Bem-vindo à SPR - Sociedade Portuguesa de Reumatologia
Artigos Publicados por Reumatologistas Portugueses - 2008
Nesta secção encontra-se uma lista de artigos publicados por reumatologistas portugueses, em diversas publicações, ao longo do ano de 2008.
Factors influencing calcaneus quantitative ultrasound measurements in an urban population
Clin Exp Rheumatol. 2008 Jan-Feb;26(1):67-72
Canhão H, Lucas R, Fonseca JE, Costa L, Romeu JC, Branco J, Barros H
OBJECTIVE:To estimate the effect of demographic, social, behavioural and anthropometric factors on quantitative ultrasound (QUS) parameters in an urban population.
METHODS:Cross-sectional evaluation of consecutive subjects selected as part of the EPIPorto study, Portugal. Information was obtained on demographic, social, clinical and behavioural characteristics using a standard protocol. Calcaneus QUS parameters (Broadband Ultrasound Attenuation - BUA, and Speed of Sound - SOS) were obtained for men and women, stratified by age group. Comparisons according to exposure levels were made using the Kruskal-Wallis test and the multivariate effect on QUS parameters was estimated by linear regression.
RESULTS: 1482 consecutive subjects (1010 females and 472 males), aged from 18 to 92 years. Higher levels of QUS parameters were found in the younger groups and progressive decrease with age were reported. Men showed higher values as compared to women in all parameters and differences between them increased with age. Differences were significant for BUA after the age of 39 and for SOS after the age of 59. In women, the multivariate model showed that age, body mass index (BMI) and smoking status were independent predictors of BUA and SOS. In men, age, BMI and calcium intake were significantly associated with BUA and SOS. CONCLUSION:The reference values in our Portuguese population are similar to others obtained in Southern European countries. In the Portuguese population, QUS parameters have age, sex and BMI as its major determinants. In addition, BUA and SOS may reflect specific bone characteristics influenced by a different set of independent determinants.
Assessment of laboratory measurements and -308 TNFalpha gene promoter polymorphisms in normal bone mineral density
Clin Rheumatol. 2008 Mar;27(3):301-7
Canhao H, Fonseca JE, Caetano-Lopes J, Saldanha C, Queiroz MV
The aim of this study was to identify and evaluate laboratory parameters associated with normal bone mineral density (BMD) and to test if -308 tumour necrosis factor (TNF) alpha gene promoter polymorphisms could influence BMD. We performed a comparative cross-sectional study of four main groups: young healthy individuals (20-30 years); subjects aged 50 years or over with normal BMD; osteoporotic subjects aged 50 years or over; osteoporotic women with active rheumatoid arthritis. Variables assessed included anthropometric features, diet intake, lifestyle, calcium-phosphorus balance, markers of bone turnover, sexual hormones, hormones related with body mass and growth, cytokines involved in inflammation and bone turnover, and -308 TNF alpha gene promoter polymorphisms. One hundred fifty-nine subjects were evaluated. Across the four groups, zinc serum levels were higher in men as compared to women. In addition, zinc serum levels were also higher in individuals with normal BMD as compared to osteoporotic subjects. Serum calcium levels were higher in normal BMD group. On the other hand, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were significantly higher in normal bone mass postmenopausal women and men as compared to age-matched osteoporotic groups. Finally, leptin was significantly lower in men, after correcting these results for body mass index values. The remaining variables assessed had a similar distribution among the different studied groups. In our population, low serum levels of leptin and high serum levels of zinc, calcium, FSH, and LH were associated with a higher BMD.
Fracture incidence and changes in quality of life in women with an inadequate clinical outcome from osteoporosis therapy: the Observational Study of Severe Osteoporosis (OSSO)
Osteoporos Int. 2008 Apr;19(4):493-501
Cooper C, Jakob F, Melo-Gomes J A, Chinn C, Martin-Mola E, Fardellone P, Adami S, Thalassinos NC, Torgerson D, Gibson A, Marin F
SUMMARY: In this observational study of women with an inadequate clinical outcome to osteoporosis therapy, those with a fracture at baseline were more likely to sustain an incident fracture and have a worse health-related quality of life than those without prior fracture.
INTRODUCTION: The Observational Study of Severe Osteoporosis (OSSO) was designed to assess the fracture incidence and health-related quality of life (HRQoL) in women with an inadequate clinical outcome to osteoporosis therapy.
METHODS: Post-menopausal women (N=1,885) with established osteoporosis and an inadequate clinical response to osteoporosis drug therapy defined as: a) a fragility fracture despite therapy for one year (index fracture, N=988), or b) discontinued drug therapy due to adverse effects and/or non-compliance (N=897), were assessed during one year for HRQoL using the EQ-5D and the QUALEFFO questionnaires.
RESULTS: One hundred and sixty-six (8.8%) women had a total of 209 incident fractures (1,139 fractures/10,000 women-years). Women with an index fracture were more likely to sustain an incident fracture than those without prior fractures (hazard ratio 1.91; 95% CI: 1.37-2.66; p<0.001). Co-morbidities or antidepressant use at baseline also increased the risk of incident fracture. Median total EQ-5D Health State Values and QUALEFFO scores were worse in women with an incident fracture regardless of index fracture status. The worst scores were reported in the EQ-5D sub-domains of self-care, usual activities and pain/discomfort.
CONCLUSIONS: Women with an inadequate response to osteoporosis therapy had a high rate of incident fracture which had an adverse impact on HRQoL.
Diabetes mellitus complicating systemic lupus erythematosus: analysis of the ucl lupus cohort and review of the literature
Rheumatology.2008 47 (Supplt 2) ii92
Cortes SG, Sharon C, Jerónimo A, Isenberg D
UEMS charter on the training of rheumatologists in Europe
Ann Rheum Dis. 2008 Apr;67(4):555-8
Da Silva JA, Faarvang KL
Bandilla K
Woolf AD
UEMS Section and Board of Rheumatology
Effects of previous antiresorptive therapy on the bone mineral density response to two years of teriparatide treatment in postmenopausal women with osteoporosis
J Clin Endocrinol Metab. 2008 Mar;93(3):852-60
Boonen S, Marin F, Obermayer-Pietsch B, Simões ME, Barker C, Glass EV, Hadji P, Lyritis G, Oertel H, Nickelsen T, EUROFORS Investigators
INTRODUCTION: EUROFORS was a 2-yr prospective, randomized trial of postmenopausal women with established osteoporosis, designed to investigate various sequential treatments after teriparatide 20 microg/d for 1 yr. The present secondary analysis examined the effects of 2 yr of open-label teriparatide in women previously treated with antiresorptive drugs for at least 1 yr.
METHODS: A subgroup of 245 women with osteoporosis who had 2 yr of teriparatide treatment were stratified by previous predominant antiresorptive treatment into four groups: alendronate (n=107), risedronate (n=59), etidronate (n=30), and non-bisphosphonate (n=49). Bone mineral density (BMD) at the lumbar spine and hip was determined after 6, 12, 18, and 24 months, and bone formation markers were measured after 1 and 6 months.
RESULTS: Significant increases in bone formation markers occurred in all groups after 1 month of teriparatide treatment. Lumbar spine BMD increased at all visits, whereas a transient decrease in hip BMD, which was subsequently reversed, was observed in all groups. BMD responses were similar in all previous antiresorptive groups. Previous etidronate users showed a higher increase at the spine but not at the hip BMD. Duration of previous antiresorptive therapy and lag time between stopping previous therapy and starting teriparatide did not affect the BMD response at any skeletal site. Treatment-emergent adverse events were similar to those reported in treatment-naive postmenopausal women with osteoporosis treated with teriparatide.
CONCLUSIONS: Teriparatide induces positive effects on BMD and markers of bone formation in postmenopausal women with established osteoporosis, regardless of previous long-term exposure to antiresorptive therapies.
Rebalancing bone turnover in favour of formation with strontium ranelate: implications for bone strength
Rheumatology (Oxford). 2008 Jul;47 Suppl 4:iv17-19
Fonseca JE
This review updates our current knowledge on the mechanism of action of strontium ranelate and analyses the way it rebalances bone turnover and how it influences bone biomechanics. Strontium ranelate is able to increase pre-osteoblast replication, osteoblast differentiation, collagen type I synthesis and bone matrix mineralization probably through a calcium-sensing receptor (CaR)-dependent mechanism. Paralleling this anabolic effect there is inhibition of osteoclast differentiation and activity mediated by an increase in osteoprotegerin (OPG) and a decrease in RANK ligand (RANKL). The overall effect is a rebalanced bone turnover in favour of improved bone geometry, cortical thickness, trabecular bone morphology and intrinsic bone tissue quality, which translates into enhanced bone strength.
Osteoimmunology - The hidden immune regulation of bone
Autoimmun Rev. 2008 Aug 20. [Epub ahead of print]
Caetano-Lopes J, Canhão H, Fonseca JE
"Osteoimmunology is an emerging field of research dedicated to the investigation of the interactions between the immune and skeletal systems. These interactions are not only mediated by the release of cytokines and chemokines but also by direct cell–cell contact. Recently, it was proposed that immunoreceptors found in the immune cells are also an essential signal for osteoclasts activation, along with receptor activator NF-κB (RANK) ligand (RANKL) and macrophage-colony stimulating factor (M-CSF). In addition, adipose tissue also produces several factors (adipokines) that are known to interfere with the immune system and bone homeostasis. Chronic inflammation strongly influences osteoimmunology determining profound metabolic, structural and functional changes in bone."
Vasculitis-like syndrome associated with Borrelia lusitaniae infection
Clin Rheumatol. 2008 Sep 16 [Epub ahead of print]
Lopes de Carvalho I, Fonseca JE, Marques JG, Ullmann A, Hojgaard A , Zeidner N, Núncio MS
We report the isolation of Borrelia lusitaniae from a 13-year-old female child presenting with a vasculitis syndrome. The patient was treated with doxycycline, 100 mg bid for 20 days, and is in remission after a follow-up of 2 years. These results should alert clinicians to the fact that B. lusitaniae may be pathogenic in humans, highlighting that patients may be seronegative or present with minimal positive antibody titres and clinical signs that are not specific for Lyme borreliosis. In order to prevent the occurrence of more serious disease manifestations via timely treatment, the analysis by molecular methods may be a useful approach when antibody titres are uninformative.
Diabetes mellitus complicating systemic lupus erythematosus - analysis of the UCL lupus cohort and review of the literature
Lupus. 2008;17(11):977-80
Cortes S, Chambers S, Jerónimo A, Isenberg D
Systemic lupus erythematosus (SLE) often coexists with other diseases. Diabetes mellitus (DM) is an example and patients with overlap SLE-DM can present with clinical features common to both disorders. In this review, we describe the patients with overlap SLE-DM, focussing on the clinical features common to both diseases that these patients can present, and on the challenges of managing such complications. A detailed review of the patients' notes (n = 485) was performed. At every outpatient appointment the patients' urine was tested for glucose, protein and blood. Patients with persistent glycosuria were investigated with fasting blood glucose and a glucose tolerance test to help make the diagnosis of DM. Particular note was made of those patients whose symptoms could be due to SLE, DM or both. Nine patients with DM were identified. Three had type 1 DM, four had type 2 DM and two were considered to have steroid-induced DM. Among these patients, three had renal involvement (two with WHO class IV lupus nephritis); two had peripheral neuropathy (one had a mixed sensory and motor neuropathy, one had a sensory peripheral neuropathy); two patients had retinopathy and cataracts and one had angina. The combination of SLE and DM is uncommon but the predisposition to renal, peripheral neuropathy and retinal disease means that great care must be taken when deciding which clinical feature is due to which disease, because active SLE requires additional immunosuppression whereas DM requires optimization of the metabolic control. Interestingly, although in theory patients with SLE and DM are in double-jeopardy of developing atherosclerosis, to date, only one of our overlap patients has developed angina.
Multinational evidence-based recommendations for the use of methotrexate in rheumatic disorders with a focus on rheumatoid arthritis: integrating systematic literature research and expert opinion of a broad international panel of rheumatologists in the 3E Initiative
Ann Rheum Dis. 2008 Nov 25
Visser K Katchamart W, Loza E, Martinez-Lopez JA, Salliot C, Trudeau J, Bombardier C, Canhão H, Carmona L, van der Heijde D et al.
OBJECTIVES: To develop evidence-based recommendations for the use of methotrexate (MTX) in daily clinical practice in rheumatic disorders.
METHODS: A total of 751 rheumatologists from 17 countries participated in the 3E (Evidence Expertise Exchange) Initiative of 2007-2008 consisting of 3 separate rounds of discussions and Delphi votes. Ten clinical questions concerning the use of MTX in rheumatic disorders were formulated. A systematic literature search in Medline, Embase, Cochrane Library and 2005-2007 ACR/EULAR meeting abstracts was conducted. Selected articles were systematically reviewed and the evidence was appraised according to the Oxford Levels of Evidence. Each country elaborated a set of national recommendations. Finally, multinational recommendations were formulated and agreement among the participants and the potential impact on their clinical practice was assessed.
RESULTS: A total of 16979 references were identified, of which 304 articles were included in the systematic reviews. Ten multinational key recommendations on the use of MTX were formulated. Nine recommendations were specific for rheumatoid arthritis, including the work-up before initiating MTX, optimal dosage and route, use of folic acid, monitoring, management of hepatotoxicity, long-term safety, mono versus combination therapy and management in the peri-operative period and before/during pregnancy. One recommendation concerned MTX as a steroid-sparing agent in other rheumatic diseases.
CONCLUSIONS: Ten recommendations for the use of MTX in daily clinical practice focussed on RA were developed, which are evidence-based and supported by a large panel of rheumatologists, enhancing their validity and practical use.
Association of IL23R and ARTS1 genes with susceptibility to ankylosing spondylitis among a Mediterranean/Portuguese population
CLINICAL AND EXPERIMENTAL RHEUMATOLOGY, 26 (4): 729-730 JUL-AUG 2008
Pimentel dos Santos F, Ligeiro D, Matos M, Ribeiro C, Brown M, Guedes-Pinto H, Trindade H, Branco JC
Characterization of HLA genetic polymorphism in a Portuguese population with ankylosing spondylitis
CLINICAL AND EXPERIMENTAL RHEUMATOLOGY, 26 (4): 730-730 JUL-AUG 2008
Pimentel dos Santos F, Ligeiro D, Matos M, Mourão A, Sousa E, Ribeiro A, Sousa M, Guedes-Pinto H, Trindade H, Branco JC
Work status, physical function and quality of life in working-age patients with ankylosing spondylitis
CLINICAL AND EXPERIMENTAL RHEUMATOLOGY, 26 (4): 739-739 JUL-AUG 2008
Pimentel dos Santos F, Mourão A, Ribeiro A Sousa MM, Barcelos A, Pinto P, Godinho F, Cruz M, Sequeira G, Branco JC
Abatacept in children with juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled withdrawal trial
Lancet. 2008 Aug 2;372(9636):383-91
Paediatric Rheumatology International Trials Organization, Pediatric Rheumatology Collaborative Study Group , Silva CA, Melo-Gomes JA, Ruperto N, Lovell DJ, Quartier P, Magalhães C, Oliveira S,
BACKGROUND: Some children with juvenile idiopathic arthritis either do not respond, or are intolerant to, treatment with disease-modifying antirheumatic drugs, including anti-tumour necrosis factor (TNF) drugs. We aimed to assess the safety and efficacy of abatacept, a selective T-cell costimulation modulator, in children with juvenile idiopathic arthritis who had failed previous treatments.
METHODS: We did a double-blind, randomised controlled withdrawal trial between February, 2004, and June, 2006. We enrolled 190 patients aged 6-17 years, from 45 centres, who had a history of active juvenile idiopathic arthritis; at least five active joints; and an inadequate response to, or intolerance to, at least one disease-modifying antirheumatic drug. All 190 patients were given 10 mg/kg of abatacept intravenously in the open-label period of 4 months. Of the 170 patients who completed this lead-in course, 47 did not respond to the treatment according to predefined American College of Rheumatology (ACR) paediatric criteria and were excluded. Of the patients who did respond to abatacept, 60 were randomly assigned to receive 10 mg/kg of abatacept at 28-day intervals for 6 months, or until a flare of the arthritis, and 62 were randomly assigned to receive placebo at the same dose and timing. The primary endpoint was time to flare of arthritis. Flare was defined as worsening of 30% or more in at least three of six core variables, with at least 30% improvement in no more than one variable. We analysed all patients who were treated as per protocol. This trial is registered, number NCT00095173.
FINDINGS: Flares of arthritis occurred in 33 of 62 (53%) patients who were given placebo and 12 of 60 (20%) abatacept patients during the double-blind treatment (p=0.0003). Median time to flare of arthritis was 6 months for patients given placebo (insufficient events to calculate IQR); insufficient events had occurred in the abatacept group for median time to flare to be assessed (p=0.0002). The risk of flare in patients who continued abatacept was less than a third of that for controls during that double-blind period (hazard ratio 0.31, 95% CI 0.16-0.95). During the double-blind period, the frequency of adverse events did not differ in the two treatment groups. Adverse events were recorded in 37 abatacept recipients (62%) and 34 (55%) placebo recipients (p=0.47); only two serious adverse events were reported, both in controls (p=0.50).
INTERPRETATION: Selective modulation of T-cell costimulation with abatacept is a rational alternative treatment for children with juvenile idiopathic arthritis.
FUNDING: Bristol-Myers Squibb.
Geographical variation in DXA bone mineral density in young European men and women. Results from the Network in Europe on male osteoporosis (NEMO) study Bone.
2008 Aug;43(2):332-9
Da Silva JA, Kaptoge S, Brixen K, Reid DM, Kröger H, Nielsen TL, Andersen M, Hagen C, Lorenc R, Boonen S, de Vernejoul MC
We collected population-based young normal hip and spine BMD data from 17 centres across Europe to assess between centre differences and to compare reference values with the US NHANES-III data. There was strong evidence of between country heterogeneity, but not between centres within countries. Hip BMD mean values were lower in European women, but SD's differed little from the NHANES-III USA results in both sexes. It may be necessary to adjust NHANES-III based T-scores by adding/subtracting a country-specific adjustment factor.
INTRODUCTION: It remains unclear whether young normal BMD reference values specific to an American population can be validly used for T-score calculation in Europeans.
METHODS: We collected population based BMD data from 1163 men and 329 women aged 19-29 years from 17 centres across Europe to compare mean and SD values with the NHANES-III study USA results. BMD(g/cm2) was measured at the hip and spine using DXA densitometers cross-calibrated with the European Spine Phantom (ESP). The only exclusions were for technically inadequate scans. A linear regression model was used to derive reference values. To allow for direct comparison with published NHANES III study data, the cross-calibrated BMD values were converted using the ESP equations to Hologic QDR 1000 units.
RESULTS: In men, the overall mean(SD) BMD values expressed in Hologic-QDR1000 units of measurement, were: femoral neck 0.912(0.132); trochanter 0.793(0.124); and L2-L4 spine 1.027(0.123). The respective estimates in women were: 0.826(0.115); 0.670(0.093); and 0.983(0.107). However the I2 statistic for heterogeneity indicated moderate to strong evidence of between-centre heterogeneity. There was, however, no significant heterogeneity observed between centres within countries, suggesting that this variation arose from national differences. Compared to the NHANES III population-based US data, the mean values in women were significantly lower at both sites due to some lower national European means. However, at all sites and in both sexes the SD's were very similar between the US and Europe. There was some evidence that recruiting volunteers resulted in biased values in women.
CONCLUSION: Our T-score normal values for the lumbar spine (L2-L4) should be more reliable for spine-specific risk assessment than some non-representative normal ranges, and should be evaluated for that purpose in Europe. If T-scores are to be used to compare individual data with ranges seen in normal young subjects of the same nationality, it may be necessary to adjust femoral NHANES III-based T-scores by adding (or subtracting) a country-specific adjustment factor. In risk assessment it is probably sufficient to use NHANES III-based hip T-scores, as supplied for the hip by densitometer manufacturers, interpreting them in light of recent international meta-analysis data on the relationship between BMD and fracture risk.
Recommendations for the diagnosis and treatment of latent and active tuberculosis in inflammatory joint diseases for candidates for therapy with tumor necrosis factor alpha inhibitors--March 2008 update.
Rev Port Pneumol. 2008 Mar-Apr;14(2):271-83
Fonseca JE, Lucas H, Canhão H, Duarte R, Rheumatoid Arthritis Study Group of Portuguese Society of Rheumatology
The Portuguese Society of Rheumatology and the Portuguese Society of Pulmonology have updated the guidelines for the diagnosis and treatment of latent tuberculosis infection (LTBI) and active tuberculosis (ATB) in patients with inflammatory joint diseases (IJD) that are candidates to therapy with tumour necrosis factor alpha (TNFalpha) antagonists. In order to reduce the risk of tuberculosis (TB) reactivation and the incidence of new infections, TB screening is recommended to be done as soon as possible, ideally at the moment of IJD diagnosis, and patient assessment repeated before starting anti-TNFalpha therapy. Treatment for ATB and LTBI must be done under the care of a TB specialist. When TB treatment is indicated, it should be completed prior to starting anti-TNFalpha therapy. If the IJD activity justifies the need for immediate treatment, anti-TNFalpha therapy can be started two months after antituberculous therapy has been initiated, in the case of ATB, and one month after in the case of LTBI; healed lesions require the exclusion of ATB. In cases of suspected active lesions, ATB should be excluded/confirmed and adequate therapy initiated. Tuberculin skin test, with two units of RT23, should be performed in all patients. If the duration is < 5 mm, the test should be repeated within 1 to 2 weeks, on the opposite forearm, and will be considered negative only if the result is again < 5 mm. Positive TST implicates LTBI treatment, unless previous proper treatment was provided. If TST is performed in immunossuppressed IJD patients, LTBI treatment should be offered to the patient before starting anti-TNFalpha therapy, even in the presence of a negative test, after risk/benefit assessment.
Anti-tumour necrosis factor agents and lipid profile: a class effect?
Ann Rheum Dis. 2008 Jun;67(6):895-6
Garcês SP, Parreira Santos MJ, Vinagre FM, Roque RM, da Silva JA
The safety and efficacy of adding etanercept to methotrexate or methotrexate to etanercept in moderately active rheumatoid arthritis patients previously treated with monotherapy
Ann Rheum Dis. 2008 Feb;67(2):182-8
van der Heijde D, Burmester G, Melo-Gomes J, Codreanu C, Mola EM, Pedersen R, Freundlich B, Chang DJ
Etanercept Study 400 Investigators
OBJECTIVE: To determine if adding etanercept (ETN) to methotrexate (MTX) or MTX to ETN for 52 weeks in rheumatoid arthritis (RA) patients with moderate disease activity provides higher efficacy.
METHODS: All patients (n = 227) received open-label ETN 25 mg subcutaneously twice-weekly and MTX orally up to 20 mg weekly for 52 weeks and had completed a 3-year study in which patients received MTX, ETN or combination therapy. Endpoints were based on Disease Activity Score (DAS) and European League Against Rheumatism (EULAR) responses.
RESULTS: Patients previously receiving combination therapy (Combination group; n = 96) had a lower disease activity at baseline. The mean DAS for those previously receiving MTX (ETN-added group; n = 55) and previously receiving ETN (MTX-added group; n = 76) were in the moderate disease activity range at baseline; Combination patients had a low disease activity. The greatest increase in DAS remission rates from baseline to week 52 was in the ETN-added group (23.6% to 41.8%, p<0.01), although Combination (37.6% to 50.0%, p<0.01) and MTX-added (26.7% to 36.8%, p = NS) also demonstrated improvements. DAS low disease activity and EULAR responses showed similar results. No new safety issues were identified.
CONCLUSION: RA patients who were partial responders to long-term MTX or etanercept monotherapy obtained a higher efficacy with combination therapy. Responses achieved by patients with combination therapy after 3 years in the previous study were sustained or improved during the fourth year of treatment. This trial supports the higher therapeutic effect of combination treatment with etanercept and MTX in RA patients with moderate disease activity despite monotherapy with one of the two agents.
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