical and radiological variability in each group with overlap between them, but 12 of the patients had very short stature and grossly disorganised hips with severe coxa vara, and the five remaining patients were less seriously affected with height only a little below the third percentile and only mild coxa vara. Both groups can be diagnosed at birth but the two cannot be differentiated on clinical and radiological grounds until after the age of three to four years when the developing severe coxa vara and difference in stature become apparent. All cases were sporadic with the exception of a concordant twin-pair

Objectives

The objective of this study was to investigate the association of four single-nucleotide polymorphisms (SNPs) of the cannabinoid receptor 2 (CNR2) gene, gene-obesity interaction, and haplotype combination with osteoporosis (OP) susceptibility.

An unusual form of chronic osteomyelitis in children is described. Three children presented with clinical signs of acute infection and radiographs revealed a pre-existing destructive bone lesion. Exploration of the lesions did not release pus, and cultures for pathogens were negative. The lesions healed but the symptoms returned intermittently over many years with the development of sclerosis and disturbance of bone growth. The lesions did not respond to antibiotics or operative treatment. All the patients were fully investigated and although the erythrocyte sedimentation rate was increased the white blood count was seldom abnormal. There were no neurological abnormalities. Two of the three cases required an osteotomy to correct malalignment. A comparison is made between the findings in these three patients with similar cases reported recently and possible causes are discussed.

A variation of the motor branch of the median nerve is described in which this branch arose more proximally and pierced the flexor retinaculum. Its significance during a carpal tunnel decompression is pointed out.

We have reviewed 15 cases of triplane fracture of the distal tibia. The mechanism of injury is lateral rotation and the anatomical pattern of the fracture depends on the state of the growth plate at the time of injury. In seven of our cases the anteromedial part of the growth plate was fused, but in eight children the plate was completely open. In six of these eight children there was a hump or projection of the medial growth plate. It is suggested that this hump stabilises the anteromedial part of the epiphysis in a manner similar to the partial anteromedial fusion seen in older children, and that this accounts for the occurrence of triplane fracture in the presence of an open growth plate.

Aims. Osteoporosis (OP) is a metabolic bone disease, characterized by a decrease in bone mineral density (BMD). However, the research of regulatory variants has been limited for BMD. In this study, we aimed to explore novel regulatory genetic variants associated with BMD. Methods. We conducted an integrative analysis of BMD genome-wide association study (GWAS) and regulatory single nucleotide polymorphism (rSNP) annotation information. Firstly, the discovery GWAS dataset and replication GWAS dataset were integrated with rSNP annotation database to obtain BMD associated SNP regulatory elements and SNP regulatory element-target gene (E-G) pairs, respectively. Then, the common genes were further subjected to HumanNet v2 to explore the biological effects. Results. Through discovery and replication integrative analysis for BMD GWAS and rSNP annotation database, we identified 36 common BMD-associated genes for BMD irrespective of regulatory elements, such as FAM3C (p. discovery GWAS. = 1.21 × 10. -25. , p. replication GWAS. = 1.80 × 10. -12. ), CCDC170 (p. discovery GWAS. = 1.23 × 10. -11. , p. replication GWAS. = 3.22 × 10. -9. ), and SOX6 (p. discovery GWAS. = 4.41 × 10. -15. , p. replication GWAS. = 6.57 × 10. -14. ). Then, for the 36 common target genes, multiple gene ontology (GO) terms were detected for BMD such as positive regulation of cartilage development (p = 9.27 × 10. -3. ) and positive regulation of chondrocyte differentiation (p = 9.27 × 10. -3. ). Conclusion. We explored the potential roles of rSNP in the genetic mechanisms of BMD and identified multiple candidate genes. Our study results support the implication of regulatory genetic variants in the development of OP. Cite this article: Bone Joint Res 2023;12(2):147–154

Aims. The purpose of this study was to use pharmacogenetics to determine the frequency of genetic variants in our total knee arthroplasty (TKA) patients that could affect postoperative pain medications. Pharmacogenetic testing evaluates patient DNA to determine if a drug is expected to have a normal clinical effect, heightened effect, or no effect at all on the patient. It also predicts whether patients are likely to experience side effects from medicine. We further sought to determine if changing the multimodal programme based on these results would improve pain control or reduce side effects. Methods. In this pilot study, buccal samples were collected from 31 primary TKA patients. Pharmacogenetics testing examined genetic variants in genes OPRM1, CYP1A2, CYP2B6, CYP2C19, CYP3A4, CYP2C9, and CYP2D6. These genes affect the pharmacodynamics and pharmacokinetics of non-steroidal anti-inflammatory drugs and opioids. We examined the frequency of genetic variants to any of the medications we prescribed including celecoxib, hydrocodone, and tramadol. Patients were randomized to one of two groups: the control group received the standard postoperative pain regimen, and the study group received a customized regimen based on the pharmacogenetic results. For the first ten postoperative days, patients recorded pain scores, medication, and side effects. Results. Genetic variants involving one or more medications in the multimodal pain protocol occurred in 13 of the 31 patients (42%). In total, eight patients (26%) had variants affecting more than one of the medications. For the 25 patients who recorded pain and medication logs, the mean pain levels and morphine equivalents (MEQs) consumed in the first ten days were higher in the control group than in the custom-guided group (p = 0.019 for pain and p = 0.655 for MEQ). Conclusion. Overall, 42% of patients had a variant involving one of the pain medications prescribed in our perioperative pain program for TKA. Ongoing research will help determine if using these data to modify a patient’s medication will improve outcomes. Cite this article: Bone Joint J 2020;102-B(6 Supple A):73–78

Recent publications have drawn attention to the fact that some brands of joint replacement may contain variants which perform significantly worse (or better) than their ‘siblings’. As a result, the National Joint Registry has performed much more detailed analysis on the larger families of knee arthroplasties in order to identify exactly where these differences may be present and may hitherto have remained hidden. The analysis of the Nexgen knee arthroplasty brand identified that some posterior-stabilized combinations have particularly high revision rates for aseptic loosening of the tibia, and consequently a medical device recall has been issued for the Nexgen ‘option’ tibial component which was implicated. More elaborate signal detection is required in order to identify such variation in results in a routine fashion if patients are to be protected from such variation in outcomes between closely related implant types. Cite this article: Bone Joint J 2023;105-B(3):221–226

Adolescent idiopathic scoliosis (AIS), defined by an age at presentation of 11 to 18 years, has a prevalence of 0.47% and accounts for approximately 90% of all cases of idiopathic scoliosis. Despite decades of research, the exact aetiology of AIS remains unknown. It is becoming evident that it is the result of a complex interplay of genetic, internal, and environmental factors. It has been hypothesized that genetic variants act as the initial trigger that allow epigenetic factors to propagate AIS, which could also explain the wide phenotypic variation in the presentation of the disorder. A better understanding of the underlying aetiological mechanisms could help to establish the diagnosis earlier and allow a more accurate prediction of deformity progression. This, in turn, would prompt imaging and therapeutic intervention at the appropriate time, thereby achieving the best clinical outcome for this group of patients. Cite this article: Bone Joint J 2022;104-B(8):915–921

Aims. The cemented Oxford unicompartmental knee arthroplasty (OUKA) features two variants: single and twin peg OUKA. The purpose of this study was to assess the stability of both variants in a worst-case scenario of bone defects and suboptimal cementation. Methods. Single and twin pegs were implanted randomly allocated in 12 pairs of human fresh-frozen femora. We generated 5° bone defects at the posterior condyle. Relative movement was simulated using a servohydraulic pulser, and analyzed at 70°/115° knee flexion. Relative movement was surveyed at seven points of measurement on implant and bone, using an optic system. Results. At the main fixation zone, the twin peg shows less relative movement at 70°/115°. At the transition zone, relative movements are smaller for the single peg for both angles. The single peg shows higher compression at 70° flexion, whereas the twin peg design shows higher compression at 115°. X-displacement is significantly higher for the single peg at 115°. Conclusion. Bony defects should be avoided in OUKA. The twin peg shows high resilience against push-out force and should be preferred over the single peg. Cite this article: Bone Joint Res 2022;11(2):82–90

Aims. Tissue inhibitors of metalloproteinases (TIMPs) are the endogenous inhibitors of the zinc-dependent matrix metalloproteinases (MMP) and A disintegrin and metalloproteinases (ADAM) involved in extracellular matrix modulation. The present study aims to develop the TIMPs as biologics for osteoclast-related disorders. Methods. We examine the inhibitory effect of a high affinity, glycosyl-phosphatidylinositol-anchored TIMP variant named ‘T1. PrαTACE. ’ on receptor activator of nuclear factor kappa-Β ligand (RANKL)-induced osteoclast differentiation. Results. Osteoclast progenitor cells transduced with T1. PrαTACE. failed to form tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts or exhibit bone-resorbing activity following treatment with RANKL. At the messenger RNA level, T1. PrαTACE. strongly attenuated expression of key osteoclast marker genes that included TRAP, cathepsin K, osteoclast stimulatory transmembrane protein (OC-STAMP), dendritic cell-specific transmembrane protein (DC-STAMP), osteoclast-associated receptor (OSCAR), and ATPase H. +. -transporting V0 subunit d2 (ATP6V0D2) by blocking autoamplification of nuclear factor of activated T cells 1 (NFATc1), the osteoclastogenic transcription factor. T1. PrαTACE. selectively extended p44/42 mitogen-activated protein kinase activation, an action that may have interrupted terminal differentiation of osteoclasts. Inhibition studies with broad-spectrum hydroxamate inhibitors confirmed that the anti-resorptive activity of T1. PrαTACE. was not reliant on its metalloproteinase-inhibitory activity. Conclusion. T1. PrαTACE. disrupts the RANKL-NFATc1 signalling pathway, which leads to osteoclast dysfunction. As a novel candidate in the prevention of osteoclastogenesis, the TIMP could potentially be developed for the treatment of osteoclast-related disorders such as osteoporosis. Cite this article: Bone Joint Res 2022;11(11):763–776

Research into COVID-19 has been rapid in response to the dynamic global situation, which has resulted in heterogeneity of methodology and the communication of information. Adherence to reporting standards would improve the quality of evidence presented in future studies, and may ensure that findings could be interpreted in the context of the wider literature. The COVID-19 pandemic remains a dynamic situation, requiring continued assessment of the disease incidence and monitoring for the emergence of viral variants and their transmissibility, virulence, and susceptibility to vaccine-induced immunity. More work is needed to assess the long-term impact of COVID-19 infection on patients who sustain a hip fracture. The International Multicentre Project Auditing COVID-19 in Trauma & Orthopaedics (IMPACT) formed the largest multicentre collaborative audit conducted in orthopaedics in order to provide an emergency response to a global pandemic, but this was in the context of many vital established audit services being disrupted at an early stage, and it is crucial that these resources are protected during future health crises. Rapid data-sharing between regions should be developed, with wider adoption of the revised 2022 Fragility Fracture Network Minimum Common Data Set for Hip Fracture Audit, and a pragmatic approach to information governance processes in order to facilitate cooperation and meta-audit. This editorial aims to: 1) identify issues related to COVID-19 that require further research; 2) suggest reporting standards for studies of COVID-19 and other communicable diseases; 3) consider the requirement of new risk scores for hip fracture patients; and 4) present the lessons learned from IMPACT in order to inform future collaborative studies. Cite this article: Bone Joint Res 2022;11(6):342–345

Aims. There is ambiguity surrounding the degree of scaphoid union required to safely allow mobilization following scaphoid waist fracture. Premature mobilization could lead to refracture, but late mobilization may cause stiffness and delay return to normal function. This study aims to explore the risk of refracture at different stages of scaphoid waist fracture union in three common fracture patterns, using a novel finite element method. Methods. The most common anatomical variant of the scaphoid was modelled from a CT scan of a healthy hand and wrist using 3D Slicer freeware. This model was uploaded into COMSOL Multiphysics software to enable the application of physiological enhancements. Three common waist fracture patterns were produced following the Russe classification. Each fracture had differing stages of healing, ranging from 10% to 90% partial union, with increments of 10% union assessed. A physiological force of 100 N acting on the distal pole was applied, with the risk of refracture assessed using the Von Mises stress. Results. Overall, 90% to 30% fracture unions demonstrated a small, gradual increase in the Von Mises stress of all fracture patterns (16.0 MPa to 240.5 MPa). All fracture patterns showed a greater increase in Von Mises stress from 30% to 10% partial union (680.8 MPa to 6,288.6 MPa). Conclusion. Previous studies have suggested 25%, 50%, and 75% partial union as sufficient for resuming hand and wrist mobilization. This study shows that 30% union is sufficient to return to normal hand and wrist function in all three fracture patterns. Both 50% and 75% union are unnecessary and increase the risk of post-fracture stiffness. This study has also demonstrated the feasibility of finite element analysis (FEA) in scaphoid waist fracture research. FEA is a sustainable method which does not require the use of finite scaphoid cadavers, hence increasing accessibility into future scaphoid waist fracture-related research. Cite this article: Bone Jt Open 2023;4(8):612–620

Aims. Deciphering the genetic relationships between major depressive disorder (MDD) and osteoarthritis (OA) may facilitate an understanding of their biological mechanisms, as well as inform more effective treatment regimens. We aim to investigate the mechanisms underlying relationships between MDD and OA in the context of common genetic variations. Methods. Linkage disequilibrium score regression was used to test the genetic correlation between MDD and OA. Polygenic analysis was performed to estimate shared genetic variations between the two diseases. Two-sample bidirectional Mendelian randomization analysis was used to investigate causal relationships between MDD and OA. Genomic loci shared between MDD and OA were identified using cross-trait meta-analysis. Fine-mapping of transcriptome-wide associations was used to prioritize putatively causal genes for the two diseases. Results. MDD has a significant genetic correlation with OA (r. g. = 0.29) and the two diseases share a considerable proportion of causal variants. Mendelian randomization analysis indicates that genetic liability to MDD has a causal effect on OA (b. xy. = 0.24) and genetic liability to OA conferred a causal effect on MDD (b. xy. = 0.20). Cross-trait meta-analyses identified 29 shared genomic loci between MDD and OA. Together with fine-mapping of transcriptome-wide association signals, our results suggest that Estrogen Receptor 1 (ESR1), SRY-Box Transcription Factor 5 (SOX5), and Glutathione Peroxidase 1 (GPX1) may have therapeutic implications for both MDD and OA. Conclusion. The study reveals substantial shared genetic liability between MDD and OA, which may confer risk for one another. Our findings provide a novel insight into phenotypic relationships between MDD and OA. Cite this article: Bone Joint Res 2022;11(1):12–22