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

Adamantinoma is a rare low-grade malignant epithelial bone tumour. We report a case of an expansile, osteolytic mid-diaphyseal tibial lesion found in a 12 year-old girl. An initial histological diagnosis of basaloid-type adamantinoma was made. Following excision, further histology demonstrated basaloid cells and acellular matrix focally surrounded by osteoclast giant cells with calcium deposits, features consistent with pilomatrixoma. Several histological variants of adamantinoma have been documented; this case details a previously unreported histological adamantinoma variant – pilomatrixoma-adaminatinoma

Liposarcoma is the most common soft tissue sarcoma accounting for 20% of all mesenchymal malignancies.We report a rare histological variant arising from the dorsum of the foot. A 55 year old lady presented with a slow growing, well defined swelling on the dorsum of the foot. Histological examination following complete excision showed a tumor with zones of dense collagenous tissue containing pleomorphic spindle cells and scattered atypical adipocytes. A diagnosis of spindle cell sarcoma was made and referred to the local Sarcoma unit. Repeat excision and histology confirmed margins free of tumor. Four years after primary excision, patient is well with no evidence of recurrence or metastasis. Spindle cell liposarcoma is a rare variant of well differentiated liposarcoma characterized by prominent spindle cell component. Previously reported cases originated in the subcutaneous tissues of shoulder girdle and upper limb. Main differential diagnoses include benign lesions such as spindle cell lipoma, and diffuse neurofibroma as well as dermatofibrosarcoma pro-tuberans and other malignancies such as sclerosing liposarcoma, myxofibrosarcoma, malignant peripheral nerve sheath tumor and fibromyxoid sarcoma. Spindle cell Liposarcomas tend to recur locally and may dedifferentiate with a potential for metastasis. Wide excision and long term follow up looking for recurrence and metastasis is necesssary in these rare variants of liposarcoma especially those arising at atypical sites as in our case

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

Ewing sarcoma (ES) is an aggressive sarcoma, and is the second most common bone sarcoma in childhood. Disease specific t(11;22)(~85–90%), t(21;22)(~5–10%), or rarer variant translocations with the involvement of chromosome 22 (~5%) are present. At the gene level, the EWSR1 gene fuses with FLI1, ERG or other ETS transcription factor family members. So far, no ES has been identified with a fusion to transcription factors other than ETS. By using a panel of molecular tools such as multicolor FISH and array-CGH, a ring chromosome containing chromosomes 20 and 22 was identified in four ES cases. Molecular karyotyping showed the translocation and amplification of regions of chromosomes 20q13 and 22q12. Cloning of the breakpoint showed an in-frame fusion between the EWSR1 and NFATc2 genes. The translocation led to the loss of the N-terminal, calcineurin-dependent control region. Consequently, the remaining intact DNA binding domain of NFATc2 is under control of the EWSR1 promoter region permitting oncogenic activation. Intriguingly, in all cases a distinct histological feature was observed. In conclusion: a new translocation involving EWS and NFATc2 was cloned that is associated with a histological variant of ES. The NFATc2 transcription factor is not a member of the ETS family of transcription factors. NFTAC2 has well characterized functions in T-cell differentiation and immune response. For the first time a direct involvement of NFATc2 in oncogenesis has been shown

Aim: To assess the effectiveness of a physiotherapist led normal variant clinic for children. Method: The study comprised all children presenting to the physiotherapy clinic at the Royal Liverpool Children’s hospital between January 2000 and January 2006. The clinic is run by two specialist physiotherapists alongside a consultant led Orthopaedic clinic, providing support as required. Physiotherapy staff are able to request and interpret radiographs and order blood tests independently. The numbers of patients, the range of conditions seen in the clinic, and the outcome of the consultations recorded in the practitioner case-notes were examined for the purpose of this study. Complete data was available for the full period under review except for the year 2003. Results: During the five year study period 1594 children were seen, a mean of 318 patients annually (range 267–387). The age distribution of patients was 33.1% (527) under the age of 2, 38.9% (620) 2–5 years, 19.3% (307) 5–10 years and 8.8% (140) 10–16 years. The most common conditions seen were genu valgum 28.7% (458), genu varum 18.4% (293), in-toeing 14.7% (234) and toe walking 6.0% (96). Most patients (94.7% n=1509) were managed independent of consultant supervision by the physiotherapist. A minority of patients required consultant review in the clinic (4.2% n=67). Fewer still were referred to another medical clinic (1.1% n=18). Conclusions: Children with a spectrum of orthopaedic conditions can be appropriately managed by a trained physiotherapist independent of consultant input

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.

Evidence has accumulated in recent years that programmed cell death (PCD) is not necessarily synonymous with the classical apoptosis, as defined by Kerr & Wyllie (J Path, 1973, 111:255–261), but that cells use a variety of pathways to undergo cell death, which are reflected by different morphologies. Although chondrocytes with the hallmark features of classical apoptosis have been demonstrated in culture, such cells are extremely rare in vivo. We have examined the morphological differences between dying chondrocytes and classical apoptotic cells in growth plate and osteoarthritic chondrocytes. Unlike classical apoptosis, chondrocyte death involves an increase in the endoplasmic reticulum and Golgi apparatus. This is likely to reflect an increase in protein synthesis with retention of proteins in the ER leading to expansion of the ER lumen, whose membranes surround and compartmentalise organelles and parts of cytoplasm. The final removal of apoptotic remains does not involve phagocytosis, but a combination of three routes: 1) auto-digestion of cellular material within compartments formed by ER membranes; 2) autophagic vacuoles and 3) extrusion of cell remnants into the lacunae. Together these processes lead to complete self-destruction of the chondrocyte as evidenced by the presence of empty lacunae. The involvement of ER suggests that the endoplasmic reticulum pathway of apoptosis may play a greater role in chondroptosis than receptor-mediated and mitochondrial pathways. Lysosomal proteases, present in autophagic digestion, are likely to be as important as caspases in the programmed cell death of chondrocytes in vivo. We propose the term ‘chondroptosis’ to reflect the fact that such cells are undergoing apoptosis, albeit in a non-classical manner, but one that appears to be typical of programmed chondrocyte death in vivo. Chondroptosis may serve to eliminate cells that are not phagocytosed by neighboring cells, which constitutes a crucial advantage for chondrocytes that are typically embedded in an extracellular matrix. Classical apoptosis in that situation is likely to lead to secondary necrosis with all its disadvantages. This may be the reason why most programmed cell death of chondrocytes in vivo appears to follow a chondroptotic pattern and not the classical apoptotic pattern. At present the initiation factors or the molecular pathways involved in chondroptosis remain unclear.

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 present a review of our Specialist Physiotherapy clinic for normal physiological variations of the lower limb (SPNV) clinics, demonstrating them to be clinically effective and cost effective.

Children with normal variation of rotational profile and limb angulation present much anxiety to parents and primary care. Providing consultation: to eliminate significant pathology and reassure families, is an important service that a Paediatric Orthopaedic department provides. In our tertiary referral department we have a Specialist Physiotherapy led clinics into which primary care practitioners refer children with whom there are concerns about lower limb development variation.

The (SPNV) Clinic was first set up by a Consultant and Senior Physiotherapist in 1999. The aim of the clinic was to reduce the waiting times for incoming referrals but ensuring they are seen in an appropriate environment by an experienced health care professional. Clinics are run by Senior Specialist Physiotherapists, alongside Consultant clinics who are available for advice and direction. This provides security for the physios, the Trust and the patient.

Over 15 years there have been more than 4000 patient visits to this clinic. Over 80% were new patient visits. 70% of these visits were discharged in one or two reviews. 97.4% of new referrals were discharged without subsequent review by an orthopaedic surgeon. The most common conditions reviewed were Genu valgum (25%), Genu Varum (16%), intoeing (17%) and flexible flat feet (11%).

The clinic has proven to be cost effective as well in drawing in up to £500,000 revenue into the trust in a single year. The department has been approached by other trusts to assist in the implementation of similar clinics.

We present this review of the patients, as a template for supporting the work of Paediatric Orthopaedic Departments. This service has facilitated the streamlining of our Consultant Paediatric Orthopaedic clinics.

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.

Purpose: The bifoliated vascularised fibula graft is an attractive alternative for reconstruction of large bone segments. The purpose of this work was to evaluate mid-term results and the usefulness of two surgical techniques: skin island flap monitoring and the arterio-venous loop.

Material and methods: This retrospective analysis included fourteen patients (eleven men and three women) treated between 1992 and 2002. Mean age was 30 years (10–54). Indications were complications of open fractures in nine patients, major bone loss in two, septic nonunion in four, and aseptic nonunion in three. Reconstruction was performed after bone tumour resection in five patients involving immediate reconstruction after failure of an infected massive allograft in four of them. Localisations were: tibia (n=6), femur (n=5), humerus (n=2), and pelvis (n=1). Average bone loss was 10 cm (7–15 cm). Minimal pinning, cerclage or screwing was used to stabilise the flap completed by internal fixation in four patients and external fixation in ten. A monitoring skin island was used for twelve patients (the island was technically impossible in two patients). Vascular anastomoses were performed in seven patients using an arteriovenous loop, performed as a preliminary measure in six.

Results: Mean follow-up was 35 months. One patient died early from tumour progression. Among the seven patients who had an arteriovenous loop, one required revision for a vascular complication. For the seven “classical” bypasses, there were three intraoperative or early complications requiring revision of the anastomoses. Nonunion developed despite early revision in the four patients whose monitoring skin island suffered. Consolidation was achieved without revision in all patients who skin island did not suffer; time to bone healing was eleven months for seven of them.

Conclusion: Bone healing was related to the quality of graft vacularisation. Clinical observation of the monitoring island was the best way to identify vascular complications early and initiate treatment. Use of a preliminary arteriovenous loop decreased the risk of vascular insufficiency inherent with long bypasses and shortened operative time.

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