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Objectives: The objective of this study is to develop classification criteria for overall hand osteoarthritis (OA), interphalangeal OA and thumb base OA based on self-reported data and radiographic features., Methods: The classification criteria sets were developed in three phases. In phase 1, we identified criteria that discriminated hand OA from controls. In phase 2, we used a consensus-based decision analysis approach to derive a clinician-based evaluation of the relative importance of the criteria. In phase 3, we refined the scoring system, determined the cut-offs for disease classification and compared the sensitivity and specificity of the European Alliance of Associations for Rheumatology (EULAR) criteria with the 1990 American College of Rheumatology (ACR) criteria., Results: In persons with hand symptoms and no other disease (including psoriasis) or acute injury that can explain the hand symptoms (mandatory criteria), hand OA can be classified based on age, duration of morning stiffness, number of joints with osteophytes and joint space narrowing, and concordance between symptoms and radiographic findings. Using a sum of scores based on each diagnostic element, overall hand OA can be classified if a person achieves 9 or more points on a 0-15 scale. The cut-off for interphalangeal OA and thumb base OA is 8 points. While the EULAR criteria demonstrated better sensitivity than the ACR criteria in the phase 1 data set, the performance of the two criteria sets was similar in two external cohorts., Conclusions: International experts developed the EULAR criteria to classify overall hand OA, interphalangeal OA and thumb base OA in clinical studies using a rigorous methodology., Competing Interests: Competing interests: IKH reports personal fees from Novartis and GSK; research grants from Pfizer and IMI-APPROACH (both paid to the institution); and unpaid role as secretary general of OARSI, all outside of the submitted work. AA reports institutional research grants from AstraZeneca and Oxford Immunotech; and personal fees from UpToDate (royalty), Springer (royalty), Cadilla Pharmaceuticals (lecture fees), NGM Bio (consulting), Limbic (consulting) and Inflazome (consulting), all outside of the submitted work. FB reports shares of 4P Pharma and 4Moving Biotech; personal fees from Boehringer Ingelgeim, Galapagos, Gilead, GSK, Merck Sereno, MSD, Novartis, Pfizer, Roche, Sanofi, Servier and Viatris; and research grant from TRB Chemedica, all outside the submitted work.Sita Bierma-Zeinstra reports research grants from Dutch Arthritis Association, EU Horizon, EU ERC and ZonMW (paid to institution), personal fees from Pfizer, Infirst healthcare, and paid role as deputy editor of Osteoarthritis and Cartilage, all outside of the submitted work.Krysia Dziedzic reports research grants from National Institute for Health and Care Research (NIHR); royalty/licence for Textbook for Rheumatology Therapists; payment for lecture at Australian Rheumatology Association Conference in May 2022; Implementation Advisor Fellows and Scholars Programme National Institute for Health and Care Excellence (UK 2019-22), Steering group member of NICE Implementation subgroup and Steering group member of OARSI Joint Effort initiative, all paid to institution and outside of the submitted work.Martin Englund reports personal fees from Cellcolabs AB (Sweden) and Key2 Compliance (Sweden), outside of the submitted work. Ying Ying Leung reports grants from National Medical Research Council (NMRC/CSA-INV/0022/2017), and personal fees from AbbVie, DKSH, Janssen, Novartis and Pfizer, outside of the submitted work. EM reports personal fees from Expanscience, Keyrus Life Science, Pierre Fabre, Rottapharm, MEDA-Mylan, Sublimed, TRB Chemedica, outside the submitted work. RR reports personal fees from from Novartis, AbbVie, Pfizer, MSD, Janssen, Lilly; support for attending EULAR, ACR and SIR; advisory board for Janssen, Novartis and Abbvie, outside of the submitted work. TAS reports grants and personal fees from AbbVie and Roche, and personal fees from Sanofi, Takeda and Novartis, outside the submitted work. ZS reports personal fees from AbbVie, Pfizer, Roche, Novartis, Lilly, Gedeon Richter, Sobi/Galapagos, outside of the submitted work. RW reports institutional research grants from Pfizer and Amgen, unrelated to this work, and is a Senior Clinical Investigator of the Research Foundation Flanders (Belgium) (FWO) (1803023N). MK reports consulting fees from Abbvie, Pfizer, Kiniksa, Flexion, Galapagos, Jansen, CHDR, Novartis and UCB (all paid to institution), outside of the submitted work. DF, JJE, MH-E, GH-B, CH, MLI, HJ, TK, CDM, MM, RHM, VR, MJPFR, FVG, LAS, CM, EG and HL report no conflicts of interest., (© European Alliance of Associations for Rheumatology, EULAR 2024. Re-use permitted under CC BY-NC-ND. No commercial re-use. No derivatives. See rights and permissions. Published by BMJ on behalf of EULAR.)

Obesity has a pivotal and multifaceted role in pain associated with osteoarthritis (OA), extending beyond the mechanistic influence of BMI. It exerts its effects both directly and indirectly through various modifiable risk factors associated with OA-related pain. Adipose tissue dysfunction is highly involved in OA-related pain through local and systemic inflammation, immune dysfunction, and the production of pro-inflammatory cytokines and adipokines. Adipose tissue dysfunction is intricately connected with metabolic syndrome, which independently exerts specific effects on OA-related pain, distinct from its association with BMI. The interplay among obesity, adipose tissue dysfunction and metabolic syndrome influences OA-related pain through diverse pain mechanisms, including nociceptive pain, peripheral sensitization and central sensitization. These complex interactions contribute to the heightened pain experience observed in individuals with OA and obesity. In addition, pain management strategies are less efficient in individuals with obesity. Importantly, therapeutic interventions targeting obesity and metabolic syndrome hold promise in managing OA-related pain. A deeper understanding of the intricate relationship between obesity, metabolic syndrome and OA-related pain is crucial and could have important implications for improving pain management and developing innovative therapeutic options in OA., (© 2024. Springer Nature Limited.)

Joint kinematic instability, arising from congenital or acquired musculoskeletal pathoanatomy or from imbalances in anabolism and catabolism induced by pathophysiological factors, leads to deterioration of the composition, structure and function of cartilage and, ultimately, progression to osteoarthritis (OA). Alongside articular cartilage degeneration, synovial fluid lubricity decreases in OA owing to a reduction in the concentration and molecular weight of hyaluronic acid and surface-active mucinous glycoproteins that form a lubricating film over the articulating joint surfaces. Minimizing friction between articulating joint surfaces by lubrication is fundamental for decreasing hyaline cartilage wear and for maintaining the function of synovial joints. Augmentation with highly viscous supplements (that is, viscosupplementation) offers one approach to re-establishing the rheological and tribological properties of synovial fluid in OA. However, this approach has varied clinical outcomes owing to limited intra-articular residence time and ineffective mechanisms of chondroprotection. This Review discusses normal hyaline cartilage function and lubrication and examines the advantages and disadvantages of various strategies for restoring normal joint lubrication. These strategies include contemporary viscosupplements that contain antioxidants, anti-inflammatory drugs or platelet-rich plasma and new synthetic synovial fluid additives and cartilage matrix enhancers. Advanced biomimetic tribosupplements offer promise for mitigating cartilage wear, restoring joint function and, ultimately, improving patient care., (© 2024. Springer Nature Limited.)

Objectives: To determine the incidence of osteoarthrits (OA) in patients with atopic disease compared with matched non-exposed patients., Methods: We conducted a retrospective cohort study with propensity score matching using claims data from Optum's de-identified Clinformatics Data Mart (CDM) (January 2003 to June 2019) and electronic health record data from the Stanford Research Repository (STARR) (January 2010 to December 2020). We included adult patients without pre-existing OA or inflammatory arthritis who were exposed to atopic disease or who were non-exposed. The primary outcome was the development of incident OA., Results: In Optum CDM, we identified 117 346 exposed patients with asthma or atopic dermatitis (mean age 52 years; 60% female) and 1 247 196 non-exposed patients (mean age 50 years; 48% female). After propensity score matching (n=1 09 899 per group), OA incidence was higher in patients with asthma or atopic dermatitis (26.9 per 1000 person-years) compared with non-exposed patients (19.1 per 1000 person-years), with an adjusted odds ratio (aOR) of 1.58 (95% CI 1.55 to 1.62) for developing OA. This effect was even more pronounced in patients with both asthma and atopic dermatitis compared with non-exposed patients (aOR=2.15; 95% CI 1.93 to 2.39) and in patients with asthma compared with patients with chronic obstructive pulmonary disease (aOR=1.83; 95% CI 1.73 to 1.95). We replicated our results in an independent dataset (STARR), which provided the added richness of body mass index data. The aOR of developing OA in patients with asthma or atopic dermatitis versus non-exposed patients in STARR was 1.42 (95% CI 1.36 to 1.48)., Conclusions: This study demonstrates an increased incidence of OA in patients with atopic disease. Future interventional studies may consider targeting allergic pathways for the prevention or treatment of OA., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To summarize proceedings of a workshop convened to discuss the current state of science in the disease of osteoarthritis (OA), identify the knowledge gaps, and examine the developmental and regulatory challenges in bringing these products to market., Design: Summary of the one-day workshop held virtually on June 22nd, 2021., Results: Speakers selected by the Planning Committee presented data on the current approach to assessment of OA therapies, biomarkers in OA drug development, and the assessment of disease progression and long-term benefit., Conclusions: Demonstrated by numerous failed clinical trials, OA is a challenging disease for which to develop therapeutics. The challenge is magnified by the slow time of onset of disease and the need for clinical trials of long duration and/or large sample size to demonstrate the effect of an intervention. The OA science community, including academia, pharmaceutical companies, regulatory agencies, and patient communities, must continue to develop and test better clinical endpoints that meaningfully reflect disease modification related to long-term patient benefit., Competing Interests: Declaration of Competing Interest One or more of the authors has received or will receive benefits for personal or professional use from a commercial party related directly or indirectly to the subject of this article., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: Further knowledge about typical hand osteoarthritis (OA) characteristics is needed for the development of new classification criteria for hand OA., Methods: In a cross-sectional multi-centre international study, a convenience sample of patients from primary and secondary/tertiary care with a physician-based hand OA diagnosis (n = 128) were compared with controls with hand complaints due to inflammatory or non-inflammatory conditions (n = 70). We examined whether self-reported, clinical, radiographic and laboratory findings were associated with hand OA using logistic regression analyses. Discrimination between groups was assessed by calculating the area under receiver operating curves (AUC)., Results: Strong associations with hand OA were observed for radiographic osteophytes (OR = 1.62, 95% CI 1.40 to 1.88) and joint space narrowing (JSN) (OR = 1.57, 95% CI 1.36 to 1.82) in the distal interphalangeal (DIP) joints with excellent discrimination (AUC = 0.82 for both). For osteophytes and JSN, we found acceptable discrimination between groups in the proximal interphalangeal joints (AUC = 0.77 and 0.78, respectively), but poorer discrimination in the first carpometacarpal joints (AUC = 0.67 and 0.63, respectively). Painful DIP joints were associated with hand OA, but were less able to discriminate between groups (AUC = 0.67). Age and family history of OA were positively associated with hand OA, whereas negative associations were found for pain, stiffness and soft tissue swelling in metacarpophalangeal joints, pain and marginal erosions in wrists, longer morning stiffness, inflammatory biomarkers and autoantibodies., Conclusions: Differences in symptoms, clinical findings, radiographic changes and laboratory tests were found in patients with hand OA versus controls. Radiographic OA features, especially in DIP joints, were best suited to discriminate between groups., Competing Interests: Competing interests: Ida K. Haugen reports a research grant from Pfizer, outside the submitted work. Francis Berenbaum reports personal fees from Boehringer, Bone Therapeutics, Expanscience, Galapagos, Gilead, GSK, Merck Sereno, MSD, Nordic, Novartis, Pfizer, Regulaxis, Roche, Sandoz, Sanofi, Servier, UCB, Peptinov, TRB Chemedica, 4P Pharma, outside the submitted work. Sita Bierma-Zeinstra reports grants from The Netherlands Organisation for Health Research and Development, CZ, European Union, Foreum, Dutch Arthritis Association, personal fees from Infirst healthcare, Pfizer and Osteoarthritis and Cartilage, outside the submitted work. Emmanuel Maheu reports personal fees from Expanscience, Mylan-Meda, TRB Chemedica, Pierre Fabre, Celgène and Fidia, and non-financial support from Pfizer, outside the submitted work. Roberta Ramonda reports honoraria for speaking engagements and for Advisory Board from Abbvie, Celgene, Novartis, Pfizer and Lilly. Tanja Stamm received speaker fees from Sanofi, AbbVie and Roche. Désirée van der Heijde reports personal fees from AbbVie, personal fees from Amgen, personal fees from Astellas, personal fees from AstraZeneca, personal fees from BMS, personal fees from Boehringer Ingelheim, personal fees from Celgene, personal fees from Cyxone, personal fees from Daichii, personal fees from Eisai, personal fees from Elly-Lilly, personal fees from Galapagos, personal fees from Gilead, personal fees from GSK, personal fees from Janssen, personal fees from Merck, personal fees from Novartis, personal fees from Pfizer, personal fees from Regeneron, personal fees from Roche, personal fees from Sanofi, personal fees from Takeda, personal fees from UCB Pharma, outside the submitted work; and Director Imaging Rheumatology BV. Ruth Wittoek reports personal fees from Abbvie, personal fees from Galapagos, personal fees from UCB, personal fees from Bristol Myers Squib, personal fees from Tilman, grants from Amgen, outside the submitted work. Margreet Kloppenburg reports grants from European League Against Rheumatism during the conduct of the study, fee for consultancy (Abbvie, Pfizer, Levicept, GlaxoSmithKline, Merck-Serono, Kiniksa, Flexion) and local investigator of industry-driven trial (Abbvie), other from Dutch Society of Rheumatology, Wolters Kluwer (UptoDate) and Springer Verlag (Reumatologie en klinische immunologie), grants from Pfizer, outside the submitted work. David Felson, Abhishek Abhishek, Tove Borgen, Gabriel Herrero-Beaumont, Mariko L. Ishimori, Helgi Jonsson, Féline P.B. Kroon, Valentin Ritschl, Elsie Greibrokk and Wilma Smeets have no conflicts of interest., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: There is conflicting evidence on the association between metabolic syndrome (MetS) with the risk of osteoarthritis (OA). We aimed to systematically summarize the empirical evidence and discuss challenges in research methodologies in addressing this question., Methods: We performed a systematic literature review based on PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews on published epidemiologic studies that examined the association between MetS and the risk of OA. We included cross-sectional studies, case-control studies, and cohort studies with appropriate covariate adjustments. We extracted information on prevalence, incidence, crude and adjusted effect estimates, and the 95% confidence intervals from the articles, or this information was provided by the authors. We listed the main methodologic issues existing in current literature and provided recommendations for future research on this topic., Results: We identified 7 eligible studies on knee OA, 3 on hip OA, and 3 on hand OA. In studies that adjusted for body mass index or weight, MetS was not significantly associated with the risk of knee OA. No significant associations were reported for hip OA. For hand OA, the data were sparse and insufficient to reach a conclusion. Studies were mostly cross-sectional, exposure included only 1 time measurement, few studies had incident outcomes, and covariate adjustment was often insufficient., Conclusion: Our review was unable to reach a definitive conclusion due to insufficient data, although the data suggest that knee and hip OA are not associated with MetS. Future longitudinal studies with incident OA cases, repeated measurement of MetS, and appropriate covariate adjustment are needed., (© 2018, American College of Rheumatology.)

Purpose: Synovitis is common in knee osteoarthritis and is associated with both knee pain and progression of disease. Semiautomated methods have been developed for quantitative assessment of structure in knee osteoarthritis. Our aims were to apply a novel semiautomated assessment method using 3D active appearance modeling for the quantification of synovial tissue volume (STV) and to compare its performance with conventional manual segmentation., Methods: Thirty-two sagittal T 1 -weighted fat-suppressed contrast-enhanced MRIs were assessed for STV by a single observer using 1) manual segmentation and 2) a semiautomated approach. We compared the STV analysis using the semiautomated and manual segmentation methods, including the time taken to complete the assessments. We also examined the reliability of STV assessment using the semiautomated method in a subset of 12 patients who had participated in a clinical trial of vitamin D therapy in knee osteoarthritis., Results: There was no significant difference in STV using the semiautomated quantitative method compared to manual segmentation, mean difference = 207.2 mm 3 (95% confidence interval -895.2 to 1309.7). The semiautomated method was significantly quicker than manual segmentation (18 vs. 71 min). For the semiautomated method, intraobserver agreement was excellent (intraclass correlation coefficient (3,1) = 0.99) and interobserver agreement was very good (intraclass correlation coefficient (3,1) = 0.83)., Conclusion: We describe the application of a semiautomated method that is accurate, reliable, and quicker than manual segmentation for assessment of STV. The method may help increase efficiency of image assessment in large imaging studies and may also assist investigation of treatment efficacy in knee osteoarthritis., (© 2019 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

The prevalence of osteoarthritis (OA) is rising for reasons that are not fully understood. In this Opinion article, we review the possibility that OA is an evolutionary mismatch disease, which is a disease more common today than in the past because genes inherited from previous generations are inadequately or imperfectly adapted to modern environmental conditions. We focus on four major environmental factors in OA pathogenesis that have become ubiquitous within the past half-century: obesity, metabolic syndrome, dietary changes and physical inactivity. Because a cure for OA does not yet exist, prevention strategies that target these modifiable environmental factors are needed to curb further increases in OA prevalence.

Purpose of Review: Osteoarthritis (OA) is a major cause of pain and disability worldwide. There is, however, a relatively poor correlation between the severity of OA based on plain radiograph changes and symptoms. In this review, we consider the mechanisms of pain in OA., Recent Findings: It is now widely recognised that OA is a disease of the whole joint. Data from large observational studies which have used magnetic resonance imaging (MRI) suggest that pain in OA is associated with a number of structural factors including the presence of bone marrow lesions (BMLs) and also synovitis. There is evidence also of alterations in nerve processing and that both peripheral and central nerve sensitisation may contribute to pain in OA. Identification of the causes of pain in an individual patient may be of benefit in helping to better target with appropriate therapy to help reduce their symptoms and improve function.

At a time when advancing understanding of osteoarthritis (OA) has created opportunities for new treatments, development of treatments has remained considerably behind advances in other rheumatic diseases. We describe elements of trial design and measurements that have inhibited success and offer suggestions that may help break the log jam. Among the problems with trials that include pain as an outcome measure are reliance on a single, non-optimal pain outcome, overestimation of likely effects of treatments on pain, and failure to identify patient subgroups most likely to respond to specific treatments. With regard to the use of structure modification as an outcome measure, demonstrating structure modification is often highly challenging, even with the use of magnetic resonance imaging. Many OA patients have advanced disease that is unlikely to respond to treatments that prevent cartilage loss. Further, prevention of cartilage loss and reduction of pain correlate weakly at best, and in at least some patients, reduction in pain may actually increase joint damage, making it impossible to demonstrate dual treatment effects on structure and pain in such scenarios. For structure outcomes, treatment effects on pain-sensitive structures such as bone and synovium may be more achievable than preventing cartilage loss. We suggest that changes in trial design related to some of these issues may increase the chances that new exciting and effective OA treatments will become available., (© 2018, American College of Rheumatology.)

Osteoarthritis (OA) is the most common joint disease in the United States, affecting more than 30 million people, and is characterized by cartilage degeneration in articulating joints. OA can be viewed as a group of overlapping disorders, which result in functional joint failure. However, the precise cellular and molecular events within which lead to these clinically observable changes are neither well understood nor easily measurable. It is now clear that multiple factors, in multiple joint tissues, contribute to degeneration. Changes in subchondral bone are recognized as a hallmark of OA, but are normally associated with late-stage disease when degeneration is well established. However, early changes such as Bone Marrow Lesions (BMLs) in OA are a relatively recent discovery. BMLs are patterns from magnetic resonance images (MRI) that have been linked with pain and cartilage degeneration. Their potential utility in predicting progression, or as a target for therapy, is not yet fully understood. Here, we will review the current state-of-the-art in this field under three broad headings: (i) BMLs in symptomatic OA: malalignment, joint pain, and disease progression; (ii) biological considerations for bone-cartilage crosstalk in joint disease; and (iii) mechanical factors that may underlie BMLs and drive their communication with other joint tissues. Thus, this review will provide insights on this topic from a clinical, biological, and mechanical perspective. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1818-1825, 2018., (© 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Objective: To explore whether metabolic syndrome and its components are associated with hand osteoarthritis (OA) using longitudinal data from the Framingham Study., Methods: Our cross-sectional analyses included 1,089 persons (ages 50-75 years), of whom 785 had longitudinal radiographs obtained 7 years apart. Of these, 586 with no hand OA at baseline were included in analyses of hand OA incidence. We explored associations between metabolic syndrome and its components (central obesity, hypertension, diabetes mellitus, triglyceridemia, and low high-density lipoprotein) and radiographic hand OA (defined as ≥2 interphalangeal joints with a Kellgren/Lawrence [K/L] grade of ≥2) using logistic regression analyses with adjustment for age, sex, and body mass index. In longitudinal analyses, metabolic syndrome was used as a predictor for change in K/L sum score and incident hand OA., Results: Metabolic syndrome was not associated with the presence of hand OA (odds ratio [OR] 1.11 [95% confidence interval (95% CI) 0.78-1.59]), change in K/L sum score (OR 0.83 [95% CI 0.59-1.17]), or incidence of hand OA (OR 0.91 [95% CI 0.58-1.44]). Hypertension was borderline significantly associated with the presence of hand OA (OR 1.25 [95% CI 0.90-1.74]), and a significant association was found between hypertension and change in K/L sum score (OR 1.47 [95% CI 1.08-1.99]). Consistent dose-response relationships were not demonstrated (data not shown). Furthermore, hypertension was not significantly associated with hand OA incidence (OR 1.23 [95% CI 0.82-1.83]). No significant associations were found between metabolic syndrome and erosive hand OA., Conclusion: We found no association between metabolic syndrome and hand OA. The role of hypertension in hand OA pathogenesis warrants further investigation., (© 2017, American College of Rheumatology.)

Objective: Osteoarthritis (OA) is the most common form of arthritis and the leading cause of disability in the elderly. Of all the joints, genetic predisposition is strongest for OA of the hand; however, only few genetic risk loci for hand OA have been identified. Our aim was to identify novel genes associated with hand OA and examine the underlying mechanism., Methods: We performed a genome-wide association study of a quantitative measure of hand OA in 12 784 individuals (discovery: 8743, replication: 4011). Genome-wide significant signals were followed up by analysing gene and allele-specific expression in a RNA sequencing dataset (n=96) of human articular cartilage., Results: We found two significantly associated loci in the discovery set: at chr12 (p=3.5 × 10 -10 ) near the matrix Gla protein (MGP) gene and at chr12 (p=6.1×10 -9 ) near the CCDC91 gene. The DNA variant near the MGP gene was validated in three additional studies, which resulted in a highly significant association between the MGP variant and hand OA (rs4764133, Beta meta =0.83, P meta =1.8*10 -15 ). This variant is high linkage disequilibrium with a coding variant in MGP , a vitamin K-dependent inhibitor of cartilage calcification. Using RNA sequencing data from human primary cartilage tissue (n=96), we observed that the MGP RNA expression of the hand OA risk allele was significantly lowercompared with the MGP RNA expression of the reference allele (40.7%, p<5*10 -16 )., Conclusions: Our results indicate that the association between the MGP variant and increased risk for hand OA is caused by a lower expression of MGP , which may increase the burden of hand OA by decreased inhibition of cartilage calcification., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: To determine radiographic hand osteoarthritis (HOA) prevalence in patients with HIV-1 infection in comparison with the general population and to address whether metabolic syndrome (MetS) may increase the risk of HOA during HIV-1 infection., Patients: Patients with HIV-1 infection and MetS (International Diabetes Federation, IDF criteria) aged 45-65 years were matched by age and gender to HIV-1-infected subjects without MetS and underwent hand radiographs. Framingham OA cohort was used as general population cohort., Methods: Radiographic HOA was defined as Kellgren-Lawrence (KL) score ≥2 on more than one joint. Radiographic severity was assessed by global KL score and number of OA joints. HOA prevalence was compared with that found in the Framingham study, stratified by age and sex. Logistic and linear regression models were used to determine the risk factors of HOA in patients with HIV-1 infection., Results: 301 patients (88% male, mean age 53.4±5.0 years) were included, 152 with MetS and 149 without it. Overall, HOA prevalence was 55.5% and was higher for those with MetS than those without it (64.5% vs 46.3%, p=0.002). When considering men within each age group, HOA frequency was greater in patients with HIV-1 infection than the general population (all ages: 55.8% vs 38.7%; p<0.0001), due to the subgroup with MetS (64.9%; p<0.0001), as well as the subgroup without MetS, although not significant (46.6%; p=0.09). Risk of HOA was increased with MetS (OR 2.23, 95% 95% CI 1.26% to 3.96%) and age (OR 1.18, 95% CI 1.12 to 1.25). HOA severity was greater for patients with MetS than those without. HOA was not associated with previous or current exposure to protease inhibitors or HIV infection-related markers., Conclusions: HOA frequency is greater in patients with HIV-1 infection, especially those with MetS, than the general population., Trial Registration Number: NCT02353767., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Competing Interests: statement The authors declare no competing interests.

Objective: Treatment of OA by stratifying for commonly used and novel therapies will likely improve the range of effective therapy options and their rational deployment in this undertreated, chronic disease. In order to develop appropriate datasets for conducting post hoc analyses to inform approaches to stratification for OA, our aim was to develop recommendations on the minimum data that should be recorded at baseline in all future OA interventional and observational studies., Methods: An Arthritis Research UK study group comprised of 32 experts used a Delphi-style approach supported by a literature review of systematic reviews to come to a consensus on core data collection for OA studies., Results: Thirty-five systematic reviews were used as the basis for the consensus group discussion. For studies with a primary structural endpoint, core domains for collection were defined as BMI, age, gender, racial origin, comorbidities, baseline OA pain, pain in other joints and occupation. In addition to the items generalizable to all anatomical sites, joint-specific domains included radiographic measures, surgical history and anatomical factors, including alignment. To demonstrate clinical relevance for symptom studies, the collection of mental health score, self-efficacy and depression scales were advised in addition to the above., Conclusions: Currently it is not possible to stratify patients with OA into therapeutic groups. A list of core and optional data to be collected in all OA interventional and observational studies was developed, providing a basis for future analyses to identify predictors of progression or response to treatment., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objectives: To study whether hand osteoarthritis (OA) is associated with increased mortality and cardiovascular events in a large community based cohort (Framingham Heart Study) in which OA, mortality and cardiovascular events have been carefully assessed., Methods: We examined whether symptomatic (≥1 joint(s) with radiographic OA and pain in the same joint) and radiographic hand OA (≥1 joint(s) with radiographic OA without pain) were associated with mortality and incident cardiovascular events (coronary heart disease, congestive heart failure and/or atherothrombotic brain infarction) using Cox proportional hazards models. In the adjusted models, we included possible confounding factors from baseline (eg, metabolic factors, medication use, smoking/alcohol). We also adjusted for the number of painful joints in the lower limb and physical inactivity., Results: We evaluated 1348 participants (53.8% women) with mean (SD) age of 62.2 (8.2) years, of whom 540 (40.1%) and 186 (13.8%) had radiographic and symptomatic hand OA, respectively. There was no association between hand OA and mortality. Although there was no significant relation to incident cardiovascular events overall or a relation of radiographic hand OA with events, we found a significant association between symptomatic hand OA and incident coronary heart disease (myocardial infarction/coronary insufficiency syndrome) (HR 2.26, 95% CI 1.22 to 4.18). The association remained after additional adjustment for pain in the lower limb or physical inactivity., Conclusions: Symptomatic hand OA, but not radiographic hand OA, was associated with an increased risk of coronary heart disease events. The results suggest an effect of pain, which may be a possible marker of inflammation., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Studies suggest that many persons with painful osteoarthritis already have extensive structural disease including malalignment, which may preclude successful stabilization or reversal of disease; this provides a strong rationale for developing strategies to prevent disease or to identify and treat it early. This article reviews a variety of approaches likely to capture those at high risk of or with early disease. However, given the absence of effective treatments, it is unclear whether structural disease could be successfully slowed or prevented in those with early symptoms or at high risk of disease., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Research for the use of biomarkers in osteoarthritis (OA) is promising, however, adequate discrimination between patients and controls may be hampered due to innate differences. We set out to identify loci influencing levels of serum cartilage oligomeric protein (sCOMP) and urinary C-telopeptide of type II collagen (uCTX-II)., Methods: Meta-analysis of genome-wide association studies was applied to standardised residuals of sCOMP (N=3316) and uCTX-II (N=4654) levels available in 6 and 7 studies, respectively, from TreatOA. Effects were estimated using a fixed-effects model. Six promising signals were followed up by de novo genotyping in the Cohort Hip and Cohort Knee study (N = 964). Subsequently, their role in OA susceptibility was investigated in large-scale genome-wide association studies meta-analyses for OA. Differential expression of annotated genes was assessed in cartilage., Results: Genome-wide significant association with sCOMP levels was found for a SNP within MRC1 (rs691461, p = 1.7 × 10(-12)) and a SNP within CSMD1 associated with variation in uCTX-II levels with borderline genome-wide significance (rs1983474, p = 8.5 × 10(-8)). Indication for association with sCOMP levels was also found for a locus close to the COMP gene itself (rs10038, p = 7.1 × 10(-6)). The latter SNP was subsequently found to be associated with hip OA whereas COMP expression appeared responsive to the OA pathophysiology in cartilage., Conclusions: We have identified genetic loci affecting either uCTX-II or sCOMP levels. The genome wide significant association of MRC1 with sCOMP levels was found likely to act independent of OA subtypes. Increased sensitivity of biomarkers with OA may be accomplished by taking genetic variation into account., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

With a frustrating lack of progress in the development of treatments for osteoarthritis, EULAR has released recommendations to reorient research into this disease. These recommendations include focused attention on noncartilagenous tissues, the interaction of structures within the joint, the pathogenesis of osteoarthritic pain, new treatment strategies and early disease.

Femoroacetabular impingement (FAI) is an increasingly recognized cause of hip pain. It is best defined as a pathologic mechanical process by which morphologic abnormalities of the acetabulum and/or femur combined with vigorous hip motion lead to repetitive collisions that damage the soft-tissue structures within the joint itself. Based on cross-sectional studies in which FAI morphology was studied before the presence of radiographic osteoarthritis (OA), and on prevalence studies in younger, asymptomatic persons, it is clear that FAI and its morphologic risk factors are common in young adult hips and predispose to the later development of OA in certain patients. Longitudinal studies also support the assertion that, in middle-aged adults, the presence of cam deformities at baseline substantially increases the risk of developing OA and the need for total hip arthroplasty. More long-term data are needed to better define the natural history of pincer deformities as well as FAI in younger cohorts.

Objective: To examine whether erosive hand osteoarthritis (OA) is associated with knee subchondral bone attrition (SBA) and systemic bone mineral density (BMD)., Methods: Associations of MRI-defined knee SBA with radiographic erosive hand OA were evaluated in 1253 Framingham participants using logistic regression with generalised estimating equations. We also examined the association between the number of erosive OA finger joints and SBA adjusted for the number of non-erosive OA finger joints. Associations between erosive hand OA and femoral neck BMD were explored in 2236 participants with linear regression. Analyses were adjusted for age, sex and body mass index., Results: Participants with erosive hand OA had increased odds of knee SBA (OR=1.60, 95% CI 1.07 to 2.38). The relation between the number of erosive OA finger joints and SBA became non-significant when adjusted for the number of non-erosive OA joints as a proxy for the burden of disease. There was a non-significant trend towards higher BMD in erosive hand OA compared with participants without hand OA., Conclusions: Erosive hand OA was associated with knee SBA, but the relation might be best explained by a heightened burden of disease. No significant relation of erosive hand OA with BMD was found.

Objective: Enthesopathy has been reported as a feature of osteoarthritis (OA) in the distal interphalangeal (DIP) joints. We previously reported that central bone marrow lesions (BML) on magnetic resonance imaging (MRI) scans are associated with OA. In this study, we evaluated whether hand and knee enthesopathy were related., Methods: We studied knee and hand radiographs of subjects from the Framingham Osteoarthritis Study. Subjects seen in 2002-2005 had bilateral posteroanterior hand radiographs, weight-bearing knee radiographs, and knee MRI scans. Hand radiographs were read for enthesophytes at the juxtaarticular nonsynovial areas of metacarpophalangeal (MCP), proximal interphalangeal (PIP), and DIP joints, and midshafts of the phalanges. We selected 100 cases of knees with central BML and 100 matched controls. Conditional logistic regression was used to assess associations., Results: Subjects with enthesophytes of at least 1 score ≥ 2 at DIP, PIP, and/or MCP were not more likely to have central knee BML (OR 0.49, 95% CI 0.17-1.40) than those without enthesophytes. Similarly, having at least 1 score ≥ 2 on the shafts was not significantly associated with having a central knee BML (OR 0.59, 95% CI 0.23-1.51). Adjustment for the presence of diabetes mellitus did not affect these results, but there was an increased prevalence of diabetes in those with hand enthesophytes (OR 3.09, 95% 1.29-7.40, enthesophyte score ≥ 2)., Conclusion: We found no increase in the prevalence of hand enthesophytes among persons with central knee BML on their knee MRI scans. This provides evidence against a systemic enthesopathic disorder in association with knee OA.

Objectives: This review article provides an overview of the current state of imaging of synovitis in osteoarthritis (OA), looking at recent advances and controversies and focusing particularly on the application of ultrasound and magnetic resonance imaging (MRI) in the assessment of the hand and knee joint. Computed tomography and nuclear medicine including positron emission tomography are also briefly discussed., Methods: PubMed and MEDLINE search for articles published up to 2010, using the keywords synovitis, osteoarthritis, rheumatoid arthritis, pathogenesis, imaging, radiography, computed tomography, nuclear medicine, magnetic resonance imaging, ultrasound, and pain., Results: Synovitis is defined as inflammation of the synovial membrane. Modern imaging techniques have demonstrated that synovial pathology is common in the early and late stages of OA and may be associated with pain. The current standard for OA imaging in clinical practice is conventional radiography but it does not allow direct visualization of synovitis. MRI without contrast administration, although widely used in clinical studies, cannot assess synovitis directly. Contrast-enhanced MRI and ultrasound, however, both allow direct visualization of synovitis including early inflammatory changes. They are regularly used to image synovitis in rheumatoid arthritis and increasingly in OA., Conclusions: Synovitis is increasingly recognized as an important feature of the pathophysiology of OA, although there is conflicting evidence with respect to its association with disease severity and clinical parameters. Contrast-enhanced MRI and ultrasound are the most important methods for assessing synovitis associated with OA., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objectives: To describe the prevalence and longitudinal course of radiographic, erosive and symptomatic hand osteoarthritis (HOA) in the general population., Methods: Framingham osteoarthritis (OA) study participants obtained bilateral hand radiographs at baseline and 9-year follow-up. The authors defined radiographic HOA at joint level as Kellgren-Lawrence grade (KLG)≥2, erosive HOA as KLG≥2 plus erosion and symptomatic HOA as KLG≥2 plus pain/aching/stiffness. Presence of HOA at individual level was defined as ≥1 affected joint. The prevalence was age-standardised (US 2000 Population 40-84 years)., Results: Mean (SD) baseline age was 58.9 (9.9) years (56.5% women). The age-standardised prevalence of HOA was only modestly higher in women (44.2%) than men (37.7%), whereas the age-standardised prevalence of erosive and symptomatic OA was much higher in women (9.9% vs 3.3%, and 15.9% vs 8.2%). The crude incidence of HOA over 9-year follow-up was similar in women (34.6%) and men (33.7%), whereas the majority of those women (96.4%) and men (91.4%) with HOA at baseline showed progression during follow-up. Incident metacarpophalangeal and wrist OA were rare, but occurred more frequently and from an earlier age in men than women. Development of erosive disease occurred mainly in those with non-erosive HOA at baseline (as opposed to those without HOA), and was more frequent in women (17.3%) than men (9.6%)., Conclusions: The usual female predominance of prevalent and incident HOA was less clear for radiographic HOA than for symptomatic and erosive HOA. With an ageing population, the impact of HOA will further increase.

Objective: Factors associated with mineralization and osteophyte formation in osteoarthritis (OA) are incompletely understood. Genetic polymorphisms of matrix Gla protein (MGP), a mineralization inhibitor, have been associated clinically with conditions of abnormal calcification. We therefore evaluated the relationship of MGP concentrations and polymorphisms at the MGP locus to hand OA., Methods: Ours was an ancillary study to a 3-year randomized trial assessing the effect of vitamin K supplementation on vascular calcification and bone loss among community-dwelling elders. We studied participants who had serum MGP concentration measured and DNA genotyped for 3 MGP genetic polymorphisms (rs1800802, rs1800801, and rs4236), and who had hand radiographs. We evaluated the cross-sectional associations of serum MGP and the 3 MGP genetic polymorphisms, respectively, with radiographic hand OA using logistic regression with generalized estimating equations, adjusting for potential confounders., Results: Radiographic hand OA in ≥ 1 joint was present in 71% of the 376 participants (mean age 74 years, mean body mass index 28 kg/m(2), 59% women). No significant association between serum MGP concentrations and radiographic hand OA was found [adjusted OR 1.0 (ref), 1.40, 1.21, and 1.21 for quartiles 1-4, respectively]. Homozygosity of the rs1800802 minor allele was associated with 0.56 times lower prevalence of hand OA compared with having ≥ 1 major allele at this locus (95% CI 0.32-0.99, p = 0.046)., Conclusion: There may be an association between hand OA and genetic polymorphism at the MGP locus that is not reflected by total MGP serum concentrations. Further studies are warranted to replicate and elucidate potential mechanisms underlying these observed associations.

Objective: To investigate the associations of index finger-to-ring finger (2D:4D) length ratio with radiographic knee and hand osteoarthritis (OA), previous knee injury, and meniscal lesions in the general population., Methods: We measured the length of the right second and fourth phalangeal and metacarpal bones on hand radiographs from 1,020 randomly recruited subjects (ages 51-92 years). Knee radiography and magnetic resonance imaging (MRI) were performed on subjects. Women and men were divided into tertiles according to their 2D:4D phalangeal and metacarpal ratios. We assessed the odds ratios (ORs) and 95% confidence intervals (95% CIs) for radiographic knee OA, severe symptomatic knee OA, radiographic hand OA, previous knee injury, and MRI-defined meniscal lesion, using logistic regression with adjustment for age and body mass index. Because hand OA may affect the 2D:4D phalangeal ratio, we performed sensitivity analyses in subjects without joint space narrowing in the second and fourth interphalangeal joints., Results: We found no significant associations between 2D:4D length ratio and radiographic knee OA, severe symptomatic knee OA, or meniscal lesions. Low 2D:4D phalangeal ratio was associated with hand OA in women (OR 1.80, 95% CI 1.11-2.93), but in the sensitivity analysis, the association was attenuated (OR 1.35, 95% CI 0.79-2.32). Low 2D:4D phalangeal ratios were associated with knee injury in men (OR 1.78, 95% CI 1.02-3.10). We found no significant associations for 2D:4D metacarpal ratios., Conclusion: Low 2D:4D phalangeal ratios in men are associated with knee injury, but we did not find any significant association with knee OA. Low 2D:4D length ratio may be a consequence, rather than a cause, of hand OA in women., (Copyright © 2011 by the American College of Rheumatology.)

Objective: Patellar bracing is a mechanical treatment strategy for patellofemoral osteoarthritis (OA) that aims to unload the lateral compartment of the joint by translating the patella medially. Our objective was to determine whether a patellar brace can correct patellar kinematics in patients with patellofemoral OA., Design: We assessed the effect of a patellar brace on three-dimensional patellar kinematics (flexion, spin and tilt; proximal, lateral and anterior translation) at sequential, static knee postures, using a validated magnetic resonance imaging (MRI)-based method, in 19 patients with radiographic lateral patellofemoral OA. Differences in kinematics between unbraced and braced conditions were assessed in the unloaded and loaded knee (15% bodyweight load) using hierarchical linear random-effects models. Random slope and quadratic terms were included in the model when significant (P<0.05)., Results: Bracing with load caused the patellae to translate 0.46 mm medially (P<0.001), tilt 1.17° medially (P<0.001), spin 0.62° externally (P=0.012) and translate 1.09 mm distally (P<0.001) and 0.47 mm anteriorly (P<0.001) over the range of knee flexion angles studied. Bracing also caused the patellae to extend in early angles of knee flexion (P<0.001). The brace caused similar trends for the unloaded condition, though magnitudes of the changes varied., Conclusion: Bracing changed patellar kinematics, but these changes did not appear large enough to be clinically meaningful because no reduction in pain was observed in the parent study., (Copyright © 2011 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: We examined reported associations between radiographic hand osteoarthritis (OA) and single-nucleotide polymorphisms (SNP) in 2 candidate genes associated with OA in other joints: estrogen receptor alpha (ESR1) and beta (ESR2)., Methods: In 539 Framingham Offspring Study participants (49% men; mean age 61 +/- 9 yrs) joint-specific radiographic hand OA was defined as Kellgren/Lawrence (K/L) scores >or= 2 in the first carpometacarpal joint (CMC), distal interphalangeal joints (DIP), first-digit interphalangeal joint (IP), or proximal interphalangeal joints (PIP). Four SNP were genotyped for ESR1 (PvuII-rs2234693, XbaI-rs9340799, rs2077647, and rs1801132) and 4 for ESR2 (rs1256031, rs1256034, rs1256059, rs944460). Logistic regression analyses were performed to evaluate the relationships between genotypes and hand OA, adjusting for age, sex, height, and weight., Results: Radiographic hand OA was identified in at least one investigated joint of DIP (39%), PIP (33%), and first CMC (40%). There was no evidence of association between OA and genotype at any polymorphism. We found no significant association between our OA phenotypes or generalized or severe generalized OA as defined by Ushiyama and heterozygosity for rs2234693 and rs9340799, although in metaanalysis with the former study this heterozygosity remained significantly associated with generalized or severe generalized OA., Conclusion: We found no significant association between hand OA and the investigated polymorphisms of ESR1 or ESR2 despite published reports of association and a priori hypotheses implicating their potential roles. However, we could not absolutely exclude associations with rs2234693, rs9340799, or rs944460.

With the recognition that osteoarthritis is a disease of the whole joint, attention has focused increasingly on features in the joint environment which cause ongoing joint damage and are likely sources of pain. This article reviews current ways of assessing osteoarthritis progression and what factors potentiate it, structural abnormalities that probably produce pain, new understandings of the genetics of osteoarthritis, and evaluations of new and old treatments.

Objectives: Vitamin K has bone and cartilage effects, and previously shown to be associated with radiographic osteoarthritis. We evaluated vitamin K's effect on hand osteoarthritis in a randomised controlled trial., Methods: This was an ancillary study to a randomised controlled trial assessing the effects of phylloquinone supplementation (vitamin K arm) versus placebo on bone loss and vascular calcification among older adults regardless of their vitamin K status. At the final 3-year study visit, we assessed the effects of vitamin K versus placebo on hand x-ray features of osteoarthritis using logistic regression and intention to treat, and also restricted analysis to the subgroup that had insufficient vitamin K concentrations at baseline., Results: This ancillary study had 378 participants (193 in vitamin K arm, 185 in placebo arm). There were no effects of randomisation to vitamin K for radiographic osteoarthritis outcomes. Those with insufficient vitamin K at baseline who attained sufficient concentrations at follow-up had trends towards 47% less joint space narrowing (p = 0.02)., Conclusions: There was no overall effect of vitamin K on radiographic hand osteoarthritis., Subjects: that were insufficient in vitamin K at baseline who attained sufficient concentrations at follow-up may have had a benefit in joint space narrowing. A clinical trial in those who are vitamin K insufficient may be warranted., Trial Registration Number: NCT00183001.

Background: Bisphosphonates may have chondroprotective effects that could be of relevance in osteoarthritis. Using data from a large fracture prevention trial, we evaluated the effect of alendronate on the progression of radiographic spinal osteophytes (OST) and disc-space narrowing (DSN)., Methods: The Fracture Intervention Trial (FIT) evaluated the effectiveness of alendronate at 5 mg/day (first 2 years) followed by 10 mg/day (third year) vs placebo over 3-4 years in preventing osteoporotic fractures. In 200 randomly selected subjects from FIT, we read baseline and follow-up lateral x rays for anterior OST and DSN (both scored 0-3 at each vertebral level) in the thoracic and lumbar spine. We calculated the mean difference in change in the sum of OST and DSN scores at T4 to L5 from baseline to follow-up, respectively, in each treatment arm using linear regression., Results: The participants' baseline characteristics were similar in the alendronate and placebo arms. The adjusted mean change in summary OST score was less in the alendronate group compared to placebo (3.2 vs 4.7, p = 0.04), indicating that OST progression was less in the alendronate group. The adjusted mean change in summary DSN score was less in the alendronate group vs placebo for the whole spine (0.4 vs 0.7, p = 0.2), particularly when limited to the lumbar spine (0.3 vs 0.6, p = 0.04)., Conclusions: In this secondary analysis of data from a randomised controlled trial, alendronate was associated with less spinal OST and DSN progression than placebo. This suggests a role for bisphosphonates in altering the pathological processes seen in osteoarthritis.

Objective: To determine whether bone attrition (flattening or depression of the subchondral bone) was associated with the presence and severity of knee pain and to evaluate the coexistence of attrition and other MRI features likely associated with pain., Methods: Participants in the Framingham Osteoarthritis Study, a community cohort unselected for OA, answered questions about knee pain and underwent knee x rays and MRI. Attrition, bone marrow lesions (BMLs) and effusions were scored on MRI using the WORMS scale. We assessed attrition in knees with and without pain, and using logistic regression examined its association with pain adjusting for age, gender, Kellgren-Lawrence (K-L)grade, BMI, BML and effusion. We also explored the relation between attrition, pain severity and nocturnal pain., Results: Attrition (Grade >2) was present in 28% (167/592) of painful knees and in 10% (106/1035) of nonpainful knees (adjusted OR 1.6 (95% CI 1.1 to 2.2)). Of knees with OA (n=368), 74% had pain if attrition was present and 58% if it was absent (adjusted OR 1.2 (95%CI 0.7 to 2.0)). Of knees without OA (n=1222), pain was reported in 39% of knees with attrition and in 27%without it (adjusted OR 2.1 (95% CI 1.1 to 4.0)). We found no association between either attrition/pain severity or attrition/nocturnal pain. Attrition often co-occurred with other OA features associated with pain such as BMLs and effusions., Conclusions: Attrition was associated independently with knee pain. Unlike knees without OA, the association was lost in OA knees where other pathological features that may cause pain also coexisted.

Objective: Investigators in trials of glucosamine report a range of estimates for efficacy, making conclusions difficult. We undertook this study to identify factors that explain heterogeneity in trials of glucosamine., Methods: We searched for reports of trial results in Ovid Medline, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and proceedings of scientific conferences. We selected reports of randomized, double-blind, placebo-controlled trials of glucosamine for pain from osteoarthritis of the knee or hip. We extracted data regarding features of design, subjects, and markers of industry involvement, including industry funding, whether a drug was supplied by industry, industry participation, and industry-affiliated authorship. We examined which factors best accounted for differences in the effect sizes of studies grouped by these characteristics, and we examined changes in I(2), a measure of heterogeneity., Results: Fifteen trials met our inclusion criteria. The summary effect size was 0.35 (95% confidence interval 0.14, 0.56). I(2) was 0.80. Except for allocation concealment, no feature of study design explained this substantial heterogeneity. Summary effect sizes ranged from 0.05 to 0.16 in trials without industry involvement, but the range was 0.47-0.55 in trials with industry involvement. The effect size was 0.06 for trials using glucosamine hydrochloride and 0.44 for trials using glucosamine sulfate. Trials using Rottapharm products had an effect size of 0.55, compared with 0.11 for the rest., Conclusion: Heterogeneity among trials of glucosamine is larger than would be expected by chance. Glucosamine hydrochloride is not effective. Among trials with industry involvement, effect sizes were consistently higher. Potential explanations include different glucosamine preparations, inadequate allocation concealment, and industry bias.

Objective: To evaluate the relationship between chondrocalcinosis and the progression of knee osteoarthritis (OA) using longitudinal magnetic resonance imaging (MRI) assessments., Methods: Longitudinal knee MRIs were obtained in the Boston OA Knee Study (BOKS) and in the Health, Aging and Body Composition (Health ABC) Study. Chondrocalcinosis was determined as present or absent on baseline knee radiographs. Cartilage morphology was graded on paired longitudinal MRIs using the Whole-Organ Magnetic Resonance Imaging Score in 5 cartilage subregions of each of the medial and lateral tibiofemoral joints. Cartilage loss in a subregion was defined as an increase in the cartilage score of > or = 1 (0-4 scale). The risk for change in the number of subregions with cartilage loss was assessed using Poisson regression, with generalized estimating equations to account for correlations. Analyses were adjusted for age, sex, body mass index, baseline cartilage score, and presence of damaged menisci., Results: In BOKS, 23 of the 265 included knees (9%) had chondrocalcinosis. In Health ABC, 373 knees were included, of which 69 knees (18.5%) had chondrocalcinosis. In BOKS, knees with chondrocalcinosis had a lower risk of cartilage loss compared with knees without chondrocalcinosis (adjusted risk ratio [RR] 0.4, 95% confidence interval [95% CI] 0.2-0.7) (P = 0.002), and there was no difference in risk in Health ABC (adjusted RR 0.9, 95% CI 0.6-1.5) (P = 0.7). Stratification by intact versus damaged menisci produced similar results within each cohort., Conclusion: In knees with OA, the presence of chondrocalcinosis was not associated with increased cartilage loss. These findings do not support the hypothesis that chondrocalcinosis worsens OA progression.

Objective: Osteoarthritis (OA) of the thumb carpo-metacarpal joint is a common condition that can lead to substantial pain, instability, deformity, and loss of motion. It has been hypothesized that instability of the trapeziometacarpal joint combined with strenuous use can potentially lead to OA. However, as yet there have been no longitudinal evaluations to determine if this hypothesis is true. We examined the relation of radial subluxation to the risk of radiographic OA at trapeziometacarpal joint., Methods: We conducted a nested case-control study. We restricted our evaluation of cases to subjects with no radiographic trapeziometacarpal OA at baseline (1967). We defined incident trapeziometacarpal OA as the development of a modified Kellgren and Lawrence grade>or=2 in that joint at a later examination (1992-1993). Radial subluxation of the base of the first metacarpal off the trapezium and the amount of the base of the first metacarpal covering the articulating surface of the trapezium were measured using a digital calculation caliper. We examined the relation of gender-specific quartile groups of radial subluxation to the risk of trapeziometacarpal OA using a conditional logistic regression model., Results: We assessed 203 men and 431 women. After adjusting for age, handedness, number of other joints with OA, and grip strength, the odds ratios for the risk of trapeziometacarpal OA in men were 1.0, 1.8, 2.7, and 3.1 from the lowest quartile of radial subluxation to the highest quartile, respectively (P for trend=0.015). There was no significant relationship between radial subluxation quartiles and incident trapeziometacarpal OA in women., Conclusion: This study provides evidence that radial subluxation predisposes to subsequent OA of the trapeziometacarpal joint in men.

This article discusses epidemiologic study designs for osteoarthritis and why traditional designs are outmoded. It reviews the design of new studies, the Osteoarthritis Initiative and Multicenter Ostroarthritis Study.

Joint damage occurs when structures protecting the joint fail. Because osteoarthritis consists of end-stage joint damage, I propose that risk factors for disease can be best understood as either impairments of joint protectors, increasing joint vulnerability, or as factors that excessively load the joint, leading to injury. I review current knowledge using this paradigm, separating factors into those increasing joint vulnerability (malalignment, muscle weakness, genetic and ethnic predispositions, aging) and those that cause excessive loading (obesity; certain physical activities). Osteoarthritis and cartilage loss can occur without pain. This review focuses separately on factors associated with pain in those with osteoarthritis. To identify sources of pain in osteoarthritis, recent studies have compared magnetic resonance imaging findings of people with osteoarthritis with and without pain, focusing on structures known to have nociceptive innervations. Those with pain are more likely to have effusions, bone marrow lesions, synovial hypertrophy, and tendinitis and bursitis around the joint. This review creates a new paradigm for understanding risk factors for osteoarthritis, using joint vulnerability and loading as a framework and focuses separately on the emerging investigative area of sources of pain.