I Carluke

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

Summary 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.

Blood metal ion concentrations after hip resurfacing arthroplasty: A COMPARATIVE STUDY OF ARTICULAR SURFACE REPLACEMENT AND BIRMINGHAM HIP RESURFACING ARTHROPLASTIES

There have been no large comparative studies of the blood levels of metal ions after implantation of commercially available hip resurfacing devices which have taken into account the effects of femoral size and inclination and anteversion of the acetabular component. We present the results in 90 patients with unilateral articular surface replacement (ASR) hip resurfacings (mean time to blood sampling 26 months) and 70 patients with unilateral Birmingham Hip Resurfacing (BHR) implants (mean time 47 months). The whole blood and serum chromium (Cr) and cobalt (Co) concentrations were inversely related to the size of the femoral component in both groups (p < 0.05). Cr and Co were more strongly influenced by the position of the acetabular component in the case of the ASR, with an increase in metal ions observed at inclinations > 45 degrees and anteversion angles of < 10 degrees and > 20 degrees. These levels were only increased in the BHR group when the acetabular component was implanted with an inclination > 55 degrees. A significant relationship was identified between the anteversion of the BHR acetabular component and the levels of Cr and Co (p < 0.05 for Co), with an increase observed at anteversion angles < 10 degrees and > 20 degrees. The median whole blood and serum Cr concentrations of the male ASR patients were significantly lower than those of the BHR men (p < 0.001). This indicates that reduced diametral clearance may equate to a reduction in metal ion concentrations in larger joints with satisfactory orientation of the acetabular component.

Reduced short-term complications and mortality following Enhanced Recovery primary hip and knee arthroplasty: results from 6,000 consecutive procedures.

Background and purpose Enhanced Recovery (ER) is a well-established multidisciplinary strategy in lower limb arthroplasty and was introduced in our department in May 2008. This retrospective study reviews short-term outcomes in a consecutive unselected series of 3,000 procedures (the “ER” group), and compares them to a numerically comparable cohort that had been operated on previously using a traditional protocol (the “Trad” group). Methods Prospectively collected data on surgical endpoints (length of stay (LOS), return to theater (RTT), re-admission, and 30- and 90-day mortality) and medical complications (stroke, gastrointestinal bleeding, myocardial infarction, and pneumonia within 30 days; deep vein thrombosis and pulmonary embolism within 60 days) were compared. Results ER included 1,256 THR patients and 1,744 TKR patients (1,369 THRs and 1,631 TKRs in Trad). The median LOS in the ER group was reduced (3 days vs. 6 days; p = 0.01). Blood transfusion rate was also reduced (7.6% vs. 23%; p < 0.001), as was RTT rate (p = 0.05). The 30-day incidence of myocardial infarction declined (0.4% vs. 0.9%; p = 0.03) while that of stroke, gastrointestinal bleeding, pneumonia, deep vein thrombosis, and pulmonary embolism was not statistically significantly different. Mortality at 30 days and at 90 days was 0.1% and 0.5%, respectively, as compared to 0.5% and 0.8% using the traditional protocol (p = 0.03 and p = 0.1, respectively). Interpretation This is the largest study of ER arthroplasty, and provides safety data on a consecutive unselected series. The program has achieved a statistically significant reduction in LOS and in cardiac ischemic events for our patients, with a near-significant decrease in return to theater and in mortality rates.

No evidence of an association between mitochondrial DNA variants and osteoarthritis in 7393 cases and 5122 controls.

Objectives Osteoarthritis (OA) has a complex aetiology with a strong genetic component. Genome-wide association studies implicate several nuclear genes in the aetiology, but a major component of the heritability has yet to be defined at the molecular level. Initial studies implicate maternally inherited variants of mitochondrial DNA (mtDNA) in subgroups of patients with OA based on gender and specific joint involvement, but these findings have not been replicated. Methods The authors studied 138 maternally inherited mtDNA variants genotyped in a two cohort genetic association study across a total of 7393 OA cases from the arcOGEN consortium and 5122 controls genotyped in the Wellcome Trust Case Control consortium 2 study. Results Following data quality control we examined 48 mtDNA variants that were common in cohort 1 and cohort 2, and found no association with OA. None of the phenotypic subgroups previously associated with mtDNA haplogroups were associated in this study. Conclusions We were not able to replicate previously published findings in the largest mtDNA association study to date. The evidence linking OA to mtDNA is not compelling at present.

The use of high-dose dual-impregnated antibiotic-laden cement with hemiarthroplasty for the treatment of a fracture of the hip: The Fractured Hip Infection trial.

Aims A fracture of the hip is the most common serious orthopaedic injury, and surgical site infection (SSI) is one of the most significant complications, resulting in increased mortality, prolonged hospital stay and often the need for further surgery. Our aim was to determine whether high dose dual antibiotic impregnated bone cement decreases the rate of infection. Patients and Methods A quasi-randomised study of 848 patients with an intracapsular fracture of the hip was conducted in one large teaching hospital on two sites. All were treated with a hemiarthroplasty. A total of 448 patients received low dose single-antibiotic impregnated cement (control group) and 400 patients received high dose dual-antibiotic impregnated cement (intervention group). The primary outcome measure was deep SSI at one year after surgery. Results The rate of deep SSI was 3.5% in the control group and 1.1% in the intervention group (p = 0.041; logistic regression adjusting for age and gender). The overall rate of non-infective surgical complications did not differ between the two groups (unadjusted chi-squared test; p > 0.999). Conclusion The use of high dose dual-antibiotic impregnated cement in these patients significantly reduces the rate of SSI compared with standard low dose single antibiotic loaded bone cement. Cite this article: Bone Joint J 2016;98-B:1534–1541.

The effect of triclosan-coated sutures on the rate of surgical site infection after hip and knee arthroplasty: a double-blind randomized controlled trial of 2546 patients

Aims Surgical site infection (SSI) is a common complication of surgery with an incidence of about 1% in the United Kingdom. Sutures can lead to the development of a SSI, as microorganisms can colonize the suture as it is implanted. Triclosan‐coated sutures, being antimicrobical, were developed to reduce the rate of SSI. Our aim was to assess whether triclosan‐coated sutures cause a reduction in SSIs following arthroplasty of the hip and knee. Patients and Methods This two‐arm, parallel, double‐blinded study involved 2546 patients undergoing elective total hip (THA) and total knee arthroplasty (TKA) at three hospitals. A total of 1323 were quasi‐randomized to a standard suture group, and 1223 being quasi‐randomized to the triclosan‐coated suture group. The primary endpoint was the rate of SSI at 30 days postoperatively. Results The baseline characteristics of age, gender and comorbidities were well matched in the two groups. The rates of superficial SSI were 0.8% in the control group and 0.7% in the intervention group (p = 0.651), and when deep and superficial SSIs were combined the rates were 2.5% and 1.8 (p = 0.266). The length of stay in hospital and the rates of medical complications did not differ significantly between the groups (p = 1.000). Conclusion This trial provided no evidence that the use of triclosan‐coated sutures in THA and TKA leads to a reduction in the rate of SSI.

Infographic: Triclosan-coated sutures and surgical site infections after hip and knee arthroplasty

Bone Joint J 2018;100-B:294–5. Hip and knee arthritis is successfully treated with total hip (THA) and total knee arthroplasty (TKA). Over 209 000 hip and knee arthroplasties were performed in 2017.1 Surgical site infections (SSI) account for 1% to 2% of complications following hip and knee li e I d s Sprowson et al. 2018 riC osan-coate utures TheBone&Joint journal and surgical site infections after arthroplasty of the hip and knee