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Background: Regular physical activity is beneficial for people with rheumatic diseases and one of the cornerstones in its management. Based on the international recommendations of the World Health Organization for the general population, the "2018 EULAR recommendations for physical activity in people with inflammatory arthritis and osteoarthritis" provide evidence-based recommendations on the prescription, performance, and implementation of physical activity exercises in this population for the first time., Aim: Translation of the 2018 EULAR recommendations into German and linguistic validation in Germany, Austria and Switzerland., Methods: A professional translation of the EULAR recommendations into the German language was performed and revised by German-speaking experts from all three countries. The translation was validated by healthcare professionals consisting of rheumatologists, occupational therapists, physiotherapists, nurses, and medical assistants in a field test. In each of the three countries, eight structured interviews were conducted on comprehensibility, wording, completeness, and feasibility. The experts then discussed changes until consensus was reached and indicated the level of agreement with the final translation., Results: The translation of the EULAR recommendations was substantially revised. Based on the results of the cognitive test, formulations were adapted in order to increase comprehensibility. The level of agreement between 10 (SD 0.0) and 8.9 (SD 1.5) was very high., Discussion: The final German version of the EULAR recommendations is comprehensible and accepted across all three German-speaking countries. It can help to improve the structure and clarity of the handling of physical activity and promote physical activity for healthcare providers and patients., (© 2021. The Author(s).)

Osteoarthritis (OA) represents the most prevalent and disabling arthritis worldwide due to its heterogeneous and progressive articular degradation. However, effective and timely diagnosis and fundamental treatment for this disorder are lacking. Metabolomics, a growing field in life science research in recent years, has the potential to detect many metabolites and thus explains the underlying pathophysiological processes. Hence, new specific metabolic markers and related metabolic pathways can be identified for OA. In this review, we aimed to provide an overview of studies related to the metabolomics of OA in animal models and humans to describe the metabolic changes and related pathways for OA. The present metabolomics studies reveal that the pathogenesis of OA may be significantly related to perturbations of amino acid metabolism. These altered amino acids (e.g., branched-chain amino acids, arginine, and alanine), as well as phospholipids, were identified as potential biomarkers to distinguish patients with OA from healthy individuals.

Introduction: Up to one third of total joint replacement patients (TJR) experience poor surgical outcome., Objectives: To identify metabolomic signatures for non-responders to TJR in primary osteoarthritis (OA) patients., Methods: A newly developed differential correlation network analysis method was applied to our previously published metabolomic dataset to identify metabolomic network signatures for non-responders to TJR., Results: Differential correlation networks involving 12 metabolites and 23 metabolites were identified for pain non-responders and function non-responders, respectively., Conclusion: The differential networks suggest that inflammation, muscle breakdown, wound healing, and metabolic syndrome may all play roles in TJR response, warranting further investigation.

Background: The objective of the research consortium PROCLAIR was to gain population level knowledge on the treatment of patients with rheumatoid arthritis (RA), axial spondylarthritis (axSpA) and osteoarthritis (OA) in Germany., Aims: A main question of the consortium was whether it is possible to identify groups of people who were exposed to a particular risk of undersupply or oversupply of treatment. In addition, the study investigated the validity of claims data for these diseases as a basis for further studies., Patients and Methods: Cross-sectional surveys were carried out among insurees of the BARMER statutory health insurance fund whose claims data included RA, axSpA and OA diagnoses. The questionnaire data were linked with the claims data of the insured persons if they agreed., Results: In all three diseases risk groups for care deficits could be identified. Persons with RA who are not treated by a specialist have less access to drug treatment. Physical therapy is prescribed for all three diagnoses at a low level, even for people undergoing joint replacement surgery. A connection between depressive symptoms and disease activity or function in axSpA was shown. In addition to the results relevant to care, the PROCLAIR network has also made contributions to critically assess the quality of health insurance data., Discussion: The combination of billing data with survey data enables a comprehensive description of the treatment of musculoskeletal diseases. Particularly relevant factors are the specialization of the physician, sociodemographic parameters of the patients and the region of residence. In particular, access to treatment cannot be investigated in randomized clinical trials.

Background: Little is known about the utilization of individual health services performed by a physician (IGeL) and the services and supplements provided outside a doctor's office (MuPaP) for osteoarthritis patients., Objectives: The aims of this study are to analyze the use of osteoarthritis-specific IGeL and MuPaP as well as predictors for their utilization., Materials and Methods: For this cross-sectional study, claims data was used to identify all persons with hip, knee, or polyarticular osteoarthritis in 2014 (n = 657,807). A random sample (n = 8995) was sent a questionnaire about their usage of IGeL and MuPaP. Furthermore, the type of physicians conducting or recommending services was evaluated. Applying multivariable logistic regression, predictors associated with the utilization of IGeL, MuPaP, and overall individual health services were analyzed., Results: After validating the data and osteoarthritis diagnosis, 2363 persons were enrolled (mean age: 65.5 years, 72% female). In the last 12 months, 39% of patients had used at least one IGeL (MuPaP: 76%), with 86% being primarily performed by orthopedists (MuPaP: 88% patient self-motivated). Knee osteoarthritis was associated with increased utilization of IGeL. Having female gender, higher income, residence in Western Germany, higher disease burden, and lower satisfaction with the healthcare system were influences on the use of overall individual health services., Conclusions: Since patients with high disease burden in particular tend to use these therapies with varying treatment success, detailed information, especially about the risks and existing evidence, should be a prerequisite for trustworthy doctor-patient relationships.

Background and Aims: Although osteoarthritis (OA) is managed mainly in primary care, general practitioners (GPs) are not always trained in its diagnosis, which leads to diagnostic delays, unnecessary resource utilization, and suboptimal patient outcomes., Methods: To address this situation, an International Rheumatologic Board (IRB) of 8 experts from 3 continents developed guidelines for the diagnosis of OA in primary care. The focus was three major topologies: hip, knee, and hand/finger OA. The IRB used American College of Rheumatology diagnostic criteria., Results: Care pathways based on clinical and radiological findings were developed to identify intervention thresholds for GPs/specialists. To optimize usefulness in the primary care setting, the guidelines were formatted as an uncomplicated, but comprehensive one-page decision tree for each topology, highlighting key aspects of the evaluation process and incorporating red flags. In a two-phase validation stage, the draft guidelines were evaluated by rheumatologists and GPs for project execution, content and perceived benefit. The strength of the guidelines lies in their user-friendly diagram and potential for broad application. Such guidelines will allow GPs to make an easy but definite diagnosis of OA and offer clear guidance about situations requiring an expert opinion. The guidelines have potential to improve patient outcomes and reduce the number of unnecessary procedures., Discussion and Conclusions: This project demonstrated the feasibility of developing easy-to-use and effective visual decision trees to facilitate the diagnosis and management of OA of the hip, knee and hand/finger in primary care. The next step should be to conduct a large impact study of implementation of these recommendations in the diagnostic management of OA in general practice in different areas.

A sample of 512 Chinese was studied and we observed that greater disc degeneration on MRI was associated with greater spine DXA BMD. Yet, this association may be confounded by facet joint osteoarthritis. BMD may not be a risk factor for lumbar disc degeneration in Chinese., Purpose: Evidence suggested that lumbar vertebral bone and intervertebral disc interact with each other in multiple ways. The current paper aims to determine the association between bone mineral density (BMD) and lumbar disc degeneration using a sample of Chinese., Methods: We studied 165 patients with back disorders and 347 general subjects from China. All subjects had lumbar spine magnetic resonance (MR) imaging and dual- energy X-ray absorptiometry (DXA) spine BMD studies, and a subset of general subjects had additional hip BMD measurements. On T2-weighted MR images, Pfirrmann score was used to evaluate the degree of lumbar disc degeneration and facet joint osteoarthritis was assessed as none, slight-moderate, and severe. Regression analyses were used to examine the associations between lumbar and hip BMD and disc degeneration, adjusting for age, gender, body mass index (BMI), lumbar region, and facet joint osteoarthritis., Results: Greater facet joint osteoarthritis was associated with greater spine BMD (P < 0.01) in both patients and general subjects. For general subjects, greater spine BMD was associated with severe disc degeneration, controlling for age, gender, BMI, and lumbar region. When facet joint osteoarthritis entered the regression model, however, greater spine BMD was associated with greater facet joint osteoarthritis (P < 0.01) but not greater disc degeneration (P > 0.05). No statistical association was observed between spine BMD and lumbar disc degeneration in patients with back disorders (P > 0.05), and between hip BMD and disc degeneration in general subjects (P > 0.05)., Conclusion: BMD may not be a risk factor for lumbar disc degeneration in Chinese. Facet joint osteoarthritis inflates DXA spine BMD measurements and therefore, may confound the association between spine BMD and disc degeneration.

The histopathological synovitis score evaluates in a graded approach, as is largely usual for diagnostic histopathological scores, the immunological and inflammatory changes caused by synovitis. A synovitis score of between 1 and ≤ 4 is classified as low-grade (osteoarthritis-related synovitis, post-traumatic synovitis, meniscopathy-related synovitis and synovitis in hemochromatosis). Synovitis scores of between ≥ 5 and 9 are classified as high-grade synovitis (rheumatoid arthritis, psoriatic arthritis, Lyme's arthritis, post-infection/reactive arthritis and peripheral arthritis in Bechterew disease); sensitivity is 61.7% and sensitivity 96.1%. According to receiver operating characteristic (ROC) analysis (AUC: 0.8-0.9), diagnostic value is good. National and international acceptance of the synovitis score has grown since the first publication in 2002 and a related follow-up publication in 2006. PubMed data analysis (as of 11.01.2017) yielded the following citation values according to "cited by PubMed Central articles" for two publications relating to the synovitis score: there were 29 cited-by-PubMed articles for DOI: 10.1078/0344-0338-5710261 , and 44 cited-in-PubMed articles for the second publication, DOI: 10.1111/j.1365-2559.2006.02508 . This makes a total of 73 PubMed citations over a period of 15 years, thereby evidencing the score's international acceptance. Immunohistochemical determination of a number of CD antigens relevant to inflammation has been proposed to further specify the synovitis score for the purposes of risk stratification of high-grade synovitis (e.g., risk of progression and sensitivity to biological agents).

Periprosthetic joint infection (PJI) is a catastrophic complication after total joint arthroplasty. It has always been difficult to diagnose PJI, which is characterised by existence of biofilm around the implants. The application of sonication has proven advantageous for pathogen detection. This meta-analysis of clinical trials was performed to evaluate the diagnostic value of sonication and to compare it with traditional bacterial culture. We assessed 16 studies that evaluated sonication fluid cultures (SFC) for the diagnosis of PJI. It was shown that sonication may be of great value in PJI diagnosis, with a pooled sensitivity of 0.79 (95 % confidence interval [CI] = 0.76-0.81), specificity of 0.95 (CI = 0.94-0.96), DOR of 71.20 (CI = 31.08-163.10), PLR of 15.25 (CI = 6.44-36.15), and NLR of 0.23 (CI = 0.18-0.30). The AUC value of the SROC was 0.90. The results of this meta-analysis showed that culture of fluid after sonication was of great value for PJI diagnosis. Sonication was more sensitive than traditional tissue culture with lower specificity, especially for patients previously taking antibiotics.

Limited data are available about the ultrasound (US)-detected inflammatory features in patients with suspicion of inflammatory arthritis (S-IA) vs. established rheumatoid arthritis (RA). Our study aimed to assess if the presence of power Doppler (PD) can be predicted by a combination of clinical, laboratory and US parameters. We conducted a real-life, retrospective cohort study comparing clinical, laboratory and US parameters of 108 patients with established RA and 93 patients with S-IA. We propose a PD signal prediction model based on a beta-binomial distribution for PD variable using a mix of outcome measures. Patients with RA in clinical remission had significantly more active inflammation and erosions on US when compared with patients with S-IA with similar disease scores (p = 0.03 and p = 0.01, respectively); however, RA patients with different disease activity score (DAS-28) scores had similar PD scores (p = 0.058). The PD scores did not correlate with erosions (p = 0.38) or DAS-28 scores (p = 0.28) in RA patients, but they correlated with high disease activity in S-IA patients (p = 0.048). Subclinical inflammation is more common in patients with RA in clinical remission or with low disease activity than in patients with S-IA; therefore, US was more useful in assessing for true remission in RA rather than diagnosing IA in patients with low disease activity scores. This is the first study to propose a PD prediction model integrating several outcome measures in the two different groups of patients. Further research into validating this model can minimise the risk of underdiagnosing subclinical inflammation., Competing Interests: Compliance with ethical standards The data was collected as standard of practice. The study analysed retrospectively the results of the US examinations of patients seen in our US clinics over a defined period of time. No ethical approval or patient’s consent were required as no patient information was used for teaching or new intervention research. The results of our study analysis had no impact on the clinical management of patients and their confidentiality was maintained. The study was approved by the local Audit Committee (University College London NHS Trust, September 2013), and the results communicated as local audit aiming to improve the referral criteria to our US clinics (November 2013). Disclosures None.

The authors aimed to test potential relations between osteoarthritis (OA) features, disability and health-related quality of life (HR-QoL) at different body locations. Outpatients consulting for pain associated to self-reported OA at varied healthcare settings were evaluated in a 3-month observational non-controlled follow-up study. Socio-demographic/anthropometric and medical data were collected at three time points. Lequesne's indices, quick-disabilities of arm, shoulder and hand (DASH) and Oswestry questionnaires provided measures of physical function and disability. HR-QoL measures were obtained with EuroQol-5 Dimensions. Multivariate analyses were used to evaluate the differences of pain severity across body regions and the correlates of disability and HR-QoL. Six thousand patients were evaluated. Pain lasted 2 years or more in 3995 patients. The mean pain severity at baseline was moderate (6.4 points). On average, patients had pain in 1.9 joints/areas. The pain was more severe when OA involved the spine or all body regions. Pain severity explained much of the variance in disability and HR-QoL; this association was less relevant in patients with OA in the upper limbs. There were considerable improvements at follow up. Pain severity improved as did disability, which showed particularly strong associations with HR-QoL improvements. Pain severity is associated with functional limitations, disability and poor HR-QoL in patients with self-reported OA. Functional limitations might have particular relevance when OA affects the upper limbs. Improvements are feasible in many patients who consult because of their pain.

Osteoarthritis is a leading cause of chronic pain and disability and one of the most common conditions diagnosed and managed in primary care. Despite the evidence that patients would value discussions about the course of osteoarthritis to help them make informed treatment decisions and plan for the future, little is known of GPs' practice of, or views regarding, discussing prognosis with these patients. A cross-sectional postal survey asked 2500 randomly selected UK GPs their views on discussing prognosis with patients with osteoarthritis and potential barriers or facilitators to such discussions. They were also asked if prognostic discussions were part of their current practice and what indicators they considered important in assessing the prognosis associated with osteoarthritis. Of 768 respondents (response rate 30.7 %), the majority felt it necessary to discuss prognosis with osteoarthritis patients (n = 738, 96.1 %), but only two thirds reported that it was part of their routine practice (n = 498, 64.8 %). Most respondents found predicting the course of osteoarthritis (n = 703, 91.8 %) and determining the prognosis of patients difficult (n = 589, 76.7 %). Obesity, level of physical disability and pain severity were considered the most important prognostic indicators in osteoarthritis. Although GPs consider prognostic discussions necessary for patients with osteoarthritis, few prioritise these discussions. Lack of time and perceived difficulties in predicting the disease course and determining prognosis for patients with osteoarthritis may be barriers to engaging in prognostic discussions. Further research is required to identify ways to assist GPs making prognostic predictions for patients with osteoarthritis and facilitate engagement in these discussions.

Osteoarthritis (OA) is a disease characterized by degradation of joints with the development of painful osteophytes in the surrounding tissues. Currently, there are a limited number of treatments for this disease, and many of these only provide temporary, palliative relief. In this review, we discuss particle-based drug delivery systems that can provide targeted and sustained delivery of imaging and therapeutic agents to OA-affected sites. We focus on technologies such as polymeric micelles and nano-/microparticles, liposomes, and dendrimers for their potential treatment and/or diagnosis of OA. Several promising studies are highlighted, motivating the continued development of delivery technologies to improve treatments for OA.

Background: The treatment strategies for osteoarthritis (OA) are well known from numerous studies. One of the challenges is long-term patient compliance to the recommended therapies without supervision., Objective: To examine the ability of salutogenic concepts to improve rehabilitative management of OA., Materials and Methods: Review article introducing salutogenic concepts and their empiric evidence, focussing on Antonovsky's sense of coherence (SOC)., Results: The SOC consists of the three components comprehensibility, manageability and meaningfulness. SOC can be quantified by SOC-13, a self-reported measurement with 13 items. Associations of the SOC with different dimensions of health (in particular with Short Form 36, SF-36) are known from cross-sectional studies. Most studies showed a stronger correlation of the mental than the physical health dimensions of SF-36 with SOC-13. This result is consistent with baseline examinations of hip and knee OA patients before rehabilitation. At the 6-month follow-up, correlations between SOC and the changes of the SF-36 scores were weak. A salutogenically orientated instruction for self-management of symptoms in cancer patients showed significant improvement in SOC., Conclusion: Increasing SOC can lead to health improvements on many levels, e.g. self-efficacy, reduction of fear, coping, education, resources and compliance to treatment. Empirical proof that interventional measures increasing SOC can improve the health of OA patients is currently unavailable.

The congenital form of ochronosis is a result of the rare autosomal recessive inherited metabolic disease alkaptonuria. The disruption of tyrosine metabolism based on a genetic defect in the enzyme homogentisate dioxygenase results in accumulation of homogentisic acid (HA) which is excreted in the urine and leads to a dark discoloration after a certain incubation time at room temperature. Furthermore, HA polymerizes forming a pigment that is deposited in connective tissues such as tendons, cartilage, bones, intervertebral discs, sclerae, ossicles, cardiac valves and coronary arteries and leads to dark brown discoloration and degeneration. The case of a 74-year-old female patient with ochronosis and classical manifestations is described and in addition a current overview of this rare disease is provided.

Osteomalacia is a rare disorder of bone metabolism leading to reduced bone mineralization. Underlying vitamin D deficiency and a disturbed phosphate metabolism (so-called hypophosphatemic osteomalacia) can cause the disease. Leading symptoms are dull localized or generalized bone pain, muscle weakness and cramps as well as increased incidence of falls. Rheumatic diseases, such as polymyalgia rheumatica, rheumatoid arthritis, myositis and fibromyalgia must be considered in the differential diagnosis. Alkaline phosphatase (AP) is typically elevated in osteomalacia while serum phosphate and/or 25-OH vitamin D3 levels are reduced. The diagnosis of osteomalacia can be confirmed by an iliac crest bone biopsy. Histological correlate is reduced or deficient mineralization of the newly synthesized extracellular matrix. Treatment strategies comprise supplementation of vitamin D and calcium and for patients with intestinal malabsorption syndromes vitamin D and calcium are also given parenterally. In renal phosphate wasting syndromes substitution of phosphate is the treatment of choice, except for tumor-induced osteomalacia when removal of the tumor leads to a cure in most cases.

The aim of the present study was to evaluate the feasibility of applying Raman spectroscopy in probing the molecular changes in terms of collagen deposition and tissue remodeling associated with two well-established experimental models of osteoarthritis (OA) in knee of rats. In order to evaluate alterations in the articular surface area, the menisci-covered tibial region was assessed into three groups as follows: control (joint preserved) and two models of experimental knee OA: collagenase-induced model (n = 8) and treadmill exercise-induced model (n = 8). Each group was examined for molecular changes using spectral parameters related to cartilage, subchondral bone, and bone tissues. A significant increase of Raman ratios related to mineralization and tissue remodeling was found (p < 0.05), suggesting that both models were successful for inducing OA in rats. The significantly lower phenylalanine content and higher crystallinity in the treadmill exercise-induced model of OA than collagenase-induced model of OA (p < 0.05) indicated that the OA pathogenesis was model-dependent. Thus, this work suggests that the Raman spectroscopy technique has potential for the diagnosis and detection of cartilage damage and monitoring of subchondral bone and bone in OA pathogenesis at the molecular level.

Hand osteoarthritis (OA) is a common disease frequently affecting middle-aged women. Prevalence estimates for OA vary widely depending on the age and sex of the population studied, the assessment tools used, and the specific joint sites analyzed OA is characterized by the degradation of articular cartilage, subchondral bone changes and osteophyte formation at the joint margins leading to joint failure. The pathogenesis of the disease and its evolution are multifactorial involving biomechanical, metabolic, hormonal, and genetic factors. Moreover, the role of inflammation has recently been advanced as pivotal in OA onset and progression. In particular, an uncommon variant of hand OA, erosive hand OA, is characterized by inflammatory and degenerative interphalangeal proximal and distal joints. The diagnosis of different types of hand OA is centered on clinical and laboratory investigations which can distinguish the peculiar aspects of these forms. Joint and bone assessments in hand OA are widely studied but there is no agreement with regard to established parameters to make a definitive diagnosis. This report focuses on the laboratory and clinimetric assessments that can be used to distinguish hand OA subtypes and addresses the debatable association with low bone mineral density in osteoporosis.

Chronic adipose tissue inflammation and its associated adipokines have been linked to the development of osteoarthritis (OA). It has been shown that caloric restriction may decrease body mass index and adiposity. The objectives of this study were to investigate the effect of lifelong caloric restriction on bone morphology, joint inflammation, and spontaneously occurring OA development in aged mice. C57BL/NIA mice were fed either a calorie-restricted (CR) or ad libitum (AL) diet starting at 14 weeks of age. All mice were sacrificed at 24 months of age. Adipose tissue and knee joints were then harvested. Bone parameters of the joints were analyzed by micro-CT. OA and joint synovitis were determined using histology and semiquantitative analysis. Lifelong caloric restriction did not alter the severity of OA development in C57BL/NIA aged mice, and there was no difference in the total joint Mankin score between CR and AL groups (p = 0.99). Mice also exhibited similar levels of synovitis (p = 0.54). The bone mineral density of the femur and the tibia was comparable between the groups with a small increase in cancellous bone volume fraction in the lateral femoral condyle of the CR group compared with the AL group. Lifelong caloric restriction did not alter the incidence of OA or joint synovitis in C57BL/NIA mice, indicating that a reduction of caloric intake alone was not sufficient to prevent spontaneous age-related OA. Nonetheless, early initiation of CR continued throughout a life span did not negatively impact bone structural properties.

Digital imaging combined with picture archiving and communication system (PACS) access allows detailed image retrieval and magnification. Calcium pyrophosphate dihydrate (CPPD) crystals preferentially deposit in fibrocartilages, the cartilage of the acromioclavicular (AC) joint being one such structure. We sought to determine if examination of the AC joints on magnified PACS imaging of chest films would be useful in identifying chondrocalcinosis (CC). Retrospective radiographic readings and chart reviews involving 1,920 patients aged 50 or more who had routine outpatient chest radiographs over a 4-month period were performed. Knee radiographs were available for comparison in 489 patients. Medical records were reviewed to abstract demographics, chest film reports, and diagnoses. AC joint CC was identified in 1.1 % (21/1,920) of consecutive chest films. Patients with AC joint CC were 75 years of age versus 65.4 in those without CC (p < 0.0002). Four hundred eighty-nine patients had knee films. Six of these patients had AC joint CC, and of these, five also had knee CC (83 %). Of the 483 without AC joint CC, 62 (12 %) had knee CC (p = 0.002). Patients with AC joint CC were more likely to have a recorded history of CPPD crystal deposition disease than those without AC joint CC (14 versus 1 %, p = 0.0017). The prevalence of AC joint CC increases with age and is associated with knee CC. A finding of AC joint CC should heighten suspicion of pseudogout or secondary osteoarthritis in appropriate clinical settings and, in a young patient, should alert the clinician to the possibility of an associated metabolic condition.

Aims of the Study: To assess and compare resistin levels in the serum and synovial fluid of patients with rheumatoid arthritis (RA; an inflammatory rheumatologic disease) and osteoarthritis (OA; a degenerative rheumatologic disease) and to study the relationship between resistin levels and prognostic factors of RA disease progression., Patients and Methods: This study included a total of 50 patients: 25 with RA and 25 with OA. Full case history was documented for all patients and all underwent a thorough clinical examination and laboratory testing. Body mass index (BMI) values were also calculated. Radiographs were made of OA patients' knees and RA patients' hands. Disease Activity Score 28 (DAS28) was calculated for RA patients. Serum and synovial fluid samples were obtained from the effused knees of all patients and tested for resistin level., Results: Serum resistin levels were higher in RA patients than in those with OA (p < 0.01). Synovial fluid resistin levels were also higher in RA than OA patients (p < 0.001). While serum resistin levels correlated with Larsen score and total leukocyte count (TLC), synovial fluid resistin levels correlated with rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) levels in addition to Larsen score and TLC., Conclusion: Resistin levels were found to be higher in the serum and synovial fluid of RA patients than in those with OA. This may suggest a role for resistin in inflammatory rheumatologic diseases. The observed statistically significant correlation between synovial fluid resistin levels and RF, ACPA and Larsen score may suggest that high synovial fluid resistin levels can be considered a poor prognostic factor for RA progression. However, further studies employing a larger cohort of patients are needed to confirm the relevance of resistin as a prognostic marker in RA patients.

Background: One hypothesis has posited whether abnormal lipid metabolism might be a causal factor in the pathogenesis of osteoarthritis (OA). Routine statin use in clinical practice provides the basis for a natural experiment in testing this hypothesis., Objective: To test the hypothesis that statins reduce the long-term occurrence of clinically defined OA., Design: Cohort design with a 10-year follow-up., Participants: 16,609 adults cardiovascular disease cohorts aged 40 years and over from the UK General Practice Research Database with data available to 31 December 2006., Intervention: Statins were summarised as annual mean daily dose and dose change over two-year time periods., Main Measures: Incident episode of clinically defined osteoarthritis was assessed within 2 years, and at 4-year and 10-year follow-up time periods, using Cox and discrete time survival analysis. Covariates included age, gender, deprivation, body mass index, cholesterol level, pain-modifying drug co-therapies, and duration and severity of cardiovascular disease., Key Results: Higher therapeutic dose of statin, with a treatment duration of at least 2 years was associated with a significant reduction in clinical OA compared to non-statin users in the follow-up time period. The estimated adjusted rate ratios were as follows: lowest statin dose quartile 1: 2.5 (95 % CI 2.3, 2.9); quartile 2: 1.3 (1.1, 1.5); quartile 3: 0.8 (0.7, 0.95); and highest statin dose quartile 4: 0.4 (0.3, 0.5). The largest statin dose increments were associated with significant reductions estimated at 18 % in OA outcome within 2 years and 40 % after 4 years, compared to non-statin users., Conclusions: This longitudinal study from a national clinical practice setting provides evidence that higher statin dose and larger statin dose increments were associated with a reduction in clinically defined OA outcome.

The aim of this study was to investigate whether calcium pyrophosphate dihydrate (CPPD) crystals are constantly detectable in sequential synovial fluid (SF) examinations of patients with initially CPPD-positive osteoarthritis (OA). For this purpose, we searched our SF database for CPPD-positive patients, who had two or more SF analyses between 2008 and 2012 to get sequential information. The database contains SF data determined by a standardised procedure. Of 1,878 samples, examined within the defined time period, 60 samples from sequential SF analyses of 23 patients were eligible for this study. The number of examinations ranged from 2 to 7 (median, 2), and the median interval between the first and last arthrocentesis was 12 months (2-43). CPPD crystals were detected in all of the sequentially examined samples according to the defined criterion of positivity. All of the subjects had OA of the knee, with a median Kellgren-Lawrence grade of 3 in the initially performed X-rays, and meniscal calcifications were found in six subjects. In conclusion, our results suggest that CPPD crystals are a regular feature of sequentially examined SF of initially CPPD-positive patients with symptomatic OA of the knee.

The term musculoskeletal condition (MSKC) comprises inflammatory and degenerative diseases of joints and bones. They are among the most common conditions in older age and cause of severe long-term pain, physical disability, and decrease in quality of life. Data from the German Health Interview and Examination Survey for Adults (DEGS1) were used to estimate the life-time prevalence of osteoarthritis, rheumatoid arthritis (RA) and osteoporosis in Germany. A total of 7,988 persons aged 18-79 years (osteoporosis 50-79 years) were asked to report doctor-diagnosed MSKC in face-to-face interviews. Women were more likely to report all MSKC and all prevalences increase with age. Osteoarthritis is reported by 22.3 % of women and 18.1 % of men, RA by 3.2 % of women and 1.9 % of men, and osteoporosis by 13.1 % of women and 3.2 % of men. MSKC are of great relevance for older adults in Germany. Data from DEGS1 provide a lot of information along to MSKC and hereby allow a closer description of the health situation of older adults. An English full-text version of this article is available at SpringerLink as supplemental.

The importance of medical imaging for clinical decision making has been steadily increasing over the last four decades. Recently, there has also been an emphasis on medical imaging for preclinical decision making, i.e., for use in pharamaceutical and medical device development. There is also a drive towards quantification of imaging findings by using quantitative imaging biomarkers, which can improve sensitivity, specificity, accuracy and reproducibility of imaged characteristics used for diagnostic and therapeutic decisions. An important component of the discovery, characterization, validation and application of quantitative imaging biomarkers is the extraction of information and meaning from images through image processing and subsequent analysis. However, many advanced image processing and analysis methods are not applied directly to questions of clinical interest, i.e., for diagnostic and therapeutic decision making, which is a consideration that should be closely linked to the development of such algorithms. This article is meant to address these concerns. First, quantitative imaging biomarkers are introduced by providing definitions and concepts. Then, potential applications of advanced image processing and analysis to areas of quantitative imaging biomarker research are described; specifically, research into osteoarthritis (OA), Alzheimer's disease (AD) and cancer is presented. Then, challenges in quantitative imaging biomarker research are discussed. Finally, a conceptual framework for integrating clinical and preclinical considerations into the development of quantitative imaging biomarkers and their computer-assisted methods of extraction is presented.

The purpose of this study is to determine the diagnostic properties of the clinical gout diagnosis (CGD) proposal in patients with gout and other rheumatic diseases. We investigated the presence of current or past history of the previously published CGD criteria: (1) >1 attack of acute arthritis, (2) mono/oligoarthritis attacks, (3) rapid progression of pain and swelling (<24 h), (4) podagra, (5) erythema, (6) unilateral tarsitis, (7) probable tophi, and (8) hyperuricemia. CGD was established in patients with greater than or equal to four out of eight of these criteria. Demographic data and comorbidities were also considered. Statistical analysis included diagnostic test evaluation (sensitivity, specificity, likelihood ratios, positive predictive values and receiving operating characteristic curves). One hundred and sixty-seven patients with the following diagnoses were included: gout (most in intercritical period, n = 75), rheumatoid arthritis (RA, n = 30), osteoarthritis (OA, n = 31) and spondyloarthritis (SpA, n = 31). All gout patients had MSU crystal demonstration and constituted the gold standard for diagnostic test evaluation. There were significant differences across diagnostic groups in most demographic variables and comorbidity. The presence of greater than or equal to four out of eight of the CGD criteria were found in 97% patients with gout, in two patients with SpA, and one each with RA and OA. The sensitivity, specificity, and LR+ of greater than or equal to four out of eight of the CGD criteria were 97.3%, 95.6%, and 22.14, respectively. The presence of more than or equal to four out of eight items from the CGD proposal is highly suggestive of gout.

Anti-cyclic citrullinated peptide antibodies (ACPA) seem to be produced locally at the site of joints inflammation in the first stage of rheumatoid arthritis (RA). A strong correlation between serum ACPA and ACPA in the synovial fluid (SF-ACPA) is now suggested. A case-control study was conducted to evaluate the usefulness of ACPA determination in SF of patients with RA. A total of 53 patients with a knee-joint effusion (26 RA, 18 peripheral spondyloarthropathies (SPA), and 9 osteoarthritis (OA)) were included in our study. SF samples were obtained by performing therapeutic arthrosynthesis. IgG serum ACPA and SF-ACPA levels were determined by the enzyme-linked immunosorbent assay (ELISA). We have also determined IgG levels in serum and SF by nephelometry. Higher levels of IgG ACPA antibodies in SF (p = 0.045) and serum (p = 0.045) were found in patients with RA with respect to SPA and OA patients. The Spearman correlation analysis showed a significant and positive correlation between ACPA in serum and SF (rho = 0.516; p = 0.007) not only in the RA group but also in patients with SPA. Serum ACPA discriminated RA from non-RA at a cut-off value of 2.7 U/ml (sensitivity, 69%; specificity, 78%; and area under the curve (AUC), 0.72), whereas SF-ACPA discriminated RA from non-RA at a higher cut-off value of 4.95 U/ml (sensitivity, 73%; specificity, 61%; and AUC, 0.71). Our study suggests that the determination of SF-ACPA give complement information to serum ACPA in patients with RA.

Initial treatment of trapeziometacarpal osteoarthritis (TMO) often consists of intra-articular injection of corticosteroids or hyaluronic acid. Several studies have shown that ultrasound (US)-guided injections demonstrate greater precision and effectiveness when compared to blind techniques. The aim of our study was to describe a simple and reliable procedure of US-guided intra-articular injection of hyaluronic acid solution in patients with TMO. Thirty-one patients with TMO received one administration per week, for 3 weeks, of US-guided intra-articular injection with 1 ml of hyaluronic acid solution. Patients were evaluated before treatment and at 1, 3, and 6 months after the first injection with visual analog scale (VAS) score and Duruöz Hand Index (DHI). One month after the end of treatment, subjective patient response to therapy was evaluated using a 6-point Likert scale. A statistically significant VAS score reduction was observed at 1 and 3 months after the end of treatment (P<0.01) but not at 6-month follow-up (P=0.6). No statistically significant difference was found on the DHI total score at 1- (P=0.08), 3- (P=0.1) and 6-month (P=0.9) follow-ups. One month after the end of treatment, 29 (93.5%) patients reported a Likert scale score of "1" or "2." The described US-guided technique of trapeziometacarpal joint injection is easy to perform and revealed excellent accuracy. Nevertheless, intra-articular injections of hyaluronic acid provided significant pain relief only for a 6-month follow-up period and did not improve hand function. No pain relief was detected at 6-month follow-up, suggesting that periodic injections should be required to gain long-term effectiveness.

18F-fluorodeoxyglucose PET (18F-FDG PET) is highly sensitive to inflammatory changes within the synovial tissue in rheumatoid arthritis (RA). However, the highest spatial resolution for soft tissue can be achieved with MRI. Here, we report on the first true hybrid PET-MRI examination of the hand in early RA exploiting the advantages of both modalities. PET-MRI was performed with a prototype of an APD-based magneto-insensitive BrainPET detector (Siemens Healthcare, Erlangen, Germany) operated within a standard 3T MR scanner (MAGNETOM Trio, Siemens). PET images were normalized, random, attenuation and scatter-corrected, iteratively reconstructed and calibrated to yield standardized uptake values (SUV) of 18F-FDG uptake. T1-weighted TSE in coronal as well as sagittal orientation prior to and following Gadolinium administration were acquired. Increased 18F-FDG uptake was present in synovitis and tenovaginitis as identified on contrast-enhanced MRI. The tracer distribution was surrounding the metacarpophalangeal joints II and III. Maximum SUV of 3.1 was noted. In RA, true hybrid 18F-FDG PET-MRI of the hand is technically feasible and bears the potential to directly visualize inflammation.

The increasing average age in developed societies is paralleled by an increase in the prevalence of many age-related diseases such as osteoarthritis (OA), which is characterized by deformation of the joint due to cartilage damage and increased turnover of subchondral bone. Consequently, deficiency in DNA repair, often associated with premature aging, may lead to increased pathology of these two tissues. To examine this possibility, we analyzed the bone and cartilage phenotype of male and female knee joints derived from 52- to 104-week-old WT C57Bl/6 and trichothiodystrophy (TTD) mice, who carry a defect in the nucleotide excision repair pathway and display many features of premature aging. Using micro-CT, we found bone loss in all groups of 104-week-old compared to 52-week-old mice. Cartilage damage was mild to moderate in all mice. Surprisingly, female TTD mice had less cartilage damage, proteoglycan depletion, and osteophytosis compared to WT controls. OA severity in males did not significantly differ between genotypes, although TTD males had less osteophytosis. These results indicate that in premature aging TTD mice age-related changes in cartilage were not more severe compared to WT mice, in striking contrast with bone and many other tissues. This segmental aging character may be explained by a difference in vasculature and thereby oxygen load in cartilage and bone. Alternatively, a difference in impact of an anti-aging response, previously found to be triggered by accumulation of DNA damage, might help explain why female mice were protected from cartilage damage. These findings underline the exceptional segmental nature of progeroid conditions and provide an explanation for pro- and anti-aging features occurring in the same individual.

In this paper, we present a semi-automated segmentation method for magnetic resonance images of the quadriceps muscles. Our method uses an anatomically anchored, template-based initialization of the level set-based segmentation approach. The method only requires the input of a single point from the user inside the rectus femoris. The templates are quantitatively selected from a set of images based on modes in the patient population, namely, sex and body type. For a given image to be segmented, a template is selected based on the smallest Kullback-Leibler divergence between the histograms of that image and the set of templates. The chosen template is then employed as an initialization for a level set segmentation, which captures individual anatomical variations in the image to be segmented. Images from 103 subjects were analyzed using the developed method. The algorithm was trained on a randomly selected subset of 50 subjects (25 men and 25 women) and tested on the remaining 53 subjects. The performance of the algorithm on the test set was compared against the ground truth using the Zijdenbos similarity index (ZSI). The average ZSI means and standard deviations against two different manual readers were as follows: rectus femoris, 0.78 ± 0.12; vastus intermedius, 0.79 ± 0.10; vastus lateralis, 0.82 ± 0.08; and vastus medialis, 0.69 ± 0.16.

Objective: This study aims to explore the potential role of circulating Dickkopf-1 (Dkk-1) and osteoprotegerin (OPG) in evaluating erosive arthritis in systemic lupus erythematosus (SLE)., Methods: Serum Dkk-1 and OPG levels were examined in 130 SLE patients including eight with erosive arthritis, 100 rheumatoid arthritis (RA) patients and 50 healthy individuals by ELISA. Comparison of serum Dkk-1 levels with presence of anti-cyclic citrullinated peptides (CCP) antibodies in evaluating erosive arthritis in SLE was carried out. Associations of Dkk-1 and OPG levels with results of clinical examination were also noted., Results: Dkk-1 levels were significantly increased in eight SLE patients with erosive arthritis, compared to 58 SLE patients with non-erosive arthritis, 64 SLE patients without arthritis, and healthy controls, while similar with RA. In contrast, no significant changes of OPG levels were found except for higher levels in RA. No differences were found in Dkk-1 levels of SLE patients with erosive arthritis subdivided according to presence or absence of anti-CCP antibodies. Moreover, higher levels of Dkk-1 were identified in anti-CCP positive SLE patients with erosive arthritis compared to those with non-erosive arthritis or without arthritis. However, no significant correlations between Dkk-1 and OPG levels or between Dkk-1 levels and other laboratory and clinical manifestations were observed., Conclusions: High levels of circulating Dkk-1 were associated with bone erosion in patients with SLE, even when anti-CCP antibodies were absent.

Background: The definition of generalized osteoarthritis in the literature is just as controversial as the discussion about correlations between GOA and Heberden's nodes (HN). Therefore, both questions were investigated in patients with proven heredity in a genealogical study of 931 family members., Material and Methods: In 106 patients with HN and 109 control subjects, 70 joints and spinal segments were investigated with respect to characteristic functional parameters. In addition, 44 joints and spinal segments were investigated radiologically., Results: GOA affects both the small and large joints as well as the spine. This phenomenon is the more pronounced the more finger joints are affected by Heberden's and Bouchard's nodes., Conclusions: GOA affects the entire musculoskeletal system. The varying manifestation in individual joints and spinal segments is probably attributable to multifactorial local and systemic factors. In an earlier study, a genetic disposition with a maximum HA prevalence of 30% was identified in the study population. Since HA is considered a genetic marker for GOA, it can be assumed that the same is true of GOA prevalence.

Few clinical cases have been published on Stickler syndrome type III, and all describe the pediatric presentation. We describe an adult presentation of the syndrome in a 67-year-old woman and provide a report on the clinical and radiographic features supporting diagnosis. A chart review and updated investigations were performed to elucidate the presenting history and disease progression in the patient. Clinically, the patient was 42 years old when she presented with a 22-year history of bilateral knee pain and atypical osteoarthritis (OA) of an inflammatory but non-erosive character. The patient also reported increasing hearing loss for high-pitched frequencies. Radiography/X-rays at age 42 years showed severe, non-erosive tri-compartmental OA changes. Atypical destructive changes were identified in the small joints. The son of the patient developed left knee pain and bilateral knee swelling since the age of 9 years. He was diagnosed with early-onset OA and also underwent bilateral knee arthroplasties in his third decade, similar to his mother. The grandson presented at age 4 years, with recurrent, acute episodes of pain and swelling in his ankles and knees and was diagnosed with pediatric OA. A mutation of the COL11A2 gene was confirmed in the patient at aged 63 years. This is the first clinical case report on the adult presentation of Stickler syndrome type III. In particular, early-onset OA or an unrecognized skeletal dysplasia can be considered as rationale for genetic testing, screening, and surveillance of both past and present family members of an affected patient.

Primary osteoarthritis (OA) of peripheral joints is a common disease mainly occurring after the age of 50. It is important to distinguish primary from secondary OA. Younger age at disease onset, rapid progression, unusual disease manifestations and co-morbidities are signs of secondary OA. This review outlines an important group of secondary OA. Hereditary metabolic diseases can exhibit joint involvement. For some of these diseases, correct diagnosis is critical, since appropriate therapy influences not only joint function and quality of life, but can also prevent relevant end-organ damage.

Osteoarthritis (OA) is the most common joint disorder worldwide, and it has an enormous socioeconomic impact both in the United States and throughout the world. The degree of articular inflammation is usually associated with the disease's progression, indicating that this process could contribute to articular damage. IL-1 beta and anti-TNF alpha are the two major cytokines players in the physiopathology of OA. Hence, we aimed to review the current literature on the effects of IL-1 and TNF-alpha neutralization as a new OA therapy. In vitro and experimental models showed a reduction in cartilage destruction with IL-1 inhibition therapy by IL-1 receptor antagonists (IL-1Ra). Despite this favorable evidence in animal models, studies on the inhibition of IL-1R in humans are still scarce. Although there is clear evidence that TNF-alpha plays a role in the pathophysiology of OA, only a few experimental trials have investigated the efficacy of blocking this pro-inflammatory cytokine in the treatment of OA. So far, the few studies available in humans using anti-TNF-alpha and IL-1 receptor antagonist are not remarkable, suggesting that further investigation and new therapeutic approaches are needed.

The objective of this study is to assess the reliability of clinical examination in patients with erosive osteoarthritis (EOA). Eighteen patients with EOA underwent clinical examination for joint tenderness, bony swelling, and inflammation by two independent, blinded assessors. All patients were also examined by ultrasound (US) by an independent radiologist. The inter-observer agreement was moderate for bony swelling and joint tenderness and fair for joint inflammation (kappa = 0.513, 0.448, and 0.402, respectively). US detected significantly more inflamed joints than clinical examination. The sensitivity and specificity of clinical examination for joint inflammation were 0.12 and 0.95, respectively. Clinical joint counts for bony swelling, tenderness, and inflammation all correlated with functional status, assessed by the functional index for hand osteoarthritis (FIHOA), whereas US joint counts for joint inflammation did not correlate with the FIHOA. No correlation was found between any clinical or US joint count and visual analog scale for pain. US detects more joints with inflammation than clinical examination in patients with EOA. US can supplement the clinical examination of patients with EOA, as US-detected subclinical joint inflammation might accelerate joint damage and thus functional impairment.

Osteoarthritis is a heterogeneous disease characterized by variable clinical features, biochemical/genetic characteristics, and responses to treatments. To optimize palliative effects of current treatments and develop efficacious disease-modifying interventions, treatments may need to be tailored to the individual or a subset of osteoarthritic joints. The purpose of this review is to explore the current literature on the clinical and physiological variability in osteoarthritis and potential for stratifying patients. Several stratifications have been reported, including mechanism of onset, stage of disease progression, involved joints, inflammatory levels, and effusion. Most of these methods revealed two to three unique subsets of osteoarthritis. Osteoarthritic joints may be stratified by an array of variables, some transient and others consistent throughout the disease process. Future research needs to continue to explore stratification techniques since these may be the key to optimizing palliative interventions and developing disease-modifying interventions for subsets within this heterogeneous disease.

Shoulder pain may occur as a secondary symptom to a wide range of conditions, including rotator cuff disorders, glenohumeral osteoarthritis, or adhesive capsulitis. One common factor linking these diseases is inflammation. Understanding the role of inflammation in shoulder disorders can help physicians to manage and treat these common problems. Here, I document a perspective on these pathologies of shoulder.

This study aimed to validate the use of the Arthritis Impact Measurement Scales 2 (AIMS-2) Hand and Finger Function and Arm Function scales for assessing disability in persons with osteoarthritis (OA) of the hand. Ninety-nine subjects with hand OA completed the AIMS-2 scales, grip strength testing, and timed manipulation tasks. Confirmatory factor analyses determined that the ten items comprising the scales separated out into hand and arm limitations. Spearman correlations revealed the appropriate associations between Hand and Finger Function scale scores and grip strength (r = -0.37) and dexterity (r = 0.36). Arm Function scale scores discriminated individuals with additional upper limb involvement from those without (Mann-Whitney test, p < 0.01). Thus, convergent construct validity of the Hand and Finger Function scale and known-group validity of the Arm Function scale were shown. These AIMS-2 scales are valid and distinct measures of disability in individuals with hand OA.

The objectives of this study were to evaluate the diagnostic value of 99mTc-HMPAO labelled white blood cell scintigraphy (WBCS) in patients with suspected osteomyelitis using late images and to study interobserver reproducibility. This study prospectively included 120 patients, and after a follow-up of one year, only 70 patients (n = 49 with implants, n = 21 without implants) were selected. The final diagnosis of infection was based either on microbiological data (n = 54) or follow-up (n = 16). We performed WBCS with 4 h and 24 h scans. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 77%, 72%, 83%, 64%, and 75% at 4 h, and 74%, 87%, 91%, 59%, and 79% at 24 h, respectively. The interobserver reproducibility shows a 63% prevalence of agreement between results (kappa = 0.5) at 4 h and 80% (kappa = 0.74) at 24 h, respectively. WBCS with 24-h images improves specificity and interobserver reproducibility in patients with suspected osteoarticular sepsis.

Background: Viscosupplementation, with hyaluronan derivates injected into the intra-space of osteoarthritic joints, is now widely used for the treatment of knee osteoarthritis. This study evaluates the results in terms of pain and disability of intra-articular injections of hyaluronan derivates into the ankle joint in patients suffering from grade II primary or secondary osteoarthritis of the ankle., Methods: Twenty-one patients with a painful ankle and radiographic evidence of grade II osteoarthritis had three weekly intra-articular injections of 2 ml of hylan G-F 20 (10 mg/ml) into the ankle joint. The primary clinical outcome measurement was the ankle osteoarthritis score (AOS) at the baseline, and at 6, 12 and 18 months., Results: Significant improvement of the AOS from baseline was seen after 6 months (p=0.0001). This improvement was maintained over time with no further changes at 12- and 18-month follow-ups. Regarding pain, the AOS improved over time from the baseline to the 18-month follow up and became statistically significant at the 12- and 18-month follow-ups (p<0.05).