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.

Ovarian reserve in adult patients with childhood-onset lupus: a possible deleterious effect of methotrexate?

OBJECTIVES: To assess ovarian reserve markers and anti-corpus luteum antibodies (anti-CoL) in adult patients with childhood-onset systemic lupus erythematosus (c-SLE). METHOD: Fifty-seven adult c-SLE female patients and 21 healthy controls were evaluated for anti-CoL. Ovarian reserve was assessed by: follicle stimulating hormone (FSH), luteinizing hormone (LH), oestradiol, anti-Müllerian hormone (AMH), and antral follicle count (AFC). Demographic data, menstrual abnormalities, disease activity, damage, and treatment were also analysed. RESULTS: The median current age was similar in adult c-SLE patients and controls (27.7 vs. 27.7 years, p = 0.414). The medians of AMH (1.1 vs. 1.5 ng/mL, p = 0.037) and AFC (6 vs. 16, p < 0.001) were significantly reduced in SLE patients compared to controls without significant menstrual abnormalities. Anti-CoL were solely observed in c-SLE patients (16% vs. 0%, p = 0.103) and were not associated with demographic data, ovarian reserve parameters, disease activity/damage, and treatment. Further evaluation of c-SLE patients treated with cyclophosphamide revealed a higher median of FSH levels compared to c-SLE patients not treated with cyclophosphamide and controls (8.8 vs. 5.7 vs. 5.6 IU/L, p = 0.032) and lower median AMH (0.4 vs. 1.5 vs. 1.5 ng/mL, p = 0.004) and AFC (4.0 vs. 6.5 vs. 16 IU/L, p = 0.001) levels. Nineteen patients treated exclusively with methotrexate demonstrated a negative correlation between the cumulative dose and AMH levels (p = 0.027, r = -0.507). CONCLUSIONS: The present study demonstrated for the first time that a high cumulative methotrexate dose is a possible cause of subclinical ovarian dysfunction in adult c-SLE patients. Further studies are required to confirm this deleterious effect in other rheumatic diseases, particularly juvenile idiopathic arthritis and idiopathic inflammatory myopathy.

Lupus pleuritis: a relevant risk factor for pulmonary tuberculosis.

The objective of the study was to evaluate risk factors for pulmonary tuberculosis in systemic lupus erythematosus (SLE). Clinical/laboratorial features of 1283 SLE patients (ACR criteria) followed at the Lupus Clinic were obtained from the electronic register database from 2001 to 2009. Pulmonary tuberculosis was diagnosed in 20 patients (1.6%) (TB+ group). As control group (TB-), 40 patients without tuberculosis matched for age, gender, ethnicity, age at SLE diagnosis, and disease duration were arbitrarily selected. All 20 patients of the TB+ group presented confirmed pulmonary tuberculosis from 1 to 23 years after SLE diagnosis (7.6 ± 8.1 years). Frequencies of previous SLE involvements (cutaneous, articular, hematological, renal, pericarditis, pneumonitis, and central nervous system) were alike in TB+ and TB- groups (p > 0.05). In contrast, prior pleuritis was more frequent in the TB+ group (40% vs. 5%, p = 0.001). In fact, pulmonary tuberculosis was diagnosed in 8/10 patients with previous pleuritis. Immunosuppressive and corticosteroid therapies at the moment of tuberculosis diagnosis were also similar in both groups (p > 0.05). We have identified pleuritis as a relevant risk factor for pulmonary tuberculosis, suggesting that previous pleural injury is a critical part of the complex interplay between altered immune system, socio-economic conditions, and increased susceptibility to this mycobacterial infection.

Characterizing hand and wrist ultrasound pattern in primary Sjögren's syndrome: a case-control study.

INTRODUCTION/OBJECTIVES: To evaluate the clinical relevance of high-resolution hand and wrist ultrasound (US) findings and their possible associations with anti-citrullinated peptide antibodies in primary Sjögren's syndrome (pSS). METHODS: Ninety-seven consecutive pSS patients (American-European Consensus Group, 2002) without meeting the American College of Rheumatology (ACR) criteria (1987) for rheumatoid arthritis (RA); 20 RA patients (ACR/European League Against Rheumatism (EULAR) criteria, 2010); and 80 healthy individuals with comparable age, gender, and ethnicity were enrolled in a case-control study. Disease activity was assessed by EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI). US was performed by one expert blinded to anti-CCP, anti-MCV, and IgM rheumatoid factor tested by ELISA. RESULTS: Frequencies of grade 3 synovitis (9.3 vs. 0%, p = 0.004), tenosynovitis (36.1 vs. 3.8%, p < 0.001), and erosions (27.8 vs. 7.5%, p = 0.001) on US were higher in pSS patients than in healthy controls. ESSDAI presented a moderate correlation with the synovitis number (p = 0.001) and tenosynovitis (p < 0.001). Most pSS patients with erosions on US (81.5%) had negative anti-CCP. Nevertheless, anti-CCP ≥ 3× cut-off value was associated with the presence of erosions in pSS (p = 0.026). Erosions in pSS were mainly small size contrasting with moderate/large size in RA (p < 0.001), and positive power Doppler synovitis predominated in RA (p < 0.001). CONCLUSIONS: US identified significant frequencies of grade 3 synovitis, tenosynovitis, and erosions in pSS. Synovitis and tenosynovitis numbers were correlated with ESSDAI. Association between erosions on US and anti-CCP (high titers) in pSS possibly identifies a subgroup with severe arthritis. These findings suggest that US is a useful method for assessing joint involvement in pSS.Key Points• US identified significant frequencies of grade 3 synovitis, tenosynovitis, and erosions in pSS patients in comparison with age- and race-healthy individuals.• Numbers of synovitis and tenosynovitis on US were correlated with ESSDAI values.• Most pSS patients with erosions on US were negative for anti-CCP, but anti-CCP ≥ 3× cut-off value was associated with the presence of erosions in this disease.• Erosions in pSS were mainly small size contrasting with moderate/large size in RA, and positive power Doppler synovitis predominated in RA.

Menstrual disturbances in patients with systemic lupus erythematosus without alkylating therapy: clinical, hormonal and therapeutic associations.

We have evaluated 36 consecutive systemic lupus erythematosus (SLE) female patients, age 18-39 years, without current or previous alkylating therapy, in order to determine the prevalence of the menstrual disturbances and their clinical, hormonal and therapeutic associations. Seventeen patients presented normal cycles, whereas menstrual alterations were observed in 19. Ovarian function was generally preserved in these groups. Sub-clinical thyroid disease (normal free T4 and elevated TSH) and slightly increased prolactin levels were detected in 8% of patients, with comparable frequencies in both groups. Similarly, the current use of azathioprine was not associated with menstrual disturbances. Percentages of prednisone current use (P = 0.3), mean dose (P = 0.062), and percentages of patients on high doses (> or = 30 mg/day; P = 0.09) were comparable in patients with or without menstrual alterations. In contrast, the mean SLEDAI levels (P = 0.02) and the frequency of patients with SLEDAI > or = 8 (P = 0.008) were higher in patients with irregular cycles. Interestingly, 5/7 (71%) of the patients with menstrual disturbances and a new significant flare (SLEDAI > or = 8) were evaluated before the introduction of high dose steroid, supporting the idea that disease activity is a major factor in menstrual disorders in SLE patients without alkylating therapy.

Anti-corpus luteum antibody: a novel serological marker for ovarian dysfunction in systemic lupus erythematosus?

OBJECTIVE: To investigate the presence of autoantibodies directed to corpus luteum (CoL) in systemic lupus erythematosus (SLE) sera and its correlation with menstrual disturbances. METHODS: We evaluated 87 female patients with SLE, < 40 years old, and 23 women with normal menses as controls. Anti-corpus luteum antibody was detected by immunoblot technique. RESULTS: Reactivity to a bovine CoL antigen was found in 22% of SLE sera. Characterization of the target antigen revealed a 67 kDa glycoprotein highly enriched in corpus luteum, but nearly absent in total ovary extract. Similarly, target antigen was also weakly detectable in tissues that produce or metabolize steroids, such as testis, adrenal cortex, and liver, and it was absent in adrenal medulla or HEp-2 cells. Anti-CoL antibody was easily distinguished from other frequent reactivities of SLE sera, including anti-RNP, anti-Sm, anti-Ro/La, anti-dsDNA, or anticardiolipin. The observation of anti-67 kDa reactivity to human CoL suggests a possible pathogenic role in gonadal dysfunction. Indeed, we observed an inverse association of anti-CoL antibody with the duration of hypergonadotropic amenorrhea. Supporting this hypothesis, in patients with normal or irregular menses, the presence of this antibody was associated with elevated serum level of follicle stimulating hormone, an early and specific sign of ovarian lesion. CONCLUSION: Anti-CoL antibody seems to be associated with early stages of ovarian dysfunction in SLE. Moreover, since similar association of antiovarian antibodies has been observed in an experimental model of autoimmune oophoritis, our findings raise the possibility of autoimmune ovarian lesion in patients with SLE.