A variant in MCF2L is associated with osteoarthritis.

Osteoarthritis (OA) is a prevalent, heritable degenerative joint disease with a substantial public health impact. We used a 1000-Genomes-Project-based imputation in a genome-wide association scan for osteoarthritis (3177 OA cases and 4894 controls) to detect a previously unidentified risk locus. We discovered a small disease-associated set of variants on chromosome 13. Through large-scale replication, we establish a robust association with SNPs in MCF2L (rs11842874, combined odds ratio [95% confidence interval] 1.17 [1.11-1.23], p = 2.1 × 10(-8)) across a total of 19,041 OA cases and 24,504 controls of European descent. This risk locus represents the third established signal for OA overall. MCF2L regulates a nerve growth factor (NGF), and treatment with a humanized monoclonal antibody against NGF is associated with reduction in pain and improvement in function for knee OA patients.

A meta-analysis of genome-wide association studies identifies novel variants associated with osteoarthritis of the hip.

OBJECTIVES: Osteoarthritis (OA) is the most common form of arthritis with a clear genetic component. To identify novel loci associated with hip OA we performed a meta-analysis of genome-wide association studies (GWAS) on European subjects. METHODS: We performed a two-stage meta-analysis on more than 78,000 participants. In stage 1, we synthesised data from eight GWAS whereas data from 10 centres were used for 'in silico' or 'de novo' replication. Besides the main analysis, a stratified by sex analysis was performed to detect possible sex-specific signals. Meta-analysis was performed using inverse-variance fixed effects models. A random effects approach was also used. RESULTS: We accumulated 11,277 cases of radiographic and symptomatic hip OA. We prioritised eight single nucleotide polymorphism (SNPs) for follow-up in the discovery stage (4349 OA cases); five from the combined analysis, two male specific and one female specific. One locus, at 20q13, represented by rs6094710 (minor allele frequency (MAF) 4%) near the NCOA3 (nuclear receptor coactivator 3) gene, reached genome-wide significance level with p=7.9×10(-9) and OR=1.28 (95% CI 1.18 to 1.39) in the combined analysis of discovery (p=5.6×10(-8)) and follow-up studies (p=7.3×10(-4)). We showed that this gene is expressed in articular cartilage and its expression was significantly reduced in OA-affected cartilage. Moreover, two loci remained suggestive associated; rs5009270 at 7q31 (MAF 30%, p=9.9×10(-7), OR=1.10) and rs3757837 at 7p13 (MAF 6%, p=2.2×10(-6), OR=1.27 in male specific analysis). CONCLUSIONS: Novel genetic loci for hip OA were found in this meta-analysis of GWAS.

Identification of new susceptibility loci for osteoarthritis (arcOGEN): a genome-wide association study.

BACKGROUND: Osteoarthritis is the most common form of arthritis worldwide and is a major cause of pain and disability in elderly people. The health economic burden of osteoarthritis is increasing commensurate with obesity prevalence and longevity. Osteoarthritis has a strong genetic component but the success of previous genetic studies has been restricted due to insufficient sample sizes and phenotype heterogeneity. METHODS: We undertook a large genome-wide association study (GWAS) in 7410 unrelated and retrospectively and prospectively selected patients with severe osteoarthritis in the arcOGEN study, 80% of whom had undergone total joint replacement, and 11,009 unrelated controls from the UK. We replicated the most promising signals in an independent set of up to 7473 cases and 42,938 controls, from studies in Iceland, Estonia, the Netherlands, and the UK. All patients and controls were of European descent. FINDINGS: We identified five genome-wide significant loci (binomial test p≤5·0×10(-8)) for association with osteoarthritis and three loci just below this threshold. The strongest association was on chromosome 3 with rs6976 (odds ratio 1·12 [95% CI 1·08-1·16]; p=7·24×10(-11)), which is in perfect linkage disequilibrium with rs11177. This SNP encodes a missense polymorphism within the nucleostemin-encoding gene GNL3. Levels of nucleostemin were raised in chondrocytes from patients with osteoarthritis in functional studies. Other significant loci were on chromosome 9 close to ASTN2, chromosome 6 between FILIP1 and SENP6, chromosome 12 close to KLHDC5 and PTHLH, and in another region of chromosome 12 close to CHST11. One of the signals close to genome-wide significance was within the FTO gene, which is involved in regulation of bodyweight-a strong risk factor for osteoarthritis. All risk variants were common in frequency and exerted small effects. INTERPRETATION: Our findings provide insight into the genetics of arthritis and identify new pathways that might be amenable to future therapeutic intervention. FUNDING: arcOGEN was funded by a special purpose grant from Arthritis Research UK.

Evaluation of the genetic overlap between osteoarthritis with body mass index and height using genome-wide association scan data.

OBJECTIVES: Obesity as measured by body mass index (BMI) is one of the major risk factors for osteoarthritis. In addition, genetic overlap has been reported between osteoarthritis and normal adult height variation. We investigated whether this relationship is due to a shared genetic aetiology on a genome-wide scale. METHODS: We compared genetic association summary statistics (effect size, p value) for BMI and height from the GIANT consortium genome-wide association study (GWAS) with genetic association summary statistics from the arcOGEN consortium osteoarthritis GWAS. Significance was evaluated by permutation. Replication of osteoarthritis association of the highlighted signals was investigated in an independent dataset. Phenotypic information of height and BMI was accounted for in a separate analysis using osteoarthritis-free controls. RESULTS: We found significant overlap between osteoarthritis and height (p=3.3×10(-5) for signals with p≤0.05) when the GIANT and arcOGEN GWAS were compared. For signals with p≤0.001 we found 17 shared signals between osteoarthritis and height and four between osteoarthritis and BMI. However, only one of the height or BMI signals that had shown evidence of association with osteoarthritis in the arcOGEN GWAS was also associated with osteoarthritis in the independent dataset: rs12149832, within the FTO gene (combined p=2.3×10(-5)). As expected, this signal was attenuated when we adjusted for BMI. CONCLUSIONS: We found a significant excess of shared signals between both osteoarthritis and height and osteoarthritis and BMI, suggestive of a common genetic aetiology. However, only one signal showed association with osteoarthritis when followed up in a new dataset.

Complications and Outcomes of the Internal Fixation of Non-displaced Femoral Neck Fracture in Old Patients: A Two-Year Follow-Up.

Background Fractures of the proximal femur are amongst the most common injuries in the elderly population. While there is a clear consensus regarding the management of displaced femoral neck fractures, the management of non-displaced fractures is less clear. Both fixation and arthroplasty are valid treatment options. Internal fixation is a less invasive procedure, but it carries the risks of non-union and avascular necrosis (AVN) of the femoral head. The literature describes varying complication rates associated with these risks. We aim to describe a series of elderly patients above the age of 65 years with non-displaced fractures of the femoral neck who were treated with internal fixation. Our objectives are to determine the union rate and complications in this group and to elucidate the factors that influence these outcomes. Methods We conducted a retrospective review of all patients aged 65 years and older who presented with femoral neck fractures at our level 1 trauma unit between 2018 and 2020. Fractures were classified using the Garden classification system, and only those with Garden 1 or 2 fractures (non-displaced) were included. Preoperative radiographs or intraoperative fluoroscopy images were used to classify fractures using the Pauwels classification. Serial postoperative radiographs and clinical notes (up to 24 months postoperatively) were reviewed to assess the union rate and the development of complications. Both non-union and AVN were analysed for their associations with age, sex, Pauwels grade and comorbidities. A subgroup analysis of the complications was performed to elucidate their association with age groups (<80 and >80 years) and types of fixations (dynamic hip screws {DHS} and cannulated screws). Results A total of 148 patients, consisting of 60 males and 88 females, were included in the analysis. The patients had a mean age of 78.5 years (ranging from 65 to 98 years). The union rate without any degree of AVN was 90.7%, with six non-unions (4.05%) and six patients experiencing AVN (4.05%). No difference in outcome was detected between the two groups based on age. High (type 2 or 3) Pauwels grade (p = 0.05) and treatment with cannulated screws (p = 0.02) were indicated as significant factors for non-union. All patients who developed AVN were noted to have a comorbidity that is known to predispose them to AVN. Conclusion Our series shows a union rate of 90.7%, which is comparable to the union rates reported in other published literature. Our results suggest that age does not independently influence the outcome of fixation for these fractures. We conclude that fractures with vertical orientation (Pauwels grade 2 or 3), when treated with cannulated screws, are more likely to result in non-union. AVN is the second most common complication after non-union, which is also associated with other risk factors for AVN.

Cementless Mobile-Bearing Total Knee Arthroplasty: 10 Years Follow-Up.

Background Although most TKR surgeries are cemented, the interest in cementless TKR has increased dramatically during the last few years because of the new generation of cementless prostheses and the increased number of young patients who need TKR. Methods Ten years of retrospective reviews of 80 patients who had cementless, complete rotating platform TKR (DePuy Synthes, Warsaw, Indiana) were performed. Patients were divided into two groups according to their age (above and below 70 years old). Functional outcomes at the final follow-up were evaluated clinically by filling out a satisfaction form, and the Oxford Knee Score as well as all medical and surgical complications were recorded for each patient. Results The 10-year cumulative implant survival rate was 100%, i.e. no patients had revision surgeries with no significant statistical difference between the two age groups. The 10-year evaluation rate was 90%. Conclusion The use of cementless TKA exhibited good survivability, long-term clinical and functional results, and no implant revision in various age groups, as well as a high satisfaction rate. There was no statistically significant difference between the results of different age groups.

The relationship between exposure to noise and hearing loss in orthopaedics.

Aims: In the UK, the agricultural, military, and construction sectors have stringent rules about the use of hearing protection due to the risk of noise-induced hearing loss. Orthopaedic staff may also be at risk due to the use of power tools. The UK Health and Safety Executive (HSE) have clear standards as to what are deemed acceptable occupational levels of noise on A-weighted and C-weighted scales. The aims of this review were to assess the current evidence on the testing of exposure to noise in orthopaedic operating theatres to see if it exceeds these regulations. Methods: A search of PubMed and EMBASE databases was conducted using PRISMA guidelines. The review was registered prospectively in PROSPERO. Studies which assessed the exposure to noise for orthopaedic staff in operating theatres were included. Data about the exposure to noise were extracted from these studies and compared with the A-weighted and C-weighted acceptable levels described in the HSE regulations. Results: A total of 15 studies were deemed eligible. These included a total of 386 orthopaedic operations and the use of 64 orthopaedic instruments. A total of 294 operations (76%) and 45 instruments (70%) exceeded the regulations on an A-weighted scale, and 22% (10 of 46) of operations exceeded the maximum C-weighted peak acceptable level of noise. Noise-induced hearing loss was reported in 28 of 55 orthopaedic staff members (50.9%). Conclusion: Safe levels of noise can be exceeded in orthopaedic operations, and when using orthopaedic instruments. Employers have clear policies about exposure to noise in the workplace but have yet to identify orthopaedic theatres as a potential at-risk area. Orthopaedic staff need education, monitoring, and protection, while employers should consider regular assessments of staff in orthopaedic theatres and offer methods to prevent noise-induced hearing loss.

A systematic review on management and outcome of irreducible knee dislocations.

BACKGROUND: Irreducible knee dislocations (IKD) are rare and can often be missed or misdiagnosed. The incidence of knee dislocation is quoted between 0.01% and 0.2% of all orthopaedic injuries, with up to 4% of these dislocations sub-classified as irreducible. The primary aim of this systematic review was to analyse cases of IKD described in the literature, with a secondary aim of producing a streamlined approach for managing these patients. PATIENTS AND METHODS: A systematic review of the literature was conducted on 1st September 2021 in accordance with the PRISMA guidelines using the online databases Medline and EMBASE. The review was registered prospectively in the PROSPERO database. Case reports or clinical studies or reporting on IKD were included. The studies were appraised using the Methodological Index for Non-Randomized Studies (MINORS) tool and Newcastle-Ottawa quality assessment scale. RESULTS: The search strategy identified 60 studies eligible for inclusion, giving a total of 114 cases of IKD. Posterolateral dislocation was most common, seen in 85% of cases. The dimple sign was present in 70%. All cases required surgical intervention to achieve joint reduction. The most commonly involved structure blocking reduction was the medial collateral ligament (MCL)±medial structures, seen in 52.4%. MCL reconstruction or repair was carried out in 32.3% cases. The overall incidence of neurovascular injury was 9% and the overall complication rate was 14.4%. CONCLUSION: Based on the findings of this SR we conclude that: the most common type of IKDs are PL dislocations, and the MCL, medial retinaculum and capsule and vastus medialis oblique form the most common structures involved in block to reduction and often will require open reduction and repair in acute setting if arthroscopic reduction fails. The most common pattern of injury to ligament is likely to be ACL, PCL, MCL±other structures but the MCL will be the most commonly repaired ligament. The dimple sign is often present and is highly pathognomonic of IKD. The incidence of neurovascular injury is uncommon. The most common post-operative complications likely to be encountered is medial skin necrosis and postoperative knee stiffness. Therefore, patients should be mobilised as early as possible with ROM in hinge brace. LEVEL OF EVIDENCE: IV.

Effect of prior Salter or Chiari osteotomy on THA with developmental hip dysplasia.

BACKGROUND: Controversy exists regarding the outcome of THA after prior pelvic osteotomy. QUESTIONS/PURPOSES: We conducted a retrospective chart and radiographic review to obtain outcome measures for perioperative complications, acetabular and femoral component revisions, Harris hip score, and survivorship and compared these outcomes for patients presenting with developmental dysplasia of the hip treated surgically using THA with and without prior pelvic osteotomy. PATIENTS AND METHODS: We performed 103 primary THAs in 87 patients with osteoarthritis secondary to developmental dysplasia of the hip with a minimum 3-year followup. Previous pelvic osteotomy was performed in 52 hips (Salter, 40; Chiari, nine; Salter and Chiari, three), and 51 hips had no previous surgery (control group). RESULTS: The pelvic osteotomy group did not have higher rates of femoral or acetabular intraoperative fracture or dislocation compared with the control group. The overall revision rate was 28.8% in the pelvic osteotomy group compared with 19.6% in the control group. The revision rate for aseptic loosening was 23.1% in the pelvic osteotomy group compared with 17.6% in the control group. Harris hip scores (range, 20-87) were not compromised, and overall survivorship rates 8 years postoperatively were not different at any time between the pelvic osteotomy (83.3%) and control (88.4%) groups. CONCLUSIONS: Prior pelvic osteotomy did not lead to a higher perioperative complication rate, higher revision rate, compromised Harris hip score, or shortened survivorship in eventual THA in developmental dysplasia of the hip. LEVEL OF EVIDENCE: Level III, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Total knee arthroplasty: the future.

Few areas in orthopaedics have evolved so dramatically over the past few decades as our knowledge of knee physiology, knee kinematics, and knee replacement surgery. This article addresses major breakthroughs in knee replacement surgery, the thought process behind these concepts, and their impact on clinical practice. It focuses on compartmental arthroplasty, use of minimally invasive surgery, advances in biomaterials, and biological solutions for treating arthritis. Compartmental knee replacements are gaining popularity, especially for medial compartment arthritis. Minimally invasive surgery (i.e., quadriceps sparing arthroplasty) has become very popular in the last few years and is being used routinely for unicompartmental knee replacement and increasingly used for total knee replacement. Computer-assisted surgery has the ability to help the surgeon place the components in the desired position, thereby avoiding component malpositioning, which can cause pain, instability, limited range of movement, excessive polyethylene wear, and subsequent implant loosening. Recent advances in the metallurgy have led to the introduction of tantalum trabecular metal which offers several advantages over other current conventional materials used for implants. Expanding knowledge regarding cartilage biochemistry and the pathogenesis of osteoarthritis has focused the research on slowing the progression of osteoarthritis and promoting cartilage matrix synthesis. Perichondrial transplantation as well as periosteal transplantation have been tried by a few investigators but they have limited and temporary success. Autologous chondrocyte implantation is another technique that is gaining popularity. The chondrocytes harvested from the patient are cultured and reimplanted after 3-4 weeks of culturing. In the future, we are likely to see advances in diagnosis as well as management of osteoarthritis. The treatment modalities will probably evolve at the cellular level and it will not be long before a patient-specific medication can be given to a asymptomatic patient in order to prevent development of osteoarthritis. Patients with end-stage osteoarthritis will be offered a combination of treatments (e.g., partial replacement of one compartment or localized cartilage repair if there is localized cartilage defect in the other compartment).

Evaluation of Internet use by paediatric orthopaedic outpatients and the quality of information available.

Parents use the Internet increasingly for information about their children's medical problems. There is no quality control for medical information content. The goals of our study were to assess Internet awareness by families seen in paediatric orthopaedic outpatients departments and the type, quality and reliability of information available, using clubfoot as an example. Parents accompanying children to the outpatient's clinic were surveyed regarding the use of the Internet for medical information. They were asked about their ability to use the Internet, and whether this helped the consultation. To assess the quality of information available, the search phrases 'clubfoot' and 'club foot' were placed in the five most commonly used World Wide Web search engines. Web sites were evaluated for authorship, content and informational value using our own agreed scoring system, ranging from 0-100 points. Sixty-one percent of the questionnaires were completed, the mothers completed 67%. Eighty-four percent reported access to the Internet. Most found their searches useful and 26% were reminded of questions to ask at consultation. When a search for 'clubfoot' was carried out we found 11% of web sites were affiliated to academic institutions. There was a significant difference when the terms 'clubfoot' or 'club foot' were searched. Twenty-eight percent offered conventional information. Thirty-six percent of web sites were not related to congenital talipes equinovarus. The average information value was 26 points (0-98). Parents frequently use the Internet for information about paediatric orthopaedic consultations, prior to consultation. The quality of clubfoot information on the Internet is variable. The development of academic-based websites should be encouraged, as these offer the most useful information.

A review of tissue glue use in facial lacerations: potential problems with wound selection in accident and emergency.

OBJECTIVES: The purpose of this study was to review the types of facial lacerations for which tissue glue was used as a closure method and assess whether current evidence was being followed. METHODS: A retrospective analysis of facial lacerations presenting to an adult Accident and Emergency Department was made over a 6-month period. RESULTS: Out of 200 facial lacerations, 45 were closed using tissue glue. The mean length of the wounds was 2.05 cm, with a range of 0.5-6 cm; 42 were linear and three were non-linear. Senior house officers closed 16 wounds, middle grade doctors closed 19, emergency nurse practitioners closed seven, and consultants closed three. Six cases were closed against current evidence (13%). This included three lacerations that were non-linear and three lacerations greater than 4 cm in length. Four out of six of these cases were closed by senior house officer grades (80%). CONCLUSION: The lack of clarity over the use of tissue glue for facial wounds may be attributable to a lack of awareness and training, and the misinterpretation of randomized trials. Greater awareness is needed of the role of tissue glue, especially among senior house officers.

Femoral neck stress fracture in a sanitary worker.

Stress fractures of the femoral neck are uncommon, it is important to have a high index of suspicion in young active people who perform repetitive vigorous activity or have recently had an increase in frequency of such activity. We report a case of femoral neck stress fracture in a sanitary worker which was treated successfully with a dynamic hip screw.

Microscooter injuries in the paediatric population.

OBJECTIVES: To illustrate the types of injuries seen by the accident and emergency department as a result of the use of non-motorized 'microscooters' in children, and to increase awareness of scooter-related triplane fractures of the ankle. STUDY DESIGN: A retrospective study conducted in an accident and emergency department of a district general hospital on all children who had a scooter-related limb injury over a 6-month period and were referred for orthopaedic review. METHODS: The analysis involved a case note review. Information recorded included the injury sustained, protective equipment worn at the time of the accident and management by the orthopaedic team. RESULTS: Scooter injuries accounted for 10 fractures in this period. There were three 'triplanar' injuries, which required operative fixation, and three injuries requiring manipulation under anaesthesia. No protective gear was worn by any of the patients. CONCLUSION: The popularity of microscooters seems to represent a significant risk of bony injury in the paediatric population. Medical personnel who manage acute paediatric trauma should be aware of scooter-related triplanar ankle injuries.

Functional outcome following internal fixation of intraarticular fractures of the distal humerus (AO type C).

The aim of this study was to evaluate the functional outcome following internal fixation of intraarticular fractures of the distal humerus (AO Type C) with a minimum follow-up of two years. A retrospective evaluation with prospective clinical review was carried out. Twenty-six consecutive patients with fractures of the distal humerus were treated over a 31-month period. Their mean age was 56 years (range, 18-82). Six patients were not available for final clinical review. Analysis of the results were based on the medical records, pre-operative and postoperative radiographs of all 26 patients and clinical review of 20 patients at a mean follow-up of 35 months (range, 24-48 months). Twenty-six fractures were fixed using the AO double column plating techniques. Radiographic evaluation of the quality of reduction was carried out using a grading system. Clinical outcome was assessed using the Broberg and Morrey functional rating index. Fourteen patients (70%) had an excellent or good outcome, five patients (25%) a fair outcome and one patient (5%) had a poor result. Three patients (15%) underwent a second procedure for hardware removal. The mean arc of flexion was 112 degrees (range, 85 to 122). Mean pronation was 75 degrees (range, 60-82) and supination was 76 degrees (range, 60-80). No patients had achieved normal grip strength; the mean grip strength was 82% (range, 46-90%) compared to the uninjured side. Fifteen patients (75%) were able to return to their pre-injury level of occupation and activity. Seventeen patients (85%) were satisfied with the final outcome. We conclude that internal fixation of intraarticular fractures of the distal humerus is an effective procedure with an excellent or good functional outcome in most patient age groups. Patients have a high level of satisfaction and the majority return to their previous level of activity.

The floating shoulder.

Ipsilateral fracture of the clavicle and scapula is considered to be a relatively rare injury. It is perceived as an unstable injury and is at times called floating shoulder. Understanding of the role played by the bony and ligament stability is important to identify true floating shoulder injury and to offer an appropriate treatment. Both conservative and surgical treatment modalities are described in the literature. Recent literature has shown the important role played by the ligaments in providing stability in ipsilateral fracture of the clavicle and scapula. In a true floating shoulder injury, it seems important to stabilise the injury by fixation of the scapular fracture. This article reviews the literature to identify the injury pattern of true floating shoulder and to look at the current evidence for the treatment of such an injury.

Gouty flexor tenosynovitis mimicking infection: a case report emphasising the value of ultrasound in diagnosis.

Tenosynovitis of the flexor tendons of the hand is a rare manifestation of gout. We present an unusual case of gouty tenosynovitis mimicking infection. The role of ultrasound in the management of this condition is emphasised.

Reliability of preoperative templating in total knee arthroplasty.

The purpose of this study was to determine the reliability of preoperative templating in primary total knee arthroplasty and the influence of the seniority of the surgeon on templating. A retrospective study of 25 randomly selected total knee replacements was undertaken, with templating of preoperative radiographs by four surgical staff members. These included a consultant, a specialist registrar and two senior house officers. Reliability for an exact match between template size and implant actually used was 49% for the femoral component and 67% for the tibial component. The statistical agreement between templated size and actual implant size was classed as only fair to moderate. There was no statistical difference in templating reliability between junior and senior surgical staff. These results indicate that the current system of templating for total knee arthoplasties is prone to error and can only be used as an approximate guide.