ObjectivesTo identify metabolic markers that can classify patients with osteoarthritis (OA) into subgroups.DesignA case-only study design was utilised.ParticipantsPatients were recruited from those who underwent total knee or hip replacement surgery due to primary OA between November 2011 and December 2013 in St. Clare's Mercy Hospital and Health Science Centre General Hospital in St. John's, capital of Newfoundland and Labrador (NL), Canada. 38 men and 42 women were included in the study. The mean age was 65.2±8.7 years.Outcome measuresSynovial fluid samples were collected at the time of their joint surgeries. Metabolic profiling was performed on the synovial fluid samples by the targeted metabolomics approach, and various analytic methods were utilised to identify metabolic markers for classifying subgroups of patients with OA. Potential confounders such as age, sex, body mass index (BMI) and comorbidities were considered in the analysis.ResultsTwo distinct patient groups, A and B, were clearly identified in the 80 patients with OA. Patients in group A had a significantly higher concentration on 37 of 39 acylcarnitines, but the free carnitine was significantly lower in their synovial fluids than in those of patients in group B. The latter group was further subdivided into two subgroups, that is, B1 and B2. The corresponding metabolites that contributed to the grouping were 86 metabolites including 75 glycerophospholipids (6 lysophosphatidylcholines, 69 phosphatidylcholines), 9 sphingolipids, 1 biogenic amine and 1 acylcarnitine. The grouping was not associated with any known confounders including age, sex, BMI and comorbidities. The possible biological processes involved in these clusters are carnitine, lipid and collagen metabolism, respectively.ConclusionsThe study demonstrated that OA consists of metabolically distinct subgroups. Identification of these distinct subgroups will help to unravel the pathogenesis and develop targeted therapies for OA.

Arginine is significantly depleted in refractory knee OA patients. Further studies within a longitudinal setting are required to examine whether arginine can predict early OA changes.

We identified the ratio of lysoPCs to PCs as a novel metabolic marker for predicting advanced knee OA. Further studies are required to examine whether this ratio can predict early OA change.

Background Although Lisfranc injuries are uncommon, representing approximately 0.2% of all fractures, they are complex and can result in persistent pain, degenerative arthritis, and loss of function. Both open reduction and internal fixation (ORIF) and primary fusion have been proposed as treatment options for these injuries, but debate remains as to which approach is better. Questions/purposes We asked whether ORIF or primary fusion led to (1) fewer reoperations for hardware removal; (2) less frequent revision surgery; (3) higher patient outcome scores; and (4) more frequent anatomic reduction. Methods A systematic review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Three trials met the criteria for inclusion within the meta-analysis. Qualifying articles for the meta-analysis had data extracted independently by two authors (NS, AF). The quality of each study was assessed using the Center for Evidence Based Medicine's evaluation strategy; data were extracted from articles rated as good and fair: two and one article, respectively. Results The risk ratio for hardware removal was 0.23 (95% confidence interval [CI], 0.11-0.45; p \ 0.001) indicating more hardware removal for ORIF than fusion. For other revision surgery, the risk ratio for ORIF was 0.36 (95% CI, 0.08-1.59; p = 0.18) favoring neither. Similarly, neither was favored using patient-reported outcomes; the standard mean difference was calculated to be 0.50 (95% CI, À2.13 to 3.12; p = 0.71). When considering the risk of nonanatomic alignment, neither was favored (risk ratio, 1.48; 95% CI, p = 0.60). Conclusions The surgeon should consider the increased risk of hardware removal along with its associated morbidity and discuss this with the patient preoperatively when considering ORIF of Lisfranc injuries. Because no new trials have been performed since 2012, further randomized controlled trials will be needed improve our understanding of these interventions. Level of Evidence Level I, therapeutic study.

BackgroundEvidence suggests that epigenetics plays a role in osteoarthrits (OA). The aim of the study was to describethe genome wide DNA methylation changes in hip and knee OA and identify novel genes and pathwaysinvolved in OA by comparing the DNA methylome of the hip and knee osteoarthritic cartilage tissues withthose of OA-free individuals.MethodsCartilage samples were collected from hip or knee joint replacement patients either due to primary OA or hip fractures as controls. DNA was extracted from the collected cartilage and assayed by Illumina Infinium HumanMethylation450 BeadChip array, which allows for the analysis of >480,000 CpG sites. Student T-test was conducted for each CpG site and those sites with at least 10 % methylation difference and a p value <0.0005 were defined as differentially methylated regions (DMRs) for OA. A sub-analysis was also done for hip and knee OA separately. DAVID v6.7 was used for the functional annotation clustering of the DMR genes. Clustering analysis was done using multiple dimensional scaling and hierarchical clustering methods.ResultsThe study included 5 patients with hip OA, 6 patients with knee OA and 7 hip cartilage samples from OA-free individuals. The comparisons of hip, knee and combined hip/knee OA patients with controls resulted in 26, 72, and 103 DMRs, respectively. The comparison between hip and knee OA revealed 67 DMRs. The overall number of the sites after considering the overlaps was 239, among which 151 sites were annotated to 145 genes. One-fifth of these genes were reported in previous studies. The functional annotation clustering of the identified genes revealed clusters significantly enriched in skeletal system morphogenesis and development. The analysis revealed significant difference among OA and OA-free cartilage, but less different between hip OA and knee OA.ConclusionsWe found that a number of CpG sites and genes across the genome were differentially methylated in OA patients, a remarkable portion of which seem to be involved in potential etiologic mechanisms of OA. Genes involved in skeletal developmental pathways and embryonic organ morphogenesis may be a potential area for further OA studies.Electronic supplementary materialThe online version of this article (doi:10.1186/s12891-015-0745-5) contains supplementary material, which is available to authorized users.