Anti-cyclic citrullinated peptide antibodies, 28-joint Disease Activity Score, and magnetic resonance imaging bone oedema at baseline predict 11 years' functional and radiographic outcome in early rheumatoid arthritis.

OBJECTIVE: To investigate the clinical and radiographic status, and to identify baseline predictors of functional status and erosive progression at 11 years' follow-up of early rheumatoid arthritis (RA) patients. METHODS: Patients enrolled in the Danish investigator-initiated randomized controlled CIMESTRA trial, which investigated a 2 year treat-to-target intervention with methotrexate and intra-articular glucocorticoids with or without cyclosporine, were followed up. The 28-joint Disease Activity Score (DAS28), Health Assessment Questionnaire (HAQ) score, and total Sharp van der Heijde score (TSS) were assessed at baseline and 11 years. Baseline magnetic resonance imaging (MRI) of unilateral wrists was scored (OMERACT RAMRIS). Multivariable linear regression analyses of baseline variables [TSS, HAQ, DAS28, age, anti-cyclic citrullinated peptide (anti-CCP) status, gender, MRI erosion score, MRI synovitis score, MRI bone marrow oedema score] were performed in 96 patients with HAQ11yrs and ∆TSS0-11yrs as dependent variables. Since outcomes were similar in the two treatment arms, data were pooled. RESULTS: In total, 120 of 160 patients completed 11 years' follow-up. They were 63 (55-72) years old, 68% were in DAS28 remission (≤ 2.4), HAQ11yrs was 0.25 (0-0.75), mean ∆TSS0-11yrs was 0.96 ± 1.52 units/year; 53%, 20%, and 27% received conventional treatment, biologics, and no treatment, respectively; and 34% had not progressed radiographically since baseline. Increased DAS28 (p = 0.02) and anti-CCP (p = 0.03) predicted HAQ11yrs, whereas anti-CCP (p = 0.03) and MRI bone marrow oedema (p = 0.01) predicted ∆TSS0-11yrs in multivariable analyses. CONCLUSIONS: Early and strict synovitis suppression with methotrexate and intra-articular glucocorticoids led to persistently high remission rates and limited erosive progression at 11 years. In this well-treated cohort, baseline anti-CCP status, DAS28, and MRI bone marrow oedema predicted functional status and/or erosive progression.

Association between baseline vitamin D metabolite levels and long-term cardiovascular events in patients with rheumatoid arthritis from the CIMESTRA trial: protocol for a cohort study with patient-record evaluated outcomes.

INTRODUCTION: Cardiovascular morbidity and mortality is increased in patients with rheumatoid arthritis (RA), and among these patients, the prevalence of hypovitaminosis D is high. Moreover, low vitamin D levels have been associated with increased cardiovascular risk in healthy subjects. OBJECTIVE: To evaluate the long-term risk of cardiovascular events in patients having low total 25-hydroxyvitamin D levels at baseline compared with patients with normal levels, in an efficiently treated, closed cohort of patients with an early diagnosis of RA. METHODS AND ANALYSIS: This study is a prospective, closed, blinded endpoint cohort study, based on secondary analyses from a previous randomised trial (CIMESTRA study; NCT00209859, approved September 1999) including 160 patients with an early diagnosis of RA from Danish University clinics. Primary outcome will be the proportion of patients with any cardiovascular event in the follow-up period, evaluated using systematic journal audits. Logistic regression models will test the hypothesis that there are more cardiovascular events in enrolled patients with a low level of vitamin D (< 50 nmol/L). Secondarily, Cox regression models, based on survival analysis, will determine the extent to which independent variables (including different levels of vitamin D at baseline) predict whether a cardiovascular event will occur, and also when this will be. ETHICS AND DISSEMINATION: All patients have received verbal and written information before enrolment, and have given written consent at baseline. To disseminate comprehension of factors of prognostic importance to cardiovascular outcome in RA, we will attempt to have a first draft ready no later than 1 year after the adjudication process has finished. If low vitamin D levels can predict cardiovascular events in RA, it is relevant to take into account in a prediction model, to be considered by patients, physicians and other decision-makers. TRIAL REGISTRATION NUMBER: The parental controlled trial is registered as NCT00209859.

Effect of a treat-to-target strategy based on methotrexate and intra-articular betamethasone with or without additional cyclosporin on MRI-assessed synovitis, osteitis, tenosynovitis, bone erosion, and joint space narrowing in early rheumatoid arthritis: results from a 2-year randomized double-blind placebo-controlled trial (CIMESTRA).

OBJECTIVES: To investigate whether a treat-to-target strategy based on methotrexate (MTX) and intra-articular (IA) betamethasone suppresses magnetic resonance imaging (MRI)-determined measures of disease activity and reduces joint destruction in early rheumatoid arthritis (eRA) patients, and to investigate whether concomitant cyclosporin A (CyA) provides an additional effect. METHOD: In the 2-year randomized, double-blind, treat-to-target trial CIMESTRA, 160 patients with eRA (< 6 months) were randomized to MTX, intra-articular betamethasone and CyA, or placebo CyA. A total of 129 patients participated in the MRI substudy, and had contrast-enhanced MR images of the non-dominant hand at months 0, 6, 12, and 24. MR images were evaluated for osteitis, synovitis, tenosynovitis, bone erosion, and joint space narrowing (JSN), using validated scoring methods. RESULTS: Significant reductions were seen at 6 months in all inflammatory parameters [synovitis, mean change -1.6 (p < 0.001, Wilcoxon), tenosynovitis, -3.5 (p < 0.001), and osteitis, -1.3 (p < 0.05)] and at 12/24 months in synovitis and tenosynovitis [-1.6/-2.2 and -3.6/-3.8, respectively; all p < 0.001]. MRI signs of inflammation were not fully eliminated, and increases in erosion and JSN scores were observed at 6 months [0.4 (p < 0.01)/0.1 (p < 0.05)], 12 months [0.8 (p < 0.001)/0.3 (p < 0.01)], and 24 months [1.0 (p < 0.001)/0.4 (p < 0.001)]. Clinical measures decreased significantly (p < 0.001) at all time points. There were no consistent statistically significant differences between treatment groups. CONCLUSIONS: In this eRA treat-to-target trial, MTX and intra-articular glucocorticoids markedly reduced, but did not eliminate, MRI osteitis, synovitis, and tenosynovitis. Accordingly, minimal but statistically significant increases in bone erosion and JSN were observed. No additional effect of CyA was demonstrated.

Clinical and radiographic outcome of a treat-to-target strategy using methotrexate and intra-articular glucocorticoids with or without adalimumab induction: a 2-year investigator-initiated, double-blinded, randomised, controlled trial (OPERA).

OBJECTIVES: To study clinical and radiographic outcomes after withdrawing 1 year's adalimumab induction therapy for early rheumatoid arthritis (eRA) added to a methotrexate and intra-articular triamcinolone hexacetonide treat-to-target strategy (NCT00660647). METHODS: Disease-modifying antirheumatic drug (DMARD)-naive patients with eRA started methotrexate (20 mg/week) and intra-articular triamcinolone (20 mg/ml) for 2 years. In addition, they were randomised to receive placebo adalimumab (DMARD group, n=91) or adalimumab (40 mg/every other week) (DMARD+adalimumab group, n=89) during the first year. Sulfasalazine and hydroxychloroquine were added if disease activity persisted after 3 months. During year 2, synthetic DMARDs continued. Adalimumab was (re)initiated if active disease reoccurred. Clinical response, remission, disability, quality of life and radiographic changes were assessed. RESULTS: One year after adalimumab withdrawal, treatment profiles and clinical responses did not differ between groups. In the DMARD/DMARD+adalimumab groups, the median 2-year methotrexate dose was 20/20 mg/week (p=0.45), triple DMARD therapy had been initiated in 33/27 patients (p=0.49), adalimumab was (re)initiated in 12/12 patients and cumulative triamcinolone dose was 160/120 mg (p=0.15). The treatment target (disease activity score, 4 variables, C-reactive protein (DAS28CRP) ≤3.2 or DAS28>3.2 without swollen joints) was achieved at all visits in ≥85% of patients in year 2; remission rates were DAS28CRP<2.6:69%/66%; Clinical Disease Activity Index ≤2.8:55%/57%; Simplified Disease Activity Index <3.3:54%/49%; American College of Rheumatology/European League against Rheumatism (28 joints):44%/45% (p=0.66-1.00). Radiographic progression (Δtotal Sharp score/year) was similar 1.31/0.53 (p=0.12). Erosive progression (Δerosion score (ES)/year) was year 1:0.57/0.06 (p=0.02); year 2:0.38/0.05 (p=0.005). Proportion of patients without erosive progression (ΔES≤0) was year 1: 59%/76% (p=0.03); year 2:64%/79% (p=0.04). CONCLUSIONS: An aggressive triamcinolone and synthetic DMARD treat-to-target strategy in eRA provided excellent 2-year clinical and radiographic disease control independent of adalimumab induction therapy. ES progression was slightly less during and following adalimumab induction therapy. TRIAL REGISTRATION NUMBER: NCT00660647.

Prediction of treatment response to adalimumab: a double-blind placebo-controlled study of circulating microRNA in patients with early rheumatoid arthritis.

At least 30% of patients with rheumatoid arthritis (RA) do not respond to biologic agents, which emphasizes the need of predictive biomarkers. We aimed to identify microRNAs (miRNAs) predictive of response to adalimumab in 180 treatment-naïve RA patients enrolled in the OPtimized treatment algorithm for patients with early RA (OPERA) Study, an investigator-initiated, prospective, double-blind placebo-controlled study. Patients were randomized to adalimumab 40 mg (n=89) or placebo-adalimumab (n=91) subcutaneously in combination with methotrexate. Expressions of 377 miRNAs were determined using TaqMan Human MicroRNA LDA, A Card v2.0 (Applied Biosystems). Associations between miRNAs and treatment response were tested using interaction analyses. MiRNAs with a P-value <0.05 using three different normalizations were included in a multivariate model. After backwards elimination, the combination of low expression of miR-22 and high expression of miR-886.3p was associated with EULAR good response. Future studies to assess the utility of these miRNAs as predictive biomarkers are needed.

Interactions between smoking, increased serum levels of anti-CCP antibodies, rheumatoid factors, and erosive joint disease in patients with early, untreated rheumatoid arthritis.

OBJECTIVES: To determine to what extent shared epitopes, smoking, and anti-cyclic citrullinated peptide (anti-CCP) antibodies are associated with disease activity and erosive disease in patients with rheumatoid arthritis (RA) at disease onset. METHOD: RA patients not previously treated with disease-modifying anti-rheumatic drugs (DMARDs) and with a disease duration of < 6 months (CIMESTRA study) were examined for shared epitopes, anti-CCP antibodies, immunoglobulin M rheumatoid factor (IgM-RF) and IgA-RF, radiographic erosive changes in hands and feet, and clinical disease activity. RESULTS: The study comprised 153 patients, of whom 104 (68%) were ever-smokers. The prevalence of patients with 0, 1, or 2 shared epitopes was 40 (48%), 71 (49%), and 33 (23%), respectively. Anti-CCP antibodies, IgM-RF, and IgA-RF were present in 89 (58%), 99 (65%), and 82 (54%) patients, respectively. Among smokers, erosive disease was associated with anti-CCP antibodies [odds ratio (OR) 3.9, 95% confidence interval (CI) 1.6-9.3], IgM-RF (OR 4.9, 95% CI 1.9-12), and IgA-RF (OR 2.8, 95% CI 1.2-6.4) but absent with regard to shared epitopes. Among never-smokers, erosive disease was not associated with either shared epitopes or antibodies. All antibody levels measured were associated with smoking and shared epitopes. CONCLUSIONS: Shared epitopes and smoking were associated with the production of anti-CCP antibodies and rheumatoid factors of IgM and IgA isotypes, which again were associated with erosive disease at presentation only in smokers. As shared epitopes and smoking were not directly associated with erosive disease, smoking may enhance the development of erosive disease in RA at different levels or through separate pathways.

Periarticular and generalised bone loss in patients with early rheumatoid arthritis: influence of alendronate and intra-articular glucocorticoid treatment. Post hoc analyses from the CIMESTRA trial.

OBJECTIVES: The aims of this study were to investigate the influence of alendronate and intra-articular betamethasone treatment on bone mineral density (BMD) changes in hand, lumbar spine and femoral neck during 1 year of a treat-to-target study (Cyclosporine, Methotrexate, Steroid in RA (CIMESTRA)). PATIENTS AND METHODS: A hundred and sixty patients with early, active rheumatoid arthritis (RA) received methotrexate, intra-articular betamethasone and ciclosporin /placebo-ciclosporin. Patients with Z-score ≤0 also started alendronate 10 mg/day. BMD of the hand (digital x-ray radiogrammetry (DXR-BMDhand)), BMD of lumbar spine and femoral neck (dual x-ray absorptiometry (DXA-BMDlumbar spine and DXA-BMDfemoral neck)) and x-rays of hands, wrists and forefeet (modified Sharp-van der Heijde score) were measured at baseline and 1 year, with complete data available in 107 patients. RESULTS: The change in BMD in hand, lumbar spine and femoral neck was negatively associated with the dose of intra-articular betamethasone (p<0.01 for all), but the bone loss in hand was modest and in the axial skeleton comparable with that of healthy individuals. Alendronate did not influence changes in DXR-BMDhand, which averaged -2.8%, whereas significant changes were observed in DXA-BMDlumbar spine and DXA-BMDfemoral neck in alendronate-treated patients (1.8% and 0.8%) compared with untreated patients (-1.8% and -2.2%) (p<0.01 and 0.02). Alendronate did not affect the radiographic progression (alendronate-treated patients: 0 (range 0-19), non-alendronate: 0 (0-18)). CONCLUSIONS: In early active RA, intra-articular betamethasone injections added to disease-modifying antirheumatic drug (DMARD) treatment led to minimal loss of hip and lumbar BMD, and the loss could be prevented by treatment with alendronate. Alendronate treatment did not affect radiographic progression.

Do changes in prescription practice in patients with rheumatoid arthritis treated with biological agents affect treatment response and adherence to therapy? Results from the nationwide Danish DANBIO Registry.

BACKGROUND: Prescription practice for tumour necrosis factor alpha (TNFalpha) inhibitors has changed towards treating patients with lower disease activity. OBJECTIVE: To determine the trend in treatment response in cohorts of patients with rheumatoid arthritis who started TNFalpha inhibitor treatment between 2000 and 2005. METHODS: 1813 patients with RA starting treatment with biological agents in 2000-5 were registered prospectively in the nationwide DANBIO Registry. Baseline disease activity and 12 months' treatment responses were determined in cohorts based on start year (2000/1; 2002; 2003; 2004; 2005). RESULTS: Despite decreasing baseline disease activity from the 2000/2001 cohort to 2005 cohort (28-joint count Disease Activity Score (DAS28): from 5.9 to 5.3 (p<0.001)), the 12 months' DAS improvement increased from 1.8 units (2000/2001 cohort) to 2.2 units (2005 cohort) (p<0.001). The fraction with good EULAR response increased from 28% (2000/2001 cohort) to 50% (2005 cohort); the fraction with no response decreased from 29% (2000/2001 cohort) to 16% (2005 cohort). ACR20/50/70 response rates increased from 53%/31%/13% (2000/2001 cohort) to 69%/51%/30% (2005 cohort). After correction for withdrawals, treatment responses were lower, but patterns unchanged. One-year drug survival was for the 2000/2001 cohort: 73%, 2002: 62%, 2003: 67%, 2004: 70%, 2005: 69%. CONCLUSION: From 2000 to 2005, significantly improved treatment responses to TNF inhibitors were seen in clinical practice despite decreasing baseline disease activity levels. This lends support to the less stringent prescription practice towards treating patients with lower disease activity that has been observed in several countries.

The course of bone mineral density and biochemical markers of bone turnover in early postmenopausal spinal cord-lesioned females.

STUDY DESIGN: A prospective observational study. OBJECTIVE: To evaluate bone mineral density (BMD) and biochemical markers of bone turnover in spinal cord-lesioned females in the early postmenopausal period. SETTING: Clinic for Spinal Cord Injuries, H:S Rigshospitalet, Denmark. MATERIAL: In all, 18 early postmenopausal females with spinal cord lesions (SCL) of more than 2 years duration were recruited. In total, 11 completed the study. METHODS: Using dual energy X-ray absorption, BMD of the lumbar spine, femoral neck, trochanter and proximal tibia was measured every 6 months for 30 months. Biochemical markers of bone turnover in blood and urine were collected at the same time points. RESULTS: A significant increase in markers of bone formation in the blood was found and markers of bone resorption in urine tended to increase. BMD values changed insignificantly but for all regions decreased, except the lumbar spine. CONCLUSION: An accelerated bone turnover occurs in early postmenopausal SCL females. At the same time, we showed an insignificant decrease in BMD data from the lower extremity.

Comparison of dual X-ray absorptiometry (DXA), digital X-ray radiogrammetry (DXR), and conventional radiographs in the evaluation of osteoporosis and bone erosions in patients with rheumatoid arthritis.

OBJECTIVE: To compare the relationship between bone mineral density (BMD) in the metacarpal bones and forearm measured by dual X-ray absorptiometry (DXA) and digital X-ray radiogrammetry (DXR) and radiological alterations in patients with early and established rheumatoid arthritis (RA). PATIENTS AND METHODS: In each of the three disease duration groups, 11 female RA patients were included. The patients were further divided into two groups according to bone erosions. BMD in the metacarpals was evaluated by DXA and DXR. RESULTS: A significant relationship between DXA-BMD and DXR-BMD was observed. DXR-BMD and the individually combined cortical thickness (CT) of the metacarpo-phalangeal (MCP) joints were related to disease duration and erosions. Patients with erosive disease had lower values of age- and sex-adjusted BMD measured with DXA, but most significantly with DXR. CONCLUSION: DXR appears to be a more sensitive method than DXA in detecting early bone loss in patients with RA. The relationship of DXR-BMD to disease duration and bone damage indicates that the DXR method may be useful in the evaluation of disease activity and progression.

Bone loss in unclassified polyarthritis and early rheumatoid arthritis is better detected by digital x ray radiogrammetry than dual x ray absorptiometry: relationship with disease activity and radiographic outcome.

OBJECTIVE: To compare changes in regional bone mineral density (BMD) of the metacarpal joints measured by dual x ray absorptiometry (DXA) and digital x ray radiogrammetry (DXR) in relation to disease activity and radiographic outcome in a two year follow up study of patients with early RA and unclassified polyarthritis. PATIENTS AND METHODS: 72 patients with symmetrically swollen and tender second and third metacarpophalangeal or proximal interphalangeal joints for at least four weeks and less than two years were included. 51 patients fulfilled the ACR criteria for RA. 21 patients had unclassified polyarthritis. The patients with RA were divided into groups according to mean disease activity, average glucocorticoid dose, and MRI and x ray detected bone erosions in the hands. Clinical and biochemical measurements were made every month and an x ray examination of the hands and BMD of the metacarpal joints every six months. RESULTS: DXR BMD decreased significantly only in patients with RA from month 6 and was associated with the mean disease activity. Patients with RA and erosive as well as non-erosive disease showed a significant decrease in the rate of bone loss, greatest in those with erosive disease. No changes in BMD measured by DXA were seen in any patient group. CONCLUSION: DXR is a useful measure of the destructive disease activity in patients with RA and unclassified polyarthritis, providing valuable information about bone changes associated with disease activity and erosive disease in early RA. DXR is better than DXA for detecting and monitoring periarticular osteoporosis of the metacarpal bone.

[Rofecoxib, a new NSAID preparation with selective COX-2 inhibition]. / Rofecoxib, et nyt NSAID-praeparat med selektiv COX-2-haemning.

NSAIDs are effective by inhibition of the enzyme cyclooxygenase, which leads to formation of prostaglandins. At the beginning of the 90-ties it became evident, that cyclooxygenase existed in two isoforms (COX-1 and COX-2). COX-1 is found in a number of tissues. In these tissues prostaglandins have several physiological functions. COX-2 is an induceable enzyme involved in inflammation. A new NSAID, rofecoxib, has selective COX-2 inhibition defined as inhibition of COX-2, but not COX-1 in the therapeutic dose range. Trial results have shown pain relief analogous to common NSAIDs (ibuprofen and diclofenac) in patients with osteoarthritis of the hip or knee. The incidence of gastric ulcers was significantly reduced in the rofecoxib treated group compared to the groups treated with common NSAIDs. It is concluded that selective COX-2 inhibition is a promising new treatment. At present it seems appropriate to consider the drug in patients with good indication for an NSAID and simultaneous gastrointestinal risk factors.

Prognostic value of renal biopsy and clinical variables in patients with lupus nephritis and normal serum creatinine.

OBJECTIVE: To evaluate factors with possible influence on the renal outcome in patients with lupus nephritis but without chronic renal insufficiency (CRI). METHODS: Renal biopsies from 94 patients were re-assessed with regard to WHO class, activity, chronicity and tubulointerstitial indices without knowledge of clinical features. The outcome parameters were CRI defined as irreversibly increased serum creatinine and renal end stage disease. RESULTS: The risk ratios (RR) of developing CRI were 2.6 for active urinary sediment, 3.1 for hyaline thrombi and 7.3 for glomerular leukocyte exudation. The RR of renal end stage disease was 5.0 when the duration of renal disease exceeded one year at the time of biopsy and 4.3 when biopsy disclosed a class IV lesion. Glomerular sclerosis was also associated to renal end stage disease. CONCLUSION: Early renal biopsy and the abovementioned signs of active renal disease carry prognostic information that may have significant therapeutic implications.

A randomised trial of differentiated prednisolone treatment in active rheumatoid arthritis. Clinical benefits and skeletal side effects.

OBJECTIVES: To study benefits and skeletal side effects of carefully monitored prednisolone treatment in patients with active rheumatoid arthritis. METHODS: One hundred and two patients with active rheumatoid arthritis were randomly allocated to treatment with disease modifying anti-inflammatory drug (DMARD) alone or DMARD and prednisolone in a one year follow up study. Prednisolone was given in a dose regimen adapted to the disease activity of the individual patient. The mean dose was 6 mg and the mean cumulated dose was 2160 mg. Patients were followed up with disease activity parameters, radiograph of the hands (Larsen score), and bone mineral density (BMD) of the lumbar spine, distal forearm and hand. At one year 26 patients had withdrawn from the investigation leaving 76 patients for evaluation. RESULTS: The results showed that disease activity in the prednisolone treated group was reduced within two weeks. In the DMARD alone group disease activity was gradually reduced over months. At six months there was no difference between the groups as evaluated by an improvement score using a number of ACR criteria. Prednisolone in the present set up was not able to protect significantly against radiological disease progression, although there was a trend towards less progression in Larsen score in the prednisolone group, a matter that was further underlined in an intention to treat analysis. BMD data revealed a significant reduction in spinal BMD in the prednisolone group, whereas prednisolone seemed to have a protective effect against bone loss in the hand and distal forearm. CONCLUSIONS: This study does not allow any firm conclusions for or against the treatment of rheumatoid arthritis with prednisolone. The data suggest that the beneficial effects of prednisolone are not as clear cut in established rheumatoid arthritis as in early disease. Furthermore the data indicate that treatment in the chosen relatively low dose does not provide sufficient control of disease. On the other hand the spinal bone loss observed in the prednisolone group does invite considerations about using higher doses.

Mortality and causes of death of 513 Danish patients with systemic lupus erythematosus.

A multicentre cohort of 513 clinic attenders with systemic lupus erythematosus (SLE) was retrospectively identified, representing 4185 patient-years of follow-up. Expected numbers of death were calculated by means of age- and sex-specific mortality rates of the general Danish population. The observed number of deaths was 122. The survival rates were 97%, 91%, 76%, 64% and 53% after 1, 5, 10, 15, and 20 years respectively. The overall mortality rate was 2.9% per year (95% CI 2.4-3.5), and the standardized mortality rate (SMR) was 4.6 (95% CI 3.8-5.5). The causes of death included active SLE (n = 19), end stage organ failure due to SLE (n = 16), infections (n = 25), malignancy (n = 9), cardiovascular disease (n = 32), and other causes (n = 21). SLE was directly related to one third of the excess mortality. In conclusion, SLE patients in the present cohort had a 4.6-fold increased mortality compared with the general population and half of the deaths were caused by SLE manifestations or infections, especially in young patients during the early period of the disease.

A multicentre study of 513 Danish patients with systemic lupus erythematosus. I. Disease manifestations and analyses of clinical subsets.

A Danish multicentre study was undertaken of the manifestations, infections, thrombotic events, survival and predictive factors of survival in 513 Danish patients with systemic lupus erythematosus (SLE) according to the 1982 classification criteria of the American College of Rheumatology. The mean duration of follow-up was 8.2 years from diagnosis and 12.8 years from first symptom. This paper describes the most common clinical and laboratory manifestations and their relationship to sex and age at the time of onset and diagnosis. Cluster analysis revealed three clinically defined clusters at the time of disease onset. Cluster 1 (57% of patients) consisted of relatively elderly patients without nephropathy or malar rash, but with a high prevalence of discoid lesions. Cluster 2 (18%) consisted of patients with nephropathy, a third of whom also developed serositis and lymphopenia. The patients of the third cluster (25%) all had malar rash and half were photosensitive. Follow-up showed that the patients of cluster 2 developed azotaemia, large proteinuria, arterial hypertension and myositis significantly more often than did the rest of the patients, but the mortality was not increased. The risk of developing renal end-stage disease was highest in men with early-onset disease.

A multicentre study of 513 Danish patients with systemic lupus erythematosus. II. Disease mortality and clinical factors of prognostic value.

In this Danish multicentre study, predictive clinical factors of mortality and survival were calculated for 513 patients with systemic lupus erythematosus (SLE), 122 of whom died within a mean observation period of 8.2 years equalling a mortality rate of 2.9% per year. Survival rates were 97%, 91%, 76% and 64% after 1, 5, 10 and 15 years, respectively. The direct causes of death included SLE (n = 35), infections (n = 25), malignancy (n = 9), cardiovascular disease (n = 32) and other causes (n = 21). Uni- and multivariate analyses of survival and mortality were performed for all deaths and for SLE-related deaths. Azotaemia (one-fifth of the patients) was a strong predictor of increased overall and SLE-related mortality, but nephropathy per se (one-half of the patients) and large proteinuria (one-sixth of the patients) were unrelated to survival. Haemolytic anaemia had a significant negative influence on survival related to mortality caused by infections. Diffuse central nervous system disease and myocarditis were related to increased SLE-related mortality, whereas photosensitivity predicted a decreased mortality. Non-fatal infections and thrombotic events predicted a decreased overall survival. Since 1980 the mortality caused by SLE manifestations has decreased significantly.

Increased bone mineral density after prolonged electrically induced cycle training of paralyzed limbs in spinal cord injured man.

Spinal cord injured (SCI) individuals have a substantial loss of bone mass in the lower limbs, equaling approximately 50% of normal values in the proximal tibia, and this has been associated with a high incidence of low impact fractures. To evaluate if this inactivity-associated condition in the SCI population can be reversed with prolonged physical training, ten SCI individuals [ages 35.3 +/- 2.3 years (mean +/- standard error [SE]); post injury time: 12.5 +/- 2.7 years, range 2-24 years; level of lesion: C6-Th4; weight: 78 +/- 3.8 kg] performed 12 months of Functional Electrical Stimulated (FES) upright cycling for 30 min per day, 3 days per week, followed by six months with only one weekly training session. Bone mineral density (BMD) was determined before training and 12 and 18 months later. BMD was measured in the lumbar spine, the femoral neck, and the proximal tibia by dual energy absorptiometry (DEXA, Nordland XR 26 MK1). Before training, BMD was in the proximal tibia (52%), as well as in the femoral neck, lower in SCI subjects than in controls of same age (P < 0.05). BMD of the lumbar spine did not differ between groups (P > 0.05). After 12 months of training, the BMD of the proximal tibia had increased 10%, from 0.49 +/- 0.04 to 0. 54 +/- 0.04 g/cm2 (P < 0.05). After a further 6 months with reduced training, the BMD in the proximal tibia no longer differed from the BMD before training (P > 0.05). No changes were observed in the lumbar spine or in the femoral neck in response to FES cycle training. It is concluded that in SCI, the loss of bone mass in the proximal tibia can be partially reversed by regular long-term FES cycle exercise. However, one exercise session per week is insufficient to maintain this increase.

Comparison of body composition by dual energy X-ray absorptiometry to other estimates of body composition during weight loss in obese patients with rheumatoid arthritis.

Body composition was determined by dual energy X-ray absorptiometry (DXA) scanning and classical reference methods (40K, 3H2O, and a combination of these in a four-compartment model) in 19 overweight patients with rheumatoid arthritis who underwent a 12-week weight-reducing regimen. The aim of the study was to investigate whether DXA provides a valid estimate of body composition. The results showed that weight as determined by DXA was highly significantly correlated to weight determined by scales. Furthermore, significant correlations were found in the body components (fat-free mass, fat mass) determined by DXA, 40K, 3H2O and the four-compartment model. Mean values differed slightly but significantly. With respect to changes in body composition, no significant correlations were found between any of the methods, except for the weight loss recorded by DXA and scales, and loss of fat mass (and fat free mass) estimated by 3H2O and the four-compartment model. The sparseness of correlations reflected the small changes in fat-free mass and fat mass (2.6 and 1.7 kg respectively), and the fact that changes were comparable to measurement errors of the various methods. We suggest that DXA scanning is a valid supplement for determination of body composition. Validation of DXA scanning requires new experimental in vitro investigations, which, incidentally, also applies to the classical reference methods.