High failure rate but promising clinical performance after implantation of a flexible medial meniscus prosthesis at 1-year follow-up.

PURPOSE: After unsatisfactory results in a first-in-human clinical investigation with an anatomically shaped medial meniscus prosthesis, the prosthesis and its fixation technique were altered. This interim analysis of a prospective single-arm clinical investigation aims to evaluate safety and clinical performance in a first-in-human study with the redesigned meniscus prosthesis system. METHODS: Ten patients suffering from medial postmeniscectomy pain syndrome were treated with the meniscus prosthesis. Patient-reported outcome measures were obtained at baseline and at 6-week, 3-, 6-, and 12-month follow-up. Radiographs and magnetic resonance imaging scans were obtained to evaluate joint degeneration and prosthesis location. RESULTS: The device alterations resolved the issues occurring with the previous design, but four prostheses were explanted after fixation failure or subluxation of the prosthesis. Five out of six patients who reached 1-year follow-up reported a clinically significant improvement of the knee injury and osteoarthritis outcome score pain subscale. Imaging revealed no adverse effects on joint degeneration. CONCLUSION: The failure mechanisms that occurred with the previous design have been resolved, but the new fixation technique introduced new safety issues. Improvement of positioning and fixation techniques are considered essential future adaptations to reduce the risk of failure. The good clinical outcomes reported by the patients reaching 1-year follow-up indicate that the medial meniscus prosthesis is a potential solution for patients suffering from postmeniscectomy pain syndrome. LEVEL OF EVIDENCE: Level II.

Sample preparation for lipid analysis of intra-articular adipose tissue by using matrix-assisted laser desorption/ionization imaging.

Mass spectrometry imaging (MSI) is a powerful technique enabling the visualization of the spatial distribution of different molecules in tissue biopsies with different pathologies. Sample handling and preparing adipose tissue for MSI is challenging and prone to molecular delocalization due to tissue melting. In this work, we developed a method for matrix-assisted laser desorption/ionization (MALDI)-MSI to study lipids in human infrapatellar fat pad (IPFP), a biomarker source in musculoskeletal pathologies, while preserving molecular spatial distribution. Cryosectioning at 15 µm with a temperature below -30 °C, thaw-mounting, and sublimation, was demonstrated to preserve IPFP's heterogeneous appearance and spatial distribution of lipids.

Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) reveals potential lipid markers between infrapatellar fat pad biopsies of osteoarthritis and cartilage defect patients.

The incidence of osteoarthritis (OA) has been expected to increase due to an aging population, as well as an increased incidence of intra-articular (osteo-) chondral damage. Lipids have already been shown to be involved in the inflammatory process of OA. This study aims at revealing region-specific lipid profiles of the infrapatellar fat pad (IPFP) of OA or cartilage defect patients by matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), which could be used as biomarkers for early OA detection. A higher presence of phospholipids was found in OA patients compared with cartilage defect patients. In addition, a higher abundance of ether-linked phosphatidylethanolamines (PE O-s) containing arachidonic acid was specifically found in OA patients compared with cartilage defect patients. These lipids were mainly found in the connective tissue of the IPFP. Specific lipid species were associated to OA patients compared with cartilage defect patients. PE O-s have been suggested as possible biomarkers for OA. As these were found more abundantly in the connective tissue, the IPFP's intra-tissue heterogeneity might play an important role in biomarker discovery, implying that the amount of fibrous tissue is associated with OA.

The preferred technique for knee synovium biopsy and synovial fluid arthrocentesis.

For knee osteoarthritis and related conditions, analysis of biomarkers hold promise to improve early diagnosis and/or offer patient-specific treatment. To compare biomarker analyses, reliable, high-quality biopsies are needed. The aim of this work is to summarize the literature on the current best practices of biopsy of the synovium and synovial fluid arthrocentesis. Therefore, PubMed, Embase and Web of Science were systematically searched for articles that applied, demonstrated, or evaluated synovial biopsies or arthrocentesis. Expert recommendations and applications were summarized, and evidence for superiority of techniques was evaluated. Thirty-one studies were identified for inclusion. For arthrocentesis, the superolateral approach in a supine position, with a 0°-30° knee flexion was generally recommended. 18-gage needles, mechanical compression and ultrasound-guidance were found to give superior results. For blind and image-guided synovial biopsy techniques, superolateral and infrapatellar approaches were recommended. Single-handed tools were preconized, including Parker-Pearson needles and forceps. Sample quantity ranged approximately from 2 to 20. Suggestions were compiled for arthrocentesis regarding approach portal and patient position. Further evidence regarding needle size, ultrasound-guidance and mechanical compression were found. More comparative studies are needed before evidence-based protocols can be developed.

High degree of consensus amongst an expert panel regarding focal resurfacing of chondral and osteochondral lesions of the femur with mini-implants.

INTRODUCTION: The rationale for the use of mini-implants for partial resurfacing in the treatment of femoral chondral and osteochondral lesions is still under debate. The evidence supporting best practise guidelines is based on studies with low-level evidence. A consensus group of experts was convened to collaboratively advance towards consensus opinions regarding the best available evidence. The purpose of this article is to report the resulting consensus statements. METHODS: Twenty-five experts participated in a process based on the Delphi method of achieving consensus. Questions and statements were drafted via an online survey of two rounds, for initial agreement and comments on the proposed statements. An in-person meeting between the panellists was organised during the 2022 ESSKA congress to further discuss and debate each of the statements. A final agreement was made via a final online survey a few days later. The strength of consensus was characterised as: consensus, 51-74% agreement; strong consensus, 75-99% agreement; unanimous, 100% agreement. RESULTS: Statements were developed in the fields of patient assessment and indications, surgical considerations and postoperative care. Between the 25 statements that were discussed by this working group, 18 achieved unanimous, whilst 7 strong consensus. CONCLUSION: The consensus statements, derived from experts in the field, represent guidelines to assist clinicians in decision-making for the appropriate use of mini-implants for partial resurfacing in the treatment of femoral chondral and osteochondral lesions. LEVEL OF EVIDENCE: Level V.

Heterogeneity of Lipid and Protein Cartilage Profiles Associated with Human Osteoarthritis with or without Type 2 Diabetes Mellitus.

Osteoarthritis (OA) is a multifactorial pathology and comprises a wide range of distinct phenotypes. In this context, the characterization of the different molecular profiles associated with each phenotype can improve the classification of OA. In particular, OA can coexist with type 2 diabetes mellitus (T2DM). This study investigates lipidomic and proteomic differences between human OA/T2DM- and OA/T2DM+ cartilage through a multimodal mass spectrometry approach. Human cartilage samples were obtained after total knee replacement from OA/T2DM- and OA/T2DM+ patients. Label-free proteomics was employed to study differences in protein abundance and matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) for spatially resolved-lipid analysis. Label-free proteomic analysis showed differences between OA/T2DM- and OA/T2DM+ phenotypes in several metabolic pathways such as lipid regulation. Interestingly, phospholipase A2 protein was found increased within the OA/T2DM+ cohort. In addition, MALDI-MSI experiments revealed that phosphatidylcholine and sphingomyelin species were characteristic of the OA/T2DM- group, whereas lysolipids were more characteristic of the OA/T2DM+ phenotype. The data also pointed out differences in phospholipid content between superficial and deep layers of the cartilage. Our study shows distinctively different lipid and protein profiles between OA/T2DM- and OA/T2DM+ human cartilage, demonstrating the importance of subclassification of the OA disease for better personalized treatments.

Mass Spectrometry-based Biomarkers for Knee Osteoarthritis: A Systematic Review.

INTRODUCTION: Knee osteoarthritis (OA) is a joint disease, affecting multiple tissues in the joint. Early detection and intervention may delay OA development and avoid total knee arthroplasty. Specific biomarker profiles for early detection and guiding clinical decision-making of OA have not yet been identified. One technique that can contribute to the finding of this 'OA biomarker' is mass spectrometry (MS), which offers the possibility to analyze different molecules in tissues or fluids. Several proteomic, lipidomic, metabolomic and other - omic approaches aim to identify these molecular profiles; however, variation in methods and techniques complicate the finding of promising candidate biomarkers. AREAS COVERED: In this systematic review, we aim to provide an overview of molecules in knee OA patients. Possible biomarkers in several tissue types of OA and non-OA patients, as well as current limitations and possible future suggestions will be discussed. EXPERT OPINION: According to this review, we do not believe one specific biomarker will function as predictive molecule for OA. Likely, a group of molecules will give insight in OA development and possible therapeutic targets. For clinical implementation of MS-analysis in clinical decision-making, standardized procedures, large cohort studies and sharing protocols and data is necessary.

A White Paper on Collagen Hydrolyzates and Ultrahydrolyzates: Potential Supplements to Support Joint Health in Osteoarthritis?

PURPOSE OF REVIEW: Osteoarthritis (OA) is the most common forms of arthritis in the general population, accounting for more pain and functional disability than any other musculoskeletal disease. There are currently no approved disease modifying drugs for OA. In the absence of effective pharmacotherapy, many patients with OA turn to nutritional supplements and nutraceuticals, including collagen derivatives. Collagen hydrolyzates and ultrahydrolyzates are terms used to describe collagens that have been broken down into small peptides and amino acids in the presence of collagenases and high pressure. RECENT FINDINGS: This article reviews the relevant literature and serves as a White Paper on collagen hydrolyzates and ultrahydrolyzates as emerging supplements often advertised to support joint health in OA. Collagen hydrolyzates have demonstrated some evidence of efficacy in a handful of small scale clinical trials, but their ability to treat and reverse advanced joint disease remains highly speculative, as is the case for other nutritional supplements. The aim of this White Paper is to stimulate research and development of collagen-based supplements for patients with OA and other musculoskeletal diseases at academic and industrial levels. This White Paper does not make any treatment recommendations for OA patients in the clinical context, but simply aims to highlight opportunities for scientific innovation and interdisciplinary collaboration, which are crucial for the development of novel products and nutritional interventions based on the best available and published evidence.

Mechanoreceptors observed in a ligamentous structure between the posterior horn of the lateral meniscus and the anterior cruciate ligament.

PURPOSE: A histological study of a structure between the posterior horn of the lateral meniscus and the anterior cruciate ligament. METHODS: Bilateral fresh-frozen cadaveric knees of two male donors (age 71 and 76 years) with no history of prior knee injury were examined. All dissections were performed by one experienced orthopaedic surgeon. Haematoxylin and Eosin staining was used to reveal tissue morphology. Goldner trichrome staining was used to evaluate the connective tissue. S100 and PGP 9.5 labelling were used for immunohistochemical analysis. RESULTS: In all cadaveric knees, a structure between the posterior horn of the lateral meniscus and the anterior cruciate ligament was identified. Histological analysis confirmed the ligamentous nature of this structure. Furthermore, Golgi tendon organs were observed within the ligamentous structure. CONCLUSION: This is the first study showing the presence of mechanoreceptors within the ligamentous structure between the posterior horn of the lateral meniscus and the anterior cruciate ligament. The ligamentous structure could contribute to stability of the knee by providing proprioceptive input, while preservation of the ligamentous structure might ensure a better functional outcome after surgery.

Aquatic Cycling Improves Knee Pain and Physical Functioning in Patients With Knee Osteoarthritis: A Randomized Controlled Trial.

OBJECTIVE: To assess the efficacy of a 12-week aquatic cycling training program for improving knee pain and physical functioning in patients with knee osteoarthritis (OA). DESIGN: Two-arm, single-blind, parallel-group randomized controlled trial. SETTINGS: OA outpatient clinic of the Maastricht University Medical Center+. PARTICIPANTS: Patients (N=111, 50-70y) with unilateral mild-to-moderate knee OA. INTERVENTIONS: Participants (aquatic cycling [AC] group, n=55) received AC sessions of 45 min each 2 times per week. Each session combined upright seated cycling with out-of-saddle positions and exercises for the upper and lower body. The usual care (UC) group (n=47) continued with UC and was offered 12 AC sessions in a local swimming pool after their trial participation. MAIN OUTCOME MEASURES: The Knee Injury and Osteoarthritis Outcome Score (KOOS) on knee pain and physical function was assessed at baseline, postintervention, and at 24-wk follow-up. Multilevel (mixed regression) analysis examined the effects. RESULTS: Average attendance rate for the AC sessions was 80%. Statistically significant differences at postintervention and follow-up were found for knee pain in mean ± SD (UC pretest, 57.89±15.26; posttest, 55.90±18.04; follow-up, 57.24±19.16; and AC pretest, 56.96±12.96; posttest, 63.55±15.33; follow-up, 64.35±17.26; estimate, 8.16; SE, 3.27; 95% confidence interval [CI], 1.67-14.64; effect size [ES], 0.50) and physical functioning (UC pretest, 66.32±16.28; posttest, 66.80±19.04; follow-up, 65.42±17.98; and AC pretest, 61.89±17.151; posttest, 70.14±17.52; follow-up, 69.00±16.84; estimate, 7.16; SE, 3.19; 95% CI, 0.83-13.49; ES, 0.43) in favor of the aquatic group. CONCLUSIONS: The results suggest that a 12-week AC training program improves self-reported knee pain and physical functioning in patients with mild-to-moderate knee OA compared to UC.

Chondroprotective Actions of Selective COX-2 Inhibitors In Vivo: A Systematic Review.

Knee osteoarthritis (OA) is a condition mainly characterized by cartilage degradation. Currently, no effective treatment exists to slow down the progression of OA-related cartilage damage. Selective COX-2 inhibitors may, next to their pain killing properties, act chondroprotective in vivo. To determine whether the route of administration is important for the efficacy of the chondroprotective properties of selective COX-2 inhibitors, a systematic review was performed according to the PRISMA guidelines. Studies investigating OA-related cartilage damage of selective COX-2 inhibitors in vivo were included. Nine of the fourteen preclinical studies demonstrated chondroprotective effects of selective COX-2 inhibitors using systemic administration. Five clinical studies were included and, although in general non-randomized, failed to demonstrate chondroprotective actions of oral selective COX-2 inhibitors. All of the four preclinical studies using bolus intra-articular injections demonstrated chondroprotective actions, while one of the three preclinical studies using a slow release system demonstrated chondroprotective actions. Despite the limited evidence in clinical studies that have used the oral administration route, there seems to be a preclinical basis for considering selective COX-2 inhibitors as disease modifying osteoarthritis drugs when used intra-articularly. Intra-articularly injected selective COX-2 inhibitors may hold the potential to provide chondroprotective effects in vivo in clinical studies.

Consumption of dairy products in relation to the presence of clinical knee osteoarthritis: The Maastricht Study.

PURPOSE: Observational studies showed inverse associations between milk consumption and knee osteoarthritis (knee OA). There is lack of information on the role of specific dairy product categories. We explored the association between dairy consumption and the presence of knee osteoarthritis in 3010 individuals aged 40-75 years participating in The Maastricht Study. METHODS: The presence of knee OA was defined according to a slightly modified version of the American College of Rheumatology (ACR) clinical classification criteria. Data on dairy consumption were appraised by a 253-item FFQ covering 47 dairy products with categorization on fat content, fermentation or dairy type. Multivariable logistic regression analyses were performed to estimate odd ratios (ORs) and 95% confidence intervals (95%CI), while correcting for relevant factors. RESULTS: 427 (14%) participants were classified as having knee OA. Significant inverse associations were observed between the presence of knee OA and intake of full-fat dairy and Dutch, primarily semi-hard, cheese, with OR for the highest compared to the lowest tertile of intake of 0.68 (95%CI 0.50-0.92) for full-fat dairy, and 0.75 (95%CI 0.56-0.99) for Dutch cheese. No significant associations were found for other dairy product categories. CONCLUSION: In this Dutch population, higher intake of full-fat dairy and Dutch cheese, but not milk, was cross-sectionally associated with the lower presence of knee OA. Prospective studies need to assess the relationship between dairy consumption, and in particular semi-hard cheeses, with incident knee OA.

Limited predictive value of pre-surgical level of functioning for functioning at 3 and 12 months after TKA.

PURPOSE: A total knee arthroplasty (TKA) is a cost-effective option to relieve pain and improve knee function in patients suffering from osteoarthritis. However, results differ among patients. The predictive value of pre-surgically assessed factors on the level of functioning after 3 and 12 months was investigated in this study. METHODS: This study used an inception cohort design and a follow-up of 12 months. One hundred and fifty patients who were to receive a TKA were assessed pre-surgically with an International Classification of Functioning, Disability and Health (ICF) core assessment set: Knee Society Score (KSS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Short-Form 12 (SF12), Patient-Specific Function Scale (PSFS), range of motion (ROM), quadriceps and hamstring strength and gait parameters. The main outcome measure was WOMAC-Function at 3 and 12 months after surgery. RESULTS: Pre-surgical physical and mental health on the SF12 and functioning and stiffness on the WOMAC explained 23% of the variance in the level of functioning 3 months after surgery. Pre-surgical knee function measured with the KSS-Knee, and functioning as assessed by WOMAC-Function explained 16% of the variance of the level of functioning 12 months after surgery. CONCLUSIONS: The results of this study show that better functioning before surgery, less knee stiffness and a better physical and mental health to some extent predict better functioning 3 months after surgery. This effect is less evident at 12 months. This study is clinically relevant since it provides benchmark data for health care providers who want to compare their individual patients. LEVEL OF EVIDENCE: II.

Functions, disabilities and perceived health in the first year after total knee arthroplasty; a prospective cohort study.

BACKGROUND: In end-stage knee osteoarthritis total knee arthroplasty (TKA) is an effective intervention to reduce pain and improve functioning in the majority of patients. However, after TKA some patients still experience pain, loss of function, deficient muscle strength or reduced walking speed. This study systematically assesses patients' functions, disabilities and health before TKA and at short- (3 months) and long-term (12 months) on all International Classification of Functioning, Disability and Health domains. METHODS: In this prospective cohort study 150 patients underwent the following tests before and at 3 and 12 months after surgery: Western Ontario and McMaster Universities Arthritis Index, Short Form 12, Knee Society Score, Patient Specific Functioning Scale, knee range of motion, quadriceps and hamstring strength, gait parameters, global perceived effect (only after surgery). All data was analyzed with repeated measures ANOVA for all measurement time points. RESULTS: Despite increased gait speed, quadriceps strength and scores on questionnaires being above pre surgical levels, patients do not reach levels of healthy persons. Walking speeds approach normal values and are higher in our study compared with the literature. Quadriceps strength stays at around 70 till 80% of norm values. However, dissatisfaction rates are below 10%, which is low compared to the literature. CONCLUSIONS: Quality of life, activities, muscle strength and gait parameters improve significantly after TKA. However, some complaints regarding activities and walking speed remain. Most striking outcome is the remaining deficit in quadriceps strength.

Measurement of lower limb alignment: there are within-person differences between weight-bearing and non-weight-bearing measurement modalities.

PURPOSE: Previous studies have compared weight-bearing mechanical leg axis (MLA) measurements to non-weight-bearing measurement modalities. Most of these studies compared mean or median values and did not analyse within-person differences between measurements. This study evaluates the within-person agreement of MLA measurements between weight-bearing full-length radiographs (FLR) and non-weight-bearing measurement modalities (computer-assisted surgery (CAS) navigation or MRI). MATERIALS AND METHODS: Two independent observers measured the MLA on pre- and postoperative weight-bearing FLR in 168 patients. These measurements were compared to non-weight-bearing measurements obtained by CAS navigation or MRI. Absolute differences in individual subjects were calculated to determine the agreement between measurement modalities. Linear regression was used to evaluate the possibility that other independent variables impact the differences in measurements. RESULTS: A difference was found in preoperative measurements between FLR and CAS navigation (mean of 2.5° with limit of agreement (1.96 SD) of 6.4°), as well as between FLR and MRI measurements (mean of 2.4° with limit of agreement (1.96 SD) of 6.9°). Postoperatively, the mean difference between MLA measured on FLR compared to CAS navigation was 1.5° (limit of agreement (1.96 SD) of 4.6°). Linear regression analysis showed that weight-bearing MLA measurements vary significantly from non-weight-bearing MLA measurements. Differences were more severe in patients with mediolateral instability (p = 0.010), age (p = 0.049) and ≥3° varus or valgus alignment (p = 0.008). CONCLUSION: The clinical importance of this study lies in the finding that there are within-person differences between weight-bearing and non-weight-bearing measurement modalities. This has implications for preoperative planning, performing total knee arthroplasty (TKA), and clinical follow-up after TKA surgery using CAS navigation or patient-specific instrumentation. LEVEL OF EVIDENCE: III.

Use of thiazolidinediones and the risk of elective hip or knee replacement: a population based case-control study.

AIMS: Osteoarthritis (OA) is the most common musculoskeletal condition in the elderly population. However, no disease modifying drug exists for this disease. In vivo animal studies have suggested that thiazolidinediones (TZD) may be used as disease modifying osteoarthritis drugs (DMOADs). To our knowledge, this has not yet been examined in humans before. The aim was to determine the risk of total joint replacement (TJR) in patients using TZDs compared with diabetic patients using other antidiabetic drugs. METHODS: A population based case-control study was performed using the Clinical Practice Research Datalink (CPRD). Cases (n = 94 609) were defined as patients >18 years of age who had undergone total knee (TKR) or hip replacement (THR) between 2000 and 2012. Controls were matched by age, gender and practice/surgery. Conditional logistic regression analyses were used to estimate the risk of TKR and THR with the use of TZDs in patients currently using one or more antidiabetic drugs. In order to determine effect with prolonged use, we also stratified TZD users by total number of prescriptions prior to surgery. We statistically adjusted our analyses for lifestyle factory, comorbidities and concomitant drug use. RESULTS: There was no difference in risk of TKR (OR 1.09, 95% CI 0.93, 1.27) and THR (OR 0.92, 95% CI 0.76, 1.10) when TZD users were compared with other AD users. Furthermore, we did not find an association with prolonged use of TZDs and TJR. CONCLUSION: Despite promising results from animal in vivo studies, this study did not find any evidence for a disease modifying osteoarthritic effect of TZDs.

Safety and efficacy of new oral anticoagulants and low-molecular-weight heparins compared with aspirin in patients undergoing total knee and hip replacements.

BACKGROUND: There has been much debate recently on the best type of thromboprophylaxis following elective total joint replacement surgery. OBJECTIVE: This study aims to compare rates of venous thromboembolism (VTE), gastro-intestinal (GI) bleeding and mortality events, with use of new oral anticoagulants (NOAC) or low-molecular-weight heparins (LMWHs) compared with aspirin in patients undergoing total joint replacement. METHODS: A population-based retrospective cohort study was performed using the Clinical Practice Research Datalink. Patients ≥18 years of age who had undergone total knee (n = 3261) or hip replacement (THR (n = 4016)) between 2008 and 2012 were included. Within this population, three cohorts were selected, based on their first prescription within the 35-day period after surgery: use of NOACs only, LMWHs only and aspirin only. Incidence rates were calculated, and Cox proportional hazard models were fitted to estimate the risk of VTE, GI bleeding and all-cause mortality with the use of NOACs and LMWHs compared with aspirin use after total knee replacement and THR. We statistically adjusted our analyses for lifestyle factors, comorbidities and concomitant drug use. RESULTS: Total knee replacement and THR patients currently on LMWHs had higher risk of VTE (HR = 17.2 (6.9-43.0) and HR = 39.5 (18.0-87.0), respectively), GI bleeding (HR = 20.9 (1.9-232.3) and HR = 2.0 (0.2-17.2), respectively) and all-cause mortality (HR = 4.3 (1.7-12.4) and HR = 4.0 (2.4-6.7), respectively). NOAC use was associated with an increased risk of GI bleeding in patients undergoing THR surgery. CONCLUSIONS: In contrast to previous studies, we found an increased risk of VTE, GI bleeding and all-cause mortality with the use of LMWHs compared with aspirin. Risk of GI bleeding was increased with the use of NOACs compared with aspirin use after THR surgery. Copyright © 2016 John Wiley & Sons, Ltd.

Effect of aqua-cycling on pain and physical functioning compared with usual care in patients with knee osteoarthritis: study protocol of a randomised controlled trial.

BACKGROUND: Over the last decade aquatic exercise has become more and more popular. One of the latest trends is aqua-cycling, where participants sit on a water-resistant stationary bike and, while immersed chest deep in the water, combine continuous cycling with upper body exercises that utilise water resistance. Since stationary cycling and aquatic exercises are frequently recommended to patients with knee osteoarthritis, combining both would seem an obvious step, and an aqua-cycling exercise programme for patients with knee osteoarthritis has indeed been developed. This study protocol gives a detailed description of the exercise programme and the methodology of a study to compare this programme with treatment involving usual care only. METHODS: The study is a single-blind, parallel-group, randomised controlled trial of Maastricht University Medical Centre+, the Netherlands. INCLUSION CRITERIA: knee pain of four to seven on a 10-point pain rating scale; a Kellgren/Lawrence score between one to three; ability to cycle; good mental health; sufficient language skills; indication for physical therapy in conjunction with impairments due to OA. EXCLUSION CRITERIA: any contra-indication for aquatic exercise; planned total knee replacement; corticosteroid injection <3 months and/or hyaluronic acid injection <6 months; severe joint complaints (other than knee joint); symptomatic and radiological apparent hip OA; inflammatory joint diseases; inability to safely enter and exit the pool; fear of water. Participants will receive two 45-min moderate intense aqua-cycling sessions weekly over a period of 12 weeks in addition to usual care or usual care only. Usual care consists of an individual intervention plan comprising lifestyle recommendations, medication routine and referral to a physical therapist. Participants will be assessed at baseline, and at 12 and 24 weeks after baseline. The primary outcome is self-reported knee pain and physical functioning. Secondary outcomes are lower limb muscle strength, functional capacity, self-reported disease severity, physical activity level, quality of life, self-efficacy and fear of movement. Daily diaries will collect information on knee pain, physical functioning, level of physical activity, pain medication routine and physical therapy (control group only) or exercise participation over two 30-day periods (during the intervention period). DISCUSSION: To our knowledge the present study is the first randomised controlled trial evaluating the effects of aqua-cycling in the pre-surgical stage of knee osteoarthritis. This trial will demonstrate if the newly designed aqua-cycling intervention, in supplement to usual care, can help to improve impairments due to knee osteoarthritis. TRIAL REGISTRATION: Netherlands Trial Register NTR3766 (21-12-2012).

Validation of statistical shape modelling to predict hip osteoarthritis in females: data from two prospective cohort studies (Cohort Hip and Cohort Knee and Chingford).

OBJECTIVES: To prospectively investigate whether hip shape variants at baseline are associated with the need for future total hip replacement (THR) in women and to validate the resulting associated shape variants of the Cohort Hip and Cohort Knee (CHECK) cohort and the Chingford cohort. METHODS: Female participants from the CHECK cohort without radiographic OA (Kellgren-Lawrence score <2) at baseline were included (1100 hips); 22 hips had a THR within 5 years of follow-up. For the Chingford cohort, with only female participants, hips without radiographic OA at baseline were selected and a nested case-control design was used, with 19 THR cases within 19 years of follow-up and 95 controls matched 5 to 1 for age and BMI. Hip shape on baseline anteroposterior pelvic radiographs was assessed by statistical shape modelling (SSM) using the same model for both cohorts. RESULTS: In the CHECK and Chingford cohorts, the respective mean age was 55.8 (s.d. 5.1) and 53.6 (s.d. 5.4) and the BMI was 26.14 (s.d. 4.3) and 25.7 (s.d. 3.3), respectively. Multiple shape variants of the hip were significantly (P < 0.05) associated with future THR in both the CHECK (modes 4, 11, 15, 17 and 22) and Chingford (modes 2 and 17) cohorts. Mode 17 [odds ratio (OR) 0.51 (95% CI 0.33, 0.80) in the CHECK cohort], representing a flattened head-neck junction and flat greater trochanter, could be confirmed in the Chingford cohort [OR 0.41 (95% CI 0.23, 0.82)]. Modes 4 and 15 of the CHECK cohort also showed non-significant trends in the Chingford cohort. CONCLUSION: Several baseline shape variants are associated with the future need for THR within a cohort. Despite differences in participant characteristics, radiographic protocol and follow-up time, we could validate at least one shape variant, suggesting that SSM is reasonably transferable between cohorts.