Objective: The aromatization of androgenic precursors in peripheral tissues, including bone, is the main source of estrogens after the menopause. CYP19, the gene encoding aromatase, has a long 5 0 -untranslated region with several variants of exon I and specific promoters. The aim of this study was to investigate the possible relationship between a common biallelic (C/G) polymorphism located on exon I.2 and bone mineral density (BMD). Design: This was designed to be an association study between CYP19 polymorphism and BMD and the risk of vertebral fractures in women. Methods: DNA was extracted from the peripheral blood of 299 women (116 premenopausal and 183 postmenopausal). CYP19 alleles were identified by a method based on the exonuclease activity of Taq-polymerase. BMD was determined by dual-energy absorptiometry. Results: In premenopausal women there were no genotype-related differences in BMD. However, postmenopausal women with the CC genotype had lower spine and hip BMD than those with the GG genotype. The association between CYP19 genotypes and BMD was independent of other variables, such as age, height, body weight, calcium intake or years since menopause. The CC genotype was also associated with an increased risk of osteoporotic vertebral fractures (odds ratio 2.0; P ¼ 0.03). Serum levels of estrone and estradiol were similar in women with CC and GG alleles. Conclusions: A common biallelic polymorphism in the 5 0 -untranslated region of the CYP19-aromatase gene was associated with significant differences in bone mass and the risk of vertebral fractures in postmenopausal women. Given the frequency of allelic variants, genotype-related differences appear to be important from the perspective of the individual as well as the general population. Further studies are needed to elucidate underlying mechanisms that may be dependent on differences in estrogen bioactivity at the bone tissue level.European Journal of Endocrinology 150 699-704

OPG concentrations are associated with disease severity and CVD prevalence in patients with RA. Whether consideration of OPG concentrations can improve CVD risk stratification in RA merits future longitudinal investigation.

DACV is generally associated with antibiotics and NSAID. In most cases it has a favorable prognosis, although a small percentage of patients may develop residual renal damage.

Objective.In nondiabetic healthy individuals, insulin secretion and sensitivity are linked by a negative feedback loop characterized by a hyperbolic function. We aimed to study the association of traditional insulin resistance (IR) factors with insulin secretion and sensitivity, and to determine whether the hyperbolic equilibrium of this relation is preserved in patients with rheumatoid arthritis (RA).Methods.This was a cross-sectional study encompassing 361 nondiabetic individuals: 151 with RA and 210 controls. Insulin, C-peptide, and IR indices by homeostatic model (HOMA2) were assessed. A multivariable analysis was performed to evaluate the differences in the correlation of traditional IR-related factors with glucose homeostasis molecules, as well as IR indices between patients and controls. Nonlinear regression analysis was used to assess the hyperbolic relation of insulin sensitivity and secretion.Results.HOMA2-IR indices were higher in patients with RA than controls. Hepatic insulin extraction, as assessed by the insulin:C-peptide molar ratio, was lower in patients with RA after multivariable analysis (0.08 ± 0.02 vs 0.14 ± 0.07, p < 0.001). Traditional IR-related factors showed significantly lower adjusted correlation coefficients with IR indices in patients with RA. The association between insulin sensitivity and secretion showed a different hyperbolic relation in patients with RA: the variability explained by the curve was lower in RA (nonlinear r2 = 0.845 vs r2 = 0.928, p = 0.001) and β coefficients (−0.74, 95% CI −0.77 to −0.70 vs −1.09, 95% CI −1.17 to −1.02, ng/ml, p < 0.001) were different in RA.Conclusion.The traditional factors associated with IR in healthy individuals are less related to IR in patients with RA. Insulin sensitivity and secretion yield a different hyperbolic equilibrium in RA.

Summary The associations of sarcopenia with osteoporosis or obesity have a very low prevalence. No trend towards an association between osteoporosis and sarcopenia is observed. Sarcopenia and obesity tend not to coincide, as if they were antagonistic disorders. Purpose To know (a) the prevalence in our region of sarcopenic osteoporosis (association of sarcopenia and osteoporosis (T-score < − 2.5)), sarcopenic obesity, and the association of osteoporosis, sarcopenia, and obesity; (b) the tendency of osteoporosis, sarcopenia, and obesity to associate with each other; and (c) the bone mineral density (BMD), the components of sarcopenia, and the prevalence of fragility fractures in these associations. Methods The study was performed in the Camargo cohort. Osteoporosis was diagnosed by DXA, sarcopenia by the EWGSOP-1 criteria, and obesity by body mass index (BMI) and fat percentage. Fractures were verified radiographically or by consulting the medical records. Results The prevalence of sarcopenic osteoporosis was 2.8% and the OR for this association 1.03 (p = 0.89). The prevalence of sarcopenic obesity by BMI was 1.4% and by fat percentage 5.9% (corresponding ORs: 0.18 (p < 0.0001) and 0.58 (p < 0.003) respectively). The prevalence of the association of osteoporosis, sarcopenia, and obesity was 0.0% when assessed by BMI and 0.8% when assessed by fat percentage. Patients with sarcopenic osteoporosis have less muscle mass and more fragility fractures than sarcopenic patients overall. In patients with sarcopenic obesity by fat percentage, muscle mass and strength, as well as physical performance, were similar to those of sarcopenic patients overall. Neither BMD nor fracture prevalence showed differences between patients with sarcopenic obesity and patients with sarcopenia or obesity in general. Conclusion Our study supports the idea that the prevalence of the mixed disorders studied is low. No significant association between osteoporosis and sarcopenia was found. Sarcopenia and obesity seem to tend to occur in different people, as if suffering from one of them hinders suffering from the other.

The C677T (rs1801133) polymorphism of MTHFR (methylenetetrahydrofolate reductase) has been associated with the risk of cardiovascular events, and also with osteoporosis in some studies. However, the results are controversial. Our objective was to determine the relationship of the polymorphism with osteoporotic fractures by means of a case-control study. C677T was analyzed in 823 subjects (365 controls, 136 with vertebral fractures and 322 with hip fracture) by using a Taqman assay. The distribution of MTHFR genotypes was similar in patients and controls. In comparison with TC/CC genotypes, the age-adjusted OR for hip fractures of the TT genotype was 1.0 (95% confidence interval 0.6-1.7) in women and 0.7 (0.3-1.8) in men. The OR for vertebral fractures was 0.8 (0.4-1.7) in women and 1.7 (0.4-6.7) in men. A meta-analysis combining these data with previous reports confirmed the lack of association between MTHFR and fractures, with an OR of 1.1 (0.7-1.9, p=0.65) for vertebral fractures and 1.2 (0.7-2.0; p=0.45) for peripheral fractures, but there was significant heterogeneity among the results of individual studies, particularly about peripheral fractures. In conclusion, the C677T polymorphism of the MTHFR gene does not appear to be associated with the overall risk of osteoporotic fractures. However, given the heterogeneity of the results of published studies, further investigations are needed to evaluate its influence in specific population subgroups.

BackgroundAlthough the prognosis of Henoch-Schönlein purpura (HSP) is usually favorable, relapses are relatively frequent.ObjectivesOur aim was to analyze the frequency, type and risk factors for relapses in a large series of unselected patients with HSP.MethodsRetrospective study of 417 patients from a single center, diagnosed with HSP according to the criteria proposed by Michel et al. (J Rheumatol 1992; 19: 721-28).Relapse was defined as a new outbreak of HSP in a previously asymptomatic patient (at least for one month). Quantitative variables were expressed as mean ± SD or as median (interquartile range), and compared with the Student t-test or the Mann-Whitney U-test, as appropriate. Dichotomous variables were expressed as percentages and compared by using the chi-square test. The variables associated with HSP relapse in the univariate analysis entered into a stepwise multivariate logistic regression. Statistical analysis was performed using SPSS 15.0.Results417 patients (240 men/177 women) were studied; median age, 7.5 years (IQR [5.3 to 20.1]). 315 (75.5%) were children or young people (≤20 years) and 102 (24.5%) adults. Clinical manifestations (onset/HSP established,%) were: skin lesions (55.9/100), nephropathy (24/41.2), gastrointestinal involvement (13.7/64.5), joint symptoms (9.1/63.1) and fever (6.2/20.4). Corticosteroids were the most frequently used drugs (35%), followed by NSAIDs (14%), and cytotoxic agents (5%).After a median follow-up of 12 (IQR [2-38]) months, complete recovery was observed in most cases (n=346; 83.2%) and persistent and usually mild nephropathy, in 32 patients (7.7%).Relapses occurred in almost one third of the patients (n=133; 31.9%). Clinical manifestations during relapses were: cutaneous (89.6%); abdominal (27.1%); renal (25.9%) and articular (16.8%). The median number of relapses was 2.4 (IQR [1-3]). The main risk factors for the development of HSP relapse in univariate analysis are shown in the TABLE. After multivariate analyses the most powerful predictive factors for relapse were joint manifestations at disease onset, gastrointestinal manifestations during the course of the disease, and corticosteroid treatment at the time of the first episode of HSP (Table).ConclusionsHSP is usually a benign entity but relapses are not uncommon. Patients with articular symptoms at onset or presenting with gastrointestinal manifestations during the course of the disease or those needing corticosteroids to control the initial episode of HSP, are more prone to develop relapses.Disclosure of InterestNone declared

The decrease in serum osteocalcin induced by tissue injury is independent of the increase in cortisol secretion triggered by the latter. In addition, another pharmacologically proven effect of cortisol on bone metabolism, OPG inhibition, could not be demonstrated in the first 24 h following surgery, in spite of the physiological increase in endogenous cortisol secretion taking place in this period.