Introduction and Objective. Evidence in literature is contradicting regarding outcomes of total knee arthroplasty (TKA) in post-traumatic osteoarthritis (PTOA) and whether they are inferior to TKA in primary osteoarthritis (OA). The aim of this review was to find out if any difference exists in the results of TKA between the two indications. Materials and Methods. The electronic databases MEDLINE, EMBASE, The Cochrane Collaboration, and PubMed were searched and screened in duplicate for relevant studies. The selected studies were further subjected to quality assessment using the modified Coleman method. The primary outcome measure was patient reported outcome, and secondary outcome measures were infection, revision, stiffness, and patella tendon rupture. Results. A total of 18 studies involved 1129 patients with a mean age of 60.6 years (range 45.7–69) and follow up of 6.3 years. The time interval from index injury to TKA was 9.1 years. Knee Society Score (KSS) in PTOA reported in 12/18 studies showed functional improvement from 42.5 to 70 post-TKA exceeding minimally clinically important difference. In TKA for primary OA vs PTOA, deep peri-prosthetic joint infection (PJI) was reported in 1.9% vs 5.4% of patients, whilst revision of prosthesis at an average of 6 years post-operatively was performed in 2.6 vs 9.7% of patients. Conclusions. TKA is a successful treatment option for PTOA. However, the risk of significant complications like PJI and implant failure requiring revision is higher than primary OA cases. Patients should be counselled about those risks. Further well-designed comparative cohort-matched studies are needed to compare outcomes between the two populations

Osteoarthritis (OA) is a prevalent, age-related joint disease, characterized by diverse progressive changes in articular cartilage and subchondral bone. Disease management is severely hampered by the absence of tools to classify patients based on underlying disease mechanisms. For that matter, increased BMI is a known risk factor for OA in the weight bearing knee joint, but also for hand OA. 1. The increased risk for OA is therefore thought to be influenced by systemic factors accompanying BMI. It was hypothesized that differences in metabolic state could be underlying OA phenotypes. In the current study we set out to explore the potential role of a large range of metabolites in blood as sensitive biomarker of OA. Plasma samples were taken from the Rotterdam Study, CHECK-, GARP/NORREF- and the LUMC-arthroplasty cohorts. OA was defined as having had arthroplasty for primary OA, stratified per location (any, hip or knee). In total 647 persons with Total Joint Arthroplasty (TJA) were included and 2125 persons were considered as controls (i.e. they had a Kellgrenn-Lawrence Score of <2 indicating no radiographic OA was present) in any of the studied joints. A total of 231 different metabolites were assessed by using the BrainShake NMR platform. Since parts of the metabolites were highly correlated, we used Principal Component Analyses (PCA) to reduce the data. 23 factors were identified, accounting for 91,4% of the variance in the data. Logistic regression models were applied to investigate the identified factors for their association to arthroplasty for primary OA, independent of age, sex, BMI and cholesterol-lowering medication (statins). The models showed two different factors robustly associated to arthroplasty as result of primary OA. A table represents the associations of these factors to arthroplasty adjusted for age, sex and BMI, as the information on statin-use was not known for all subjects. Analyses showed that additional correction for statins did not change the results. When stratifying the arthroplasty phenotypes for joint location, factor 11, characterized by e.g. linoleic acid, was found to be associated to arthroplasty in the hip (THA). Similarly, Factor 22, representing saturated fatty acids and degree of unsaturation, was consistently associated with arthroplasty, independent of the site. When analyzing the metabolites involved in the factors individually these associations were confirmed for most contributors of the factors, except the ratio of saturated fatty acids to total fatty acids. Our preliminary analyses showed that persons with arthroplasty for primary OA compared to controls have different values for factors composed for fatty acids. The identification of groups of fatty acid metabolites as being connected to OA phenotypes indicates an inflammation driven pathway which might give a better understanding of the mechanisms behind OA

Introduction and Objective. Osteonecrosis of the femoral head (ONFH) is an evolving and disabling condition that often leads to subchondral collapse in late stages. It is the underlying diagnosis for approximately 3%–12% of total hip arthroplasties (THAs) and the most frequent aetiology for young patients undergoing THA. To date, the pathophysiological mechanisms underlying ONFH remain poorly understood. In this study, we investigated whether ONFH without an obvious etiological factor is related to impaired osteoblast activities, as compared to age-matched patients with primary OA. Materials and Methods. We cultured osteoblasts isolated from trabecular bone explants taken from the femoral head of patients with ONFH and from intertrochanteric region of patients with ONFH or with OA and compared their in vitro mineralisation capacity and secretion of paracrine factors. Results. Compared to patients with OA, osteoblasts obtained from the intertrochanteric region of patients with ONFH showed reduced mineralisation capacity, which further decreased in osteoblasts from the femoral head of the same patient. Lower mineralisation of osteoblasts from patients with ONFH correlated with lower mRNA levels of genes encoding osteocalcin and bone sialoprotein and higher osteopontin expression. Osteoblasts from the intertrochanteric region of patients with ONFH secreted lower osteoprtegerin levels than those from patients with OA, resulting in a higher receptor activator of NF-κB ligand (RANKL)-to-osteoprotegerin (OPG) ratio. Notably, the RANKL-to-OPG ratio, as well as the secretion of the proresorptive factors interleukin-6 and prostaglandin E. 2. , was higher in osteoblasts from the femoral head of patients with ONFH than in those from the intertrochanteric region. Conclusions. ONFH is associated with a reduced mineralisation capacity of osteoblasts and increased secretion of proresorptive factors

Repeat revision hip replacements can lead to severe bone loss necessitating salvage procedures such as proximal or total femoral replacement. We present medium term outcomes from our experience of the Limb Preservation System (LPS) in patients with failed revision hip arthroplasties. All patients undergoing proximal femoral or total femoral replacement from 2003–2007 at our unit were reviewed. Data was collected preoperatively and at annual assessment post procedure for a minimum of 5 years. This included clinical review, functional outcome scores (WOMAC, Oxford Hip Score, Harris Hip Score) and radiographic evaluation. A total of 17 patients underwent femoral replacement (13 proximal, 4 total) using the LPS during the study period. Within this cohort there were 13 males and 4 females with a mean age of 64 years (range 47–86). Median follow up was 7 years (range 5–9 years). Primary diagnoses were DDH (7), Primary OA (5), RA (2), proximal femoral fracture (2) and phocomelia (1). Five patients (29%) required further revision surgery for infection (2 patients) or recurrent dislocations (3 patients). No stems required revision due to aseptic loosening or stem failure at 5–9 years. Compared to preoperative assessment, there was significant improvement in median outcome scores at 5 years (WOMAC increased by 33 points, Oxford hip score by16 points and Harris hip score by 43 points). 82% of patients maintained functional independence at latest review. The Limb Preservation System offers a salvage procedure for failed revision total hip arthroplasty with significant symptom and functional improvement in most patients at medium term follow up

The Trident acetabular system is the second most common cementless cup implanted in the UK. Recent studies have shown that malseating of the liner can be as high as 16.4%. We felt this was very high and were prompted to review our series and early clinical outcomes. We reviewed 118 hips in 110 patients, implanted between from 2005-2007. We reviewed initial post operative X-rays using the technique described by Howcroft to identify malseating. The posterior approach was used in all cases. All cups were Trident PSL and all 85 Patients had OA, 10 RA, 8 AVN, 5 DDH, 3 OA post trauma, 2 Perthes, 2 Psoriatic Arthritis, 3 other. We only identified 3 malseated cups in 118 hips. 2 were in patients with OA secondary to trauma and 1 in primary OA. The rate of malseating for trainees operating was 5 % and only 1% when consultants were operating. There were no adverse events in these patients. No-one required revision. Oxford Hip Score (OHS) improved from 47 pre-op to 20 post op. This was compared to 47 and 22 in the correctly seated group (115 cases). Surprisingly the subgroup with the poorest OHS at 1 year had surgery for DDH, with a mean OHS of 31. The reasons for this are unclear. Contrary to other studies our malseating rate is very low. We do not feel that malseating is a problem with Trident if adequate exposure is obtained. In those patients with sclerotic bone, we suggest over reaming the rim of the acetabulum by 1mm to avoid excess deformation of the shell which may lead to difficulty with seating the liner. We suggest trainees are supervised closely when using Trident

Summary. PCA-III, a phosphocitrate analog, acts not only as a potent calcification inhibitor but also as a protective agent for extracellular matrices. PCA-III has potential as a disease-modifying drug in the treatment of primary osteoarthritis and posttraumatic osteoarthritis in humans. Introduction. Phosphocitrate (PC) inhibits the development of primary osteoarthritis (OA) in Hartley guineas pigs but not menisectomy-induced OA in rabbits (1). We sought to examine the molecular mechanisms underlying the disease-modifying activity of PC, and evaluate the effect of PCA-III, a PC analog (PCA), on the development of primary and secondary OA. Patients & Methods. Meniscal explant and microarray. OA menisci were obtained from OA patients undergoing joint replacement surgery. OA meniscal explants were cultured in medium containing PC (three wells) and medium without PC (three wells). Total RNA was extracted from the explant, and subjected to microarray analysis. RT-PCR. OA fibroblast-like synoviocytes were treated with basic calcium phosphate (BCP) crystals in the absence or presence of PCA-III. RNAs were extracted, and subjected to semi-quantitative RT-PCR to examine the expression of MMP1 and IL-1b. Micromass culture. A droplet of OA chondrocyte suspension was placed in each well of a 24-well plate. After placing all droplets, the wells were fed with chondrogenesis medium with PCA-III (five wells) and without PCA-III (five wells). The production of proteoglycans was examined by alcian blue staining. Animal treatment. The first group of Hartley guinea pigs (n=5) received injections of PCA-III and the second group received injections of saline as control. Two months later, partial-menisectomy surgery was performed on the right knee of all guinea pigs. After the surgery, injections of PCA-III and saline were resumed. All animal were euthanatised four months later, and both knees were examined. Results. PC inhibited the expression of many genes classified into the molecular function group of MMP activity. Of the 23 genes classified into MMP activity, the expression of 16 genes, including CPM, ADAM28, MMP7, MMP10, MMP1, MMP3, ADAMTS5, ADAMTS1, and ADAMTS9, was inhibited. In contrast, the expression of many genes classified into the molecular function group of extracellular matrix structural constituents, was induced by PC, including COL2A1, COL11A1, COL1A1 and ACAN. PC also inhibited the expression of numerous genes classified into the biological process of inflammatory response (data not shown). PCA-III, similar to PC, inhibited BCP crystals-induced expression of MMP1 and IL-1b). In addition, PC-III strongly stimulated the production of proteoglycans by OA chondrocytes while inhibiting calcium deposition (not shown). Microscopic examination of the Indian ink stained medial tibia plateau of the left knees (non-surgery knee) of the guinea pigs indicated that PCA-III inhibited the development of primary OA in the Hartley guinea pigs. Microscopic examination also indicated that PCA-III inhibited the development of partial-menisectomy-induced OA or posttraumatic OA in the post-operative knees. Discussion/Conclusion. PC is thought to act as a potential structural disease-modifying drug for crystal-associated OA by inhibiting crystal deposition within the OA joints. However, PC and its analogs are not only potent calcification inhibitors, but also protective agents for extracellular matrices. Our findings indicate that PCA-III has potential as a disease-modifying drug for both human crystal-associated OA and posttraumatic OA

In uncemented total hip arthroplasty (THA), the optimal femoral component should allow both maximum cortical contact with proximal load transfer and accurate restoration of individual joint biomechanics. This is often compromised due to a high variability in proximal femoral anatomy. The aim of this on-going study is to assess the variation in proximal femoral canal shape and its association with geometric and anthropometric parameters in primary hip OA. In a retrospective cohort study, AP-pelvis radiographs of 98 consecutive patients (42 males, 56 females, mean age 61 (range:45-74) years, BMI 27.4 (range:20.3-44.6) kg/m2) who underwent THA for primary hip OA were reviewed. All radiographs were calibrated and femoral offset (FO) and neck-shaft-angle (NSA) were measured using a validated custom programme. Point-based active shape modelling (ASM) was performed to assess the shape of the inner cortex of the proximal femoral meta- and diaphysis. Independent shape modes were identified using principal component analysis (PCA). Hierarchical cluster analysis of the shape modes was performed to identify natural groupings of patients. Differences in geometric measures of the proximal femur (FO, NSA) and demographic parameters (age, height, weight, BMI) between the clusters were evaluated using Kruskal-Wallis one-way-ANOVA or Chi-square tests, as appropriate. In the entire cohort, mean FO was 39.0 mm, mean NSA was 131 degrees. PCA identified 10 independent shape modes accounting for over 90% of variation in proximal femoral canal shape within the dataset. Cluster Analysis revealed 6 shape clusters for which all 10 shape modes demonstrated a significantly different distribution (p-range:0.000-0.015). We observed significant differences in age (p=0.032), FO (p<0.001) and NSA (p<0.001) between the clusters. No significant differences with regard to gender or BMI were seen. Our preliminary analysis has identified 6 different patterns of proximal femoral canal shape which are associated with significant differences in femoral offset, neck-shaft-angle and age at time of surgery. We are currently evaluating the entire dataset of 345 patients which will allow a comprehensive classification of variation in proximal femoral shape and joint geometry. The present data may optimise preoperative planning and improve future implant design in THA

TRIM32 is a candidate gene at the 9q33.1 genetic susceptibility locus for hip osteoarthritis (OA). Increased cartilage degradation typical of OA has previously been demonstrated in Trim32 knockout mice. Our aim is to investigate the role of TRIM32 in human and murine articular tissue. TRIM32 expression in human articular cartilage was examined by immunostaining. TRIM32 expression was compared in femoral head chondrocytes from patients with and without primary hip OA (n=6/group) and examined by Western blotting. Aggrecanolysis by femoral head explants from Trim32 knockout (T32KO) and wild-type (WT) mice was compared following stimulation with IL1α or retinoic acid (RA) and was assessed by DMMB assay (n=4/group). Expression of chondrocyte phenotype markers was measured by qPCR and compared between articular chondrocytes from WT and T32KO mice following catabolic (IL1α/TNFα) or anabolic (Oncostatin-M (OSM)/IGF1) stimulation. TRIM32 expression was demonstrated in human articular cartilage; TRIM32 expression by chondrocytes was reduced in patients with hip OA (p=0.03). Greater aggrecanolysis occurred in cartilage explants from T32KO mice after treatment with no stimulation (p=0.03), IL1α (p=0.02), and RA (p=0.001). Unstimulated T32KO chondrocytes expressed reduced Col2a1 (p=8.53×10. −5. ), and Sox9 (p=2.35×10. −6. ). Upon IL1α treatment, T32KO chondrocytes expressed increased Col10a1 (p=0.0003). Upon anabolic stimulation, T32KO chondrocytes expressed increased Col2a1 (OSM: p=0.001; IGF: p=0.001), and reduced Sox9 (OSM: p=0.0002; IGF: p=0.0006). These results indicate that altered TRIM32 expression in human articular tissue is associated with OA, and that Trim32 knockout results in increased cartilage degradation in murine femoral head explants. Predisposition to cartilage degeneration with reduced Trim32 expression may involve increased chondrocyte hypertrophy upon catabolic cytokine stimulation and dysregulation of Col2a1 and Sox9 expression upon anabolic stimulation

Aim

Osteoarthritis (OA) is caused by complex interactions between genetic and environmental factors. Epigenetic mechanisms control the expression of genes and are likely to regulate the OA transcriptome. We performed integrative genomic analyses to define methylation-gene expression relationships in osteoarthritic cartilage.

Objectives

This study looked to analyse the expression levels of microRNA-140-3p and microRNA-140-5p in synovial fluid, and their correlations to the severity of disease regarding knee osteoarthritis (OA).

Objectives

To define Patient Acceptable Symptom State (PASS) thresholds for the Oxford hip score (OHS) and Oxford knee score (OKS) at mid-term follow-up.

There is no diagnostic, non-invasive method for the early detection of loosening after total hip arthroplasty. In a pilot study, we have analysed two serum markers of bone remodelling, procollagen I C-terminal extension peptide (PICP) and cross-linked N-terminal telopeptide (NTx), as well as the diagnostic performance of NTx for the assessment of osteolysis. We recruited 21 patients with loosening (group I), 18 with a well-fixed prosthesis (group II) and 17 at the time of primary arthroplasty for osteoarthritis (OA) (group III). Internal normal reference ranges were obtained from 30 healthy subjects (group IV).

The serum PICP level was found to be significantly lower in patients with OA and those with loosening, when compared with those with stable implants, while the NTx level was significantly increased only in the group with loosening, suggesting that collagen degradation depended on the altered bone turnover induced by the implant. This hypothesis was reinforced by the finding that the values in the pre-surgery patients and stable subjects were comparable with the reference range of younger healthy subjects.

A high specificity and positive predictive value for NTx provided good diagnostic evidence of agreement between the test and the clinical and radiological evaluations. The NTx level could be used to indicate stability of the implant. However, further prospective, larger studies are necessary.