Objectives. Previous genome-wide association studies (GWAS) have reported significant association of the single nucleotide polymorphism (SNP) rs8044769 in the fat mass and obesity-associated gene (FTO) with osteoarthritis (OA) risk in European populations. However, these findings have not been confirmed in Chinese populations. Methods. We systematically genotyped rs8044769 and evaluated the association between the genetic variants and OA risk in a case-controlled study including 196 OA cases and 442 controls in a northern Chinese population. Genotyping was performed using the Sequenom MassARRAY iPLEX platform. Results. We found that the variant T allele of rs8044769 showed no significant association of OA risk (p = 0.791), or association with body mass index (BMI) (pmeta = 0.786) in an additive genetic model. However, we detected a significant interaction between rs8044769 genotypes and BMI on OA risk (p = 0.037), as well as a borderline interaction between rs8044769 genotypes and age on OA risk (p = 0.062). Conclusions. Our findings indicate that rs8044769 in the FTO gene may not modify individual susceptibility to OA or increased BMI in the Chinese population. Further studies are warranted to validate and extend our findings. Cite this article: Prof L. Jiang. No association of the single nucleotide polymorphism rs8044769 in the fat mass and obesity-associated gene with knee osteoarthritis risk and body mass index: A population-based study in China. Bone Joint Res 2016;5:169–174. DOI: 10.1302/2046-3758.55.2000589

Objectives. Degenerative disc disease (DDD) and osteoarthritis (OA) are relatively frequent causes of disability amongst the elderly; they constitute serious socioeconomic costs and significantly impair quality of life. Previous studies to date have found that aggrecan variable number of tandem repeats (VNTR) contributes both to DDD and OA. However, current data are not consistent across studies. The purpose of this study was to evaluate systematically the relationship between aggrecan VNTR, and DDD and/or OA. Methods. This study used a highly sensitive search strategy to identify all published studies related to the relationship between aggrecan VNTR and both DDD and OA in multiple databases from January 1996 to December 2016. All identified studies were systematically evaluated using specific inclusion and exclusion criteria. Cochrane methodology was also applied to the results of this study. Results. The final selection of seven studies was comprehensively evaluated and includes results for 2928 alleles. The most frequent allele among all the studies was allele 27. After comparing the distributions of each allele with others, statistically significant differences have been found in the distribution of the alleles by the two groups, with an over-representation of allele (A)21 (disease: 3.22%, control: 0.44%). Thus, carrying A21 increased the risk of DDD. Such an association was not found to be statistically significant when considering the risk of OA. Conclusions. The findings suggest that VNTR A21 seems to be associated with higher risk to DDD, however, such an association may not be statistically significant regarding the risk of OA. Cite this article: L. Cong, G. Tu, D. Liang. A systematic review of the relationship between the distributions of aggrecan gene VNTR polymorphism and degenerative disc disease/osteoarthritis. Bone Joint Res 2018;7:308–317. DOI: 10.1302/2046-3758.74.BJR-2017-0207.R1

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

The aetiology and pathophysiology of non-union is still unclear, but in this condition there is an abnormal bone metabolism. The paracrine matrix RAS has been implicated in the regulation of bone remodeling and injury responses, possibly via its effects on kinins. The influence of the local RAS or the genetic influence of the ACE/ BK2R genes to bone remodelling may thus be central to the disorder, or augmented in these conditions. We thus compared the distribution of the ACE I/D and BK2R “+9/-9” functional polymorphisms in patients with non-union and compared them to appropriate control. Gene analysis was performed on buccal cells collected from all subjects and the data was analysed for 59 patients (46 males, 13 females; mean age 40.1±15.7 years) with non-union and 81 control subjects (49 males, 32 females; mean age 51.4±22.81 years. The overall genotype distribution was consistent with Hardy-Wein-berg equilibrium for the overall and individual groups for ACE (p0.16), B1BKR (p0.68) and B2BKR genotypes (p0.12). As the -9 allele is associated with greater gene transcription and higher mRNA expression of the receptor we combined the -9/-9 homozygous and -9/+9 heterozygous groups and compared them with the homozygous +9/+9 groups. This showed a significant difference between the non-union and control groups, with the +9/+9 homozygous being less prominent in the former (p=0.03). The B2BKR -9 allele is associated with the incidence of non-union in fracture healing, in this first study to address this question. We found no association with either the ACE I/D or B1BKR genotypes. In conclusion, with previous findings that the absence of the -9 allele of the B2BKR +9/-9 polymorphism is associated with greater gene transcription and higher mRNA expression of the receptor our findings are suggestive that increased BK activity via the B2BKR may predispose to the development of non-union

Objectives

Excessive acetabular coverage is the most common cause of pincer-type femoroacetabular impingement. To date, an association between acetabular over-coverage and genetic variations has not been studied. In this study we investigated the association between single nucleotide polymorphisms (SNPs) of paralogous Homeobox (HOX)9 genes and acetabular coverage in Japanese individuals to identify a possible genetic variation associated with acetabular over-coverage.

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. 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

Objectives. Given the function of adiponectin (ADIPOQ) on the inflammatory condition of obesity and osteoarthritis (OA), we hypothesized that the ADIPOQ gene might be a candidate gene for a marker of susceptibility to OA. Methods. We systematically screened three tagging polymorphisms (rs182052, rs2082940 and rs6773957) in the ADIPOQ gene, and evaluated the association between the genetic variants and OA risk in a case-controlled study that included 196 OA patients and 442 controls in a northern Chinese population. Genotyping was performed using the Sequenom MassARRAY iPLEX platform. Results. The single nucleotide polymorphism (SNP) rs182052 was found to be potentially associated with knee OA risk (additive model: odds ratio = 1.38; 95% confidence interval 1.07 to 1.76; p = 0.012). Furthermore, a non-significant association was observed for rs182052 and body mass index with regard to OA risk in interaction analyses (p = 0.063). Similarly, no significant interaction was detected for rs182052 and age with regard to OA risk (p = 0.614). Conclusion. These findings suggest that the SNP rs182052 in the ADIPOQ gene may potentially modify individual susceptibility to knee OA in the Chinese population. Further studies are warranted to investigate our findings in more depth. Cite this article: L. Jiang, X. Zhu, J. Rong, B. Xing, S. Wang, A. Liu, M. Chu, G. Huang. Obesity, osteoarthritis and genetic risk: The rs182052 polymorphism in the ADIPOQ gene is potentially associated with risk of knee osteoarthritis. Bone Joint Res 2018;7:494–500. DOI: 10.1302/2046-3758.77.BJR-2017-0274.R1

Aim. Periprosthetic joint infection (PJI) is one of the most serious and frequent complications in prosthetic surgery. Despite significant improvements in the criteria for diagnosis of PJI, the diagnostic workflow remains complex and, sometimes, inconclusive. Host immune factors hold great potential as diagnostic biomarkers in bone and joint infections. We have recently reported that the synovial concentration of the humoral pattern recognition molecule long pentraxin 3 (PTX3) is a sensitive and specific marker of PJI in total hip and knee arthroplasty patients (THA and TKA) undergoing revision surgery [1]. However, the contribution to risk and diagnosis of PJI of the genetic variation in PTX3 and inflammatory genes that are known to affect its expression (IL-1b, IL-6, IL-10, and IL-17A) has not been addressed. Therefore, we assessed these relationships in a cohort of THA and TKA patients who underwent prosthesis revision by focusing on a panel of single nucleotide polymorphisms (SNPs) in the PTX3, IL-1β, IL-6, IL-10 and IL-17A genes. Method. A case-control retrospective study was conducted on an historic cohort of patients that received THA or TKA revision and were diagnosed with PJI (cases) or aseptic complications (controls) [1]. Samples of saliva were collected from 93 subjects and used for extraction of genomic DNA to perform genotyping of the PTX3, IL-1β, IL-6, IL-10 and IL-17A polymorphisms. Moreover, whenever available, samples of synovial fluid and plasma [1] were used to measure the concentration of the IL-1β, IL-10, and IL-6 proteins by immunoassay. Uni-and multivariate analyses were performed to evaluate the relationships between genetic, biochemical, and clinical variables. Results. The rs3024491 (IL-10) and rs2853550 (IL-1b) SNPs were found to be strongly associated with the risk of PJI. The synovial levels of PTX3, IL-1β, IL-10, and IL-6 were higher in cases than in controls, and a clear correlation emerged between the synovial concentration of PTX3 and IL-1b in cases only. Also, we identified a causal relationship between rs2853550, synovial concentration of IL-1b and that of PTX3 (that is induced by IL-1b). Conclusions. Our findings suggest that SNPs in the IL-10 and IL-1b genes could be used for early identification of THA and TKA patients with high risk of PJI. It is therefore conceivable that integrating genetic data into current diagnostic criteria would improve diagnosis of PJI

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

Aim. Unexpected negative-cultures (UNC) are a common diagnostic problem in periprosthetic joint infection (PJI) of the hip and knee when using culture-based methods. A novel molecular approach (MC)1 based on the identification of the vast majority of bacterial species in a single assay using species-specific bacterial interspacing region length polymorphisms and phylum-specific 16S rDNA sequence polymorphisms has demonstrated clinical utility in PJI diagnostics (1). In addition, MC provides an estimate of the leukocyte concentration in the specimen analysed. The aim of this retrospective, blinded study was to evaluate the performance of MC in identifying the microbiological content and determining the leukocyte count in synovial fluid (SF) collected from hip and knee revision arthroplasty cases with UNC. It was also assessed whether antibiotic treatment would have been changed if the result from MC had been known. Method. A total of 89 SF samples from 70 patients (43 female; 27 male) who underwent revision arthroplasty (14 hip; 75 knee) were included. Using European and Bone Joint Infection Society (EBJIS) criteria, 82 cases were classified as infected (77 UNC and 5 septic culture-positive controls), five as non-infected (aseptic culture-negative controls), and two as likely infected, but infected by clinical observation. MC was performed and evaluated together with SF parameters. Antibiotic treatment, clinical outcome, patient demographics and surgical details were analysed. Results. Overall, 29.1% (23/79) of UNC had a positive yield by MC, of which 2/23 (8.7%) had two microorganisms detected simultaneously. Of the 25 microorganisms identified by MC, 12/25 (48%) were clinically relevant after re-evaluation of the patients’ microbiological history. The microorganisms detected were 5/25 (20%) Streptococcus pneumoniae/mitis, 4/25 (16%) Staphylococcus epidermidis, 3/25 (12%) Cutibacterium acnes, 3/25 (12%) Streptococcus agalactiae, 2/25 (8%) Streptococcus bovis, 2/25 (8%) Staphylococcus aureus, and 2/25 (8%) Haemophilus parainfluenzae. The prevalence of Enterococcus faecalis, Bacteroides fragillis, Staphylococcus lugdunensis, Corynebacterium striatum among all MC results was 1/25 (4%) each species. In total, 13/23 (56%) cases were associated with patients receiving antibiotic therapy at the time of SF collection. The yield for leukocyte counts provided the molecular technique was consistently much higher in the UNC and clearly septic groups than in the clearly aseptic group. Overall, 20/61 (32.8%) patients with UNC could have been managed differently and more accurately after MC assessment. Conclusions. MC shows clinical value in the diagnosis and management of PJI with UNC. The included leukocyte count shows promising results. Acknowledgments. This work was partially funded by Inbiome

Aim. Previous studies had indicated that interleukin-1 beta (IL-1β) gene single nucleotide polymorphisms (SNPs) associate with different inflammatory diseases. However, potential links between these polymorphisms and susceptibility to extremity chronic osteomyelitis (COM) in Chinese population remain unclear. This study aimed to investigate relationships between IL-1β gene polymorphisms (rs16944, rs1143627, rs1143634 and rs2853550) and the risk of developing extremity COM in Chinese population. Method. Altogether 233 extremity COM patients and 200 healthy controls were genotyped for the four tag SNPs of the IL-1β gene using the SNapShot genotyping method. Comparisons were performed regarding genotype distribution, mutant allele frequency and four genetic models (dominant, recessive, homozygous and heterozygous models) of the 4 SNPs between the two groups. Results. Significant associations were identified between rs16944 polymorphism and the risk of developing COM by dominant model (P = 0.026, OR = 1.698, 95% CI 1.065–2.707) and heterozygous model (P = 0.030, OR = 1.733, 95% CI 1.055 – 2.847). Although no statistical differences were found of rs1143627 polymorphism between the two groups, there existed a trend that rs1143627 may be linked to an elevated risk of developing COM by outcomes of dominant (P = 0.061), homozygous (P = 0.080) and heterozygous (P = 0.095) models. However, no statistical correlations were found between rs1143634 and rs2853550 polymorphisms and susceptibility to COM in Chinese population. Conclusions. To our knowledge, we reported for the first time that IL-1β gene rs16944 polymorphism may contribute to the increased susceptibility to extremity COM in Chinese population, with genotype of AG as a risk factor

Aims. The aim of this study was to screen the entire genome for genetic markers associated with risk for anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) injury. Methods. Genome-wide association (GWA) analyses were performed using data from the Kaiser Permanente Research Board (KPRB) and the UK Biobank. ACL and PCL injury cases were identified based on electronic health records from KPRB and the UK Biobank. GWA analyses from both cohorts were tested for ACL and PCL injury using a logistic regression model adjusting for sex, height, weight, age at enrolment, and race/ethnicity using allele counts for single nucleotide polymorphisms (SNPs). The data from the two GWA studies were combined in a meta-analysis. Candidate genes previously reported to show an association with ACL injury in athletes were also tested for association from the meta-analysis data from the KPRB and the UK Biobank GWA studies. Results. There was a total of 2,214 cases of ACL and PCL injury and 519,869 controls within the two cohorts, with three loci demonstrating a genome-wide significant association in the meta-analysis: INHBA, AEBP2, and LOC101927869. Of the eight candidate genes previously studied in the literature, six were present in the current dataset, and only COL3A1 (rs1800255) showed a significant association (p = 0.006). Conclusion. Genetic markers in three novel loci in this study and one previously-studied candidate gene were identified as potential risk factors for ACL and PCL injury and deserve further validation and investigation of molecular mechanisms. Cite this article: Bone Jt Open 2021;2(6):414–421

Aim. Previous studies have indicated that TNF-α and lymphotoxin-α (LTA) gene polymorphisms associate with the development of several different inflammatory diseases. However, potential associations of such gene polymorphisms with the susceptibility to extremity chronic osteomyelitis remain unknown. This study aimed to investigate potential links between TNF-α gene polymorphisms (rs1800629, rs361525, rs1799964, rs1800630, rs1799724 and rs1800750) and LTA gene polymorphism (rs909253) and the risk of developing extremity chronic osteomyelitis in Chinese population. Method. A total of 233 patients with extremity chronic osteomyelitis and 200 healthy controls were genotyped for the above 7 polymorphisms of TNF-α and LTA genes using the genotyping method*. Results. Significant difference was found regarding the genotype distribution of rs909253 between patients and healthy controls (P = 0.002). The mutant allele C frequency of rs909253 in patient group was significantly higher than that in control group (P = 0.001). Significant associations were identified between rs909253 and the risk of developing chronic osteomyelitis by dominant model (P = 0.040), recessive model (P = 0.002) and homozygous model (P = 0.001). Additionally, the mutant allele T frequency in rs1799964 in patient group was significantly higher than that in control group (P = 0.035). Significant link was found between rs1799964 and susceptibility to chronic osteomyelitis by recessive model (P = 0.048). However, no significant outcomes were identified regarding other TNF-α gene polymorphisms between the two groups. Conclusions. The present study demonstrated that rs909253 and rs1799964 polymorphisms may associate with the risk of developing chronic osteomyelitis in Chinese population. *SNaPshot

Aims. Despite the interest in the association of gut microbiota with bone health, limited population-based studies of gut microbiota and bone mineral density (BMD) have been made. Our aim is to explore the possible association between gut microbiota and BMD. Methods. A total of 3,321 independent loci of gut microbiota were used to calculate the individual polygenic risk score (PRS) for 114 gut microbiota-related traits. The individual genotype data were obtained from UK Biobank cohort. Linear regressions were then conducted to evaluate the possible association of gut microbiota with L1-L4 BMD (n = 4,070), total BMD (n = 4,056), and femur total BMD (n = 4,054), respectively. PLINK 2.0 was used to detect the single-nucleotide polymorphism (SNP) × gut microbiota interaction effect on the risks of L1-L4 BMD, total BMD, and femur total BMD, respectively. Results. We detected five, three, and seven candidate gut microbiota-related traits for L1-L4 BMD, total BMD, and femur BMD, respectively, such as genus Dialister (p = 0.004) for L1-L4 BMD, and genus Eisenbergiella (p = 0.046) for total BMD. We also detected two common gut microbiota-related traits shared by L1-L4 BMD, total BMD, and femur total BMD, including genus Escherichia Shigella and genus Lactococcus. Interaction analysis of BMD detected several genes that interacted with gut microbiota, such as phospholipase D1 (PLD1) and endomucin (EMCN) interacting with genus Dialister in total BMD, and COL12A1 and Discs Large MAGUK Scaffold Protein 2 (DLG2) interacting with genus Lactococcus in femur BMD. Conclusion. Our results suggest associations between gut microbiota and BMD, which will be helpful to further explore the regulation mechanism and intervention gut microbiota of BMD. Cite this article: Bone Joint Res 2021;10(11):734–741

Aim. Cyclooxygenase-2 (COX-2) enzyme is one of the major mediators during inflammation reactions, and COX-2 gene polymorphisms of rs20417 and rs689466 have been reported to be associated with several inflammatory diseases. However, potential links between the two polymorphisms and risk of developing post-traumatic osteomyelitis remain unclear. The present study aimed to investigate associations between the rs20417 and rs689466 polymorphisms and susceptibility to post-traumatic osteomyelitis in Chinese population. Methods. A total of 189 patients with definite diagnosis of post-traumatic osteomyelitis and 220 healthy controls were genotyped for rs20417 and rs689466 using the genotyping method*. Chi-square test was used to compare differences of genotype distributions as well as outcomes of five different genetic models between the two groups. Results. Significant association was found between rs689466 and post-traumatic osteomyelitis by recessive model (GG vs. AA + AG) (OR = 1.74, 95% CI: 1.098–2.755, P =0.018). Although no statistical differences were identified of rs689466 between the two groups by allele model (P = .098) or homozygous model (P = 0.084), outcomes revealed a tendency that allele G may be a risk factor and people of GG genotype may be in a higher risk to develop post-traumatic osteomyelitis in Chinese population. However, no significant link was found between rs20417 and susceptibility to post-traumatic osteomyelitis in this Chinese cohort. Conclusions. To our knowledge, we reported for the first time that COX-2 gene polymorphism rs689466 may contribute to the increased susceptibility to post-traumatic osteomyelitis in Chinese population. *SNaPshot®

Aims: As inflammation plays a key role in the etiology of intervertebral disc degeneration, we suggest a possible contribution of pro-inflammatory gene polymorphisms in the pathogenesis of adolescent idiopathic scoliosis (AIS). The nucleus pulposus of scoliotic discs responds to exogenous stimuli by secreting interleukin-6 (IL-6) and other inflammatory cytokines. The association between matrix metalloproteinases (MMPs) and disc degeneration has been reported by several investigators. A human MMP-3 promoter 5A/6A gene polymorphism regulates MMP-3 genes expression, while the G/C polymorphism of the promoter region of IL-6 gene influences levels and functional activity of the IL-6 protein. Methods: We conducted a case-control study to investigate whether the 5A/6A polymorphism of the MMP-3 gene and the G/C polymorphism of the promoter region of IL-6 gene were associated with susceptibility to AIS. Results: The frequency of the 5A/5A genotype of MMP-3 gene polymorphism in patients with scoliosis was almost 3 times higher than in controls (30.2 % vs 11.2 %, p 0.001) and the frequency of the G/G genotype of IL-6 gene polymorphism in patients with scoliosis was almost 2 times higher than in controls (52.8 % vs 26.2 %, p < 0.001). 5A/5A genotype of MMP-3 gene polymorphism and G/G genotype of IL-6 gene polymorphism are independently associated with an higher risk of scoliosis (odds ratio respectively 3.34 and 10.54). Conclusions: This is the first study that has evaluated the possibility that gene variants of IL-6 and MMPs might be associated with scoliosis and suggests that MMP-3 and IL-6 promoter polymorphisms constitute important factors for the genetic predisposition to scoliosis

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. Methods. Chinese patients with OP were recruited between March 2011 and December 2015 from our hospital. In this study, a total of 1267 post-menopausal female patients (631 OP patients and 636 control patients) were selected. The mean age of all subjects was 69.2 years (sd 15.8). A generalized multifactor dimensionality reduction (GMDR) model and logistic regression model were used to examine the interaction between SNP and obesity on OP. For OP patient-control haplotype analyses, the SHEsis online haplotype analysis software (. http://analysis.bio-x.cn/. ) was employed. Results. The logistic regression model revealed that the C allele of rs2501431 and the G allele of rs3003336 were associated with increased OP risk, compared with those with wild genotype. However, no significant correlations were found when analyzing the association of rs4237 and rs2229579 with OP risk. The GMDR analysis suggested that the interaction model composed of two factors, rs3003336 and abdominal obesity (AO), was the best model with statistical significance (p-value from sign test (P. sign. ) = 0.012), indicating a potential gene-environment interaction between rs3003336 and AO. Overall, the two-locus models had a cross-validation consistency of 10/10 and had a testing accuracy of 0.641. Abdominally obese subjects with the AG or GG genotype have the highest OP risk, compared with subjects with the AA genotype and normal waist circumference (WC) (odds ratio (OR) 2.23, 95% confidence interval (CI) 1.54 to 3.51). Haplotype analysis also indicated that the haplotype containing the rs3003336-G and rs2501431-C alleles was associated with a statistically increased OP risk. Conclusion. Our results suggested that the C allele of rs2501431 and the G allele of rs3003336 of the CNR2 gene, interaction between rs3003336 and AO, and the haplotype containing the rs3003336-G and rs2501431-C alleles were all associated with increased OP risk. Cite this article: Bone Joint Res 2019;8:544–549

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

Introduction and Hypothesis: Genetic studies of osteoporosis have analysed single polymorphisms in individual genes with inconclusive results. An alternative approach may involve haplotypes and gene-gene interactions. The aim of the study was to test the association between COLlAl, ESRl, VDR and TGFBl polymorphisms or haplotypes and BMD in Spanish postmeno-pausal women. Methods: Sixteen polymorphisms were analysed in 719 postmenopausal women. ANOV A, ANCOV A and Xi2 tests were used to perform the statistical analysis. Results: COLlAl -1997G> T (p=0.04) and TGFBl Leu10Pro (p=0.02) were found to be associated with adjusted lumbar spine BMD (LS BMD). Interactions were observed between: the C0LlAl -1997 Grr and Sp1 polymorphisms (p< 0.0l for LS BMD); and the COLlAl 1663 indelT and VDR ApaI polymorphisms (p< 0.0l for FN BMD). The COLlAl GDs and ESRl LPX haplotypes were associated with FN BMD (p=0.03 and p=0.03). Conclusion: Polymorphisms at COLlAl and TGFBl and haplotypes at COLlAl and ESRl were associated with BMD in a cohort of postmenopausal Spanish women. Moreover, COLlAl polymorphisms showed significant interactions among them and with the VDR 3’ pol ymorphisms