Age-related reference data of bone microarchitecture, volumetric bone density, and bone strength parameters in a population of healthy Brazilian men: an HR-pQCT study.

In a cross-sectional cohort of 340 healthy Brazilian men aged 20 to 92 years, data on density, structure, and strength of the distal radius and tibia were obtained using high-resolution peripheral quantitative computed tomography (HR-pQCT) to develop age- and site-specific reference curves. Age-dependent changes differed between the sites and bone compartments (trabecular and cortical). INTRODUCTION: The aim of this study was to establish age-related reference curves for bone densities, microarchitectural properties, and estimated failure load measured by HR-pQCT (distal radius and tibia) in men. Also, to correlate bone stiffness with the other HR-pQCT parameters, areal bone mineral density (BMD) by DXA and trabecular bone score (TBS). METHODS: Healthy Brazilian men (n = 340) between the ages of 20 and 92 years were recruited. Non-dominant radius and left tibia were scanned using HR-pQCT (Xtreme CT I). Standard and automated segmentation methods were performed, and bone strength estimated by FE analysis. Bone mineral density at lumbar spine, total hip, femoral neck, and TBS were measured using DXA (Hologic, QDR4500). RESULTS: Age-related reference curves were constructed at the distal radius and tibia for volumetric bone density, morphometry, and estimated bone strength parameters. There was a linear relationship with age only for thickness measurements of distal radius (trabecular: R2 0.108, p<0.001; cortical: R2 0.062, p=0.002) and tibia (trabecular: R2 0.109, p<0.001; cortical: R2 0.063, p=0.010), and bone strength at distal radius (R2 0.157, p<0.001). The significant correlations (p <0.05) found by Pearson's correlations (r) between bone stiffness and all other variables measured by HR-pQCT and DXA showed to be stronger at the tibia site than the distal radius. CONCLUSION: The current study expands the HR-pQCT worldwide database and presents an adequate methodology for the construction of reference data in other populations. Moreover, the correlation of bone strength estimated by FEA with other bone microstructural parameters provided by HR-pQCT helps to determine the contribution of each of these variables to fracture risk prediction in men.

Incidence and risk factors for osteoporotic non-vertebral fracture in low-income community-dwelling elderly: a population-based prospective cohort study in Brazil. The São Paulo Ageing and Health (SPAH) study.

We ascertained the incidence of non-vertebral fracture in a low-income Brazilian elderly cohort. To the best of our knowledge, this is the first population-based study to demonstrate the frequency of non-vertebral fracture in elderly Latin Americans. Age, prior fracture, and bone mineral density (BMD) at hip were predictors of fracture. INTRODUCTION: No data on incidence of osteoporotic non-vertebral fracture have been reported in low-income countries where the population's aging has been faster. Even in developed countries, currently available prospective data on major fracture rates beyond hip are scarce. The aim of this study is to describe the incidence and risk factors for non-vertebral fracture in a longitudinal prospective Brazilian population-based elderly cohort. METHODS: Seven hundred seven older adults (449 women, 258 men) were evaluated at baseline and after a mean follow-up of 4.3 ± 0.8 years. Clinical questionnaire, bone mineral density (BMD), and laboratory tests were performed at baseline. New non-vertebral fracture (hip, proximal humerus, rib, forearm) was determined during the follow-up. Multivariate Poisson regression models were used to identify independent predictors of fracture. RESULTS: The age-standardized incidence of non-vertebral fracture was 1562.3/100,000 (1085.7-2248.1/100,000) person-years (pyr) in women and 632.8/100,000 (301.7-1327.3/100,000) in men. Concerning to hip fractures, the incidence was 421.2/100,000 (210.7-842.3/100,000) pyr in women and 89.9/100,000 (12.7-638.5/100,000) in men. In a multivariate analysis, age (RR 2.07, 95% CI 1.13-3.82, p = 0.019, each 10-year increase), prior non-vertebral fracture (RR 3.08, 95% CI 1.36-6.95, p = 0.007), and total hip BMD (RR 1.68, 95% CI 1.11-2.56, p = 0.015, each 1 SD decrease) were predictors of new non-vertebral fracture. In men, fitting a model of risk factors for fracture was prevented by the limited number of events in male sample. CONCLUSION: This is the first population-based study to ascertain the incidence of major non-vertebral fractures in elderly Latin Americans, confirming the high frequency of the disorder. Age, prior fracture, and hip BMD were predictors of the short-term incidence of fracture.

Is there an association between upper limb claudication and handgrip strength in Takayasu arteritis?

Limb vascular claudication and hand muscle weakness are common symptoms of Takayasu arteritis (TAK). However, no studies have correlated these two symptoms. Therefore, the aim of the study was to evaluate handgrip strength and its correlation with both upper-limb vascular claudication and imaging of the vessels. This cross-sectional study compared 36 patients with TAK who were matched by age, gender, and body mass index with 36 individuals without TAK (CTR). Hand strength (assessed with handgrip dynamometer), functional capacity (Health Assessment Questionnaire, HAQ), upper-limb vascular claudication symptoms (patients' selfreported form), and disease activity (Indian Takayasu Clinical Activity Score [ITAS] 2010; Physician Global Assessment [PGA], C-reactive protein, and erythrocyte sedimentation rate) were evaluated as well as vessel imaging (e.g., angiotomography or angioresonance) and blood pressure. The median age of the patients was 42.0 years (35.5-51.5 years), whereas the mean disease duration was 13.1±6.8 years. No patient had active disease. Compared to the CTR, the patients with TAK showed reduced strength in the left-hand (22.9±5.9 vs 26.3±5.6 kg; p=0.014) and increased HAQ scores [0.50 (0.12-0.87) vs 0.00 (0.00-0.00); p<0.001]. Both groups had comparable blood pressure. Among patients with TAK, lefthand strength was inversely correlated with HAQ (Spearman correlation: rho=-0.584; p<0.001) and positively correlated with right-hand strength (rho=0.644; p<0.001). Moreover, neither hand's strengths in the patients were correlated with subclavian stenosis imaging, blood pressure or limb vascular claudication. The reduction of strength in the upper left limb is inversely related to the functional capacity (HAQ score) of TAK. This reduction appears unrelated to classical vascular claudication, vessel imaging or blood pressure.

Is there a reliable association between patient-reported limb claudication and vascular imaging methods in Takayasu arteritis?

Vessel imaging in Takayasu arteritis (TAK) is often performed in clinical practice following laboratory test abnormalities or clinical symptoms, such as limb claudication. Conversely, the association between limb claudication and vessel imaging manifestations has not been assessed. This observational, cross-sectional study analyzed 139 adult TAK patients from 2000 to 2018. Their arterial vessel imaging information (especially significant stenosis and occlusion data) was registered and crosschecked with clinical and laboratory data. When vessel imaging was performed, the median age and disease duration of the patients were 38 (27.3-47.0) and 5.0 (1.0-12.0) years, respectively. There was no association between arterial abnormalities and demographic data, constitutional symptoms or laboratory parameters. Limb claudication was reported in 42 patients (30.2%): 17.3% reported it in the upper left limb (ULL), 12.2% reported it in the upper right limb (URL), 12.9% reported it in the lower left limb (LLL), and 12.2% reported it in the lower right limb (LRL). When crossmatched with imaging, both ULL and URL were associated with left vertebral artery stenosis/occlusion, and URL was associated with right iliac artery stenosis/occlusion, but no other association was found. In contrast, both LLL and LRL claudication were associated with infrarenal aortic, left iliac and right iliac artery stenosis/ occlusion (p<0.05). Moreover, the ULL and URL claudication symptoms were significantly associated with each other (p<0.001). Upper limb claudication was associated only with left vertebral artery stenosis/occlusion, whereas the subclavian arteries were not, suggesting that the symptom might not be fully explained by limb ischemia. In contrast, lower limb claudication was associated especially with infrarenal aortic and/or iliac arteries stenosis/occlusion.

Distal radius and tibia bone microarchitecture impairment in female patients with diffuse systemic sclerosis.

Radius and tibia bone microarchitecture, analyzed through a high-resolution peripheral quantitative computed tomography, were significantly impaired in female patients with diffuse systemic sclerosis compared with healthy controls. Acroosteolysis, quality of life-grip strength, hand disability, and disease duration were significantly associated with this bone deterioration. INTRODUCTION: The effect of diffuse systemic sclerosis (dSSc) on the bone is not completely understood. The objective of this study was to analyze the volumetric bone mineral density (vBMD), microarchitecture, and biomechanical parameters at the distal radius and tibia using high-resolution peripheral quantitative computed tomography (HR-pQCT, XtremeCT) in female patients with dSSc and identify clinical and laboratory variables associated with these parameters. METHODS: Thirty-eight women with dSSc and 76 healthy controls were submitted to HR-pQCT at the distal radius and tibia. Clinical and laboratory findings, bone mineral density(BMD), nailfold capillaroscopy (NC), total passive range of motion(ROM), and quality of life (health assessment questionnaire-HAQ) were associated with HR-pQCT (Scanco Medical AG, Brüttisellen, Switzerland) parameters. Multiple linear regression models adjusted for clinical and laboratory variables, ROM and HAQ, were performed. RESULTS: Density, microarchitecture, and biomechanical parameters at the distal radius and tibia were significantly impaired in dSSc patients compared with healthy controls (p < 0.001). Multiple linear regression models showed that lower trabecular density (Tb.vBMD) (radius R2 = 0.561, p = 0.002; and tibia R2 = 0.533, p = 0.005), and lower trabecular number (Tb.N) (tibia R2 = 0.533, p = 0.005) were significantly associated with acroosteolysis. Higher trabecular separation (Tb.Sp) was associated with disease duration and higher HAQ-grip strength (radius R2 = 0.489, p = 0.013), while cortical density (Ct.vBMD) was associated with ROM (radius R2 = 0.294, p = 0.002). CONCLUSION: Bone microarchitecture in patients with dSSc, analyzed through HR-pQCT, showed impairment of trabecular and cortical bone at distal radius and tibia. Variables associated with hand involvement (acroosteolysis, quality of life-grip strength, and ROM) and disease duration may be considered prognostic factors of this bone impairment.

Risk factors for bone loss in juvenile-onset systemic lupus erythematosus: a prospective study.

OBJECTIVE: Juvenile-onset systemic lupus erythematosus (JoSLE) is associated with low bone mass for age and fractures; nevertheless, risk factors for bone impairment are poorly understood. The aim of this study was to evaluate risk factors for bone mass loss in JoSLE patients. METHODS: Forty-nine female JoSLE patients were evaluated at baseline and after a 3.5-year follow-up regarding clinical, laboratory (including bone turnover markers), areal bone mineral density (aBMD) and bone microarchitecture parameters using high-resolution peripheral quantitative computed tomography (HR-pQCT). Based on the difference between final and baseline aBMD value, the patients were divided into three groups: aBMD gain (BG), aBMD loss (BL) and aBMD no change (NC). RESULTS: The mean patient age was 18.7 ± 3.3 years. Sixty-one percent of patients presented with aBMD gain, 18.4% aBMD loss, and 20.4% remained stable during this follow-up period. Comparing the BL with the BG group, there was a higher frequency of alcohol consumption (p = 0.009), a higher frequency of inadequate calcium intake (p = 0.047) and lower levels of baseline procollagen type 1 amino-terminal propeptide (P1NP) (p = 0.036) in the BL group. Moreover, worsening of HR-pQCT parameters trabecular volumetric density (p = 0.003) and cortical thickness (p = 0.009) was observed in the BL group. In addition, a higher frequency of renal activity was observed comparing the BL + NC with the BG group (p = 0.036). CONCLUSIONS: This is the first longitudinal study that has analyzed the risk factors of bone loss in JoSLE patients. The authors emphasize the importance of evaluating lifestyle habits and renal disease activity in these young women. Furthermore, this study suggests that trabecular and cortical compartments deteriorated, and low levels of P1NP may be a predictor of bone impairment in JoSLE.

Monocytes from male patients with ankylosing spondylitis display decreased osteoclastogenesis and decreased RANKL/OPG ratio.

The present study investigates the osteoclastogenic capacity of peripheral blood mononuclear cells (PBMCs) in male patients with ankylosing spondylitis (AS). We demonstrated that monocytes from these patients display a lower capacity to generate osteoclasts compared to cells from healthy controls, and osteoclastogenesis was negatively correlated with disease duration. INTRODUCTION: Ankylosing spondylitis (AS) is a disease characterized by new bone growth that leads to syndesmophyte formation but AS patients frequently present with low bone mineral density/fractures. Osteoclastogenesis in AS patients is poorly studied and controversial. The aim of this study is to determine if the osteoclastogenic capacity of PBMCs is different in AS patients compared to controls and the relationship between osteoclastogenesis and clinical/laboratory parameters. METHODS: PBMCs from 85 male AS patients and 59 controls were tested for CD16+ cells and induced to differentiate into osteoclasts over 3 weeks in vitro. Serum levels of RANKL, osteoprotegerin (OPG), C-terminal telopeptide of type I collagen (CTX), and amino-terminal pro-peptide of type I collagen (P1NP) were also evaluated. RESULTS: PBMCs from AS patients had fewer CD16+ cells and produced fewer osteoclasts compared to controls. Apoptosis occurred less frequently in osteoclasts obtained from AS patients than in osteoclasts from the controls. A lower RANKL/OPG and CTX/P1NP were observed in AS patients compared to controls. AS patients taking NSAIDs presented no difference regarding the number of OCs produced and the percentage of CD16+ cells compared to controls. However, patients taking TNF inhibitors (TNFi) presented lower OC numbers than controls. A negative correlation was demonstrated between the number of osteoclasts generated from PBMCs of AS patients and disease duration. CONCLUSION: Monocytes from male AS patients display a lower capacity to generate osteoclasts in vitro compared to cells from controls. Osteoclastogenesis was negatively correlated with disease duration. This finding supports the idea that osteoclasts play a role in the physiopathology of bone disease in AS patients.

Increased visceral adipose tissue and altered adiposity distribution in premenopausal lupus patients: correlation with cardiovascular risk factors.

Objective Visceral adipose tissue (VAT) correlates with cardiovascular risk factors and has never been assessed in systemic lupus erythematosus (SLE). Our aim was to evaluate VAT in premenopausal SLE patients. Methods Sixty-three premenopausal SLE patients and 186 age-matched healthy women were included. Demographic, anthropometric, disease and treatment parameters were evaluated. VAT was measured by dual X-ray absorptiometry (DXA) with APEX 4.0 software. Results SLE patients had a disease duration of 5.25 ± 3.80 years, SLEDAI activity score of 4.35 ± 5.13, SLICC/ACR-DI of 0.70 ± 0.80, current prednisone dose of 11.60 ± 12.10 mg/day and cumulative glucocorticoid dose of 22.34 ± 12.94 g. Overweight/obese SLE patients and controls had similar VAT parameters ( p > 0.05). Among individuals with BMI <25 kg/m2, SLE patients and controls had similar weight, fat mass and fat percentage ( p > 0.05) but patients had higher values of VAT parameters (VAT mass: 260.60 ± 117.23 vs. 194.77 ± 71.42 g, p = 0.001; VAT area: 54.05 ± 24.30 vs. 40.40 ± 14.82 cm2, p = 0.001; VAT volume: 281.75 ± 126.81 vs. 210.61 ± 77.29 cm3, p = 0.001) and trunk/limb fat mass ratio (0.78 ± 0.21 vs. 0.67 ± 0.12, p = 0.002) compared to controls. In SLE, VAT area correlated with weight ( r = 0.66, p < 0.001), non-HDL cholesterol ( r = 0.53, p < 0.001), LDL cholesterol ( r = 0.48, p < 0.001) and triglycerides ( r = 0.33, p = 0.008), but not with disease duration, SLEDAI, SLICC/ACR-DI or current glucocorticoid use ( p > 0.05). Conclusion This study provides original evidence that SLE is associated with increased VAT and altered adiposity distribution. The correlation with traditional risk factors for cardiovascular disease, independent of current glucocorticoid dose and disease activity, suggests the role of visceral fat as an additional tool for risk assessment in these young patients.

Characteristics of 1555 childhood-onset lupus in three groups based on distinct time intervals to disease diagnosis: a Brazilian multicenter study.

Objective The objective of this study was to compare demographic data, clinical/laboratorial features and disease activity at diagnosis in three different groups with distinct time intervals between onset of signs/symptoms and disease diagnosis. Methods A multicenter study was performed in 1555 childhood-onset systemic lupus erythematosus (American College of Rheumatology criteria) patients from 27 pediatric rheumatology services. Patients were divided into three childhood-onset systemic lupus erythematosus groups: A: short time interval to diagnosis (<1 month); B: intermediate time interval (≥1 and <3 months); and C: long time interval (≥3 months). An investigator meeting was held to define the protocol. Demographic data, SLICC classification criteria and SLEDAI-2 K were evaluated. Results The number of patients in each group was: A = 60 (4%); B = 522 (33.5%); and C = 973 (62.5%). The median age at diagnosis (11.1 (4.2-17) vs. 12 (1.9-17.7) vs. 12.5 (3-18) years, P = 0.025) was significantly lower in group A compared with groups B and C. The median number of diagnostic criteria according to SLICC (7 (4-12) vs. 6 (4-13) vs. 6 (4-12), P < 0.0001) and SLEDAI-2 K (18 (6-57) vs. 16 (2-63) vs. 13 (1-49), P < 0.0001) were significantly higher in group A than the other two groups. The frequency of oral ulcers in the palate (25% vs. 15% vs. 11%, P = 0.003), pleuritis (25% vs. 24% vs. 14%, P < 0.0001), nephritis (52% vs. 47% vs. 40%, P = 0.009), neuropsychiatric manifestations (22% vs. 13% vs. 10%, P = 0.008), thrombocytopenia (32% vs. 18% vs. 19%, P = 0.037), leucopenia/lymphopenia (65% vs. 46% vs. 40%, P < 0.0001) and anti-dsDNA antibodies (79% vs. 66% vs. 61%, P = 0.01) were significantly higher in group A compared with the other groups. In contrast, group C had a less severe disease characterized by higher frequencies of synovitis (61% vs. 66% vs. 71%, P = 0.032) and lower frequencies of serositis (37% vs. 33% vs. 25%, P = 0.002), proteinuria >500 mg/day (48% vs. 45% vs. 36%, P = 0.002) and low complement levels (81% vs. 81% vs. 71%, P < 0.0001) compared with groups A or B. Conclusions Our large Brazilian multicenter study demonstrated that for most childhood-onset systemic lupus erythematosus patients, diagnosis is delayed probably due to mild disease onset. Conversely, the minority has a very short time interval to diagnosis and a presentation with a more severe and active multisystemic condition.

Age-related reference curves of volumetric bone density, structure, and biomechanical parameters adjusted for weight and height in a population of healthy women: an HR-pQCT study.

In a cross-sectional cohort of 450 healthy women aged 20 to 85 years, data on the density, structure, and strength of the distal radius and tibia were obtained using high-resolution peripheral quantitative computed tomography (HR-pQCT) and were adjusted for age, weight, and height. Age-dependent patterns of change differed between the sites and between the trabecular and cortical compartments. In postmenopausal women, the trabecular bone remained relatively stable at the distal tibia, but the cortical compartment changed significantly. Cortical porosity exhibited a very weak correlation with stiffness. INTRODUCTION: The aim of this study is to provide information on age-related, weight-related, and height-related changes in the volumetric bone mineral density (vBMD), structure, and biomechanical parameters of the cortical and trabecular compartments in a healthy female population using HR-pQCT. METHODS: For a cross-sectional Brazilian cohort of 450 women aged 20 to 85 years, age-related reference curves of the vBMD, structure, and biomechanical parameters of the distal radius (DR) and distal tibia (DT) were constructed and adjusted for weight and height, and comparisons between premenopausal and postmenopausal women were performed. RESULTS: Reference curves were obtained for all parameters. At the DR, age-related changes varied from -8.68% (cortical thickness [Ct.Th]) to 26.7% (trabecular separation [Tb.Sp]). At the DT, the changes varied from -12.4% (Ct.Th) to 26.3% (Tb.Sp). Cortical porosity (Ct.Po) exhibited the largest percent changes: 342.2% at the DR and 381.5% at the DT. In premenopausal women, Ct.Th remained constant; in postmenopausal women, structural trabecular parameters (trabecular number (Tb.N), trabecular thickness (Tb.Th), Tb.Sp) did not change, whereas cortical parameters and stiffness were significantly altered. Cortical vBMD showed the greatest absolute decrease at both sites, and the slopes were highly negative after menopause. Pearson correlations between stiffness (S) and HR-pCT parameters revealed a significant correlation between the densities and structures of the trabecular and cortical compartments. A weak correlation was observed between S and Ct.Po (DR r = -0.162, DT r = -0.273; p < 0.05). CONCLUSIONS: These data provide reference curves from healthy women and demonstrate that density and structural and biomechanical parameters differ between the radius and tibia and between the trabecular and cortical compartments. In postmenopausal women, the trabecular bone remained relatively stable at the tibia site, whereas the cortical compartment changed significantly.

Evaluation of bone mineral density and microarchitectural parameters by DXA and HR-pQCT in 37 children and adults with X-linked hypophosphatemic rickets.

In X-linked hypophosphatemic (XLH) rickets, dual-energy X-ray absorptiometry (DXA) measurements must be analyzed with caution. High-resolution peripheral quantitative computed tomography (HR-pQCT) analysis suggested that XLH primarily affects the cancellous compartment, with the tibia more affected than the radius. Effective treatment of XLH appears to positively affect bone mineralization, mainly in the bone cortex. INTRODUCTION: The purpose of this study is to evaluate bone mineral density (BMD) and microarchitecture in 37 patients (13 children and 24 adults) with XLH confirmed by PHEX mutations from a tertiary center compared to healthy controls. METHODS: Areal BMD (aBMD) was evaluated by DXA, whereas volumetric BMD (vBMD) and microarchitectural parameters were analyzed by HR-pQCT. RESULTS: Adult XLH patients had higher lumbar aBMD (p < 0.01) than the controls. At the radius, the vBMD was similar between XLH patients and controls. At the tibia, XLH patients had lower total vBMD (p = 0.04), likely resulting from decreased trabecular vBMD (p < 0.01), and this difference was observed in the children and adult groups. Analysis based on metabolic status showed that the adult XLH patients with non-compensated disease had lower cortical vBMD at the tibia than the compensated XLH patients (p = 0.03). The microarchitectural differences at the radius and tibia included lower trabecular number (p < 0.01), greater trabecular separation (p < 0.01), and higher trabecular network inhomogeneity (p < 0.01) in XLH patients compared to their controls. At the radius, adults exhibited greater trabecular deficits than were seen in children. CONCLUSIONS: In XLH patients, DXA measurements must be analyzed with caution due to the interference of anatomic and anthropometric factors. HR-pQCT analysis suggested that XLH primarily affects the cancellous compartment, with the tibia more affected than the radius. Effective treatment of XLH appears to positively affect bone mineralization, mainly in the bone cortex.

Biologic therapies and bone loss in rheumatoid arthritis.

INTRODUCTION: Rheumatoid arthritis (RA) is a common systemic autoimmune disease of unknown cause, characterized by a chronic, symmetric, and progressive inflammatory polyarthritis. One of the most deleterious effects induced by the chronic inflammation of RA is bone loss. During the last 15 years, the better knowledge of the cytokine network involved in RA allowed the development of potent inhibitors of the inflammatory process classified as biological DMARDs. These new drugs are very effective in the inhibition of inflammation, but there are only few studies regarding their role in bone protection. The principal aim of this review was to show the evidence of the principal biologic therapies and bone loss in RA, focusing on their effects on bone mineral density, bone turnover markers, and fragility fractures. METHODS: Using the PICOST methodology, two coauthors (PC, LM-S) conducted the search using the following MESH terms: rheumatoid arthritis, osteoporosis, clinical trials, TNF- antagonists, infliximab, adalimumab, etanercept, certolizumab, golimumab, IL-6 antagonists, IL-1 antagonists, abatacept, tocilizumab, rituximab, bone mineral density, bone markers, and fractures. The search was conducted electronically and manually from the following databases: Medline and Science Direct. The search period included articles from 2003 to 2015. The selection included only original adult human research written in English. Titles were retrieved and the same two authors independently selected the relevant studies for a full text. The retrieved selected studies were also reviewed completing the search for relevant articles. The first search included 904 titles from which 253 titles were selected. The agreement on the selection among researchers resulted in a Kappa statistic of 0.95 (p < 0.000). Only 248 abstracts evaluated were included in the acronym PICOST. The final selection included only 28 studies, derived from the systematic search. Additionally, a manual search in the bibliography of the selected articles was made and included into the text and into the section of "small molecules of new agents." CONCLUSION: Treatment with biologic drugs is associated with the decrease in bone loss. Studies with anti-TNF blocking agents show preservation or increase in spine and hip BMD and also a better profile of bone markers. Most of these studies were performed with infliximab. Only three epidemiological studies analyzed the effect on fractures after anti-TNF blocking agent's treatment. IL-6 blocking agents also showed improvement in localized bone loss not seen with anti-TNF agents. There are a few studies with rituximab and abatacept. Although several studies reported favorable actions of biologic therapies on bone protection, there are still unmet needs for studies regarding their actions on the risk of bone fractures.

Objectively measured physical activity and its influence on physical capacity and clinical parameters in patients with primary Sjögren's syndrome.

Objective The objectives of this paper are to objectively measure habitual physical activity levels in patients with primary Sjögren's syndrome (pSS) with mild disease activity and to determine to which extent it may be associated with physical capacity and function and clinical features. Methods In this cross-sectional study, 29 women with pSS were objectively assessed for habitual physical activity levels (using accelerometry) and compared with 20 healthy women (CTRL) frequency-matched for physical activity levels, age, body mass index, and body fat percentage with regard to physical capacity and function, fatigue, depression, pain, and health-related quality of life. Results pSS showed 8.5 min/day of moderate-to-vigorous physical activity (MVPA) when only MVPA accumulated in bouts ≥ 10 min was considered; when considering total MVPA (including bouts < 10 min), average levels were 26.3 min/day, with 62% of pSS patients achieving the recommendation (≥ 21.4 min/day). Moreover, pSS showed lower VO2peak, lower muscle strength and function, higher fatigue, and poorer health-related quality of life when compared with CTRL ( p < 0.05). These differences (except for aerobic capacity) were sustained even when only individuals achieving the minimum of 21.4 min/day of total MVPA in both groups were compared. Finally, MVPA time was significantly correlated with aerobic conditioning, whereas total counts and sedentary time were associated with lower-body muscle strength and the bodily-pain domain of SF-36 in patients with pSS. Conclusion When compared to physical activity-matched healthy controls, pSS patients showed reduced physical capacity and function, increased fatigue and pain, and reduced health-related quality of life. Except for aerobic conditioning, these differences were sustained when only more physically active participants were compared, indicating that minimum recommended levels of physical activity for the general population may not be sufficient to counteract pSS comorbidities.

Autoimmune hemolytic anemia in systemic lupus erythematosus at diagnosis: differences between pediatric and adult patients.

Objective To determine the overall prevalence of autoimmune hemolytic anemia (AIHA), and to compare clinical and laboratory features in a large population of children and adult lupus patients at diagnosis. Methods This retrospective study evaluated the medical charts of 336 childhood-onset systemic lupus erythematosus (cSLE) and 1830 adult SLE (aSLE) patients followed in the same tertiary hospital. Demographic data, clinical features and disease activity were recorded. AIHA was defined according to the presence of anemia (hemoglobin <10 g/dL) and evidence of hemolysis (reticulocytosis and positive direct antiglobulin test (DAT)/Coombs test) at SLE diagnosis. Evans syndrome (ES) was defined by the combination of immune thrombocytopenia (platelet count <100,000/mm3) and AIHA. Results The frequency of AIHA at diagnosis was significantly higher in cSLE patients compared to aSLE (49/336 (14%) vs 49/1830 (3%), p = 0.0001), with similar frequency of ES (3/336 (0.9%) vs 10/1830 (0.5%), p = 0.438). The median of hemoglobin levels was reduced in cSLE vs aSLE patients (8.3 (2.2-10) vs 9.5 (6.6-10) g/dL, p = 0.002) with a higher frequency of multiple hemorrhagic manifestations (41% vs 7%, p = 0.041) and erythrocyte transfusion due to bleeding (24% vs 5%, p = 0.025). cSLE patients also had more often constitutional involvement (84% vs 31%, p < 0.001), fever (65% vs 26%, p < 0.001), weight loss > 2 kg (39% vs 6%, p < 0.001), reticuloendothelial manifestations (48% vs 8%, p < 0.001), hepatomegaly (25% vs 2%, p < 0.001) and splenomegaly (21% vs 2%, p = 0.004). Other major organ involvements were common but with similar frequencies in cSLE and aSLE ( p > 0.05). Median systemic lupus erythematosus disease activity index 2000 (SLEDAI-2 K) was comparable in cSLE and aSLE (p = 0.161). Conclusions We identified that AIHA was not a common condition in cSLE and aSLE, with distinct features characterized by a higher prevalence/severity in children and concomitant constitutional symptoms in the majority of them.

Anti-ribosomal P antibody: a multicenter study in childhood-onset systemic lupus erythematosus patients.

Objectives Anti-ribosomal P protein (anti-P) autoantibodies are highly specific for systemic lupus erythematosus (SLE). However, the evaluation of this autoantibody in childhood-onset SLE (cSLE) populations has been limited to a few small series, hampering the interpretation of the clinical and laboratorial associations. Therefore, the objective of this multicenter cohort study was to evaluate demographic, clinical/laboratorial features, and disease damage score in cSLE patients with and without the presence of anti-P antibody. Methods This was a retrospective multicenter study performed in 10 pediatric rheumatology services of São Paulo state, Brazil. Anti-P antibodies were measured by ELISA in 228 cSLE patients. Results Anti-P antibodies were observed in 61/228 (27%) cSLE patients. Frequencies of cumulative lymphadenopathy (29% vs. 15%, p = 0.014), acute confusional state (13% vs. 5%, p = 0.041), mood disorder (18% vs. 8%, p = 0.041), autoimmune hemolytic anemia (34% vs. 15%, p = 0.001), as well as presence of anti-Sm (67% vs. 40%, p = 0.001), anti-RNP (39% vs. 21%, p = 0.012) and anti-Ro/SSA antibodies (43% vs. 25%, p = 0.016) were significantly higher in cSLE patients with anti-P antibodies compared to those without these autoantibodies. A multiple regression model revealed that anti-P antibodies were associated with autoimmune hemolytic anemia (odds ratio (OR) = 2.758, 95% confidence interval (CI): 1.304-5.833, p = 0.008) and anti-Sm antibody (OR = 2.719, 95% CI: 1.365-5.418, p = 0.004). The SLICC/ACR damage index was comparable in patients with and without anti-P antibodies ( p = 0.780). Conclusions The novel association of anti-P antibodies and autoimmune hemolytic anemia was evidenced in cSLE patients and further studies are necessary to determine if anti-P titers may vary with this hematological manifestation.

Outcomes of 847 childhood-onset systemic lupus erythematosus patients in three age groups.

Objective The objective of this study was to assess outcomes of childhood systemic lupus erythematosus (cSLE) in three different age groups evaluated at last visit: group A early-onset disease (<6 years), group B school age (≥6 and <12 years) and group C adolescent (≥12 and <18 years). Methods An observational cohort study was performed in ten pediatric rheumatology centers, including 847 cSLE patients. Results Group A had 39 (4%), B 395 (47%) and C 413 (49%). Median disease duration was significantly higher in group A compared to groups B and C (8.3 (0.1-23.4) vs 6.2 (0-17) vs 3.3 (0-14.6) years, p < 0.0001). The median Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR-DI) (0 (0-9) vs 0 (0-6) vs 0 (0-7), p = 0.065) was comparable in the three groups. Further analysis of organ/system damage revealed that frequencies of neuropsychiatric (21% vs 10% vs 7%, p = 0.007), skin (10% vs 1% vs 3%, p = 0.002) and peripheral vascular involvements (5% vs 3% vs 0.3%, p = 0.008) were more often observed in group A compared to groups B and C. Frequencies of severe cumulative lupus manifestations such as nephritis, thrombocytopenia, and autoimmune hemolytic anemia were similar in all groups ( p > 0.05). Mortality rate was significantly higher in group A compared to groups B and C (15% vs 10% vs 6%, p = 0.028). Out of 69 deaths, 33/69 (48%) occurred within the first two years after diagnosis. Infections accounted for 54/69 (78%) of the deaths and 38/54 (70%) had concomitant disease activity. Conclusions This large multicenter study provided evidence that early-onset cSLE group had distinct outcomes. This group was characterized by higher mortality rate and neuropsychiatric/vascular/skin organ damage in spite of comparable frequencies of severe cumulative lupus manifestations. We also identified that overall death in cSLE patients was an early event mainly attributed to infection associated with disease activity.

Bone impairment assessed by HR-pQCT in juvenile-onset systemic lupus erythematosus.

UNLABELLED: High-resolution peripheral quantitative computed tomography (HR-pQCT) analysis of female juvenile-onset systemic lupus erythematosus (JoSLE) patients revealed trabecular/cortical bone damage and reduced bone strength primarily at the distal radius compared to healthy controls. We demonstrated for the first time that JoSLE patients with vertebral fracture (VF) present trabecular impairment at the distal radius. INTRODUCTION: This study investigated the volumetric bone mineral density (vBMD), microarchitecture, and biomechanical features at the distal radius and tibia using HR-pQCT and laboratory bone markers in JoSLE patients compared to controls to determine whether this method discriminates JoSLE patients with or without VF. METHODS: We compared 56 female JoSLE patients to age- and Tanner-matched healthy controls. HR-pQCT was performed at the distal radius and tibia. Serum levels of the amino-terminal pro-peptide of type I collagen, the C-terminal telopeptide of type I collagen, intact parathormone, sclerostin, and 25-hydroxyvitamin D (25OHD) were evaluated. VFs were analyzed using VFA-dual-energy X-ray absorptiometry (DXA) (Genant's method). RESULTS: Reduced density and strength parameters and microarchitecture alterations of cortical and trabecular bones were observed in JoSLE patients compared to controls, primarily at the distal radius (p < 0.05). Patients with VF exhibited a significant decrease in trabecular bone parameters solely at the distal radius (Total.BMD, p = 0.034; Trabecular.BMD [Tb.BMD], p = 0.034; bone volume (BV)/trabecular volume (TV), p = 0.034; apparent modulus, p = 0.039) and higher scores for disease damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR-DI), p = 0.002). Bone metabolism markers were similar in all groups. Logistic regression analysis of parameters that were significant in univariate analysis revealed that Tb.BMD (OR 0.98, 95 % CI 0.95-0.99, p = 0.039) and SLICC/ACR-DI (OR 7.37, 95 % CI 1.75-30.97, p = 0.006) were independent risk factors for VF. CONCLUSION: In conclusion, this study is the first demonstration of bone microstructure and strength deficits in JoSLE patients, particularly at the distal radius. Our results demonstrated that VF was associated with trabecular radius alteration and emphasized the potential detrimental effect of disease damage on this condition.

Visceral fat measured by DXA is associated with increased risk of non-spine fractures in nonobese elderly women: a population-based prospective cohort analysis from the São Paulo Ageing & Health (SPAH) Study.

The present study investigates the relationship between visceral fat measured by dual-energy X-ray absorptiometry (DXA) and the incidence of non-spine fractures in community-dwelling elderly women. We demonstrated a potential negative effect of visceral fat on bone health in nonobese women. INTRODUCTION: The protective effect of obesity on bone health has been questioned because visceral fat has been demonstrated to have a deleterious effect on bone. The aim of this study was to investigate the association of visceral fat measured by DXA with the incidence of non-spine fractures in community-dwelling elderly women. METHODS: This longitudinal prospective population-based cohort study evaluated 433 community-dwelling women aged 65 years or older. A specific clinical questionnaire, including personal history of a fragility fracture in non-spine osteoporotic sites, was administered at baseline and after an average of 4.3 years. All incidences of fragility fractures during the study period were confirmed by affected-site radiography. Visceral adipose tissue (VAT) was measured in the android region of a whole-body DXA scan. RESULTS: The mean age was 72.8 ± 4.7 years, and 28 incident non-spine osteoporotic fractures were identified after a mean follow-up time of 4.3 ± 0.8 years. According to the Lipschitz classification for nutritional status in the elderly, 38.6 % of women were nonobese (BMI ≤ 27 kg/m2) and 61.4 % were obese/overweight. Logistic regression models were used to estimate the relationship between VAT and non-spine fractures in elderly women. After adjusting for age, race, previous fractures, and BMD, VAT (mass, area, volume) had a significant association with the incidence of non-spine fractures only in nonobese elderly women (VAT mass: OR, 1.42 [95 % CI, 1.09-1.85; p = 0.010]; VAT area: OR, 1.19 [95 % CI, 1.05-1.36; p = 0.008]; VAT volume: OR, 1.40 [95 % CI, 1.09-1.80; p = 0.009]). CONCLUSION: This study suggests a potential negative effect of visceral adiposity on bone health in nonobese women.

Associations between OPG and RANKL polymorphisms, vertebral fractures, and abdominal aortic calcification in community-dwelling older subjects: the Sao Paulo Ageing & Health Study (SPAH).

This is the first study analyzing concomitantly osteoprotegerin (OPG)/receptor activator of nuclear factor kappa B ligand (RANKL) polymorphisms and OPG/RANKL serum levels and their association with bone mineral density (BMD), vertebral fractures, and vascular aortic calcification in a cohort of 800 subjects in community-dwelling older individuals. INTRODUCTION: Osteoprotegerin (OPG) and RANKL play an important role in osteoclast activation and differentiation as well as in vascular calcification. At present, there are no studies of OPG or RANKL gene polymorphisms in Brazilian older populations. The aim of this study was to evaluate OPG/RANKL polymorphism and their association with vertebral fractures (VFs) and aortic calcification. METHODS: Eight hundred subjects (497 women/303 men) were genotyped for the OPG 1181G>C (rs2073618), 163C>T (rs3102735), 245T>G (rs3134069), and 209G>A (rs3134070) and RANKL A>G (rs2277438) single-nucleotide polymorphisms (SNPs). VFs were evaluated by spine radiography (Genant's method). Aortic calcification was quantified using Kauppila's method. RESULTS: The isolated genotype analyses and single-allele frequency data showed association of OPG 163C, 245G, and 209A alleles with presence of VFs (P < 0.05). Multiple logistic regression of subjects with absence of VFs vs. those with VFs (grades II/III) revealed only OPG 209A homozygosity as a risk factor for higher-grade VFs (odds ratio (OR) = 4.17, 95 % CI 1.03-16.93, P = 0.046). Regarding aortic calcification, the isolated genotype analysis frequency data revealed a significant association of OPG 1181G, 163C, 245G, and 209A alleles with absent aortic calcification (P < 0.05). Multiple logistic regression data confirmed that the OPG 209A allele was protective for aortic calcification (OR = 0.63, 95 % CI 0.45-0.88, P = 0.007) and the OPG 1181C allele was a risk factor for aortic calcification (OR = 1.26, 95 % CI 1.00-1.58, P = 0.046). CONCLUSION: This study showed that the OPG 209AA genotype was a risk factor for higher-grade VFs, the OPG 209A allele was protective for aortic calcification, and the OPG 1181C was a risk factor for aortic calcification, supporting the involvement of OPG polymorphisms in the analyzed phenotypes and the concept that the related pathogenesis is multifactorial.

RANKL and OPG gene polymorphisms: associations with vertebral fractures and bone mineral density in premenopausal systemic lupus erythematosus.

UNLABELLED: Premenopausal women with systemic lupus erythematosus (SLE) have a higher prevalence of low bone mineral density and vertebral fractures. Multiple genetic loci for osteoporotic fracture were identified in recent genome-wide association studies. This study provides a novel data demonstrating that receptor activator of NF-κB ligand (RANKL)/osteoprotegerin (OPG) polymorphisms likely plays an important role in the bone remodeling process in SLE premenopausal women. INTRODUCTION: The purpose of this study was to evaluate single-nucleotide polymorphisms (SNPs) of the RANKL, RANK, and OPG genes in premenopausal SLE patients and their association with sRANKL and OPG serum levels, vertebral fractures, and bone mineral density (BMD). METHODS: A total of 211 premenopausal SLE patients (American College of Rheumatology (ACR) criteria) and 154 healthy controls were enrolled. SNPs of RANKL 290A>G (rs2277438), OPG 1181G>C (rs2073618), 245T>G (rs3134069), 163A>G (rs3102735), and RANK A>G (rs3018362) were obtained by real-time PCR. sRANKL/OPG serum levels were determined by ELISA. BMD and vertebral fractures were evaluated by dual-energy X-ray absorptiometry (DXA). RESULTS: SLE patients and controls had similar frequencies of the RANKL 290 G allele (p = 0.94), OPG 1181 C allele (p = 0.85), OPG 245 G allele (p = 0.85), OPG 163 G allele (p = 0.78), and RANK G allele (p = 0.87). Further analysis of the SLE patients revealed that the frequency of the RANKL 290 G allele was lower in patients with fractures than that in patients without fractures (28.1 vs 46.9%, p = 0.01). In addition, the frequency of the OPG 245 G allele was higher in patients with low BMD than that in patients with normal BMD (31.4 vs 18.1%, p = 0.04). No association of OPG 1181 G>C, OPG 163 A>G, and RANK A>G SNPs with BMD/fractures was found. Additionally, no association was observed between RANKL/OPG/RANK SNPs and sRANKL/OPG serum levels. CONCLUSIONS: Our study provides novel data demonstrating that RANKL/OPG genetic variations appear to play a role in bone remodeling, particularly in its major complication, fracture, in premenopausal patients with SLE.