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Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
14708887 Proteome analysis of diseased joints from mice suffering from collagen-induced arthritis. 2003 Dec Strains of mice that are susceptible to autoimmunity have provided experimental models to analyze the molecular basis for the complex multifactorial inheritance of human autoimmune disease. In this study proteins associated with collagen-induced arthritis (CIA) in mice were experimentally identified using a global proteomics approach. Two-dimensional gels of proteins from inflamed and non-inflamed joints showed a distinguished protein profile visualizing about 530 Coomassie-stained protein spots in the pH 4-7 range. A total of 76 spots were identified by peptide mass fingerprinting with good confidence. They included proteins of cytoskeletal origin, chaperones, enzymes and also some signal transduction molecules. Comparison to gels from non-inflamed paws pointed to proteins that were differentially expressed between the control and diseased state. Ferritin light chain and antioxidant protein 2 were slightly more abundant, lymphoid enhancer binding factor 1 slightly, but significantly, less abundant in inflamed paws. Fourteen of the identified proteins were the products of genes that had increased transcript levels in the diseased state. However, on the protein level no significant differences were found in comparison to the controls. This study provides us with the framework for more detailed approaches to understanding the complex disease arthritis that go beyond global proteomics.
15361395 Hand cortical bone mass and its associations with radiographic joint damage and fractures 2004 Oct OBJECTIVE: To investigate the relationship between hand bone mineral density (BMD) and radiographic joint damage, and between hand BMD and fractures in 50-70 year old women with longstanding RA. METHODS: Demographic, clinical data, and imaging data on hand radiographs and Genants vertebral deformity score on spine radiographs were collected from 135 women with RA of > or =5 years, recruited from three European rheumatology clinics. Metacarpal hand BMD was measured by digital hand x ray radiogrammetry (DXR), and hip and lumbar spine BMD by dual x ray absorptiometry (DXA). Multiple regression analyses were used to examine associations between hand BMD and radiographic joint damage, and hand BMD and fractures. RESULTS: Hand BMD was strongly and independently associated with radiographic hand joint damage in a linear regression model adjusted for age, centre, BMI, disease duration, RF, 18 deformed joint count, ESR, and femoral neck BMD. In a multivariate logistic regression model adjusted for relevant variables, hand BMD and femoral neck BMD, but not spine BMD, were independently associated with vertebral deformities and with non-vertebral fractures. CONCLUSION: BMD measured by DXR on conventional hand radiographs in patients with RA may potentially be used as an indicator of joint damage and of vertebral and non-vertebral fracture risk.
12355009 Synovial tissue of the hip at power Doppler US: correlation between vascularity and power 2002 Oct PURPOSE: To correlate power Doppler ultrasonographic (US) findings of the vascularity of synovial tissue of the hip joint with the results of histopathologic examination of the same tissue to assess the value of power Doppler US in the visualization of synovitis. MATERIALS AND METHODS: The hip joints of 24 patients with osteoarthritis (n = 15) or rheumatoid arthritis (n = 9) of the hip joint were examined with US before arthroplasty. The vascularity of the synovial membrane was classified qualitatively by using power Doppler US. During surgery, a section of the synovial tissue examined at power Doppler US preoperatively was resected. The vascularity of the tissue specimen was investigated and graded qualitatively by a pathologist who was not aware of the US findings. Visual qualitative grading was controlled by means of analysis of the US images and histopathologic specimens with a digital image evaluation system. Correlations between power Doppler US and histopathologic examination findings were calculated by using Spearman rank correlation and Pearson correlation tests. RESULTS: The correlation between the qualitative power Doppler US results and the qualitative vascularity grades was 0.92 (P <.01, Spearman rho). The correlation between quantitative and qualitative results was 0.93 (P <.01, Spearman rho) for US imaging and 0.97 (P <.01, Spearman rho) for histopathologic examination. CONCLUSION: Study results showed power Doppler US to be reliable for qualitative grading of the vascularity of synovial tissue of the hip.
14623946 Central role of mitochondria and p53 in Fas-mediated apoptosis of rheumatoid synovial fibr 2004 Mar OBJECTIVE: Fas-mediated apoptosis is preferentially observed in synoviocytes of patients with rheumatoid arthritis (RA) and is associated with the pathophysiological process of RA. To clarify the molecular mechanisms of Fas-mediated apoptosis of RA synoviocytes, we investigated the role of the mitochondrial pathway and tumour suppressor p53 in this process. METHODS: Cultured synovial fibroblasts were prepared from RA patients. After treatment of RA synovial fibroblasts with anti-Fas monoclonal antibody, the expression levels of activated caspase-9 and -3, Bid cleavage, cytochrome c release and phosphorylation of p53 at Ser15 were assessed using immunoblot analysis. The mitochondrial membrane potential (DeltaPsim) was evaluated with a fluorescence-based detection assay. Apoptotic cells were determined by a DNA fragmentation assay in the presence or absence of caspase inhibitors. Expression of p53-regulated apoptosis-inducing protein 1 (p53AIP1) was measured by real-time PCR. RA synovial fibroblasts stably transfected with a dominant-negative (DN) p53 were prepared in order to investigate the role of p53 during Fas-induced apoptosis. RESULTS: Fas ligation induced Bid cleavage, loss of DeltaPsim, cytochrome c release to the cytosol and activation of caspase-9 and -3 in RA synovial fibroblasts. Treatment with a caspase-9-specific inhibitor almost completely inhibited Fas-mediated apoptosis. Moreover, p53 activation after Fas ligation was evidenced by its phosphorylation at Ser15 and up-regulation of the p53 target gene p53AIP1. Fas-mediated apoptosis was significantly suppressed by anti-sense p53 oligonucleotides and by p53DN. CONCLUSION: Our findings strongly suggest the involvement of mitochondria and p53 in Fas-mediated apoptosis of RA synovial fibroblasts.
15318821 [Effects of immunosuppressive therapy on cellular immunity status in elderly patients with 2004 Apr The article presents the findings of the immunological study of 57 elderly patients with rheumatoid arthritis, which had been given for a long period of time methotrexate (MT) and sulfasaline (SF). It was established that MT and SF basic therapy have led to progressive decreasing in absolute and relative quantity and an average diameter of CD4+, CD8, CD16, CD19 lymphocytes. It also resulted in lowering proliferative response of mononuclear lymphocytes (ML) to mitogens, increasing spontaneous and Fas-induced apoptosis of ML. The study revealed peculiarities of cellular immunity alterations in the patients with rheumatoid arthritis who developed infectious complication of the basic therapy. A prognostic role and critical values of the absolute and relative content of natural killers, structure and size of nucleus of natural killers and cytotoxic T-cells, spontaneous and Fas-induced apoptosis with regard to the risk of infectious complications of MT and SF therapies was established in elderly patients with RA.
12784422 OMERACT Rheumatoid Arthritis Magnetic Resonance Imaging Studies. Core set of MRI acquisiti 2003 Jun This article describes the 2002 OMERACT rheumatoid arthritis magnetic resonance image scoring system (RAMRIS) for evaluation of inflammatory and destructive changes in RA hands and wrists, which was developed by an international MRI-OMERACT group. MRI definitions of important RA joint pathologies, and a "core set" of basic MRI sequences for use in RA are also suggested.
12469632 [Nerve regulation of cardiac rhythm in rheumatoid arthritis and multiple sclerosis patient 2002 AIM: To study nervous regulation of cardiac rhythm (CR) in patients with rheumatoid arthritis (RA) and multiple sclerosis (MS). MATERIAL AND METHODS: Nervous regulation of cardiac rhythm was studied in 57 patients with RA and MS vs 40 healthy subjects. RESULTS: It was found that nervous regulation of CR in RA and MS patients at rest is characterized by imbalance of functions of the autonomic nervous system with enhancement of ergotropic effects in patients with RA and deficiency of trophotropic impacts in growing ergotropic component in patients with MS. Stress tests led to dysfunction of CR central regulation with disturbed activity of the subcortical nervous centers (SNC) and autonomic maintenance of the processes, were characterized in emotional stress by insufficient activity of SNC and enhancement of parasympathetic effects in RA patients, hyperactivation of SNC with intensification of sympathetic impacts in MS patients manifesting in destabilizing effect of the sympathetic nervous system in both groups of patients. CONCLUSION: The findings should be taken into consideration when vegetotropic drugs are used in the treatment of RA and MS patients.
15552518 Benefit/risk of combination therapies. 2004 Sep It is now accepted that rheumatoid arthritis is not a benign disease, and has considerable morbidity and increased mortality rates. Monotherapy with disease modifying anti-rheumatic drugs (DMARDs) is often ineffective, and rarely leads to sustained clinical remission. Many clinical trials suggest the effectiveness of using combination therapies, and also the benefit of aggressive management early in the course of the disease. However, recent publications studying a variety of combination therapies in rheumatoid arthritis have shown diverse results. Drug combinations at an early stage of rheumatoid arthritis which slow radiographic progression appear to be the most convincing. These data suggest that practitioners should begin with intensive therapy in early disease, and not reserve combination therapy for those who fail monotherapy. The therapeutic strategy should be positioned according to the severity of the disease: in RA with markers indicating severity, combination should be initiated at the start of therapy while it should be instituted in a rapid step-up fashion in mild RA if insufficient efficacy is seen for monotherapy. In general, combinations appear safe and well-tolerated, but continued caution with appropriate monitoring of long-term results and possible toxicities is required.
15593225 Effects of oral prednisolone on biomarkers in synovial tissue and clinical improvement in 2004 Dec OBJECTIVE: To create greater understanding of the changes in synovial tissue parameters that occur in conjunction with clinical response by using an effective therapy, in order to facilitate the planning of future studies with therapeutic agents for rheumatoid arthritis (RA). METHODS: Twenty-one patients with active RA were randomized to receive either oral prednisolone (n = 10) or placebo (n = 11) for 2 weeks. In all patients, synovial tissue biopsy specimens were obtained by arthroscopy directly before treatment and after 14 days of treatment. Immunohistochemical analysis was performed to characterize the cell infiltrate and vascularity. Stained tissue sections were analyzed by digital imaging. Statistical analysis was performed using an analysis of covariance model. RESULTS: After treatment, the mean Disease Activity Score in 28 joints (DAS28) was 2.0 units lower (95% confidence interval [95% CI] 1.0-3.0) in patients who received prednisolone than in those who received placebo. In the prednisolone group, the mean (+/-SD) DAS28 decreased from 6.27 +/- 0.95 to 4.11 +/- 1.43 after therapy; minimal change was observed in the placebo group. For macrophages, the estimated effect of prednisolone was large. Patients receiving active treatment had fewer (mean 628 cells/mm(2) [95% CI 328-927]) macrophages after therapy compared with those receiving placebo. A reduction in the total number of CD68+ macrophages, from 1,038 +/- 283 cells/mm(2) before treatment to 533 +/- 248 cells/mm(2) after treatment, was observed in the prednisolone group. There were clear trends toward decreased infiltration by T cells, plasma cells, and fibroblast-like synoviocytes after active treatment. We observed a trend toward a reduction in alphavbeta3+ newly formed blood vessels and expression of vascular growth factors after prednisolone therapy. CONCLUSION: Prednisolone therapy in RA is associated with a marked reduction in macrophage infiltration in synovial tissue, suggesting that synovial macrophage numbers could be used as a biomarker for clinical efficacy.
11965594 p53, proto-oncogene and rheumatoid arthritis. 2002 Apr OBJECTIVE: To review the literature published in the past 6 years concerning the role of p53 tumor-suppressor protein in rheumatoid arthritis (RA). METHODS: A MEDLINE search was performed to identify all publications that covered the role of p53 in RA. In addition, selected articles related to proto-oncogenes and matrix metalloproteinases were included in this review. RESULTS: p53 protein is expressed in RA fibroblast-like synoviocytes (FLSs), and its overexpression is a characteristic feature of RA. The overexpression of p53 is probably induced by DNA strand breaks caused by the genotoxic environment of RA joints, in some cases because of p53 mutations. Independent studies from 3 groups indicated that p53 mutations can and do occur in RA synovial tissue samples derived from a subset of RA patients. Inactivation of p53 may contribute to the invasiveness of FLSs and to the high-level expression of cartilage degradation enzymes as well. Gene transfer or gene knockout studies using a collagen-II-induced RA animal model to examine the role of p53 in RA have been reported. Initial results are positive and indicate that gene transfer of p53 may be clinically useful for the management of RA. CONCLUSIONS: p53 protein is expressed in RA FLSs, and its overexpression is a characteristic feature of RA. p53 mutations occur in the synovial tissues derived from a subset of RA patients. The clinical implications of p53 expression and the functional importance of somatic mutations in RA, however, are still unclear. Further research is needed to fully understand the implications of these findings and develop corresponding new therapeutic strategies.
12428224 Association of baseline levels of markers of bone and cartilage degradation with long-term 2002 Nov OBJECTIVE: The known risk factors for radiologic progression in rheumatoid arthritis (RA) are not optimally discriminative in patients with early disease who do not have evidence of radiologic damage. We sought to determine whether urinary C-terminal crosslinking telopeptide of type I (CTX-I) and type II (CTX-II) collagen (markers of bone and cartilage destruction, respectively) are associated with long-term radiologic progression in patients with early RA. METHODS: This was a prospective study of 110 patients with early RA who were participating in the COBRA (Combinatietherapie Bij Reumatoïde Artritis) clinical trial and followup study, a randomized controlled trial comparing the efficacy of oral pulse prednisolone, methotrexate, plus sulfasalazine with sulfasalazine alone. We investigated the relationship between baseline levels of urinary CTX-I and CTX-II and the mean annual progression of joint destruction over a median of 4 years, as measured by changes in the modified Sharp score (average of 2 independent readers). RESULTS: In multivariate logistic regression analysis, baseline urinary CTX-I and CTX-II levels in the highest tertile were the strongest predictors of radiologic progression (Sharp score increase >2 units/year; odds ratio 7.9 and 11.2, respectively), independently of treatment group, erythrocyte sedimentation rate (ESR), Disease Activity Score in 28 joints, rheumatoid factor (RF), and baseline joint damage (Sharp score). The likelihood ratios for a positive test were 3.8 and 8.0 for CTX-I and CTX-II, respectively, which compared favorably with the likelihood ratios for the ESR (3.0), baseline joint damage (1.6), and RF (1.8). When patients were grouped according to the presence (Sharp score >/=4, n = 49) and absence (Sharp score <4, n = 61) of joint damage at baseline, CTX-I and CTX-II levels were predictive only in those without baseline joint damage (odds ratio 14.9 and 25.7, respectively). CONCLUSION: High baseline levels of urinary CTX-I and CTX-II independently predict an increased risk of radiologic progression over 4 years in patients with early RA, especially those without radiologic joint damage. Urinary CTX-I and CTX-II may be useful for identifying individual RA patients at high risk of progression very early in the disease, before erosions can be detected radiographically. Such patients may be in special need of treatments that inhibit bone and cartilage degradation.
12447635 Elevated plasma levels of beta-thromboglobulin and platelet factor 4 in patients with rheu 2002 Nov The efficacy of plasma levels of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) as markers of the presence and activity of vasculiditic processes in rheumatic diseases were evaluated, first by serial measurement of their levels in a patient with rheumatoid arthritis and a chronic leg ulcer in the course of treatment, and second in 11 patients with rheumatoid arthritis without cutaneous vasculitis, and in nine patients with a variety of rheumatic diseases with cutaneous vasculitis. In the former, plasma levels of beta-TG and PF4 were elevated and slowly reduced in parallel with healing, raised again after relapse, and normalized after disappearance of the leg ulcer. In the latter, both plasma levels were elevated in all of the nine patients with cutaneous vascular lesions and in one of the 11 patients rheumatoid arthritis without skin lesions. Levels of beta-TG and PF4 may be useful to estimate the presence of vascular lesions in rheumatic disorders.
12687509 A prospective study of sicca symptoms in patients with rheumatoid arthritis. 2003 Apr 15 OBJECTIVE: To investigate sicca symptoms in patients with rheumatoid arthritis (RA) with respect to constancy, temporal changes of prevalence, and possible risk factors. METHODS: A prospective cohort study of 70 patients with RA was conducted over 5 years. The main variables of interest were the 6 questions on sicca symptoms used in the preliminary European criteria for Sjögren's syndrome. RESULTS: Fourteen patients were lost to followup. We found that 84.2% (95% confidence interval [95% CI] 59.5-95.8) of the patients reporting sicca symptoms at baseline also reported them at followup. During the study period, sicca symptoms increased by 52.6% in general (P = 0.02) and by 80.0% for the ocular components (P = 0.04). Sicca symptoms (odds ratio [OR] = 8.35, 95% CI 1.91-36.49) and pain (OR = 1.03, 95% CI 1.00-1.07) at baseline were identified as independent predictive factors for sicca symptoms at followup. CONCLUSIONS: Sicca symptoms in patients with RA are remarkably constant over time. There is also a substantial time-dependent increase in the prevalence of such symptoms. As the prevalence of ocular sicca symptoms in general populations tend to level out with age, there seems to be a disease-related increase of ocular symptoms over time in patients with RA. Present pain and sicca symptoms constitute risk factors for future sicca symptoms.
14871458 HMGB1 is a potent trigger of arthritis. 2004 Mar Rheumatoid arthritis is a chronic inflammatory disease characterized by synovial inflammation and structural damage of joints. Although the cause of rheumatoid arthritis (RA) remains unknown, the excessive production of proinflammatory cytokines such as tumour necrosis factor (TNF) and interleukin-1 (IL-1) by intra-articular macrophages occupies a critical pathogenic role in the development and progression of the disease. High mobility group box chromosomal protein 1 (HMGB1) is a recently identified mediator of interest in human and experimental arthritides. HMGB1 can either be actively secreted from macrophages or passively released from necrotic cells of all kinds. Activated macrophages and unprogrammed cell death caused by ischaemia or activated complement are all prominent features of chronic arthritis, contributing to the persistent synovial inflammation. HMGB1 is cytoplasmically and extracellularly overexpressed in inflammatory synovial tissue in human RA as well as experimental collagen-induced arthritis. Elevated levels of HMGB1 are also present in synovial fluid samples from RA patients. Synovial tissue from rats with experimental arthritis exhibits aberrant deposition of HMGB1 preceding the onset of clinical signs of arthritis, and the expression becomes prominent after the onset of clinical disease. The synovial levels of HMGB1 are comparable with those of TNF and IL-1beta at the peak of manifest disease. HMGB1-targeted intervention with either neutralizing antibodies or the antagonistic A box domain of HMGB1 ameliorates collagen-induced arthritis both in mice and rats, and inhibits the local overexpression of IL-1beta in the joints. It is thus conceivable that therapeutic HMGB1 blockade may contribute to future treatment of human chronic arthritis.
15096329 Estimated prediagnosis radiological progression: an important tool for studying the effect 2005 Jan OBJECTIVE: To determine if intrapatient comparisons between prediagnosis and subsequent radiological progression could be used to assess effects of DMARDs in an RA inception cohort. PATIENTS AND METHODS: 149 non-randomised patients with newly diagnosed RA in four groups were analysed: patients treated with (a) methotrexate (n = 56); (b) sulfasalazine (n = 55); (c) auranofin (n = 19); and (d) controls who were poor treatment responders (n = 19). Radiographs were quantified using the Larsen erosion score. The prediagnosis radiological progression from the onset of RA symptoms to diagnosis was calculated and compared with the observed progression rate during the first year after diagnosis while receiving DMARD treatment. RESULTS: Mean (SD) disease duration from onset of symptoms until diagnosis was 6.7 (4.0) months. Mean (SD) baseline Larsen score was 13.2 (9.3), giving a mean (SD) estimated prediagnosis progression rate of 23.6 (12.4) Larsen score units/year. Control and auranofin groups showed radiological progression after diagnosis similar to the progression predicted by prediagnosis progression rates. Patients receiving methotrexate or sulfasalazine showed a marked reduction (71% and 73%, respectively; p<0.001) in radiographic progression compared with prediagnosis progression. CONCLUSIONS: Prediagnosis rates of radiological progression can be used quantitatively to obtain information on the potential efficacy of DMARDs, and indicate that methotrexate and sulfasalazine, but not auranofin, significantly retard radiographic damage in the first year after diagnosis.
12904889 The TNF-alpha transgenic mouse model of inflammatory arthritis. 2003 Aug Rheumatoid arthritis is a chronic inflammatory disorder that affects multiple peripheral joints. It is the most common form of inflammatory arthritis and is characterized by synovial hyperplasia, immune cell infiltration, cartilage destruction, and bone erosion. To gain insight into the etiology of the disease, a variety of animal models have been established. Twelve years ago George Kollias' laboratory generated a transgenic (Tg) mouse that over-expresses human TNF-alpha, and develops an erosive polyarthritis with many characteristics observed in rheumatoid arthritis patients. The phenotype of this mouse model validated the theory that TNF-alpha is at the apex of the pro-inflammatory cascade in rheumatoid arthritis, and foreshadowed the remarkable success of anti-TNF-alpha therapy that has transformed the effective management of this disease. As such, the TNF-Tg mice are very useful tools for dissecting the molecular mechanisms of the pathogenic process and evaluating the efficacy of novel therapeutic strategies for rheumatoid arthritis. In this review we (1) provide a brief summary of TNF-alpha biology and the role of this dominant cytokine in rheumatoid arthritis, (2) describe the various TNF-Tg models and their phenotypes, and (3) give examples of how this model has been used experimentally.
11958437 Lipid peroxidation, some extracellular antioxidants, and antioxidant enzymes in serum of p 2002 Mar The aims of our study were to assess whether the increased oxidative stress in inflamed joints is reflected by serum lipid peroxidation and also to check alterations in the levels of extracellular antioxidants and antioxidant enzyme activities in patients with rheumatoid arthritis. Serum malondialdehyde and ceruloplasmin levels and the activity of CuZn superoxide dismutase were higher, while transferrin levels and the activities of glutathione peroxidase and catalase were lower in patients (n = 37) than in healthy controls (n = 30). Disease activity score correlated positively with serum malondialdehyde level and CuZn superoxide dismutase activity. Probably, superoxide radicals in serum could be dismutated to produce hydrogen peroxide by increased CuZn superoxide dismutase activity, but hydrogen peroxide could not have been detoxified due to decreased activities of serum glutathione peroxidase and catalase. Hydrogen peroxide possibly converted to hydroxyl radical by iron due to lower transferrin level might have led to increased serum lipid peroxidation in patients with rheumatoid arthritis.
11958435 The CD14+ CD16+ monocyte subset in rheumatoid arthritis and systemic lupus erythematosus. 2002 Mar Most human peripheral blood monocytes strongly express surface CD14, but not CD16 (CD14+ +/CD 16-). A smaller group of monocytes express lower levels of CD14 and also express CD16 (CD14+/CD16+). This subgroup has different functional characteristics and is expanded in a number of disease states. We aimed to determine the percentage of circulating CD14+ /CD16+ monocytes in rheumatoid arthritis and systemic lupus erythematosus (SLE) and relate this to disease measures. Peripheral blood was sampled from 31 SLE patients, 19 rheumatoid arthritis patients, and 19 healthy controls. The percentage of CD14+/CD16+ monocytes was determined by immunofluorescence labelling and dual colour flow cytometry. The percentage of CD14+/CD16+ monocytes was significantly lower in rheumatoid arthritis (median 4.90%) than in normal subjects (median 7.30%, P = 0.014), and in rheumatoid arthritis than in SLE patients (median 9.40%, P = 0.009). The percentage of CD14+/CD16+ monocytes in SLE was not significantly different from that in healthy subjects. This lower percentage of CD14+/CD16+ monocytes in rheumatoid arthritis may be important in the pathogenesis of this disease.
14872222 [Automation and computerization of the articular and Ritchie's indexes calculation]. 2003 Oct Compilation and calculation of some articular indexes is time consuming. Therefore the authors present a data base for automatic compilation and calculation of articular and Ritchie's indexes. Moreover the program allows to determine the number of the swollen and painful joints.
15517643 Physiological risk factors for falls in older people with lower limb arthritis. 2004 Nov OBJECTIVE: To investigate physiological risk factors for falls in people with self-reported lower limb arthritis. METHODS: Six hundred eighty-four community-dwelling men and women aged 75-98 years (mean 80.0, SD 4.4), categorized with and without lower limb arthritis, underwent quantitative tests of strength, peripheral sensation, vision, reaction time, balance, and pain. A 12-month history of falls was also obtained. RESULTS: Subjects with self-reported lower extremity arthritis performed significantly worse in tests of knee and ankle muscular strength, lower limb proprioception, postural sway, and leaning balance than subjects without lower extremity arthritis, while being comparable in vision, tactile sensitivity, and reaction time. This pattern of specific impairments was also evident when group results for the arthritis subjects were compared with community normative values and presented as a physiological profile. The arthritis group suffered significantly more falls [relative risk (RR) 1.22, 95% CI 1.03-1.46] and injurious falls (RR 1.27, 95% CI 1.01-1.60) in the previous 12 months than the nonarthritis group. Within the arthritis group, reduced knee extension strength and increased sway were identified as significant predictors of falls. CONCLUSION: Older people with lower limb arthritis are at increased risk of falling due to deficits in neuromuscular systems. A physiological falls-risk profile based on mean test scores for the arthritis group highlights deficits in muscular strength, knee proprioception, and standing balance, indicating the need for targeted falls prevention interventions for this population.