ObjectivesFor the non-vitamin-K oral anticoagulants, data on bleeding when used for 42 days as thromboprophylaxis after total knee arthroplasty (TKA) are scarce. This pilot study assessed feasibility of a multicentre randomised clinical trial to evaluate major and clinically relevant non-major bleeding during 42-day use of dabigatran, nadroparin and rivaroxaban after TKA.Patients and methodsIn 70 weeks, between July 2012 and November 2013, 198 TKA patients were screened for eligibility in the Martini Hospital (Groningen, the Netherlands). Patients were randomly assigned to dabigatran (n=45), nadroparin (n=45) or rivaroxaban (n=48). The primary outcome was the combined endpoint of major bleeding and clinically relevant non-major bleeding. Secondary endpoints of this study were the occurrence of clinical venous thromboembolism (VTE) (pulmonary embolism or deep venous thrombosis), compliance, duration of hospital stay, rehospitalisation, adverse events and Knee Injury and Osteoarthritis Outcome Score (KOOS).ResultsThe primary outcome was observed in 33.3% (95% CI 20.0% to 49.0%), 24.4% (95% CI 12.9% to 39.5%) and 27.1% (95% CI 15.3% to 41.8%) of patients who received dabigatran, nadroparin or rivaroxaban, respectively (p=0.67). Major bleeding was found in two patients who received nadroparin (p=0.21). Clinically relevant non-major bleeding was observed in 33.3% (95% CI 20.0% to 49.0%), 22.2% (95% CI 11.2% to 37.1%) and 27.1% (95% CI 15.3% to 41.8%) for dabigatran, nadroparin and rivaroxaban, respectively (p=0.51). Wound haematoma was the most observed bleeding event. VTE was found in one patient who received dabigatran (p=0.65). The presurgery and postsurgery KOOS qQuestionnaires were available for 32 (71%), 35 (77%) and 35 (73%) patients for dabigatran, nadroparin and rivaroxaban, respectively. KOOS was highly variable, and no significant difference between treatment groups in mean improvement was observed.ConclusionsA multicentre clinical trial may be feasible. However, investments will be substantial. No differences in major and clinically relevant non-major bleeding events were found between dabigatran, nadroparin and rivaroxaban during 42 days after TKA. KOOS may not be suitable to detect functional loss due to bleeding.Trial registration numberNCT01431456.

IntroductionTwo novel agents, dabigatran and rivaroxaban, recently gained market authorisation for prevention of venous thromboembolism (VTE) after hip and knee arthroplasty. However, safety data of the new oral anticoagulants with a long-term use of 42 days are not available for total knee arthroplasty (TKA). Furthermore, there are no clinical trials comparing dabigatran and/or rivaroxaban with nadroparin, which is used in most Dutch departments of orthopaedic surgery. Our aim is to compare the 42-day use of dabigatran and rivaroxaban versus nadroparin after TKA in a clinical explorative pilot study by assessing the incidence of major bleeding and clinically relevant non-major bleeding using a standardised model of bleeding definitions.Methods and analysisA randomised open-label pilot study was conducted. Patients ≥18 years and weighing more than 40 kg who were scheduled for a primary elective TKA were included. Patients were randomly assigned to three groups. Patients took either a daily oral dose of dabigatran etexilate 220 mg (n=50), 10 mg of oral rivaroxaban (n=50) or subcutaneous nadroparin 0.3 ml (n=50) for 42 days. The primary safety outcome measure was the incidence of bleeding events. Major bleeding events and clinically relevant non-major bleeding events were defined according to accepted guidelines. The secondary measures of this study were the occurrence of VTE, time until the bleeding event, compliance, duration of hospital stay, rehospitalisation, outpatient clinic visits and interventions following complications. Additionally, coagulation monitoring, knee flexion range of motion and Knee injury and Osteoarthritis Outcome Score were evaluated.DisseminationThe results of this trial provided insight into the validity of design for an adequately powered multicentre study investigating the safety of the new oral anticoagulants compared with nadroparin, an anticoagulant applied for prevention of VTE after knee arthroplasty in the Dutch situation.Trial registration numberClinicalTrials.gov: NCT01431456.

IntroductionTotal hip arthroplasty (THA) has proven to be an excellent treatment for treating osteoarthritis of the hip. Since Sir John Charnley, the metal-on-polyethylene (MoP) bearing has been the gold standard, outperforming 1st-generation metal-onmetal (MoM) THAs like the McKee THA. 1 However, polyethylene (PE) wear leading to particle-induced osteolysis and component loosening has been considered a drawback of the MoP articulation couple. Therefore, in the late 1980s, 2ndgeneration MoM bearings were developed, with improvements in fixation, metallurgy, sphericity and radial clearance. These new MoM designs showed promising wear performance, 2,3 but as there was a lack of comparative clinical trials, Pseudotumours, cobalt and clinical outcome in small head metal-on-metal versus conventional metal-on-polyethylene total hip arthroplasty Abstract Background: Metal-on-metal total hip arthroplasty (MoM THA) is associated with the formation of pseudotumours. Studies mainly concern pseudotumour formation in large head MoM THA. We performed a long-term follow-up study, comparing pseudotumour incidence in small head metal-on-metal (SHMoM) THA with conventional metal-onpolyethylene (MoP) THA. Predisposing factors to pseudotumour formation were assessed. Methods: From a previous randomised controlled trial comparing SHMoM (28 mm) cemented THA with conventional MoP cemented THA, patients were screened using a standardised CT protocol for the presence of pseudotumours. Serum cobalt levels and functional outcome were assessed. Results: 56 patients (33 MoP and 23 MoM) were recruited after mean follow-up of 13.4 years (SD 0.5). The incidence of pseudotumours was 1 (5%) in the SHMoM THA cohort and 3 (9%) in the MoP THA cohort. Prosthesis survival was 96% for both SHMoM and MoP THAs. Serum cobalt levels did not exceed acceptable clinical values (<5 µg/L) whereas no differences in cobalt levels were detected at follow-up between both groups. Oxford and Harris Hip Scores were good and did not differ between SHMoM and MoP THA. Conclusions: This long-term follow-up study shows a low incidence of pseudotumour formation and good functional outcome in cemented head-taper matched SHMoM and MoP THA.

Purpose: There are three main tissues remodeled as part of osteoarthritis (OA); cartilage, bone and the synovial membrane, which may represent separate phenotypes that needs to be treated differently. Recent data has shown that type II collagen degradation (CTX-II) is a biomarker of cartilage and subchondral turnover. C3M is a biomarker of synovial inflammation and turnover. It is estimated that about 10-30% of OA patients have synovitis. The aim of the study was identify different subtypes of OA related to progression. Methods: Fasting serum (n¼767) and urine (n¼620) samples were collected at baseline from patients with painful knee OA participating in the placebo arms of two phase III RCTs (NCT00486434 and NCT00704847). Serum C3M (MMP-derived type III collagen neo-epitope [Nordic Bioscience, Denmark]) and creatinine-corrected urinary CTX-II (type II collagen C-terminal telopeptide [IDS PLC, United Kingdom]) were measured. The relationship between the biomarkers and the 5 WOMAC pain subscale questions of the baseline-reported WOMAC pain level, using the sum of target and non-target knee, were analyzed: A; during walking on a flat surface, B; using stairs (up or down), C; at night while in bed, D; sitting or lying and E; while standing. Joint space width was analyzed at baseline and after 24 month. The data were analyzed by Spearman's correlations on log-transformed data and by backward multiple regression analysis, where WOMAC or radiographic scores were set as the dependent variable and biomarkers, age, gender and BMI as covariates. Results: Levels of CTX-II significantly correlated with WOMAC with all 5 sub-questions (p<0.01), while level of C3M was correlated with question B and E (p<0.05). When adjusting for age, BMI, and gender, CTX-II remained significantly associated with all sub-questions: A) r¼0.20, p<0.0001; B) r¼0.16, p¼0.0005; C) r¼0.11, p¼0.017; D) r¼0.13, p¼0.0046; and E) r¼0.17, p¼0.0002. C3M became non-significant; B) r¼0.08, p¼0.063 and E) r¼0.08, p¼0.069. CTX-II was significantly correlated to the mean JSW of the two knees (r¼-0.17, p<0.0001), whereas C3M was significantly correlated to joint space narrowing of the target knee (r¼0.11, p¼0.013). Conclusions: Diagnostically, urinary CTX-II was associated with all types of pain. Most prominent with WOMAC sub-question A, walking on a flat surface, which may indicate that CTX-II is related to pain coming from continuous skeletal load-supported by the strong correlation with JSW and previous data suggestion origins of subchondral bone turnover and articular cartilage. C3M, which are released in synovitis, was weakly correlated with B and E, using stairs and standing still, respectively. C3M was correlated to progression indicating that patients with elevated C3M and consequently synovial inflammation had a higher likelihood of being a progressor. These biomarkers may assist in identification of the inflammation driven OA phenotype, which needs to be treated different than non-inflammatory OA.

BackgroundAseptic loosening of total hip arthroplasties is generally caused by periprosthetic bone resorption due to tissue reactions on polyethylene wear particles. In vitro testing of polyethylene cups incorporated with vitamin E shows increased wear resistance. The objective of this study is to compare vitamin E-stabilized highly cross-linked polyethylene with conventional cross-linked polyethylene in “reversed hybrid” total hip arthroplasties (cemented all-polyethylene cups combined with uncemented femoral stems). We hypothesize that the adjunction of vitamin E leads to a decrease in polyethylene wear in the long-term. We also expect changes in bone mineral density, less osteolysis, equal functional scores and increased implant survival in polyethylene cemented cups incorporated with vitamin E in the long-term.DesignA double-blinded randomized controlled trial will be conducted. Patients to be included are aged under 70, suffer from non-inflammatory degenerative joint disease of the hip and are scheduled for a primary total hip arthroplasty. The study group will receive a reversed hybrid total hip arthroplasty with a vitamin E-stabilized highly cross-linked polyethylene cemented cup. The control group will receive a reversed hybrid total hip arthroplasty with a conventional cross-linked polyethylene cemented cup. Radiological follow-up will be assessed at 6 weeks and at 1, 3, 5, 7 and 10 years postoperatively, to determine polyethylene wear and osteolysis. Patient-reported functional status (HOOS), physician-reported functional status (Harris Hip Score) and patients’ physical activity behavior (SQUASH) will also be assessed at these intervals. Acetabular bone mineral density will be assessed by dual energy X-ray absorptiometry (DEXA) at 6 weeks and at 1 year and 2 years postoperatively. Implant survival will be determined at 10 years postoperatively.DiscussionIn vitro results of vitamin E-stabilized polyethylene are promising, showing increased wear resistance. However, controlled clinical follow-up data are not available at this moment.This randomized controlled trial has been designed to determine wear, bone mineral density, functional outcome and survival in reversed hybrid total hip arthroplasty comparing cemented vitamin E-stabilized highly cross-linked polyethylene cups with cemented conventional cross-linked polyethylene cups.Trial registrationDutch Trial Registry NTR3049