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.

Abstract. Introduction. Adverse reactions to pain medication and pain can delay discharge after outpatient knee arthroplasty (TKA). Pharmacogenomics is an emerging tool that might help reduce adverse events by tailoring medication use based on known genetic variations in the CYP genes determining drug metabolism. This study was undertaken to evaluate whether pre-operative pharmacogenomic testing could optimize peri-operative pain management in patients undergoing total knee arthroplasty (TKA). Methods. This prospective, randomized study was performed in adults undergoing primary TKA. Patients in the experimental group underwent pre-operative pharmacogenomic evaluation and medication adjustments. Medications were not optimized for control patients. The Overall Benefit of Analgesic Score (OBAS) at 24 hours post-op was the primary outcome. Postoperative pain scores (VAS scale), total opioid use, time in recovery, and time to discharge were also compared. Results. 76 patients enrolled. 93% of patients had a poor-intermediate phenotype for at least one of four CYP genes. OBAS did not differ significantly between the two groups (4.2 control vs. 4.7 experimental; 95% CI −1.1 to 2.1) and was below the minimum clinically important difference of 2.0 points. Furthermore, there were no differences in any OBAS subscale including pain, satisfaction, or nausea. There were no differences in time in the recovery area or to discharge from hospital, or narcotic use. Conclusions. Despite many patients having a poor-intermediate phenotype for a CYP gene, pharmacogenomic testing prior to TKA and medication adjustment did not improve anesthesia or pain management outcomes, time to discharge or mean total opioid use after surgery

Aims. Lumbar spinal stenosis (LSS) is a common skeletal system disease that has been partly attributed to genetic variation. However, the correlation between genetic variation and pathological changes in LSS is insufficient, and it is difficult to provide a reference for the early diagnosis and treatment of the disease. Methods. We conducted a transcriptome-wide association study (TWAS) of spinal canal stenosis by integrating genome-wide association study summary statistics (including 661 cases and 178,065 controls) derived from Biobank Japan, and pre-computed gene expression weights of skeletal muscle and whole blood implemented in FUSION software. To verify the TWAS results, the candidate genes were furthered compared with messenger RNA (mRNA) expression profiles of LSS to screen for common genes. Finally, Metascape software was used to perform enrichment analysis of the candidate genes and common genes. Results. TWAS identified 295 genes with permutation p-values < 0.05 for skeletal muscle and 79 genes associated for the whole blood, such as RCHY1 (PTWAS = 0.001). Those genes were enriched in 112 gene ontology (GO) terms and five Kyoto Encyclopedia of Genes and Genomes pathways, such as ‘chemical carcinogenesis - reactive oxygen species’ (LogP value = −2.139). Further comparing the TWAS significant genes with the differentially expressed genes identified by mRNA expression profiles of LSS found 18 overlapped genes, such as interleukin 15 receptor subunit alpha (IL15RA) (PTWAS = 0.040, PmRNA = 0.010). Moreover, 71 common GO terms were detected for the enrichment results of TWAS and mRNA expression profiles, such as negative regulation of cell differentiation (LogP value = −2.811). Conclusion. This study revealed the genetic mechanism behind the pathological changes in LSS, and may provide novel insights for the early diagnosis and intervention of LSS. Cite this article: Bone Joint Res 2023;12(6):387–396

The February 2023 Research Roundup³⁶⁰ looks at: Clinical and epidemiological features of scaphoid fracture nonunion; Routine sterile glove and instrument change at the time of abdominal wound closure to prevent surgical site infection (ChEETAh); Characterization of genetic risk of end-stage knee osteoarthritis treated with total knee arthroplasty; Platelet-rich plasma or autologous blood injection for plantar fasciitis; Volume and outcomes of joint arthroplasty; The hazards of absolute belief in the p-value laid bare.

Aims

Degenerative cervical spondylosis (DCS) is a common musculoskeletal disease that encompasses a wide range of progressive degenerative changes and affects all components of the cervical spine. DCS imposes very large social and economic burdens. However, its genetic basis remains elusive.

Aims

Osteoarthritis (OA) is a common degenerative joint disease worldwide, which is characterized by articular cartilage lesions. With more understanding of the disease, OA is considered to be a disorder of the whole joint. However, molecular communication within and between tissues during the disease process is still unclear. In this study, we used transcriptome data to reveal crosstalk between different tissues in OA.

Aims

We aimed to develop a gene signature that predicts the occurrence of postmenopausal osteoporosis (PMOP) by studying its genetic mechanism.

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.

Aims

This study investigated the effects of β-caryophyllene (BCP) on protecting bone from vitamin D deficiency in mice fed on a diet either lacking (D-) or containing (D+) vitamin D.

Aims. Deciphering the genetic relationships between major depressive disorder (MDD) and osteoarthritis (OA) may facilitate an understanding of their biological mechanisms, as well as inform more effective treatment regimens. We aim to investigate the mechanisms underlying relationships between MDD and OA in the context of common genetic variations. Methods. Linkage disequilibrium score regression was used to test the genetic correlation between MDD and OA. Polygenic analysis was performed to estimate shared genetic variations between the two diseases. Two-sample bidirectional Mendelian randomization analysis was used to investigate causal relationships between MDD and OA. Genomic loci shared between MDD and OA were identified using cross-trait meta-analysis. Fine-mapping of transcriptome-wide associations was used to prioritize putatively causal genes for the two diseases. Results. MDD has a significant genetic correlation with OA (r. g. = 0.29) and the two diseases share a considerable proportion of causal variants. Mendelian randomization analysis indicates that genetic liability to MDD has a causal effect on OA (b. xy. = 0.24) and genetic liability to OA conferred a causal effect on MDD (b. xy. = 0.20). Cross-trait meta-analyses identified 29 shared genomic loci between MDD and OA. Together with fine-mapping of transcriptome-wide association signals, our results suggest that Estrogen Receptor 1 (ESR1), SRY-Box Transcription Factor 5 (SOX5), and Glutathione Peroxidase 1 (GPX1) may have therapeutic implications for both MDD and OA. Conclusion. The study reveals substantial shared genetic liability between MDD and OA, which may confer risk for one another. Our findings provide a novel insight into phenotypic relationships between MDD and OA. Cite this article: Bone Joint Res 2022;11(1):12–22

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.

Evidence suggests that the alleviation of pain is enhancedby a strong patient-clinician relationship and attending to a patient’s social and mental health. There is a limited role for medication, opioids in particular.

Orthopaedic surgeons can use comprehensive biopsychosocial strategies to help people recover and can work with colleagues who have the appropriate expertise in order to maximize pain alleviation with optimal opioid stewardship.

Preparing patients for elective surgery and caring for them after unplanned injury or surgery can benefit from planned and practiced strategies based in communication science.

Cite this article: Bone Joint J 2020;102-B(9):1122–1127.

The coronavirus disease 2019 (COVID-19) pandemic has led to unprecedented challenges to healthcare systems worldwide. Orthopaedic departments have adopted business continuity models and guidelines for essential and non-essential surgeries to preserve hospital resources as well as protect patients and staff. These guidelines broadly encompass reduction of ambulatory care with a move towards telemedicine, redeployment of orthopaedic surgeons/residents to the frontline battle against COVID-19, continuation of education and research through web-based means, and cancellation of non-essential elective procedures. However, if containment of COVID-19 community spread is achieved, resumption of elective orthopaedic procedures and transition plans to return to normalcy must be considered for orthopaedic departments. The COVID-19 pandemic also presents a moral dilemma to the orthopaedic surgeon considering elective procedures. What is the best treatment for our patients and how does the fear of COVID-19 influence the risk-benefit discussion during a pandemic? Surgeons must deliberate the fine balance between elective surgery for a patient’s wellbeing versus risks to the operating team and utilization of precious hospital resources. Attrition of healthcare workers or Orthopaedic surgeons from restarting elective procedures prematurely or in an unsafe manner may render us ill-equipped to handle the second wave of infections. This highlights the need to develop effective screening protocols or preoperative COVID-19 testing before elective procedures in high-risk, elderly individuals with comorbidities. Alternatively, high-risk individuals should be postponed until the risk of nosocomial COVID-19 infection is minimal. In addition, given the higher mortality and perioperative morbidity of patients with COVID-19 undergoing surgery, the decision to operate must be carefully deliberated. As we ramp-up elective services and get “back to business” as orthopaedic surgeons, we have to be constantly mindful to proceed in a cautious and calibrated fashion, delivering the best care, while maintaining utmost vigilance to prevent the resurgence of COVID-19 during this critical transition period.

Cite this article: Bone Joint Open 2020;1-6:222–228.

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.

Introduction. Pharmacogenetics evaluates a patient's DNA to determine if a particular drug is expected to have a normal clinical effect, heightened effect, or no effect at all on a patient. It may also predict which patients are most likely to experience side effects from the medications. The purpose of this study was to use pharmacogenetic testing to determine how frequently total knee arthroplasty (TKA) patients have genetic variants to standard postoperative pain medications. We further sought to determine if changing the multimodal program based on these results would improve pain control and reduce side effects. Methods. In this prospective, randomized study, buccal cheek swab samples were collected from 31 primary TKA patients. Pharmacogenetics testing was performed on the samples to examine genetic variants in genes OPRM1, CYP1A2, CYP2B6, CYP2C19, CYP3A4, CYP2C9, and CYP2D6. These genes affect the pharmacodynamics and pharmacokinetics of NSAIDs and opioids. We examined the frequency of a genetic variant to one of the multimodal medications we prescribe including celecoxib, hydrocodone, and tramadol. Subjects included 9 men and 22 women. Patients were randomized to one of two groups: the control group received the standard postoperative pain regimen; the study group received a customized regimen based on the pharmacogenetic results. For the first 10 postoperative days patients recorded pain scores, amount of pain medication taken, and any side effects experienced. Results. Genetic variations to one or more medications in our standard postoperative pain management protocol occurred in 13 of the 31 patients (42%). 8 patients (26%) had a variation of gene CYP2C9 affecting celecoxib. 11 patients (35%) had a variation of gene OPRM1 and/or CYP2D6 affecting the response to hydrocodone. 4 patients (13%) had a variation of gene CYP2D6 that altered their response to tramadol. Of the 31 patients tested, only 18 (58%) had no genetic variants related to the pain medications we routinely prescribe. 8 patients (26%) had variants affecting more than one of the medications. (Table 1, below) Both the average pain levels and morphine equivalents consumed in the first 10 days were higher in the control group than in the study group. Conclusion. 42% of patients in this study demonstrated a pharmacogenetic variant to one of the commonly used multimodal pain medications. Our early data suggests that customizing pain regimens based on this information can help reduce pain and the amount of pain medication used postoperatively. For figures, tables, or references, please contact authors directly

Objectives

We have previously investigated an association between the genome copy number variation (CNV) and acetabular dysplasia (AD). Hip osteoarthritis is associated with a genetic polymorphism in the aspartic acid repeat in the N-terminal region of the asporin (ASPN) gene; therefore, the present study aimed to investigate whether the CNV of ASPN is involved in the pathogenesis of AD.

Toll-like receptors (TLRs) are crucial components of the immune system that recognize microbial infection and trigger anti-microbial host defense responses. Gram positive bacteria are causative factors of bone infections, as they alter the balance of coordinated activities during bone remodeling, stimulating osteoclastogenesis. The aim of the study was to investigate whether genetic variation in TLR2 and TLR4 genes predisposes to bone infections’ susceptibility. One hundred and twenty patients with bone infections (osteomyelitis) and 200 healthy controls were genotyped for two single nucleotide polymorphisms (SNPs), R753Q [A/G] in TLR2 gene and T399I [C/T] in TLR4 gene. DNA was extracted from whole blood and the above SNPs were typed with PCR-RFLP (Polymerase Chain Reaction- Restriction Fragment Length Polymorphism) method for genotype identification. All patients were infected by Gram-positive bacteria, predominantly Staphylococcus aureus. Statistical analysis was carried out using the chi-square test. We observed a significantly increased frequency in patients carrying the GA genotype of TLR2 R753Q polymorphism compared to controls (p<0.05). We also found that the A allele was more common in patients than in controls. All individuals carrying the A allele were heterozygous for this variant, while homozygous mutant individuals were not detected in the patients and the control group. In contrast, we found that the TLR4 T399I [C/T] SNP was similarly distributed among the two groups (patients and controls). The mechanism through which TLR2 mediates its effect in bone infections is under investigation. A significant difference was observed in the genotype frequency of TLR2 R753Q [A/G] polymorphism in patients, suggesting that genetic variability in TLR2 gene may be associated with susceptibility to osteomyelitis in response to bacterial invasion in the bone