Browse

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

ID PMID Title PublicationDate abstract
16012023 Rat bite fever mimicking rheumatoid arthritis. 2005 We report a case of Streptobacillus moniliformis polyarthritis mimicking a rheumatoid arthritis, in a pet shop employee. In culture of fluid joint growth a curious Gram-negative bacillus was identified by polymerase chain reaction as Streptobacillus moniliformis. The outcome was good after surgical debridment and rifampin-clindamycin combination during 4 weeks.
14618373 Lack of evidence for inhibition of angiogenesis as a central mechanism of the antiarthriti 2005 Mar OBJECTIVES: The aim of this study was to investigate whether methotrexate (MTX) has an antiangiogenic effect and whether this property plays a role in the control of rheumatoid arthritis (RA). METHODS: A human placenta angiogenesis assay was used to examine the antiangiogenic effects of MTX in vitro. In addition, DBA/1 mice were used to compare the antiarthritic effect of MTX in collagen-induced arthritis (CIA) and its antiangiogenic effect in a murine in vivo matrigel model for angiogenesis. RESULTS: The spreading of microvessels from placental vessel fragments was not significantly inhibited by MTX. Treatment with MTX reduced significantly the incidence of CIA in DBA/1 mice in a dose-dependent manner. However, treatment with the same doses of MTX did not significantly reduce vessel growth in subcutaneous depots of bFGF-enriched matrigel. CONCLUSION: These data support the hypothesis that inhibition of angiogenesis does not significantly contribute to the antiarthritic effect of MTX seen in patients and animal models for RA. Therefore, the combination of MTX with antiangiogenic drugs appears to be a rational strategy in the treatment of RA.
15922390 Bee venom induces apoptosis through caspase-3 activation in synovial fibroblasts of patien 2005 Jul Bee venom (BV) has been used traditionally for the control of pain and inflammation in various chronic inflammatory diseases, including rheumatoid arthritis (RA) in Oriental medicine. However, it is still unclear how BV exerts its beneficial effects on the clinical course of RA patients. To investigate the effect of BV on the treatment of rheumatoid synovitis, we examined the inhibition of cell growth and induction of apoptosis in human rheumatoid synovial fibroblasts. Rheumatoid synovial fibroblasts were surgically obtained from patients with RA. Cell proliferation and viability were assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The apoptosis of synovial cells treated with 10 microg/ml BV for 24 h was identified by 4,6-diamidino-2-phenylindole (DAPI) staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assay, DNA fragmentation assay, RT-PCR, and Western blot analysis. It was demonstrated that rheumatoid synovial cells treated with 10 microg/ml BV for 24 h exhibited apoptotic features and fragmentation of DNA. In addition, BV induces apoptosis in rheumatoid synovial cells through a decrease in BCL2 expression and an increase in BAX and caspase-3 (CASP3) expression. It is suggested that BV inhibits the proliferation of rheumatoid synovial cells through induction of apoptosis by CASP3 activation.
16418123 Gender differences in emotion regulation and relationships with perceived health in patien 2005 Emotion regulation has been associated with perceived health in rheumatoid arthritis, which is diagnosed three times more often in women than men. Our aim was to examine gender differences in styles of emotion regulation (ambiguity, control, orientation, and expression) and gender-specificity of the associations between emotion regulation and perceived health (psychological well-being, social functioning, physical functioning, and disease activity) in 244 female and 91 male patients with rheumatoid arthritis. Women reported more emotional orientation than men, but did not differ from men with regard to ambiguity, control, and expression. Structural equation modelling showed that relationships between emotion regulation and perceived health were more frequent and stronger for women than men. This held especially for the affective dimension of health, while associations were similar for both women and men with regard to social and physical functioning. Only for women, the association between ambiguity and disease activity was significant, which appeared to be mediated by affective functioning. The observations that women are more emotionally oriented than men and that emotion regulation is more interwoven with psychological health in women than men, support the usefulness of a gender-sensitive approach in research and health care of patients with rheumatoid arthritis.
16277672 Rheumatoid arthritis seropositive for the rheumatoid factor is linked to the protein tyros 2005 The protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene encodes for lymphoid tyrosine phosphatase LYP, involved in the negative regulation of early T-cell activation. An association has recently been reported between the PTPN22-620W functional allele and rheumatoid factor-positive (RF+) rheumatoid arthritis (RA), among other autoimmune diseases. Expected linkage proof for consistency cannot be definitely produced by an affected sib-pair (ASP) analysis. Our aim was therefore to search for linkage evidence with the transmission disequilibrium test. DNA from the French Caucasian population was available for two samples of 100 families with one RA patient and both parents, and for 88 RA index cases from RA ASP families. Genotyping was carried out by PCR-restriction fragment length polymorphism. The analysis was performed using the transmission disequilibrium test, genotype relative risk and ASP-based analysis. The transmission disequilibrium test of the PTPN22-620W allele revealed linkage and association for RF+ RA (61% of transmission, P = 0.037). The genotype relative risk showed the risk allele in 34% of RF+ RA patients and in 24% of controls derived from nontransmitted parental chromosomes (P = 0.047, odds ratio = 1.69, 95% confidence interval = 1.03-2.78). The ASP investigation showed no enriched risk allele in RA multiplex families, resulting in a lack of power of ASP analysis, explaining the published negative results. This study is the first to show linkage of PTPN22 to RF+ RA, consistent with PTPN22 as a new RA gene.
15742432 Detection of the p53 regulator murine double-minute protein 2 in rheumatoid arthritis. 2005 Mar OBJECTIVE: Rheumatoid arthritis (RA) is characterized by hyperplasia of synovial lining tissue, which is involved directly in the damage of cartilage and bone. One of the factors thought to contribute to this synovial lining hyperplasia is dysregulation of, or functional abnormality in, the tumor suppressor protein p53. The protein known as murine double-minute protein 2 (MDM2) is the major negative regulator of p53, and in tumors contributes to increased cell proliferation. The detection of MDM2 in rheumatoid synovium has not previously been described. We investigated whether this protein is detectable in cells and tissues derived from patients with RA. METHODS: Expression of MDM2 protein was examined in fibroblast-like synoviocytes (FLS) by methods including permeabilization flow cytometry, immunofluorescence, and Western blotting, and in synovial tissues using immunohistochemistry. The proliferative capacity of these cells was also examined using 3H/thymidine incorporation. Cell cycle analysis was performed by propidium iodide incorporation. RESULTS: MDM2 was detected in RA FLS and synovial tissues. MDM2 protein was identified in CD14-positive and CD14-negative synovial lining cells and CD14-positive sublining cells. RA FLS exhibited faster proliferative rates and higher levels of MDM2 expression than FLS derived from patients with osteoarthritis (OA). Both OA and RA FLS were found to be in similar phases of the cell cycle at the time of MDM2 protein analysis. CONCLUSION: The abundant expression of MDM2 in RA may be a contributing factor to the hypoapoptotic phenotype of lining tissue through its capacity to downregulate p53 levels and effects. Further studies are required to determine the relationship between this cell-cycle protein profile, tissue hyperplasia, and the functional abnormality of p53 in RA.
16979122 Influence of leflunomide on gastrointestinal Candida albicans infection induced in naive a 2006 Nov Mucosal Candida albicans infection in immunocompromised individuals being treated with recently advanced drugs can progress to systemic disease. One such medication applied in patients with rheumatoid arthritis is leflunomide. The object of the present study was to investigate the effect of leflunomide on a model of gastrointestinal (g.i.) C. albicans infection induced in naïve or arthritic mice and on the host resistance to systemic re-infection. Newborn mice were orally inoculated with 1 x 10(5) colony forming units (CFU) of C. albicans and at age of 5 weeks they were treated with 5 mg/kg or 20 mg/kg of leflunomide for 10 consecutive days. Both doses elevated the yeast colonization of the stomach, without the dissemination into the internal organs. This was in parallel with the enhanced delayed type hypersensitivity (DTH) reaction to the yeast. Contrary to that, leflunomide caused a shift to Th2 reactivity by prevalence of IL-4 to IFN-gamma and a suppression of anti-Candida antibody synthesis by a higher dose. It might be supposed that infection increased autoimmune response in arthritic mice, according to stimulated DTH reaction to collagen. The administration of leflunomide during the simultaneous development of infection and arthritis diminished anti-Candida and anti-collagen antibody synthesis compared to untreated infected arthritic mice. The improved survival of arthritic infected animals against severe systemic re-infection was not changed after administration of leflunomide to re-infected arthritic mice. We can conclude that although leflunomide influenced cytokine secretion and suppressed anti-Candida antibody production it neither provokes a progression from gastrointestinal to systemic C. albicans infection nor increases the susceptibility to severe C. albicans re-infection of arthritic mice.
16581463 Arthroscopic synovectomy of the knee joint in rheumatoid arthritis: surgical steps for com 2006 Apr For successful arthroscopic total synovectomy in rheumatoid arthritis of the knee, proper sequential steps are required. First, we resect hypertrophied synovial villi on the intercondylar notch to make a gateway for the posterior compartments. We also perform synovectomy at the posterolateral chamber because of the narrower space of the chamber than that of the posteromedial chamber and the intra-articular crowding due to swollen synovial villi with the passage of operation time. Special care should be taken not to overlook both posterior back corners and roofs, which cannot be seen through the transnotch view, even with a 70 degrees arthroscope. The posterior back corners and roofs can be visualized by using the trans-septal approach technique. In this approach, we prefer to perforate the posterior septum in the posterolateral-to-posteromedial direction to avoid damaging the neurovascular structures because the structures are located just behind and lateral to the midline septum and the posteromedial capsule bulges a bit more posteriorly than the posterolateral capsule. Attention is then directed to the medial, lateral, and suprapatellar compartments, and finally the retropatellar compartment. Our surgical steps are safe and effective for complete synovectomy of the rheumatoid arthritic knee joint and other synovial disorders.
17067220 [Prosthetic knee infection caused by Listeria monocytogenes in a woman with rheumatoid art 2006 Jun Listeria are gram-positive bacilli that can be isolated from soil and in the normal fecal flora of many mammals. It is a uncommon pathogen in the general population, but immunocompromised individuals can develop several focal infections, most notably meningoencephalitis and sepsis. Nevertheless, infectious arthritis caused by Listeria monocytogenes is a exceptional event. We report a new case of prosthetic knee arthritis due to Listeria in a woman with seropositive rheumatoid arthritis and Waldenström s macroglobulinemia receiving prednisone and methotrexate. In addition, we review the literature on listeria joint infections.
15781364 Use of volar plate for reconstructing the radial collateral ligament after metacarpophalan 2005 Mar We present a technique for reconstructing the radial collateral ligament using the volar plate after metacarpophalangeal arthroplasty of fingers in rheumatoid arthritis. This technique is indicated when the original collateral ligament is very attenuated and cannot be directly imbricated. The technique is surgically simple, has the advantage of using locally available tissue, and has produced results that are both clinically and radiologically satisfactory.
16583421 Different patterns of illness-related interaction in couples coping with rheumatoid arthri 2006 Apr 15 OBJECTIVE: To learn more about the effect of rheumatoid arthritis (RA) on couples' relationships and how couples manage the illness within their dyad. METHODS: Eight women with RA (ages 31-60 years) and their partners, and 4 men with RA (ages 43-75 years) and their partners were recruited from the rheumatology case load of a hospital in the UK. Interpretative phenomenologic analysis was used for data collection and analysis. During semistructured interviews, couples were asked about the effect of RA on their lives and relationship. RESULTS: This study found clear differences in the way couples managed the illness of one partner and in the nature of their illness-related interactions. Based on these differences, the couples were allocated to 1 of 3 groups: the shared illness management group (SIM), the ill partner in charge group (IPIC), or the conflict over management group (COM). In the SIM group, both partners attended appointments and shared decisions about illness management. In the IPIC group, the ill person claimed and was conceded the right to make autonomous decisions about illness management. In the COM group, the well partner was dissatisfied with the way the ill person was managing the illness, and conflict resulted. CONCLUSION: Heterogeneity exists in the intradyad management of RA. Identifying each couple's style of illness management could make medical consultations and education programs more responsive to the needs and preferences of patients and their partners. Dissatisfaction of either partner with illness management and resulting conflict could be addressed, with benefits for both partners and possible improvement in disease management.
17549869 Tumour necrosis factor-alpha as a new therapeutic target for rheumatoid arthritis: an upda 2005 Dec In rheumatoid arthritis (RA), the conventional therapies (first-line, second-line, third-line drugs) provide more or less effective symptomatic relief for a decade or so from the onset of the disease. However, the chronic inflammatory destructive processes involving connective tissue, cartilage and bone with their attendant disability progress relentlessly in majority of patients. Secondly, use of 'second-line' and 'third-line' drugs in RA are limited due to their side effects. Studies in animals and RA patients have confirmed that tumour necrosis factor-alpha (TNFalpha), an inflammatory cytokine, is of major importance in the rheumatoid disease process and thus, it might be an effective therapeutic target in RA. Animal model experiments and clinical trials were conducted with anti-TNFalpha monoclonal antibody (anti-TNFalpha MoAb) in RA recently. This anti-TNFalpha MoAb therapy was found to be both effective and safe which documented the coming-of-age of cytokine-based immunointervention in RA. Researchers are optimistic that modern medicine would certainly witness the application of this noble immunotherapy enabling to selectively target cytokines, e.g. TNFalpha, in RA as well as in other inflammatory autoimmune diseases in the near future.
16510808 Long-term results of the modified Hoffman procedure in the rheumatoid forefoot. Surgical t 2006 Mar BACKGROUND: Rheumatoid arthritis commonly affects the forefoot, causing metatarsalgia, hallux valgus, and deformities of the lesser toes. Various types of surgical correction have been described, including resection of the lesser-toe metatarsal heads coupled with arthrodesis of the great toe, resection arthroplasty of the proximal phalanx or metatarsal head, and metatarsal osteotomy. We report the results at an average of five and a half years following thirty-seven consecutive forefoot arthroplasties performed in twenty patients by one surgeon using a technique involving resection of all five metatarsal heads. METHODS: All patients were treated with the same technique of resection of all five metatarsal heads through three dorsal incisions. All surviving patients were asked to return for follow-up, which included subjective assessment (with use of visual analogue pain scores, AOFAS [American Orthopaedic Foot and Ankle Society] foot scores, and SF-12 [Short Form-12] mental and physical disability scores), physical examination, and radiographic evaluation. RESULTS: All results were satisfactory to excellent in the short term (six weeks postoperatively), and no patient sought additional surgical treatment for the feet. A superficial infection subsequently developed in two feet, and two feet had delayed wound-healing. At an average of 64.9 months postoperatively, the average AOFAS forefoot score was 64.5 points and the average hallux valgus angle was 22.3 degrees. There were no reoperations. CONCLUSIONS: Resection of all five metatarsal heads in patients with metatarsalgia and hallux valgus associated with rheumatoid arthritis can be a safe procedure that provides reasonable, if rarely complete, relief of symptoms.
16436492 The effect of infliximab on bone metabolism markers in patients with rheumatoid arthritis. 2006 Jun OBJECTIVE: The aim of this study was to evaluate urinary excretion of N-telopeptide of type I collagen (NTX) and deoxypyridinoline (DPD), markers of bone resorption, and serum bone alkaline phosphatase (BAP) level, a marker of bone formation and an early marker of osteoblast differentiation, in patients with rheumatoid arthritis (RA) treated with infliximab. METHODS: Seventeen male and female patients (age 60.7+/-2.53 yr; mean disease duration 12.9+/-3.01 yr; Steinbrocker's class II-IV) with RA, diagnosed according to the criteria of the American College of Rheumatology (ACR), took part in the study between March 2003 and January 2005. None of the patients had a history of oestrogen replacement therapy. All patients were treated with infliximab combined with methotrexate. Infliximab was infused intravenously at 3 mg/kg at baseline, 2 and 6 weeks, then every 8 weeks. To evaluate disease activity, ESR, CRP, the numbers of swollen and tender joints, modified Stanford Health Assessment Questionnaire (mHAQ) score and ACR score were measured. Levels of NTX and DPD in urine and BAP in serum were measured in all patients. RESULTS: ESR, CRP, the number of swollen joints and tender joints, and mHAQ score had decreased significantly 6 weeks after initial treatment and were still low 6 months after initial treatment. NTX levels had decreased significantly 6 weeks after the initial treatment and were still low 6 months after initial treatment. DPD levels had decreased 6 months after initial infusion. Mean serum BAP level did not differ significantly among the three time points. NTX levels were statistically corresponding with the number of swollen joints and mHAQ scores. DPD levels were statistically lower corresponding with ESR. CONCLUSION: Infliximab therapy may inhibit generalized bone loss in patients with RA. NTX is a more sensitive marker than DPD.
16386446 Clinical evaluation of a cohort of patients with rheumatoid arthritis treated with anti-TN 2006 Jan OBJECTIVES: TNF-alpha inhibitors have been effective in randomized controlled studies for the treatment of RA. The purpose of this study was to evaluate the clinical, laboratory, and radiological responses in a cohort of unselected patients with RA treated with TNF-alpha inhibitors in the community. METHODS: Using the Swiss Clinical Quality Management in Rheumatoid Arthritis, a centralized system of data gathering for RA patients, we obtained the following information regarding patients treated with a TNF-alpha inhibitor in the Geneva Canton before 02/2003: demographics; clinical data (disease activity, functional status, treatments received and type of TNF-alpha inhibitor used); laboratory and radiographic data. RESULTS: A total of 66 patients (mean age = 60.5 years) with long-standing disease (mean duration = 12.5 years) were analyzed. Sixteen patients (24%) discontinued anti-TNF-alpha, half within the first 6 months of the study. Mean DAS score decreased from 4.8+ /- 0.4 to 3.8 +/- 0.4 (P < 0.01); HAQ scores (mean = 1.35) remained unchanged; pain, evaluated on a 10-point scale, decreased from 5.0 at baseline to 3.3 (P < 0.001). CRP values decreased steadily from 17.9 at baseline to 5.6 at 20 months or later. The progression of radiographic damage decelerated in 30 patients, accelerated in 12, and remained unchanged in one. CONCLUSIONS: The responses of this community-based group of patients with severe, long-standing RA to TNF-alpha inhibitors revealed a reassuring similarity to those of patients enrolled in controlled clinical trials.
16861538 Periarticular bone findings in rheumatoid arthritis: T2-weighted versus contrast-enhanced 2006 Aug OBJECTIVE: The purpose of this study was to establish the relative predictive value of T2-weighted and contrast-enhanced T1-weighted MRI techniques for bone erosions that are evident on CT. Because it is known that MRI depicts abnormalities in the periarticular bone of patients with rheumatoid arthritis, we wanted to compare the outcomes of T2-weighted versus contrast-enhanced T1-weighted MRI techniques. MATERIALS AND METHODS: Eleven patients with rheumatoid arthritis underwent CT imaging of their most affected wrist. Fast spin-echo T2-weighted MR images were then acquired with spectral fat saturation. Enhanced T1-weighted spin-echo images acquired before and after IV administration of gadopentetate dimeglumine were used to determine the percent enhancement. Imaging examinations were scored for 15 anatomic zones. The CT score was based on cortical bone erosion. The MR score was based on periarticular bone marrow signal alteration. RESULTS: Both T2-weighted MR images with spectral fat saturation and enhanced T1-weighted images were concordant for the presence or absence of bone abnormalities in 122 of 165 zones (74%). Of the 43 zones that were discordant for an abnormality by the two MR techniques, the T2-weighted images were positive in five zones, and enhanced T1-weighted images were positive in 38 zones (p < 0.001). Of the 43 zones that were discordant by the two MR techniques, enhanced T1-weighted images were concordant with CT in 20 zones, whereas the T2-weighted images were concordant with CT in 23 zones (p = 0.76). A greater proportion of lesions detected by the T2-weighted images were "edema-like" signal patterns. CONCLUSION: In rheumatoid arthritis, contrast-enhanced T1-weighted MRI depicts more periarticular bone abnormalities than fat-suppressed T2-weighted MRI. These MR techniques are equally predictive of frank, erosive disease that is evident on CT.
16980215 Chemokine inhibition in inflammatory arthritis. 2006 Oct Synovial inflammation in rheumatoid arthritis (RA) and other arthritides is, in part, dependent on migration of inflammatory cells as well as retention of these cells at the site of inflammation. Chemokines play a critical role in these processes and represent an attractive target for therapeutic intervention. Animal models of RA have shown that it is possible to induce clinical improvement by specifically targeting chemokines or their receptors. Although at present only very limited data exist, initial data suggest that it may be possible to reduce synovial inflammation in patients with RA by specific chemokine blockade. Innovative trial design may help to screen for potentially interesting chemokine antagonists in an early stage of development.
15642151 The role of T-cell interleukin-17 in conducting destructive arthritis: lessons from animal 2005 Interleukin-17 (IL-17) is a T cell cytokine spontaneously produced by cultures of rheumatoid arthritis (RA) synovial membranes. High levels have been detected in the synovial fluid of patients with RA. The trigger for IL-17 is not fully identified; however, IL-23 promotes the production of IL-17 and a strong correlation between IL-15 and IL-17 levels in synovial fluid has been observed. IL-17 is a potent inducer of various cytokines such as tumor necrosis factor (TNF)-alpha, IL-1, and receptor activator of NF-kappaB ligand (RANKL). Additive or even synergistic effects with IL-1 and TNF-alpha in inducing cytokine expression and joint damage have been shown in vitro and in vivo. This review describes the role of IL-17 in the pathogenesis of destructive arthritis with a major focus on studies in vivo in arthritis models. From these studies in vivo it can be concluded that IL-17 becomes significant when T cells are a major element of the arthritis process. Moreover, IL-17 has the capacity to induce joint destruction in an IL-1-independent manner and can bypass TNF-dependent arthritis. Anti-IL-17 cytokine therapy is of interest as an additional new anti-rheumatic strategy for RA, in particular in situations in which elevated IL-17 might attenuate the response to anti-TNF/anti-IL-1 therapy.
16173327 Diagnostic value and clinical significance of anti-CCP in patients with advanced rheumatoi 2005 Aug OBJECTIVES: To investigate the prevalence of anticyclic citrullinated peptide (anti-CCP) in patients with advanced rheumatoid arthritis (RA) and to compare it with those in control subjects. Further, to study the relation between the anti-CCP and the disease activity parameters in these patients. PATIENTS AND METHODS: Seventy-six RA patients who had a mean disease duration of 9.8 years were included. Eighty-three age-matched non-RA volunteers were enrolled as the control group. Disease duration, duration of morning stiffness, swollen and tender joint counts, hand deformity, patient's assessment of pain, anti-CCP, rheumatoid factor (RF) and acute phase proteins were evaluated. The functional disability was also assessed with the Modified Health Assessment Questionnaire (HAQ). RESULTS: Thirty-seven sera (48.7%) in the patient group and one serum (1.2%) in the control group were positive for anti-CCP. RF was positive in 45% of the RA cases and in 5% of controls. Sensitivity and specificity of anti-CCP reactivity for RA were 49.0% and 99.0%, respectively. HAQ score and duration of morning stiffness were found to be significantly associated with anti-CCP positivity. Disease duration, swollen joint count and anti-CCP positivity were the most important variables predicting hand deformity. CONCLUSION: The prevalence, sensitivity and specificity of anti-CCP in patients with advanced RA were found to be similar to those reported in patients with early disease. Anti-CCP was significantly associated with some parameters of both disease activity and severity. Anti-CCP might be a useful parameter in clinical evaluation of patients with advanced RA.
16511920 Loss of cortical bone from the metacarpal diaphysis in patients with rheumatoid arthritis: 2006 Mar OBJECTIVE: To identify factors associated with the loss of cortical diaphyseal bone over time in patients with rheumatoid arthritis (RA). METHODS: We measured the combined cortical thickness (CCT) of the second metacarpal bone from digitized hand radiographs in an RA cohort. We estimated the rate of loss of CCT, and tested the effect of factors that could accelerate the rate. RESULTS: We studied 649 patients, who had 2990 hand radiographs. The median interval between the first and last followup radiograph was 2 years (range 0 to 23 yrs). The mean CCT at baseline was 4.04 mm (standard deviation 1.18). CCT loss was greatest during the earliest observation stages, following a square-root function of time at a rate of 0.393 mm/year(1/2) (95% CI 0.360, 0.423). Patients with a mean erythrocyte sedimentation rate (ESR) < 30 mm/h lost CCT at a rate of 0.303 mm/year(1/2) (95% CI 0.247, 0.358); those with a mean ESR > 30 and < or = 60 mm/h lost CCT at 0.395 mm/year(1/2) (95% CI 0.345, 0.446); and those with ESR > 60 mm/h lost CCT at 0.554 mm/year(1/2) (95% CI 0.480, 0.628). Patients who received a cumulative dose of glucocorticoids > or = 11.7 g lost CCT at 0.659 mm/year(1/2) (95% CI 0.577, 0.742), compared to 0.361 mm/year(1/2) (0.323, 0.401) in patients who did not receive glucocorticoids. In a multivariable model, the effect of the ESR and cumulative glucocorticoids was independent of age at RA onset, RA duration, sex, ethnic group, body mass index, presence of rheumatoid nodules, rheumatoid factor, and the HLA-DRB1 shared epitope. CONCLUSION: Early rapid loss of cortical diaphyseal bone occurs in patients with RA, followed by gradual slowing. Systemic inflammation and glucocorticoids seem to accelerate bone loss independently of other risk factors. Cortical diaphyseal bone may be an important target of the disease process in RA.