HR-pQCT in vivo imaging of periarticular bone changes in chronic inflammatory diseases: Data from acquisition to impact on treatment indications.

Imaging is essential for the assessment of bone and inflammatory joint diseases. There are several imaging techniques available that differ regarding resolution, radiation exposure, time expending, precision, cost, availability or ability to predict disease progression. High-resolution peripheral quantitative computed tomography (HR-pQCT) that was introduced in 2004 allows the in vivo evaluation of peripheral bone microarchitecture and demonstrated high precision in assessing bone changes in inflammatory musculoskeletal diseases. This review summarizes the use of HR-pQCT for the evaluation of the hand skeleton in inflammatory joint diseases. We conducted a review of the literature regarding the protocols that involve hand joints assessment and evaluation of bone changes as erosions and osteophytes in chronic inflammatory diseases. Apart from measuring bone density and structure of the radius and the tibia, HR-pQCT has contributed to assessment of bone erosions and osteophytes, considered the hallmark of diseases as rheumatoid arthritis and psoriatic arthritis, respectively. In this way, there are some conventions recently established by rheumatic study groups that we just summarized here in order to standardize HR-pQCT measurements.

Effects of DMARDs on citrullinated peptide autoantibody levels in RA patients-A longitudinal analysis.

OBJECTIVE: To study whether stable treatment with DMARDs affects anti-CCP2 antibody levels in patients with rheumatoid arthritis. METHODS: In this longitudinal observational study 100 RA patients were followed for anti-CCP2 IgG antibody (U/L) and total IgG level (mg/dL) every 6 months for a total period of 2.5 years. All patients received stable DMARD treatment during this period. Five groups comprising each 20 patients were analyzed as follows: (1) methotrexate (MTX) alone, (2) tumor necrosis factor inhibitors (TNFi), (3) tocilizumab (TCZ), (4) rituximab (RTX), and (5) abatacept (ABA). RESULTS: Baseline demographic and disease-specific characteristics were comparable between the 5 groups. Anti-CCP2 antibody levels did not show significant changes in patients treated with MTX (mean ± SEM: -24.1 ± 8.1%), TNFi (-14.0 ± 11.1%) or TCZ (-24.3 ± 11.3%) between baseline and the 2.5 years follow-up. In contrast, anti-CCP2 antibody levels significantly decreased during treatment with RTX (-75.6 ± 4.4%) and ABA (-82.5 ± 3.7%). With respect to total IgG levels, no significant changes were observed with MTX (-1.6 ± 3.5%), TNFi (2.5 ± 3.4%), TCZ (-4.4 ± 3.1%), or ABA (-2.4 ± 3.8%) over 2.5 years. In contrast, total IgG levels significantly decreased during treatment with RTX (-22.0 ± 3.7%). CONCLUSIONS: DMARDs targeting the adaptive immune response such as ABA and RTX significantly lowered anti-CCP2 IgG levels, while cytokine inhibitors and methotrexate had no significant effects on anti-CCP2 IgG levels. RTX is the only DMARD, which also lowers total IgG level.

Antimodified protein antibody response pattern influences the risk for disease relapse in patients with rheumatoid arthritis tapering disease modifying antirheumatic drugs.

OBJECTIVE: To perform a detailed analysis of the autoantibody response against post-translationally modified proteins in patients with rheumatoid arthritis (RA) in sustained remission and to explore whether its composition influences the risk for disease relapse when tapering disease modifying antirheumatic drug (DMARD) therapy. METHODS: Immune responses against 10 citrullinated, homocitrullinated/carbamylated and acetylated peptides, as well as unmodified vimentin (control) and cyclic citrullinated peptide 2 (CCP2) were tested in baseline serum samples from 94 patients of the RETRO study. Patients were classified according to the number of autoantibody reactivities (0-1/10, 2-5/10 and >5/10) or specificity groups (citrullination, carbamylation and acetylation; 0-3) and tested for their risk to develop relapses after DMARD tapering. Demographic and disease-specific parameters were included in multivariate logistic regression analysis for defining the role of autoantibodies in predicting relapse. RESULTS: Patients varied in their antimodified protein antibody response with the extremes from recognition of no (0/10) to all antigens (10/10). Antibodies against citrullinated vimentin (51%), acetylated ornithine (46%) and acetylated lysine (37%) were the most frequently observed subspecificities. Relapse risk significantly (p=0.011) increased from 18% (0-1/10 reactivities) to 34% (2-5/10) and 55% (>5/10). With respect to specificity groups (0-3), relapse risk significantly (p=0.021) increased from 18% (no reactivity) to 28%, 36% and finally to 52% with one, two or three antibody specificity groups, respectively. CONCLUSIONS: The data suggest that the pattern of antimodified protein antibody response determines the risk of disease relapse in patients with RA tapering DMARD therapy. TRIAL REGISTRATION NUMBER: 2009-015740-42; Results.

High-resolution Quantitative Computed Tomography Demonstrates Structural Defects in Cortical and Trabecular Bone in IBD Patients.

BACKGROUND AND AIMS: To investigate the macro- and microstructural changes of bone in patients with inflammatory bowel disease [IBD] and to define the factors associated with bone loss in IBD. METHODS: A total of 148 subjects, 59 with Crohn's disease [CD], 39 with ulcerative colitis [UC], and 50 healthy controls were assessed for the geometric, volumetric and microstructural properties of bone using high-resolution peripheral quantitative computed tomography. In addition, demographic and disease-specific characteristics of IBD patients were recorded. RESULTS: IBD patients and controls were comparable in age, sex, and body mass index. Total [p = 0.001], cortical [p < 0.001], and trabecular volumetric bone mineral density [BMD] [p = 0.03] were significantly reduced in IBD patients compared with healthy controls. Geometric and microstructural analysis revealed significantly lower cortical area [p = 0.001] and cortical thickness [p < 0.001] without differences in cortical porosity, pore volume, or pore diameter. CD showed a more severe bone phenotype than UC: cortical bone loss was observed in both diseases, but CD additionally showed profound trabecular bone loss with reduced trabecular BMD [p = 0.008], bone volume [p = 0.008], and trabecular thickness [p = 0.009]. Multivariate regression models identified the diagnosis of CD, female sex, lower body mass index, and the lack of remission as factors independently associated with bone loss in IBD. CONCLUSION: IBD patients develop significant cortical bone loss, impairing bone strength. Trabecular bone loss is limited to CD patients, who exhibit a more severe bone phenotype compared with UC patients.

Serum phosphate and hip bone mineral density as additional factors for high vascular calcification scores in a community-dwelling: the São Paulo Ageing & Health Study (SPAH).

OBJECTIVE: To analyze the association between abdominal aortic calcification scores (AACS) and bone metabolism parameters in a well-characterized general population of older adults. BACKGROUND: Several studies suggest a link between bone mineral metabolism disorders and vascular calcification; although only few of them analyze bone mineral density(BMD), laboratory bone markers and cardiovascular parameters at the same time and none were done in a miscegenated population. METHODS: This cross-sectional study included 815 subjects ≥ 65 years old. The risk factors for osteoporosis and cardiovascular disease as well as a wide array of demographic and lifestyle characteristics were collected using a standardized questionnaire. BMD was measured by DXA. Kauppila's method was used to quantify the AAC score (AACS) by spine X-rays. Laboratory analyses were also performed. RESULTS: AAC was observed in 63.2% of subjects with a median AACS of 2 (IQR: 0-7). AACS were categorized in quartiles and the highest quartile of AACS (>7) were compared with the three lower quartiles of AACS (≤ 7). Logistic regression analysis was performed using parameters with statistical significance in the univariate analysis. The best logistic regression model revealed that AACS>7 was negatively associated with femoral neck BMD and positively associated with phosphorus, adjusted by age, current smoking, LDL, and arterial hypertension in the elderly community-dwelling population. CONCLUSIONS: We identified that higher serum phosphate levels and lower hip BMD are independent bone variables that are associated with elevated vascular calcification scores, supporting the search for effective prevention and treatment strategies that may simultaneously reduce these modifiable risk factors in older subjects.

The impact of asymptomatic vertebral fractures on quality of life in older community-dwelling women: the São Paulo Ageing & Health Study

OBJECTIVES: The aim of this study was to investigate the impact of asymptomatic vertebral fractures on the quality of life in older women as part of the Sao Paulo Ageing & Health Study. METHODS: This study was a cross-sectional study with a random sample of 180 women 65 years of age or older with or without vertebral fractures. The Quality of Life Questionnaire of the European Foundation for Osteoporosis was administered to all subjects. Anthropometric data were obtained by physical examination, and the body mass index was calculated. Lateral thoracic and lumbar spine X-ray scans were obtained to identify asymptomatic vertebral fractures using a semi-quantitative method. RESULTS: Women with asymptomatic vertebral fractures had lower total scores [61.4(15.3) vs. 67.1(14.2), p = 0.03] and worse physical function domain scores [69.5(20.1) vs. 77.3(17.1), p = 0.02] for the Quality of Life Questionnaire of the European Foundation for Osteoporosis compared with women without fractures. The total score of this questionnaire was also worse in women classified as obese than in women classified as overweight or normal. High physical activity was related to a better total score for this questionnaire (p = 0.01). Likewise, lower physical function scores were observed in women with higher body mass index values (p<0.05) and lower physical activity levels (p,0.05). Generalized linear models with gamma distributions and logarithmic link functions, adjusted for age, showed that lower total scores and physical function domain scores for the Quality of Life Questionnaire of the European Foundation for Osteoporosis were related to a high body mass index, lower physical activity, and the presence of vertebral fractures (p<0.05). CONCLUSION: Vertebral fractures are associated with decreased quality of life mainly physical functioning in older community-dwelling women regardless of age, body mass index, and physical activity. Therefore, the results highlight the importance of preventing and controlling asymptomatic vertebral fractures to reduce their impact on quality of life among older women.

Osteoporotic fractures in the Brazilian community-dwelling elderly: prevalence and risk factors.

The risk of osteoporotic fractures is known to vary among populations. There are no studies analyzing concomitantly clinical, densitometric, and lab risk factors in miscigenated community-dwelling population of Brazil. A total of 1007 elderly subjects (600 women and 407 men) from São Paulo, were evaluated using a questionnaire that included risk factors for osteoporotic fractures. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry at the hip and lumbar spine. Laboratory blood tests were also obtained. The prevalence of osteoporotic fractures was 13.2% (133 subjects), and the main fracture sites were distal forearm (6.0%), humerus (2.3%), femur (1.3%), and ribs (1.1%). Women had a higher prevalence (17.5%; 95% confidence interval [CI]: 14.6-20.6) than men (6.9%; 95% CI: 4.4-9.3) (p<0.001). After adjusting for significant variables, logistic regression revealed that female gender (odds ratio [OR]=2.7; 95% CI; 1.6-4.5; p<0.001), current smoking (OR=1.9; 95% CI: 1.2-3.3; p=0.013), and the femoral neck T-score (OR=0.7; 95% CI: 0.5-0.9; p=0.001) remain significant risk factors for osteoporotic fractures in the community-dwelling elderly. Our findings identified that female gender, current smoking, and low hip BMD are independent risk factors for osteoporotic fractures.

Mycophenolate mofetil is effective in reducing lupus glomerulonephritis proteinuria.

Mycophenolate mofetil (MMF) significantly reduces proteinuria in experimental model of human membranous nephropathy (Heymann nephritis). Twenty consecutive SLE patients with persistent isolated severe proteinuria and/or proteinuric flare were studied for 18 months of MMF therapy. All of them presented stable renal function and 12 had biopsy proven membranous glomerulonephritis (WHO class V). The starting daily dose for MMF was 1.5 g to a maximum of 3 g. Patients were divided into: partial response, >or=50% decrease of baseline proteinuria; complete response, normal proteinuria levels (less than 0.3 g/24 h); flare, increase of at least 50% of the mean baseline proteinuria. All 20 SLE patients (100%) presented a 50% reduction of baseline proteinuria which was achieved in 8.2+/-3.3 months of MMF therapy, at a mean daily dose of 2.3+/-0.5 g. A significant decrease in 24-h protein excretion was observed compared to entry (3.47+/-1.26 vs. 1.33+/-0.67 g, P<0.0001) as well as a correspondent increase of serum albumin (3.2+/-0.4 vs. 3.7+/-0.4 mg/dl, P=0.02) and reduction of prednisone dose (33.7+/-20.0 to 18.6+/-14.1 mg/day, P=0.01). Complete response was observed in 11 SLE patients (55%) in 12.2+/-3.0 months of therapy with a significant decrease in proteinuria (P<0.0001), prednisone dose (P<0.0001) and an increase of serum albumin (P=0.003). Interestingly, initial proteinuria or serum albumin levels did not identify patients with complete response and those with partial response at the end of the study (P=0.543 and 0.657, respectively). Our pilot prospective study suggests that MMF appears to be effective in reducing severe persistent proteinuria in lupus glomerulonephritis, even in patients unresponsive to other immunosuppressive treatments.