The effect of antimalarials on the safety and persistence of treatment with biologic agents or Janus kinase inhibitors in rheumatoid arthritis.

OBJECTIVES: To test the association of use of antimalarials with the overall safety of treatment in RA patients receiving one or multiple courses of biologic (b)DMARDs or a Janus kinase inhibitor (JAKi). METHODS: BiobadaBrasil is a multicentric registry-based cohort study of Brazilian patients with rheumatic diseases starting their first bDMARD or JAKi. The present analysis includes RA patients recruited from January 2009 to October 2019, followed up over one or multiple (up to six) courses of treatment (latest date, 19 November 2019). The primary outcome was the incidence of serious adverse events (SAEs). Total and system-specific adverse events (AEs) and treatment interruption served as secondary outcomes. Negative binomial regression with generalized estimating equations (to estimate multivariate incidence rate ratios, mIRR) and frailty Cox proportional hazards models were used for statistical analyses. RESULTS: The number of patients enrolled was 1316 (2335 treatment courses, 6711 patient-years [PY]; 1254.5 PY on antimalarials). The overall incidence of SAEs was 9.2/100 PY. Antimalarials were associated with reduced risk of SAEs (mIRR: 0.49; 95% CI: 0.36, 0.68; P < 0.001), total AEs (0.68; 95% CI: 0.56, 0.81; P < 0.001), serious infections (0.53; 95% CI: 0.34, 0.84; P = 0.007) and total hepatic AEs (0.21; 95% CI: 0.05, 0.85; P = 0.028). Antimalarials were also related to better survival of treatment course (P = 0.003). There was no significant increase in the risk of cardiovascular AEs. CONCLUSION: Among RA patients on treatment with bDMARDs or JAKi, concomitant use of antimalarials was associated with reduced the incidence of serious and total AEs and with longer treatment course survival.

Malignancy in the Upadacitinib Clinical Trials for Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis, and Non-radiographic Axial Spondyloarthritis.

INTRODUCTION: This article aims to describe malignancies in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), or non-radiographic axial spondyloarthritis (nr-axSpA) treated with upadacitinib (UPA) or active comparators. METHODS: This integrated safety analysis includes data from 11 phase 3 UPA trials across RA (6 trials), PsA (2 trials), AS (2 trials; one phase 2b/3), and nr-axSpA (1 trial). Treatment-emergent adverse events (TEAEs) were summarized for RA (pooled UPA 15 mg [UPA15], pooled UPA 30 mg [UPA30], adalimumab 40 mg [ADA], methotrexate monotherapy [MTX]), PsA (pooled UPA15, pooled UPA30, ADA), AS (pooled UPA15), and nr-axSpA (UPA15). TEAEs were reported as exposure-adjusted event rates (events/100 patient-years). RESULTS: Median treatment duration ranged from 1.0 to 4.0 years (with a maximum of 6.6 years in RA). Across treatments and indications, rates of malignancy excluding nonmelanoma skin cancer (NMSC) ranged from 0.2 to 1.1, while NMSC ranged from 0.0 to 1.4. In RA, rates of malignancy excluding NMSC were generally similar between UPA15, UPA30, ADA, and MTX (breast and lung cancer were the most common). In RA and PsA, Kaplan-Meier analyses revealed no differences in event onset of malignancy excluding NMSC with UPA15 versus UPA30 over time. In RA, NMSC rates were higher with UPA30 than UPA15; both UPA15 and UPA30 were higher than ADA and MTX. In PsA, rates of malignancy excluding NMSC and NMSC were generally similar between UPA15, UPA30, and ADA. In AS and nr-axSpA, malignancies were reported infrequently. Few events of lymphoma were reported across the clinical programs. CONCLUSION: Rates of malignancy excluding NMSC were generally similar between UPA15, UPA30, ADA, and MTX and were consistent across RA, PsA, AS, and nr-axSpA. A dose-dependent increased rate of NMSC was observed with UPA in RA. TRIAL REGISTRATION: ClinicaTrials.gov identifier: NCT02706873, NCT02675426, NCT02629159, NCT02706951, NCT02706847, NCT03086343, NCT03104400, NCT03104374, NCT03178487, and NCT04169373.

Factors associated with poor outcomes in SLE patients with COVID-19: Data from ReumaCoV-Brazil register.

OBJECTIVES: To evaluate factors associated with COVID-19 severity outcomes in patients with systemic lupus erythematosus (SLE). METHODS: This was a cross-sectional analysis of baseline data of a prospective, multi-stage cohort study-"The ReumaCoV Brazil"-designed to monitor patients with immune-mediated rheumatologic disease (IMRD) during the SARS-CoV-2 pandemic. SLE adult patients with COVID-19 were compared with those without COVID-19. SLE activity was evaluated by the patient global assessment (PGA) and SLE Disease Activity Index 2000 (SLEDAI-2K). RESULTS: 604 SLE patients were included, 317 (52.4%) with COVID-19 and 287 (47.6%) in the control group. SLE COVID-19 patients reported a lower frequency of social isolation and worked more frequently as health professionals. There was no difference in the mean SLEDAI-2K score between groups in the post-COVID-19 period (5.8 [8.6] vs. 4.5 [8.0]; p = 0.190). However, infected patients reported increased SLE activity according to the Patient Global Assessment (PGA) during this period (2.9 [2.9] vs. 2.3 [2.6]; p = 0.031. Arterial hypertension (OR 2.48 [CI 95% 1.04-5.91], p = 0.041), cyclophosphamide (OR 14.32 [CI 95% 2.12-96.77], p = 0.006), dyspnea (OR: 7.10 [CI 95% 3.10-16.23], p < 0.001) and discontinuation of SLE treatment medication during infection (5.38 [CI 95% 1.97-15.48], p = 0.002), were independently associated with a higher chance of hospitalization related to COVID-19. Patients who received telemedicine support presented a 67% lower chance of hospitalization (OR 0.33 [CI 95% 0.12-0.88], p = 0.02). CONCLUSION: Hypertension and cyclophosphamide were associated with a severe outcome, and telemedicine can be a useful tool for SLE patients with COVID-19.

COVID-19 was not associated or trigger disease activity in spondylarthritis patients: ReumaCoV-Brasil cross-sectional data.

OBJECTIVES: To evaluate the disease activity before and after COVID-19 and risk factors associated with outcomes, including hospitalization, intensive care unit (ICU) admission, mechanical ventilation (MV) and death in patients with spondylarthritis (SpA). METHODS: ReumaCoV Brazil is a multicenter prospective cohort of immune-mediated rheumatic diseases (IMRD) patients with COVID-19 (case group), compared to a control group of IMRD patients without COVID-19. SpA patients enrolled were grouped as axial SpA (axSpA), psoriatic arthritis (PsA) and enteropathic arthritis, according to usual classification criteria. RESULTS: 353 SpA patients were included, of whom 229 (64.9%) were axSpA, 118 (33.4%) PsA and 6 enteropathic arthritis (1.7%). No significant difference was observed in disease activity before the study inclusion comparing cases and controls, as well no worsening of disease activity after COVID-19. The risk factors associated with hospitalization were age over 60 years (OR = 3.71; 95% CI 1.62-8.47, p = 0.001); one or more comorbidities (OR = 2.28; 95% CI 1.02-5.08, p = 0.001) and leflunomide treatment (OR = 4.46; 95% CI 1.33-24.9, p = 0.008). Not having comorbidities (OR = 0.11; 95% CI 0.02-0.50, p = 0.001) played a protective role for hospitalization. In multivariate analysis, leflunomide treatment (OR = 8.69; CI = 95% 1.41-53.64; p = 0.023) was associated with hospitalization; teleconsultation (OR = 0.14; CI = 95% 0.03-0.71; p = 0.01) and no comorbidities (OR = 0.14; CI = 95% 0.02-0.76; p = 0.02) remained at final model as protective factor. CONCLUSIONS: Our results showed no association between pre-COVID disease activity or that SARS-CoV-2 infection could trigger disease activity in patients with SpA. Teleconsultation and no comorbidities were associated with a lower hospitalization risk. Leflunomide remained significantly associated with higher risk of hospitalization after multiple adjustments.

Incidence and risk factors for moderate/severe COVID-19 in rheumatic diseases patients on hydroxychloroquine: a 24-week prospective cohort.

OBJECTIVES: To evaluate the incidence of COVID-19 and its main outcomes in rheumatic disease (RD) patients on hydroxychloroquine (HCQ) compared to household cohabitants (HC). METHODS: This is a 24-week nationwide prospective multi-centre cohort with a control group without RD and not using HCQ. All participants were monitored through scheduled phone interviews performed by health professionals. Details regarding COVID-19 symptoms, and epidemiological, clinical, and demographic data were recorded on a specific web-based platform. COVID-19 was defined according to the Brazilian Ministry of Health criteria and classified as mild, moderate or severe. RESULTS: A total of 9,585 participants, 5,164 (53.9%) RD patients on HCQ and 4,421 (46.1%) HC were enrolled from March 29th, 2020 to September 30th, 2020, according to the eligibility criteria. COVID-19 confirmed cases were higher in RD patients than in cohabitants [728 (14.1%) vs. 427 (9.7%), p<0.001] in a 24-week follow-up. However, there was no significant difference regarding outcomes related to moderate/ severe COVID-19 (7.1% and 7.3%, respectively, p=0.896). After multiple adjustments, risk factors associated with hospitalisation were age over 65 (HR=4.5; 95%CI 1.35-15.04, p=0.014) and cardiopathy (HR=2.57; 95%CI 1.12-5.91, p=0.026). The final survival analysis demonstrated the probability of dying in 180 days after a COVID-19 diagnosis was significantly higher in patients over 65 years (HR=20.8; 95%CI 4.5-96.1) and with 2 or more comorbidities (HR=10.8; 95%CI 1.1-107.9 and HR=24.8; 95%CI 2.5-249.3, p=0.006, respectively). CONCLUSIONS: Although RD patients have had a higher COVID-19 incidence than individuals from the same epidemiological background, the COVID-19 severity was related to traditional risk factors, particularly multiple comorbidities and age, and not to underlying RD and HCQ.

Characteristics associated with COVID-19 vaccine hesitancy: A nationwide survey of 1000 patients with immune-mediated inflammatory diseases.

OBJECTIVES: To identify potential predictors of COVID-19 vaccine hesitancy (C19-VH) in adults with immune-mediated inflammatory diseases (IMID). METHODS: A total of 1000 IMID patients were enrolled in this web-based cross-sectional study. A standardised and self-administered survey was designed by members of the Brazilian Society of Rheumatology Steering Committee for Infectious and Endemic diseases and distributed to IMID patients spread across Brazil. RESULTS: Of the 908 (90.8%) respondents eligible for analysis, 744 (81.9%) were willing to get vaccinated against COVID-19. In our multivariable logistic regression model, concurrent malignancy, fibromyalgia, hydroxychloroquine use, and recent corticosteroid pulse therapy were independently associated with higher odds of C19-VH. The short duration of COVID-19 vaccine clinical trials was the main reason for C19-VH. CONCLUSION: We identified novel characteristics potentially associated with C19-VH among adults with IMID. Greater awareness on the safety and efficacy of COVID-19 vaccines is needed for both IMID patients and attending physicians.

Health-Related Quality of Life in Psoriatic Arthritis: Findings and Implications.

OBJECTIVES: To assess the quality of life (QOL) and its associated factors in patients with psoriatic arthritis (PsA) who would start treatment with biologic drugs at the Brazilian Unified Health System. METHODS: A cross-sectional study was performed at a single center pharmacy in Belo Horizonte, State of Minas Gerais, Brazil. EQ-5D was used to assess the patients' QOL. The functional status was assessed using the Health Assessment Questionnaire-Disability Index, whereas disease activity was evaluated through the Bath Ankylosing Spondylitis Disease Activity Index and the Clinical Disease Activity Index. Simple and multiple linear regression analyses were performed to assess the factors associated with QOL. RESULTS: A total of 212 patients with PsA were included, of which 185 (87.3%) reported having some pain/discomfort, and 148 (69.8%) presented some level of anxiety/depression. Patients with PsA had a mean QOL score of 0.651 (SD 0.12) with a significant reduction in female patients, concomitant use of nonsteroidal anti-inflammatory drugs, comorbidity, and worse clinical and functional status. Poor QOL was associated with worse functional status by the Health Assessment Questionnaire-Disability Index, disease activity by the Bath Ankylosing Spondylitis Disease Activity Index, and with diagnoses of osteoporosis, hypothyroidism, and depression. CONCLUSION: PsA and its associated comorbidities negatively affect the QOL, evidencing the need for a comprehensive and effective clinical approach.

Safety of the Methotrexate-leflunomide Combination in Rheumatoid Arthritis: Results of a Multicentric, Registry-based, Cohort Study (BiobadaBrasil).

OBJECTIVE: To evaluate the safety of the methotrexate (MTX)-leflunomide (LEF) combination in rheumatoid arthritis (RA), comparing it with other therapeutic schemes involving conventional synthetic (cs-) and biologic (b-) disease-modifying antirheumatic drugs (DMARDs) or Janus kinase inhibitors (JAKi). METHODS: Patients with RA starting a treatment course with a csDMARD (without previous use of bDMARD or JAKi) or their first bDMARD/JAKi were followed up in a registry-based, multicentric cohort study in Brazil (BiobadaBrasil). The primary outcome was the incidence of serious adverse events (SAEs); secondary outcomes included serious infections. Multivariate Cox proportional hazards models and propensity score matching analysis (PSMA) were used for statistical comparisons. RESULTS: In total, 1671 patients (5349 patient-years [PY]) were enrolled; 452 patients (1537 PY) received MTX + LEF. The overall incidence of SAEs was 5.6 per 100 PY. The hazard of SAEs for MTX + LEF was not higher than for MTX or LEF (adjusted HR [aHR] 1.00, 95% CI 0.76-1.31, P = 0.98). MTX + LEF presented a lower hazard of SAEs (aHR 0.56, 95% CI 0.36-0.88, P = 0.01) and infectious SAEs (aHR 0.48, 95% CI 0.25-0.94, P = 0.03) than bDMARDs/JAKi with MTX or LEF. MTX + LEF presented lower hazard of SAEs than MTX + sulfasalazine (SSZ; aHR 0.33, 95% CI 0.16-0.65, P = 0.002). Analysis using PSMA confirmed the results obtained with traditional multivariate Cox analysis. CONCLUSION: In our study, MTX + LEF presented a relatively good overall safety profile in comparison to MTX + SSZ and schemes involving advanced therapies in RA.

Fibroblast-like synoviocytes from fluid and synovial membrane from primary osteoarthritis demonstrate similar production of interleukin 6, and metalloproteinases 1 and 3.

OBJECTIVES: The objective of the study was to compare the production of metalloproteinases (MMP)-1, -3 and interleukin (IL)-6 by fibroblast-like synoviocytes (FLS) derived from synovial fluid (FD-FLS), and FLS derived from synovial tissue (TD-FLS) of patients with primary osteoarthritis (OA). The more accessible FD-FLS could facilitate the study of the role of these cells in OA pathophysiology. METHODS: MMP-1, MMP-3, and IL-6 levels were measured in the supernatant culture at baseline and 22 hours after stimulation with TNF-α and IL-1 ß. RESULTS: There was no difference at baseline between MMP-1, MMP-3 and IL-6 production by FD-FLS and TDFLS. Analogous to baseline, stimulation of FD-FLS and TD-FLS with IL-1ß and TNF-α did not result in difference on MMP-3 and IL-6 production. However, TD-FLS produced more MMP-1 than FD-FLS after stimulation with IL-1ß (p=0.01). Additionally, there was a positive correlation for production of MMP-1, MMP-3 and IL-6 between FD-FLS and TD-FLS (r=0.40 and p<0.0008; r=0.66 and p<0.0001; r=0.76 and p<0.0001, respectively). Supporting this statistical significant positive correlation, the Bland-Altman plotting, showed a homogeneous distribution of the values and low mean disagreement rates between all results of FD-FLS and TD-FLS (23.1%, 56.8% and 48.1%, respectively). CONCLUSIONS: Our data demonstrated functional similarity between FD-FLS and TD-FLS and support the use of a more accessible source of FLS for the study of the pathogenesis of joint destruction and therapeutic targets in primary OA.

Bioelectrical Impedance Analysis-Derived Measurements in Chronic Hepatitis C: Clinical Relevance of Fat-Free Mass and Phase Angle Evaluation.

OBJECTIVE: Because cirrhotic patients are at high risk of malnutrition and sarcopenia, we evaluated the prevalence of low fat-free mass index (FFMI) and low phase angle (PhA) among patients with chronic hepatitis C (CHC). METHODS: In total, 135 subjects with CHC (50.4% males; mean age, 52.4 ± 11.8 years; 65.9% noncirrhotic and 34.1% compensated cirrhotic patients) were prospectively included and evaluated by bioelectrical impedance analysis. Subjective global assessment was used to evaluate malnutrition. RESULTS: Low FFMI and low PhA were identified in 21.5% and 23.7% of the patients, respectively. Compensated cirrhotic patients had lower PhA values than those without cirrhosis. Low FFMI was associated with male sex (odds ratio [OR], 2.74; 95% confidence interval [CI], 1.00-7.01; P = .04) and malnutrition (OR, 4.27; 95% CI, 1.42-12.90; P = .01). Low PhA was associated with cirrhosis (OR, 3.92; 95% CI, 1.56-9.86; P = .004), malnutrition (OR, 5.52; 95% CI, 1.73-17.62; P = .004), and current alcohol use (OR, 2.77; 95% CI, 1.01-7.58; P = .05). Reactance (Xc) normalized for height (H), an indicator of muscle strength, was independently associated with male sex, age, hypertension, and serum albumin. CONCLUSION: Host factors, including clinical comorbidities, lifestyle, and nutrition status, are associated with low FFMI and low PhA in noncirrhotic and in compensated cirrhotic patients with CHC. These findings highlight the relevance of evaluating body composition in patients chronically infected by hepatitis C virus independently of the stage of liver disease.

Association between pre-sarcopenia, sarcopenia, and bone mineral density in patients with chronic hepatitis C.

BACKGROUND: Preserved skeletal muscle is essential for the maintenance of healthy bone. Loss of bone mineral density (BMD) and muscle strength, considered a predictor of BMD, have been demonstrated in patients with cirrhosis, but they are poorly studied in chronic hepatitis C (CHC) without cirrhosis. Thus, we aimed to evaluate the prevalence of low BMD and its association with body composition, muscle strength, and nutritional status in CHC. METHODS: One hundred and four subjects [mean age, 50.5 ± 11.3 years; 75.0% males; 67.3% non-cirrhotic; and 32.7% with compensated cirrhosis] with CHC, prospectively, underwent scanning of the lean tissue, appendicular skeletal muscle mass (ASM), fat mass, lumbar spine, hip, femoral neck, and whole-body BMD by dual-energy X-ray absorptiometry. Muscle strength was assessed by dynamometry. Sarcopenia was defined by the presence of both low, ASM/height2 (ASMI) and low muscle strength according to the European Working Group on Sarcopenia in Older People criteria. The cut-off points for low ASMI and low muscle strength, for women and men, were < 5.45 and < 7.26 kg/m2 and < 20 and < 30 kg, respectively. According to the adopted World Health Organization criteria in men aged > 50 years, the T-score of osteopenia is between -1.0 and -2.49 standard deviation (SD) below the young average value and of osteoporosis is ≥-2.5 SD below the young normal mean for men, and the Z-score of low bone mass is ≤-2.0 SD below the expected range in men aged < 50 years and women in the menacme. Nutritional status evaluation was based on the Controlling Nutritional Status score. RESULTS: Low BMD, low muscle strength, pre-sarcopenia, sarcopenia, and sarcopenic obesity were observed in 34.6% (36/104), 27.9% (29/104), 14.4% (15/104), 8.7% (9/104), and 3.8% (4/104) of the patients, respectively. ASMI was an independent predictor of BMD (P < 0.001). Sarcopenia was independently associated with bone mineral content (P = 0.02) and malnutrition (P = 0.01). In 88.9% of the sarcopenic patients and in all with sarcopenic obesity, BMI was normal. The mid-arm muscle circumference was positively correlated with ASMI (r = 0.88; P < 0.001). CONCLUSIONS: This is the first study to demonstrate that ASM is an independent predictor of BMD in CHC. Mid-arm muscle circumference coupled with handgrip strength testing should be incorporated into routine clinical practice to detect low muscle mass, which may be underdiagnosed when only BMI is used. These findings may influence clinical decision-making and contribute to the development of effective strategies to screen the musculoskeletal abnormalities in CHC patients, independently of the stage of the liver disease.

Guidelines for the treatment of antiphospholipid syndrome.

The antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial and venous thrombosis, gestational morbidity and presence of elevated and persistently positive serum titers of antiphospholipid antibodies. The treatment of APS is still controversial, because any therapeutic decision potentially faces the risk of an insufficient or excessive antithrombotic coverage associated with anticoagulation and its major adverse effects. This guideline was elaborated from nine relevant clinical questions related to the treatment of APS by the Committee of Vasculopathies of the Brazilian Society of Rheumatology. Thus, this study aimed at establishing a guideline that included the most relevant and controversial questions in APS treatment, based on the best scientific evidence available. The questions were structured by use of the PICO (patient, intervention or indicator, comparison and outcome) process, enabling the generation of search strategies for evidence in the major primary scientific databases (MEDLINE/PubMed, Embase, Lilacs, Scielo, Cochrane Library, Premedline via OVID). A manual search for evidence and theses was also conducted (BDTD and IBICT). The evidence retrieved was selected based on critical assessment by using discriminatory instruments (scores) according to the category of the therapeutic question (JADAD scale for randomized clinical trials and Newcastle-Ottawa scale for non-randomized studies). After defining the potential studies to support the recommendations, they were selected according to level of evidence and grade of recommendation, according to the Oxford classification.

Diretrizes para o tratamento da síndrome do anticorpo antifosfolipídeo / Guidelines for the treatment of antiphospholipid syndrome

A síndrome do anticorpo antifosfolipídeo (SAF) é uma doença sistêmica autoimune caracterizada por trombose arterial e venosa, morbidade gestacional e presença de níveis séricos de anticorpos antifosfolipídeos elevados e persistentemente positivos. O tratamento da SAF ainda é sujeito a controvérsias, já que qualquer decisão terapêutica potencialmente irá confrontar-se com o risco de uma cobertura antitrombótica insuficiente ou com o risco excessivo associado à anticoagulação e seus principais efeitos adversos. Esta diretriz foi elaborada a partir de nove questões clínicas relevantes e relacionadas ao tratamento da SAF pela Comissão de Vasculopatias da Sociedade Brasileira de Reumatologia. O objetivo deste trabalho foi criar uma diretriz que incluísse as questões mais relevantes e controversas no tratamento da SAF, com base na melhor evidência científica disponível. As questões foram estruturadas por meio do P.I.C.O. (paciente, intervenção ou indicador, comparação e outcome/desfecho), o que possibilitou a geração de estratégias de busca da evidência nas principais bases primárias de informação científica (MEDLINE/Pubmed, Embase, Lilacs/Scielo, Cochrane Library, Premedline via OVID). Também realizou-se busca manual da evidência e de teses (BDTD e IBICT). A evidência recuperada foi selecionada a partir da avaliação crítica, utilizando instrumentos (escores) discriminatórios de acordo com a categoria da questão terapêutica (JADAD para ensaios clínicos randomizados e New Castle Ottawa Scale para estudos não randomizados). Após definir os estudos potenciais para sustento das recomendações, eles foram selecionados pela força da evidência e pelo grau de recomendação, segundo a classificação de Oxford.

The antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial and venous thrombosis, gestational morbidity and presence of elevated and persistently positive serum titers of antiphospholipid antibodies. The treatment of APS is still controversial, because any therapeutic decision potentially faces the risk of an insufficient or excessive antithrombotic coverage associated with anticoagulation and its major adverse effects. This guideline was elaborated from nine relevant clinical questions related to the treatment of APS by the Committee of Vasculopathies of the Brazilian Society of Rheumatology. Thus, this study aimed at establishing a guideline that included the most relevant and controversial questions in APS treatment, based on the best scientific evidence available. The questions were structured by use of the PICO (patient, intervention or indicator, comparison and outcome) process, enabling the generation of search strategies for evidence in the major primary scientific databases (MEDLINE/PubMed, Embase, Lilacs, Scielo, Cochrane Library, Premedline via OVID). A manual search for evidence and theses was also conducted (BDTD and IBICT). The evidence retrieved was selected based on critical assessment by using discriminatory instruments (scores) according to the category of the therapeutic question (JADAD scale for randomized clinical trials and Newcastle-Ottawa scale for non-randomized studies). After defining the potential studies to support the recommendations, they were selected according to level of evidence and grade of recommendation, according to the Oxford classification.

Chronic gastritis and bone mineral density in women.

We conducted a cross-sectional study of bone mineral density in women with Helicobacter pylori gastritis or autoimmune gastritis. Eighty-five patients were enrolled: 24 patients (mean age 55.2 +/- 13.5 years) with autoimmune gastritis, 34 patients (mean age 63.7 +/- 7.3 years) with H. pylori gastritis, and 27 H. pylori-negative patients with normal gastric mucosa (mean age 62.5 +/- 7.0 years). Gastric mucosa was evaluated by histology and immunohistochemistry. Bone mineral density was measured by dual-energy X-ray absorptiometry. Autoimmune gastritis patients presented severe gastric body mucosa atrophy, based on the absence of parietal cells in 15 (62.5%) patients and the presence of only scattered parietal cells in the remaining nine (37.5%) patients. Among the H. pylori gastritis patients, 21 (62%) presented with different degrees of gastric mucosa atrophy. Bone mineral densities (mean +/- SD, g/mm(2)) were not different among patients with autoimmune gastritis and H. pylori gastritis and the controls. Our results suggest that H. pylori-associated gastritis and autoimmune gastritis would not to be risk factors for decreased bone mineral density in women.

The presence of Helicobacter pylori in postmenopausal women is not a factor to the decrease of bone mineral density.

BACKGROUND: Osteoporosis affects approximately 30% of postmenopausal women. Gastrectomy, pernicious anemia, and more recently Helicobacter pylori infection, have all been implicated in the pathogenesis of osteoporosis. A reduced parietal cell mass is a common feature in these conditions. AIM: To study a possible relationship between chronic gastritis, parietal cell density of the oxyntic mucosa and bone mineral density in postmenopausal women, as chronic gastritis, Helicobacter pylori infection and osteoporosis are frequently observed in the elderly. METHODS: Fifty postmenopausal women (61.7 +/- 7 years) were submitted to gastroduodenal endoscopy and bone densitometry by dual energy X-ray absorptiometry. Glandular atrophy was evaluated objectively by the determination of parietal cell density. Helicobacter pylori infection was evaluated by histology, urease test and breath test with 13C. RESULTS: Thirty-two patients (64%) presented chronic multifocal gastritis, and 20 of them (40%) showed signs of gastric mucosa atrophy. Lumbar spine osteoporosis was found in 18 patients (36%). The parietal cell density in patients with and without osteoporosis was 948 +/- 188 and 804 +/- 203 cells/mm(2), respectively. Ten osteoporotic patients (55%) and 24 non-osteoporotic patients (75%) were infected by Helicobacter pylori. CONCLUSION: Postmenopausal women with osteoporosis presented a well-preserved parietal cell density in comparison with their counterparts without osteoporosis. Helicobacter pylori infection was not different between the two groups. We concluded that neither atrophic chronic gastritis nor Helicobacter pylori seem to be a reliable risk factor to osteoporosis in postmenopausal women.

The presence of Helicobacter Pylori in postmenopausal women is not a factor to the decrease of bone mineral density

BACKGROUND: Osteoporosis affects approximately 30 percent of postmenopausal women. Gastrectomy, pernicious anemia, and more recently Helicobacter pylori infection, have all been implicated in the pathogenesis of osteoporosis. A reduced parietal cell mass is a common feature in these conditions. AIM: To study a possible relationship between chronic gastritis, parietal cell density of the oxyntic mucosa and bone mineral density in postmenopausal women, as chronic gastritis, Helicobacter pylori infection and osteoporosis are frequently observed in the elderly. METHODS: Fifty postmenopausal women (61.7 ± 7 years) were submitted to gastroduodenal endoscopy and bone densitometry by dual energy X-ray absorptiometry. Glandular atrophy was evaluated objectively by the determination of parietal cell density. Helicobacter pylori infection was evaluated by histology, urease test and breath test with 13C. RESULTS: Thirty-two patients (64 percent) presented chronic multifocal gastritis, and 20 of them (40 percent) showed signs of gastric mucosa atrophy. Lumbar spine osteoporosis was found in 18 patients (36 percent). The parietal cell density in patients with and without osteoporosis was 948 ± 188 and 804 ± 203 cells/mm², respectively. Ten osteoporotic patients (55 percent) and 24 non-osteoporotic patients (75 percent) were infected by Helicobacter pylori. CONCLUSION: Postmenopausal women with osteoporosis presented a well-preserved parietal cell density in comparison with their counterparts without osteoporosis. Helicobacter pylori infection was not different between the two groups. We concluded that neither atrophic chronic gastritis nor Helicobacter pylori seem to be a reliable risk factor to osteoporosis in postmenopausal women.

RACIONAL: A osteoporose afeta aproximadamente 30 por cento das mulheres na pós-menopausa. Gastrectomia, anemia perniciosa e mais recentemente, a infecção pelo H. pylori, têm sido implicados na patogênese da osteoporose. A diminuição da massa de células parietais constitui aspecto comum a estas condições. OBJETIVOS: Estudar possível relação entre gastrite crônica, densidade de células parietais da mucosa oxíntica e a densidade mineral óssea em mulheres na pós-menopausa. MÉTODOS: Cinqüenta mulheres na pós-menopausa (média de idade 61.7 ± 7 anos) foram submetidas a endoscopia digestiva alta e a densitometria óssea pela absorciometria com raio-X de dupla energia. A atrofia glandular foi avaliada, histologicamente e pela determinação da densidade das células parietais na mucosa do corpo gástrico. A infecção pelo H. pylori foi avaliada através da histologia, teste da urease e teste respiratório com C13. RESULTADOS: Trinta e dois pacientes (64 por cento) apresentaram gastrite crônica e 20 (40 por cento) deles apresentaram sinais de atrofia de mucosa gástrica através da análise histopatológica rotineira. Osteoporose da coluna lombar foi encontrada em 18 (36 por cento) pacientes. A densidade de células parietais em pacientes com e sem osteoporose foi 948 ± 188 e 804 ± 2003 células/mm², respectivamente. Dez pacientes (55 por cento) com osteoporose e 24 por cento (75 por cento) pacientes sem osteoporose estavam infectados pelo H. pylori. CONCLUSÃO:Mulheres na pós-menopausa com osteoporose apresentaram mucosa gástrica e população de células parietais mais conservadas em relação àquelas sem osteoporose. A infecção pelo H.pylori não foi estatisticamente diferente entre mulheres com e sem osteoporose, indicando que a infecção por esta bactéria, com ou sem atrofia da mucosa gástrica, não se constitui em fator de risco para osteoporose em mulheres na pós-menopausa.

Tratamento farmacológico da osteoporose e utilização do hormônio da paratireóide / Pharmacologic treatment of osteoporosis and parathyroid hormone use

A osteoporose é um distúrbio osteometabólico sistêmico, de evolução silenciosa, cuja principal conseqüência é o aumento do risco de fraturas. Decorre do desequilíbrio entre a formação e a reabsorção ósseas, por favorecimento da última. Acomete mais freqüentemente mulheres na pós-menopausa, estimando-se que 30% daquelas com mais de 50 anos terão osteoporose. Nesse grupo de pacientes, o risco de fratura de fêmur é de 17,4% para o tempo restante da vida. Várias drogas têm se mostrado eficazes em aumentar a massa óssea e diminuir o risco de fraturas vertebrais e não-vertebrais. Até o desenvolvimento do paratormônio como agente terapêutico para a osteoporose, todas as drogas em uso tinham a inibição da reabsorção óssea como mecanismo de ação, fato que limitava o resultado terapêutico, sobretudo em casos mais graves ou não-responsivos. Este artigo faz uma revisão sobre o tratamento farmacológico da osteoporose, enfatizando o emprego do paratormônio.