It has been suggested that matrix metalloproteinase-3 (MMP-3, stromelysin-1) has an important role in the degeneration of intervertebral discs (IVDs). A human MMP-3 promoter 5A/6A polymorphism was reported to be involved in the regulation of MMP-3 gene expression. We suggest that IVD degeneration is associated with 5A/6A polymorphism. We studied 54 young and 49 elderly Japanese subjects. Degeneration of the lumbar discs was graded using MRI in the younger group and by radiography in the elderly. 5A/6A polymorphism was determined by polymerase-chain reaction-based assays. We found that the 5A5A and 5A6A genotype in the elderly was associated with a significantly larger number of degenerative IVDs than the 6A6A (p < 0.05), but there was no significant difference in the young. In the elderly, the IVD degenerative scores were also distributed more highly in the 5A5A and 5A6A genotypes (p = 0.0029). Our findings indicate that the 5A allele is a possible risk factor for the acceleration of degenerative changes in the lumbar disc in the elderly

Low bone mass and osteopenia have been described in the axial and peripheral skeleton of patients with adolescent idiopathic scoliosis (AIS). Recently, many studies have shown that gene polymorphism is related to osteoporosis. However, no studies have linked the association between IL6 gene polymorphism and bone mass in AIS. This study examined the association between bone mass and IL6 gene polymorphism in 198 girls with AIS. The polymorphisms of IL6-597 G→A, IL6-572 G→C and IL6-174 G→A and the bone mineral density in the lumbar spine and femoral neck were analysed and compared with their levels in healthy controls. The mean bone mineral density at both sites in patients with AIS was decreased compared with controls (p = 0.0022 and p = 0.0013, respectively). Comparison of genotype frequencies between AIS and healthy controls revealed a statistically significant difference in IL6-572 G→C polymorphism (p = 0.0305). There was a significant association between the IL6-572 G→C polymorphism and bone mineral density in the lumbar spine, with the CC genotype significantly higher with the GC (p = 0.0124) or GG (p = 0.0066) genotypes. These results suggest that the IL6-572 G→C polymorphism is associated with bone mineral density in the lumbar spine in Korean girls with AIS

Aims. The purpose of this study is to determine an individual’s age-specific prevalence of total knee arthroplasty (TKA) after cruciate ligament surgery, and to identify clinical and genetic risk factors associated with undergoing TKA. Methods. This study was a retrospective case-control study using the UK Biobank to identify individuals reporting a history of cruciate ligament surgery. Data from verbal history and procedural codes recorded through the NHS were used to identify instances of TKA. Patient clinical and genetic data were used to identify risk factors for progression from cruciate ligament surgery to TKA. Individuals without a history of cruciate ligament reconstruction were used for comparison. Results. A total of 2,576 individuals with a history of cruciate ligament surgery were identified, with 290 (11.25%) undergoing TKA. In patients with prior cruciate ligament surgery, prevalence of TKA was 0.75% at age 45 years, 9.10% at age 65 years, and 20.43% at age 80 years. Patients with prior cruciate ligament surgery were 4.6 times more likely to have undergone TKA by age 55 years than individuals without prior cruciate ligament surgery. In the cruciate ligament surgery cohort, BMI > 30 kg/m. 2. (odds ratio (OR) 4.01 (95% confidence interval (CI) 2.74 to 5.87)), a job that always involved heavy manual or physical labour (OR 2.72 (95% CI 1.57 to 4.71)), or a job that always involved walking and standing (OR 2.58 (95% CI 1.58 to 4.20)) were associated with greater TKA odds. No single-nucleotide polymorphism (SNP) was associated with risk of TKA following cruciate ligament surgery. Conclusion. Patients with a history of prior cruciate ligament surgery have substantially higher risk of TKA and undergo arthroplasty at a relatively younger age than individuals without a history of prior cruciate ligament surgery. Physically demanding work and obesity were associated with higher odds of TKA after cruciate ligament surgery, but no SNP was associated with risk of TKA. Cite this article: Bone Joint J 2024;106-B(3):249–255

Aims. The aim of this study was to determine the diagnostic utility of histological analysis in spinal biopsies for spondylodiscitis (SD). Patients and Methods. Clinical features, radiology, results of microbiology, histology, and laboratory investigations in 50 suspected SD patients were evaluated. In 29 patients, the final (i.e. treatment-based) diagnosis was pyogenic SD; in seven patients, the final diagnosis was mycobacterial SD. In pyogenic SD, the neutrophil polymorph (NP) infiltrate was scored semi-quantitatively by determining the mean number of NPs per (×400) high-power field (HPF). Results. Of the 29 pyogenic SD patients, 17 had positive microbiology and 21 positive histology (i.e. one or more NPs per HPF on average). All non-SD patients showed less than one NP per HPF. The presence of one or more NPs per HPF had a diagnostic sensitivity of 72.4%, specificity 100%, accuracy 100%, positive predictive value (PPV) 81.0%, and negative predictive value (NPV) 61.9%. Sensitivity, specificity, and accuracy were greater using the criterion of positive histology and/or microbiology than positive histology or microbiology alone. Granulomas were identified histologically in seven mycobacterial SD patients, and positive microbiology was detected in four. Conclusion. The diagnosis of pyogenic SD was more often confirmed by positive histology (one or more NPs per HPF on average) than by microbiology, although diagnostic sensitivity was greater when both histology and microbiology were positive. Cite this article: Bone Joint J 2019;101-B:246–252

Dupuytren’s disease is a benign fibroproliferative disease of unknown aetiology. It is often familial and commonly affects Northern European Caucasian men, but genetic studies have yet to identify the relevant genes. Transforming growth factor beta one (TGF-β1) is a multifunctional cytokine which plays a central role in wound healing and fibrosis. It stimulates the proliferation of fibroblasts and the deposition of extracellular matrix. Previous studies have implicated TGF-β1 in Dupuytren’s disease, suggesting that it may represent a candidate susceptibility gene for this condition. We have investigated the association of four common single nucleotide polymorphisms in TGF-β1 with the risk of developing Dupuytren’s disease. A polymerase chain reaction-restriction fragment length polymorphism method was used for genotyping TGF-β1 polymorphisms. DNA samples from 135 patients with Dupuytren’s disease and 200 control subjects were examined. There was no statistically significant difference in TGF-β1 genotype or allele frequency distributions between the patients and controls for the codons 10, 25, −509 and −800 polymorphisms. Our observations suggest that common TGF-β1 polymorphisms are not associated with a risk of developing Dupuytren’s disease. These data should be interpreted with caution since the lack of association was shown in only one series of patients with only known, common polymorphisms of TGF-β1. To our knowledge, this is the first report of a case-control association study in Dupuytren’s disease using single nucleotide polymorphisms in TGF-β1

We investigated the effect of vitamin D receptor gene (VDRG) polymorphism on the responsiveness to 1,25(OH). 2. D. 3. in human osteoblast-like cells. The cells were obtained from the femoral heads of 18 women with osteoarthritis of the hip. Three different restriction enzymes, BsmI, ApaI, and TaqI, were used to analyse the polymorphism. The genotypes of the 18 patients were bbAaTT (8), bbaaTT (6), BbAaTt (3), and BbAATt (1). Our findings showed that there were no differences according to the VDR genotype, but there was a statistically significant difference in the production of osteocalcin between BbAaTt and bbAaTT, and between BbAaTt and bbaaTT. Northern blot analysis of osteocalcin and VDR mRNA showed no significant differences among the three VDR genotypes. These findings suggest that VDR gene polymorphism affects the individual responsiveness of 1,25(OH). 2. D. 3.

Two collagen type IX gene polymorphisms that introduce a tryptophan residue into the protein’s triple-helical domain have been linked to an increased risk of lumbar disc disease. To determine whether a particular subset of symptomatic lumbar disease is specifically associated with these polymorphisms, we performed a prospective case-control study of 107 patients who underwent surgery of the lumbar spine. Patients were assigned to one of five clinical categories (fracture, disc degeneration, disc herniation, spinal stenosis without spondylolisthesis and spinal stenosis with spondylolisthesis) based on history, imaging results, and findings during surgery. Of the 11 tryptophan-positive patients, eight had spinal stenosis with spondylolisthesis and three had disc herniation. The presence of the tryptophan allele was significantly associated with African-American or Asian designation for race (odds ratio 4.61, 95% CI 0.63 to 25.35) and with the diagnosis of spinal stenosis with spondylolisthesis (odds ratio 6.81, 95% CI 1.47 to 41.95). Our findings indicate that tryptophan polymorphisms predispose carriers to the development of symptomatic spinal stenosis associated with spondylolisthesis which requires surgery

The role of heritable thrombophilic risk factors in the pathogenesis of the Perthes’ disease is controversial. The clinical and radiological findings of Perthes’ disease may be indistinguishable from those of Gaucher’s disease, and the most common Jewish N370S Gaucher mutation is threefold greater in patients with Perthes’ disease. Familial osteonecrosis of the femoral head is associated with variant mutations of collagen type II (COL2A1 mutations). We therefore studied the potential role of genetic thrombophilia and the Gaucher and COL2A1 mutations in children with Perthes’ disease. Genomic DNA of 119 children with radiologically-confirmed Perthes’ disease diagnosed between 1986 and 2005 was analysed for the thrombophilic polymorphisms Factor V Leiden, 677T-MTHFR and FIIG20210A. The results were compared with those of a group of 276 children without Perthes’ disease. DNA was also analysed for the Gaucher mutations N370S, G insertion (84GG), L444P, Intron 2 (IVS2+1G> A) and R496H. Enzymic assays confirmed the Gaucher disease status. Collagen (COL2A1) mutations of the 12q13 gene were also analysed. The prevalence of thrombophilic markers was similar among the 119 patients with Perthes’ disease and the 276 control subjects. The prevalence of the Gaucher mutation was consistent with Israeli population carriership data and did not confirm an earlier-claimed association with Perthes’ disease. All 199 patients were negative for the studied COL2A1 mutations. We found no genetic association between Perthes’ disease and either Gaucher’s disease or COL2A1 mutations or increased genetic thrombophilia among our patients compared with the control group. A systematic review of case-control studies suggested that there was a positive association between Perthes’ disease and Factor V Leiden. The impact of this association upon the disease, although not consistent across the studies, remains unclear

Periprosthetic joint infection (PJI) remains an extremely challenging complication. We have focused on this issue more over the last decade than previously, but there are still many unanswered questions. We now have a workable definition that everyone should align to, but we need to continue to focus on identifying the organisms involved. Surgical strategies are evolving and care is becoming more patient-centred. There are some good studies under way. There are, however, still numerous problems to resolve, and the challenge of PJI remains a major one for the orthopaedic community. This annotation provides some up-to-date thoughts about where we are, and the way forward. There is still scope for plenty of research in this area.

Cite this article: Bone Joint J 2022;104-B(11):1193–1195.

Aims

Accurate diagnosis of chronic periprosthetic joint infection (PJI) presents a significant challenge for hip surgeons. Preoperative diagnosis is not always easy to establish, making the intraoperative decision-making process crucial in deciding between one- and two-stage revision total hip arthroplasty (THA). Calprotectin is a promising point-of-care novel biomarker that has displayed high accuracy in detecting PJI. We aimed to evaluate the utility of intraoperative calprotectin lateral flow immunoassay (LFI) in THA patients with suspected chronic PJI.

Aims

The aims of this study were to determine the diagnostic yield of image-guided biopsy in providing a final diagnosis in patients with suspected infectious spondylodiscitis, to report the diagnostic accuracy of various microbiological tests and histological examinations in these patients, and to report the epidemiology of infectious spondylodiscitis from a country where tuberculosis (TB) is endemic, including the incidence of drug-resistant TB.

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.

We assessed the efficacy of intraoperative frozen-section histology in detecting infection in failed arthroplasties in 106 hips and knees. We found inflammatory changes consistent with infection (an average of one or more neutrophil polymorphs or plasma cells per high-power field in several samples) in 18 cases; there was a significant growth on bacterial culture in 20 cases. Compared with the bacterial cultures, the frozen sections provided two false-negative results and three false-positive results (sensitivity, 90%; specificity, 96%; and accuracy, 95%). The positive predictive value was 88%, the negative value, 98%. These results support the inclusion of intra-operative frozen-section histology in any protocol for revision arthroplasty for loose components

Heritable thrombophilic disorders have been proposed as one of the causes for Legg-Calvé-Perthes disease. A total of 62 patients diagnosed with this disease between 1988 and 1997 and 50 controls were screened for thrombophilia. The incidence and relationship of thrombophilia to the severity of the disease were evaluated. One patient and none of the controls had protein S deficiency. One of the control group and one of the patients had protein C deficiency with the latter child also having a combined deficiency with a mutant factor V gene. The number of children with a mutant factor V gene, protein C deficiency, who were homozygous for the C 677T polymorphism of methylenetetra-hydrofolate reductase or were heterozygous for mutant G20210A prothrombin did not differ statistically in the study and the control groups. No patient had antithrombin deficiency or positive lupus anticoagulant. We found no correlation between thrombophilia and the extent of the disease. The most common risk factors for arteriovenous thromboembolism showed no statistical significance in our patients compared with the control group or with the general population. These data do not confirm an aetiological role for thrombophilia in Perthes’ disease

Aims

The STRYDE nail is an evolution of the PRECICE Intramedullary Limb Lengthening System, with unique features regarding its composition. It is designed for load bearing throughout treatment in order to improve patient experience and outcomes and allow for simultaneous bilateral lower limb lengthening. The literature published to date is limited regarding outcomes and potential problems. We report on our early experience and raise awareness for the potential of adverse effects from this device.

Aims

The diagnosis of periprosthetic joint infection (PJI) can be difficult. All current diagnostic tests have problems with accuracy and interpretation of results. Many new tests have been proposed, but there is no consensus on the place of many of these in the diagnostic pathway. Previous attempts to develop a definition of PJI have not been universally accepted and there remains no reference standard definition.

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.

Aims

The aim of this study was to evaluate the diagnostic value of preoperative serum CRP, white blood cell count (WBC), percentage of neutrophils (%N), and neutrophil to lymphocyte ratio (NLR) when using the fracture-related infection (FRI) consensus definition.

Aims

This study aimed to investigate the role of quantitative histological analysis in the diagnosis of fracture-related infection (FRI).

Aims

Biopsy of the periprosthetic tissue is an important diagnostic tool for prosthetic joint infection (PJI) as it enables the detection of the responsible microorganism with its sensitivity to antibiotics. We aimed to investigate how often the bacteria identified in the tissue analysis differed between samples obtained from preoperative biopsy and intraoperative revision surgery in cases of late PJI; and whether there was a therapeutic consequence.