Long-term effects on bone mineral density after four years of treatment with two intensive combination strategies, including initially high-dose prednisolone, in early rheumatoid arthritis patients: the COBRA-light trial.

In this study, no difference in bone loss was observed between patients with early RA initially treated with COmbinatietherapie Bij Reumatoide Artritis (COBRA) (including initially 60 mg/day prednisolone) and patients treated with COBRA-light (including initially 30 mg/day prednisolone) during 4-year observation. PURPOSE: To assess changes in bone mineral density (BMD) after 4 years in early rheumatoid arthritis (RA) patients initially treated with COBRA-light or COBRA therapy. METHODS: In a 1 year, open-label, randomised, non-inferiority trial, patients were assigned to COBRA-light (methotrexate 25 mg/week plus initially prednisolone 30 mg/day) or COBRA (methotrexate 7.5 mg/week, sulfasalazine 2 g/day plus initially prednisolone 60 mg/day) therapy. After 1 year, antirheumatic treatment was at the discretion of treating rheumatologists. BMD was measured at baseline and after 1, 2 and 4 years at hips and lumbar spine with dual-energy X-ray absorptiometry. BMD changes between treatment strategies on average over time were compared with GEE analysis. RESULTS: Data from 155 out of 162 patients could be analysed: 68% were female with a mean age of 52 (SD 13) years. Both COBRA-light and COBRA therapy showed declines in BMD at the total hip of -3.3% and -1.7%, respectively (p = 0.12), and the femoral neck, -3.7% and -3.0%, respectively (p = 0.95). At the lumbar spine, both treatment groups showed minor decline in BMD over 4 years: -0.5% and -1.0%, respectively (p = 0.10). CONCLUSION: In a treat-to-target design in early RA, over 4 years, no differences between groups were found in change in BMD at total hip, femoral neck and the lumbar spine. At the hip, bone loss was around 3% in both groups, while mild bone loss was observed at lumbar spine, both in patients starting prednisolone 60 and 30 mg/day. These data suggest that the well-known negative effects of prednisolone can be modulated by modern treatment of RA.

Long-Term Clinical Outcomes in a Cohort of Adults With Childhood-Onset Systemic Lupus Erythematosus.

OBJECTIVE: Childhood-onset systemic lupus erythematosus (SLE) is a severe, lifelong, multisystem autoimmune disease. Long-term outcome data are limited. This study was undertaken to identify clinical characteristics and health-related quality of life (HRQoL) of adults with childhood-onset SLE. METHODS: Patients participated in a single study visit comprising a structured history and physical examination. Disease activity (scored using the SLE Disease Activity Index 2000 [SLEDAI-2K]), damage (scored using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index [SDI]), and HRQoL (scored using the Short Form 36 Health Survey) were assessed. Medical records were reviewed. RESULTS: In total, 111 childhood-onset SLE patients were included; the median disease duration was 20 years, 91% of patients were female, and 72% were white. Disease activity was low (median SLEDAI-2K score 4), and 71% of patients received prednisone, hydroxychloroquine (HCQ), and/or other disease-modifying antirheumatic drugs. The vast majority of new childhood-onset SLE-related manifestations developed within 2 years of diagnosis. Damage such as myocardial infarctions began occurring after 5 years. Most patients (62%) experienced damage, predominantly in the musculoskeletal, neuropsychiatric, and renal systems. Cerebrovascular accidents, renal transplants, replacement arthroplasties, and myocardial infarctions typically occurred at a young age (median age 20 years, 24 years, 34 years, and 39 years, respectively). Multivariate logistic regression analysis showed that damage accrual was associated with disease duration (odds ratio [OR] 1.15, P < 0.001), antiphospholipid antibody positivity (OR 3.56, P = 0.026), and hypertension (OR 3.21, P = 0.043). Current HCQ monotherapy was associated with an SDI score of 0 (OR 0.16, P = 0.009). In this cohort, HRQoL was impaired compared to the overall Dutch population. The presence of damage reduced HRQoL scores in 1 domain. High disease activity (SLEDAI-2K score ≥8) and changes in physical appearance strongly reduced HRQoL scores (in 4 of 8 domains and 7 of 8 domains, respectively). CONCLUSION: The majority of adults with childhood-onset SLE in this large cohort developed significant damage at a young age and had impaired HRQoL without achieving drug-free remission, illustrating the substantial impact of childhood-onset SLE on future life.

Comprehensive approach to study complement C4 in systemic lupus erythematosus: Gene polymorphisms, protein levels and functional activity.

Genetic variation of the genes encoding complement component C4 is strongly associated with systemic lupus erythematosus (SLE), a chronic multi-organ auto-immune disease. This study examined C4 and its isotypes on a genetic, protein, and functional level in 140 SLE patients and 104 healthy controls. Gene copy number (GCN) variation, silencing CT-insertion, and the retroviral HERV-K(C4) insertion) were analyzed with multiplex ligation-dependent probe amplification. Increased susceptibility to SLE was found for low GCN (≪2) of C4A. Serositis was the only clinical manifestation associated with low C4A GCN. One additional novel silencing mutation in the C4A gene was found by Sanger sequencing. This mutation causes a premature stop codon in exon 11. Protein concentrations of C4 isoforms C4A and C4B were determined with ELISA and were significantly lower in SLE patients compared to healthy controls. To study C4 isotypes on a functional level, a new C4 assay was developed, which distinguishes C4A from C4B by its binding capacity to amino or hydroxyl groups, respectively. This assay showed high correlation with ELISA and detected crossing over of Rodgers and Chido antigens in 3.2% (8/244) of individuals. The binding capacity of available C4 to its substrates was unaffected in SLE. Our study provides, for the first time, a complete overview of C4 in SLE from genetic variation to binding capacity using a novel test. As this test detects crossing over of Rodgers and Chido antigens, it will allow for more accurate measurement of C4 in future studies.

Content Validity of a Short Calcium Intake List to Estimate Daily Dietary Calcium Intake of Patients with Osteoporosis.

PURPOSE: Calcium supplements are prescribed for prevention of osteoporotic fractures, but there is controversy whether excess of calcium intake is associated with cardiovascular events. While an accurate estimation of dietary calcium intake is a prerequisite to prescribe the adequate amount of supplementation, the most adequate tools for estimating intake are time-consuming. The aim of this study is to validate a short calcium intake list (SCaIL) that is feasible in daily clinical practice. METHODS: Based on the food groups contributing most to daily dietary calcium intake and portion sizes determined in an earlier study, a three-item, 1-min SCaIL was designed. As a reference method, an extensive dietary history (DH) with specific focus on calcium-rich foods and extra attention for portion sizes was performed. Beforehand, a difference of ≥250 mg calcium between both methods was considered clinically relevant. RESULTS: Sixty-six patients with either primary (n = 40) or secondary (n = 26) osteoporosis were included. On average, the SCaIL showed a small and clinically non-relevant difference in calcium intake with the DH: 24 ± 350 mg/day (1146 ± 440 vs. 1170 ± 485 mg, respectively; p = 0.568). Sensitivity and specificity of the SCaIL, compared to the DH, were 73 and 80%, respectively. However, in 50% of the individuals, a clinically relevant difference of ≥250 mg calcium was observed between both methods, while in 17% this was even ≥500 mg. CONCLUSIONS: The SCaIL is a quick and easy questionnaire to estimate dietary calcium intake at a group level, but is not sufficiently reliable for use in individual patients. Remarkably, the mean dietary calcium intake estimated by the DH of 1170 mg/day indicates that a large proportion of osteoporosis patients might not even need calcium supplementation, although more data are needed to confirm this finding.

Autoantibody Specificities and Type I Interferon Pathway Activation in Idiopathic Inflammatory Myopathies.

Myositis is a heterogeneous group of autoimmune diseases, with different pathogenic mechanisms contributing to the different subsets of disease. The aim of this study was to test whether the autoantibody profile in patients with myositis is associated with a type I interferon (IFN) signature, as in patients with systemic lupus erythematous (SLE). Patients with myositis were prospectively enrolled in the study and compared to healthy controls and to patients with SLE. Autoantibody status was analysed using an immunoassay system and immunoprecipitation. Type I IFN activity in whole blood was determined using direct gene expression analysis. Serum IFN-inducing activity was tested using peripheral blood cells from healthy donors. Blocking experiments were performed by neutralizing anti-IFNAR or anti-IFN-α antibodies. Patients were categorized into IFN high and IFN low based on an IFN score. Patients with autoantibodies against RNA-binding proteins had a higher IFN score compared to patients without these antibodies, and the IFN score was related to autoantibody multispecificity. Patients with dermatomyositis (DM) and inclusion body myositis (IBM) had a higher IFN score compared to the other subgroups. Serum type I IFN bioactivity was blocked by neutralizing anti-IFNAR or anti-IFN-α antibodies. To conclude, a high IFN score was not only associated with DM, as previously reported, and IBM, but also with autoantibody monospecificity against several RNA-binding proteins and with autoantibody multispecificity. These studies identify IFN-α in sera as a trigger for activation of the type I IFN pathway in peripheral blood and support IFN-α as a possible target for therapy in these patients.

Effect of twelve-month physical exercise program on patients with osteoporotic vertebral fractures: a randomized, controlled trial.

UNLABELLED: We performed a randomized clinical trial to evaluate the effect of a 12-month physical exercise program on quality of life, balance, and functional mobility in postmenopausal women with osteoporotic vertebral fractures. All three outcomes improved in the intervention group and were better than in the controls. INTRODUCTION: Th aim of this study was to evaluate the effectiveness of a structured physical exercise intervention on quality of life, functional mobility, and balance in patients with osteoporotic vertebral fractures and back pain. METHODS: Seventy-eight postmenopausal women with vertebral fractures were randomized into an exercise group (n = 40) and a control group (n = 38). The mean age was 69.2 ± 7.7 years. All women had at least one osteoporotic vertebral fracture and suffered from chronic back pain. Patients with a history of vertebral and non-vertebral fracture within the past 6 months were excluded. The 40-min exercise program was conducted twice weekly for 1 year. Participants in the control group were instructed to continue their usual daily activities. Participants were assessed at baseline and at 12 months using the Quality of Life Questionnaire (QUALEFFO-41). Balance was measured with the Balance Master® System NeuroCom® and functional mobility was measured with the "timed up and go" test and "sit-to-stand" test. RESULTS: Total QUALEFFO-41 score after 12 months was significantly better in the exercise group (44.2 ± 7.5) compared to the control group (56.6 ± 9.4), p < 0.0001. Quality of life improved in domains: "Pain", "Physical function: Jobs around the house", "Physical function: Mobility", "Social function", "General health perception" in the exercise group as compared to the control group. After 12 months, balance as assessed by "Tandem Walk and Sway" became significantly better in the exercise group as compared to the control group (p = 0.02). A significant improvement in the "timed up and go" test (p = 0.02) and the "sit-to-stand" test (p = 0.01) was shown in the exercise group compared to the control group. CONCLUSIONS: This is the first 12 month-randomized clinical trial of exercise in osteoporotic women with a vertebral fracture that demonstrates improvement of three key outcome measures: quality of life, functional mobility, and balance.

Systemic lupus erythematosus: review of synthetic drugs.

INTRODUCTION: Synthetic drugs are prescribed for nearly all patients with systemic lupus erythematosus (SLE), a multisystem autoimmune disease, to ameliorate symptoms and positively influence outcome. While only 2 biologic agents have been approved for the treatment of SLE, synthetic drugs are still the mainstay of therapy in SLE. The highly variable and unpredictable course of SLE poses a challenge for physicians as to what drug(s) should be prescribed for which patient. AREAS COVERED: Previous and recent studies have evaluated several synthetic drugs in the treatment of SLE. This article reviews currently available evidence for the efficacy and safety of synthetic drugs in SLE and discusses future treatment perspectives. EXPERT OPINION: Hydroxychloroquine should be considered an anchor drug in SLE because of the multiple beneficial effects of this agent. When patients present with persistent disease activity despite hydroxychloroquine therapy or need higher dosages and/or prolonged use of glucocorticoids (GCs), additional immunosuppressants should be promptly prescribed. Based on available evidence, azathioprine and mycophenolate mofetil are the drugs of first choice. Determination of a 'safe' GC dose for chronic daily use is of major importance and should be subject of further studies in large patient populations.

Making the invisible visible: bioelectrical impedance analysis demonstrates unfavourable body composition in rheumatoid arthritis patients in clinical practice.

OBJECTIVES: To examine differences between the assessment of body composition by body mass index (BMI) and bioelectrical impedance analysis (BIA) in patients with rheumatoid arthritis (RA). METHOD: The body composition of RA patients was assessed during their visit to the outpatient department of a Dutch academic hospital using BMI, fat-free mass index (FFMI), and fat mass index (FMI). FFMI and FMI were determined by single-frequency BIA. RESULTS: Sixty-five consecutive RA patients (83% women, mean age 58 years, median disease duration 7 years) with moderately active disease [mean Disease Activity Score using 28 joint counts (DAS28) = 3.40; mean Rheumatoid Arthritis Disease Activity Index (RADAI) score = 3.49] and moderate disability [mean Health Assessment Questionnaire (HAQ) score = 0.87] were included. Based on BMI, 2% of our study population were underweight, 45% had a healthy body composition, and 54% were overweight or obese. Based on BIA, 18% of the patients showed a low FFMI and 74% had a high or very high FMI. Low FFMI was found in 44% of the women with a normal BMI, and high FMI was found in 40% of the women and 75% of the men with a normal BMI. CONCLUSIONS: A high frequency of unfavourable body composition, predominantly reduced FFMI and elevated FMI, was found in a cohort of RA patients with moderately active disease, turning BMI into an unreliable method for assessment of body composition in RA. BIA, however, might be the preferred method to assess FFMI and FMI in RA patients in clinical practice, as it is easy to use and relatively inexpensive.

Elevated risk of clinical fractures and associated risk factors in patients with systemic lupus erythematosus versus matched controls: a population-based study in the United Kingdom.

UNLABELLED: The incidence of clinical fractures and the associated factors were assessed in patients with systemic lupus erythematosus (SLE) versus matched controls. We found an increased fracture risk in SLE patients compared to controls. Glucocorticoid use, longer disease duration, neuropsychiatric disease complications and previous osteoporotic fractures were identified as associated factors. INTRODUCTION: The aims of this study were to estimate the risk of clinical fractures in patients with SLE versus matched controls and to evaluate the risk factors associated with clinical fractures in SLE. METHODS: This is a population-based cohort study using the Clinical Practice Research Datalink (from 1987-2012). Each SLE patient (n = 4,343) was matched with up to six controls (n = 21,780) by age and sex. Clinical fracture type was stratified according to the WHO definitions into osteoporotic and non-osteoporotic fracture. Cox proportional hazards calculated relative rates (RR) of clinical fracture and time interaction terms to evaluate the timing patterns of fracture. Clinical fracture rates in SLE patients, stratified by age, gender, type of fracture, disease duration and therapy variables, were compared with those rates in controls. RESULTS: Follow-up durations were 6.4 years in SLE patients and 6.6 years in controls. SLE patients had a 1.2-fold increased clinical fracture risk compared to controls (adjusted RR = 1.22, 95% CI = 1.05-1.42), and the risk further increased with a longer disease duration. Glucocorticoid (GC) use in the previous 6 months raised the risk of clinical fracture (adjusted RR = 1.27, 95% CI = 1.02-1.58). Cerebrovascular events, seizures and previous osteoporotic fractures were identified as predictors of clinical fractures. CONCLUSIONS: We found an increased risk of clinical fracture in SLE patients compared to controls. GC use in the previous 6 months and longer disease duration are associated with the increased fracture risk in SLE. Patients with neuropsychiatric organ damage or previous osteoporotic fractures are also at increased risk of the occurrence of clinical fractures.

Optimizing fracture prevention: the fracture liaison service, an observational study.

UNLABELLED: The response rate to the invitation to the fracture liaison service and reasons for non-response were evaluated in 2,207 fragility fracture patients. Fifty-one percent responded; non-responders were most often not interested (38 %) or were hip fracture patients. After 1 year of treatment, 88 % was still persistent and 2 % had a new fracture. INTRODUCTION: To increase the percentage of elderly fracture patients undergoing a dual energy x-ray absorptiometry (DXA) measurement, and to investigate why some patients did not respond to invitation to our fracture liaison service (FLS). METHODS: In four Dutch hospitals, fracture patients ≥ 50 years were invited through a written or personal invitation at the surgical outpatient department, for a DXA measurement and visit to our FLS. Patients who did not respond were contacted by telephone. In patients diagnosed with osteoporosis, treatment was started. Patients were contacted every 3 months during 1 year to assess drug persistence and the occurrence of subsequent fractures. RESULTS: Of the 2,207 patients who were invited, 50.6 % responded. Most frequent reasons for not responding included: not interested (38 %), already screened/under treatment for osteoporosis (15.7 %), physically unable to attend the clinic (11.5 %), and death (5.2 %). Hip fracture patients responded less frequently (29 %) while patients with a wrist (60 %) or ankle fracture (65.2 %) were more likely to visit the clinic. In 337 responding patients, osteoporosis was diagnosed and treatment was initiated. After 12 months of follow-up, 88 % of the patients were still persistent with anti-osteoporosis therapy and only 2 % suffered a subsequent clinical fracture. CONCLUSION: In elderly fracture patients, the use of a FLS leads to an increased response rate, a high persistence to drug treatment, and a low rate of subsequent clinical fractures. Additional programs for hip fracture patients are required, as these patients have a low response rate.

Depression in systemic lupus erythematosus, dependent on or independent of severity of disease.

OBJECTIVES: To estimate the prevalence of depression in subjects with systemic lupus erythematosus (SLE) in relation to the general population and to unravel the relation between depression and SLE disease characteristics. METHODS: One hundred and two subjects with SLE (mean age 44.4 years) were studied using the Beck Depression Inventory (BDI) score to estimate the prevalence of depression. The BDI scores in subjects with SLE were compared with BDI scores from a pan-European population based study (Outcome in Depression International Network (ODIN) study, n = 7934), i.e. the general population. RESULTS: The mean BDI score was higher in SLE subjects (10.1 points) compared with the BDI scores derived from the general population (10.1 versus 5.6 points, respectively, p < 0.001). This corresponds to a prevalence of depression of 16.6% and 6.7%, respectively. There was no association between disease activity or organ damage and BDI scores in subjects with SLE (p > 0.1). Only 7% of SLE subjects with high BDI scores used antidepressants. CONCLUSION: The mean BDI score and prevalence of depression are significantly higher in SLE subjects compared with the general population. No association was found between SLE disease characteristics and BDI scores. The number of depressed SLE subjects treated with antidepressants is low, suggesting inadequate recognition and treatment of depression in SLE.

Six-year follow-up study of bone mineral density in patients with systemic lupus erythematosus.

UNLABELLED: Long-term bone mineral density (BMD) changes and the associated factors in systemic lupus erythematosus (SLE) patients were assessed. Despite the remarkably low overall bone loss, significant spine bone loss was associated with the use of glucocorticoids, use of antimalarials, and lower 25-hydroxyvitamin D levels, stressing the importance of prevention of osteoporosis and vitamin D deficiency in SLE patients. INTRODUCTION: The aim of this study is to assess the BMD changes in patients with SLE and to identify the associated factors. METHODS: Demographic and clinical data of 126 SLE patients were collected, and BMD measurements of the lumbar spine and the total hip were performed by dual-energy X-ray absorptiometry at baseline and follow-up. Statistical analyses were performed using independent Mann-Whitney U tests and linear regression analyses. RESULTS: At baseline, 39.7 % of the patients (90 % female, mean age 39 ± 12.2 years) had osteopenia, and 6.3 % had osteoporosis. The median follow-up duration was 6.7 years (range 1.9-9.3 years). Mean changes in BMD at the lumbar spine (-0.08 %/year) and the hip (-0.20 %/year) were not significant. During follow-up, 70 % of the patients used glucocorticoids. The mean ± SD daily glucocorticoid dose was 5.0 ± 5.0 mg. In multiple regression analysis, BMD loss at the spine was significantly associated with higher daily glucocorticoid dose and lower baseline 25-hydroxyvitamin D levels. BMD loss at the hip was associated with lower 25-hydroxyvitamin D levels at baseline, reduction of body mass index, and baseline use of antimalarials. CONCLUSIONS: In this 6-year follow-up study, bone loss was remarkably low. A dose-dependent relationship between glucocorticoid use and spinal bone loss was found. In addition, the use of antimalarials and lower 25-hydroxyvitamin D levels at baseline were associated with BMD loss. These findings underline the importance of prevention and treatment of vitamin D deficiency and osteoporosis in SLE, especially in patients using glucocorticoids or antimalarials.

Glucocorticoid-induced osteoporosis.

Glucocorticoid-induced osteoporosis is one of the most important side-effects of glucocorticoid use, leading to an increased fracture risk. In this review, recent advances in the understanding of the mechanisms of glucocorticoid-induced osteoporosis are summarised. Methods to identify persons at risk for fractures are discussed, as well as the new ACR recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis (2010). Different treatment options are summarised considering the pathogenesis of glucocorticoid-induced osteoporosis. Improved insights into pathogenesis might result in development of new treatment possibilities.

The association between circulating antibodies against domain I of beta2-glycoprotein I and thrombosis: an international multicenter study.

BACKGROUND: Diagnosis of the antiphospholipid syndrome (APS) is difficult as a result of limited specificity of existing assays for detecting clinically relevant antiphospholipid antibodies. Anti-beta2-glycoprotein I (beta 2GPI) antibodies play a central role in the disease process of APS. OBJECTIVES: We have investigated the relation between antiphospholipid antibodies with specificity for domain I of beta 2GPI and thrombosis/pregnancy morbidity in an international multicenter study. PATIENTS/METHODS: Four hundred and seventy-seven patients derived from nine different centres met the inclusion criterion of having anti-beta 2GPI antibodies in their plasma/serum. Clinical data and results of tests for lupus anticoagulant, anti-cardiolipin antibodies and anti-beta 2GPI antibodies were established at the different centres of inclusion. After being re-tested for the presence of IgG and/or IgM anti-beta 2GPI antibodies, the samples were tested for the presence of IgG-directed against domain I of beta 2GPI and results were correlated with the thrombotic and obstetric history. RESULTS: Re-testing for the presence of anti-beta 2GPI antibodies resulted in inclusion of 442/477 patients. IgG class anti-domain I antibodies were present in plasma of 243/442 patients (55%). 201/243 (83%) had a history of thrombosis. This resulted in an odds ratio of 3.5 (2.3-5.4, 95% confidence interval) for thrombosis. Anti-domain I IgG antibodies were also significantly correlated with obstetric complications [odds ratio: 2.4 (1.4-4.3, 95% confidence interval)]. CONCLUSION: In this multicenter study, the detection of IgG antibodies that are directed against domain I of beta 2GPI proved to be more strongly associated with thrombosis and obstetric complications than those detected using the standard anti-beta 2GPI antibody assay.

Prevention of glucocorticoid-induced osteoporosis.

Glucocorticoid-induced osteoporosis is the most common cause of secondary osteoporosis. The role of the Wnt signaling pathway in bone formation and the ratio of receptor activator for NF-kappaB ligand versus osteoprotegerin in bone resorption are exciting new insights. The absolute fracture risk helps both clinicians and patients to interpret the results of bone density measurement, which may have a positive influence on adherence to therapy. The bisphosphonates alendronate and risedronate are the first-line treatment in the prevention of glucocorticoid-induced osteoporosis, because both increase the bone mineral density of the spine and hips and reduce the vertebral fracture rate. Treatment with the anabolic agent parathyroid hormone (1 - 34) strongly stimulates bone turnover, and seems to be superior to treatment with alendronate. It might be attractive for glucocorticoid-treated patients with new vertebral fractures during treatment with bisphosphonates, and/or with severe fracture risk.

Prevalence of and risk factors for the metabolic syndrome in women with systemic lupus erythematosus.

OBJECTIVE: To examine the prevalence of the metabolic syndrome and the relationship between metabolic syndrome score (MetS score) and disease characteristics and cardiovascular events (CVEs) in women with SLE. METHODS: Demographic and clinical data were collected in 141 female SLE patients. The prevalence of the metabolic syndrome was defined by a modified National Cholesterol Education Program (NCEP/ATP III) definition. Metabolic syndrome was defined as MetS score >or= 3. RESULTS: Twenty-three (16%) of the 141 SLE patients (mean age 39+/-12 years, mean disease duration 6.2+/-6.6 years) fulfilled the criteria of the metabolic syndrome. The mean MetS score was significantly higher in patients with SLE and a history of cardiovascular events (CVEs) than in those without a previous CVE. In linear multiple regression analysis, a high MetS score was significantly associated with previous intravenous methylprednisolone use, older age, higher ESR, higher C3 levels and higher serum creatinine levels. CONCLUSIONS: In our female SLE patients, a high prevalence of the metabolic syndrome was found as compared to healthy women in the Amsterdam Growth and Health Longitudinal Study. Independent risk factors for high MetS score in patients with SLE are previous treatment with intravenous methylprednisolone, renal insufficiency, older age, higher ESR and higher C3 levels. These results suggest that assessment of the metabolic syndrome in patients with SLE might be important to identify subgroups of patients that are at disproportional high risk of developing cardiovascular disease and diabetes mellitus.

Raised plasma levels of asymmetric dimethylarginine are associated with cardiovascular events, disease activity, and organ damage in patients with systemic lupus erythematosus.

BACKGROUND: Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide inhibitor and a new independent risk factor for endothelial dysfunction and cardiovascular disease. OBJECTIVE: To investigate the relationship between plasma ADMA levels and cardiovascular events (CVEs) and disease characteristics in patients with systemic lupus erythematosus (SLE). METHODS: Demographic and clinical data were collected and plasma ADMA levels were measured in 107 patients with SLE. A modified organ damage index was calculated as defined by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), excluding CVE as an item. RESULTS: Cardiovascular disease, defined as > or =1 previous arterial CVE, was recorded in 16/107 (15%) patients with SLE and increased across tertiles of ADMA levels (p = 0.023 for trend). Mean plasma ADMA levels were significantly higher in patients with SLE with a history of CVEs than in patients without a CVE history (p = 0.018). In multiple regression analysis a high SLEDAI score, high modified SDI, high titre of anti-dsDNA antibodies, and low serum HDL were significantly associated with high plasma ADMA levels. CONCLUSION: In patients with SLE, plasma ADMA levels are significantly associated with CVEs, measures of disease activity, and organ damage, independently of an unfavourable lipid profile.

The effect of intravenous pamidronate versus oral alendronate on bone mineral density in patients with osteoporosis.

Intravenous pamidronate is frequently used for the treatment of osteoporosis in patients who cannot tolerate oral bisphosphonates. The aim of the present study was to compare the changes in bone mineral density (BMD) after 1 year of treatment with either oral alendronate or intravenous pamidronate in patients with osteoporosis. We studied 40 consecutive patients starting treatment for osteoporosis: 20 received oral alendronate 10 mg/day and 20 received intravenous pamidronate 60 mg/3 months. Patients were started on intravenous pamidronate in the case of intolerance (within 1 month of start of treatment) of an oral bisphosphonate or in the case of contraindications for an oral bisphosphonate. BMD (spine and total hip) was measured with dual X-ray absorptiometry (DEXA) at the start of treatment and after 1 year. The BMD of the lumbar spine increased by 4.0% (P<0.05 vs baseline) in both groups, and the BMD of the hip increased by 3.3% and 2.9% (P<0.05 vs baseline) in the alendronate and pamidronate groups, respectively. The increases in BMD of the vertebral spine and the total hip after 1 year are comparable in the alendronate and pamidronate groups. We conclude that intravenous pamidronate can be used successfully as an alternative treatment in patients with gastrointestinal intolerance of an oral bisphosphonate.