Guidelines for the prevention and treatment of glucocorticoid-induced osteoporosis: an update of Brazilian Society of Rheumatology (2020).

The Brazilian guidelines for prevention and treatment of glucocorticoid-induced osteoporosis were updated and important topics were included such as assessment of risk fracture using FRAX Brazil, use of denosumab, and also recommendations for the use of glucocorticoid pulse therapy and inhaled glucocortiocoid. INTRODUCTION: Glucocorticoids (GCs) are used in almost all medical specialties and the incidences of vertebral/nonvertebral fractures range from 30 to 50% in individuals treated with GCs for over 3 months. Thus, osteoporosis and frailty fractures should be prevented and treated in patients initiating treatment or already being treated with GCs. The Committee for Osteoporosis and Bone Metabolic Disorders of the Brazilian Society of Rheumatology (BSR) established in 2012 the Brazilian Guidelines for glucocorticoid-induced osteoporosis (GIO). Herein, we provide a comprehensive update of the original guidelines based on improved available scientific evidence and/or expert experience. METHODS: From March to June 2020, the Osteoporosis Committee of the BRS had meetings to update the questions presented in the first consensus (2012). Thus, twenty-six questions considered essential for the preparation of the recommendations were selected. A systematic literature review based on real-life scenarios was undertaken to answer the proposed questions. The MEDLINE, EMBASE, and SCOPUS databases were searched using specific search keywords. RESULTS: Based on the review and expert opinion, the recommendations were updated for each of the 26 questions. We included 48 new bibliographic references that became available after the date of the publication of the first version of the consensus. CONCLUSION: We updated the Brazilian guidelines for the prevention/treatment of GIO. New topics were added in this update, such as the assessment of risk fracture using FRAX Brazil, the use of denosumab, and approaches for the treatment of children and adolescents. Furthermore, we included recommendations for the use of inhaled GCs and GC pulse therapy in clinical settings.

Kinin B1 Receptor Acts in Adipose Tissue to Control Fat Distribution in a Cell-Nonautonomous Manner.

The kinin B1 receptor (B1R) plays a role in inflammatory and metabolic processes. B1R deletion (B1 -/-) protects mice from diet-induced obesity and improves insulin and leptin sensitivity. In contrast, genetic reconstitution of B1R exclusively in adipose tissue reverses the lean phenotype of B1 -/- mice. To study the cell-nonautonomous nature of these effects, we transplanted epididymal white adipose tissue (eWAT) from wild-type donors (B1 +/+) into B1 -/- mice (B1 +/+→B1 -/-) and compared them with autologous controls (B1 +/+→B1 +/+ or B1 -/-→B1 -/-). We then fed these mice a high-fat diet for 16 weeks and investigated their metabolic phenotypes. B1 +/+→B1 -/- mice became obese but not glucose intolerant or insulin resistant, unlike B1 -/-→B1 -/- mice. Moreover, the endogenous adipose tissue of B1 +/+→B1 -/- mice exhibited higher expression of adipocyte markers (e.g., Fabp4 and Adipoq) and changes in the immune cell pool. These mice also developed fatty liver. Wild-type eWAT transplanted into B1 -/- mice normalized circulating insulin, leptin, and epidermal growth factor levels. In conclusion, we demonstrated that B1R in adipose tissue controls the response to diet-induced obesity by promoting adipose tissue expansion and hepatic lipid accumulation in cell-nonautonomous manners.

Screening for vitamin D deficiency in a tropical area: results of a sun exposure questionnaire.

BACKGROUND: Vitamin D deficiency is pandemic while resources available to measure 25-hydroxyvitamin D (25OHD) are limited. The present study aimed to verify whether sun exposure measured by a structured questionnaire could predict serum 25OHD concentrations in healthy Caucasian individuals living in a tropical area. METHODS: A cross-sectional study was carried out in subjects living in the greater São Paulo area, Brazil. Two groups of 50 young (20 to 40 years old) and 50 older (60 to 80 years old) subjects (N = 200) answered a structured questionnaire on sun exposure and had blood samples drawn for serum 25OHD concentration measurement during both summer and winter. Anthropometric data were also recorded. Correlation between the questionnaire variables (duration of sun exposure, amount of exposed skin, total sun exposure score - TSES and other data) and serum 25OHD concentration was evaluated. RESULTS: Mean serum 25OHD concentration was 17.60 ± 7.3 ng/mL with no difference between age groups (p = 0.293). TSES weakly correlated with serum 25OHD levels (r = 0.264; p < 0.001). Separate analyzes by age groups demonstrated that TSES correlated significantly with serum 25OHD concentration only in the older subjects during summer (r = 0.322; p = 0.023). Using linear regression analyses, TSES and body mass index (BMI) were significantly associated with serum 25OHD levels. On the other hand, Receiver operating characteristic (ROC) analysis for TSES showed no significance as a screening tool for vitamin D deficiency (p = 0.172). CONCLUSION: Sun exposure questionnaire associated with BMI correlates with serum 25OHD concentration with very low accuracy. The use of the questionnaire does not discriminate between vitamin D sufficient and deficient individuals.

Physical Activity Questionnaires Do Not Accurately Estimate Fitness in Older Women.

The objective was to compare the performance of the International Physical Activity Questionnaire (IPAQ) and Baecke questionnaire to estimate maximal oxygen uptake (VO2max) in healthy older women. One hundred healthy women aged 60 years and older answered the IPAQ and Baecke questionnaires and underwent a cardiopulmonary exercise test. The 6-min walk (6MWT), timed up and go (TUG), and handgrip strength test (HST) were also performed. Mean age and body mass index were 68.5 ± 6.3 years and 27 ± 4.7 kg/m2, respectively. No significant correlation was seen between VO2max, IPAQ and Baecke questionnaires. IPAQ did not correlate with any functional tests while Baecke correlated weakly with the 6MWT and TUG test. VO2max correlated significantly with the 6MWT (r = .38; p = .0001), HST (r = .34; p = .001), and TUG (r = -.41; p = .0001). In a multivariate regression model, TUG was the best estimator for VO2max (R2 = .217; p = .0001). In conclusion, IPAQ and Baecke questionnaires do not associate significantly with VO2max in older women.

Brazilian guidelines for the diagnosis and treatment of postmenopausal osteoporosis.

Osteoporosis is the leading cause of fractures in the population older than 50 years. This silent disease affects primarily postmenopausal women and the elderly, and the morbidity and mortality rates are high. The main goal of treating osteoporosis is the prevention of fractures. The identification of populations at risk through early diagnosis and treatment is essential. The last Brazilian guideline for the treatment of postmenopausal osteoporosis was elaborated in 2002. Since then, new strategies for diagnosis and risk stratification have been developed, and drugs with novel action mechanisms have been added to the therapeutic arsenal. The Osteoporosis and Osteometabolic Diseases Committee of the Brazilian Society of Rheumatology, in conjunction with the Brazilian Medical Association and other Societies, has developed this update of the guidelines for the treatment of postmenopausal osteoporosis according to the best scientific evidence available. This update is intended for professionals in many medical and health specialties involved in the treatment of osteoporosis, for physicians in general and for health-related organizations.

Brazilian guidelines for the diagnosis and treatment of postmenopausal osteoporosis / Diretrizes brasileiras para o diagnóstico e tratamento da osteoporose em mulheres na pós-menopausa

Abstract Osteoporosis is the leading cause of fractures in the population older than 50 years. This silent disease affects primarily postmenopausal women and the elderly, and the morbidity and mortality rates are high. The main goal of treating osteoporosis is the prevention of fractures. The identification of populations at risk through early diagnosis and treatment is essential. The last Brazilian guideline for the treatment of postmenopausal osteoporosis was elaborated in 2002. Since then, new strategies for diagnosis and risk stratification have been developed, and drugs with novel action mechanisms have been added to the therapeutic arsenal. The Osteoporosis and Osteometabolic Diseases Committee of the Brazilian Society of Rheumatology, in conjunction with the Brazilian Medical Association and other Societies, has developed this update of the guidelines for the treatment of postmenopausal osteoporosis according to the best scientific evidence available. This update is intended for professionals in many medical and health specialties involved in the treatment of osteoporosis, for physicians in general and for health-related organizations.

Resumo A osteoporose é a principal causa de fraturas na população acima de 50 anos. É uma doença silenciosa que afeta especialmente as mulheres na pós-menopausa e idosos e tem elevada taxa de morbimortalidade. O principal objetivo do tratamento da osteoporose é a prevenção das fraturas. A identificação dessa população de risco através do diagnóstico e tratamento precoces é de fundamental importância. A última diretriz brasileira para tratamento da osteoporose em mulheres na pós-menopausa foi elaborada em 2002. Desde então foram desenvolvidas novas estratégias de diagnóstico da osteoporose, bem como fármacos com novos mecanismos de ação foram adicionados ao arsenal terapêutico. A Comissão de Osteoporose e Doenças Osteometabólicas da Sociedade Brasileira de Reumatologia em conjunto com a Associação Médica Brasileira e sociedades afins desenvolveu esta atualização da diretriz do tratamento da osteoporose em mulheres na pós-menopausa de acordo com as melhores evidências científicas disponíveis. Esta atualização é destinada aos profissionais das várias especialidades médicas e da área da saúde envolvidos no tratamento da osteoporose, médicos em geral e organizações relacionadas à saúde.

Assessment of Early Treatment Response With DWI After CT-Guided Radiofrequency Ablation of Functioning Adrenal Adenomas.

OBJECTIVE: The objective of this study was to establish the suitability of the apparent diffusion coefficient (ADC) as a parameter for evaluating early treatment response after percutaneous ablation of functional adrenal adenomas. SUBJECTS AND METHODS: Seventeen adult patients with functioning adrenal adenomas underwent radiofrequency ablation. Serum hormone levels were analyzed before and up to 6 months after ablation. MRI findings (nodule size in cm, signal intensity index, ADC maps, and nodule-to-muscle ADC ratio) were analyzed before and up to 30 days after ablation. A consensus review of all scans was performed by two attending abdominal imaging radiologists. The procedure was considered successful if serum hormone levels normalized and no contrast enhancement of the adrenal lesion was seen on follow-up MRI. RESULTS: Of 17 patients who underwent radiofrequency ablation, complete response was achieved in 16 patients with partial response in one patient. Of the four parameters of interest, only ADC maps and nodule-to-muscle ADC ratio showed statistically significant differences (p < 0.05). CONCLUSION: This prospective study suggests that apparent diffusion coefficient values may help radiologists monitor early treatment response after CT-guided radiofrequency ablation of functioning adrenal adenomas.

Early pharmacological inhibition of angiotensin-I converting enzyme activity induces obesity in adulthood.

We have investigated early programming of body mass in order to understand the multifactorial etiology of obesity. Considering that the renin-angiotensin system (RAS) is expressed and functional in the white adipose tissue (WAT) and modulates its development, we reasoned whether early transitory inhibition of angiotensin-I converting enzyme activity after birth could modify late body mass development. Therefore, newborn Wistar rats were treated with enalapril (10 mg/kg of body mass) or saline, starting at the first day of life until the age of 16 days. Between days ninetieth and hundred and eightieth, a group of these animals received high fat diet (HFD). Molecular, biochemical, histological, and physiological data were collected. Enalapril treated animals presented hyperphagia, overweight, and increased serum level of triglycerides, total cholesterol and leptin, in adult life. Body composition analyses revealed higher fat mass with increased adipocyte size in these animals. Molecular analyses revealed that enalapril treatment increases neuropeptide Y (NPY) and cocaine- and amphetamine-regulated transcript (CART) gene expression in hypothalamus, fatty acid synthase (FAS), and hormone-sensitive lipase (HSL) gene expression in retroperitoneal WAT, and decreases peroxixome proliferators-activated receptor (PPAR)γ, PPARα, uncoupling protein (UCP)2, and UCP3 gene expression in WAT. The results of the current study indicate that enalapril administration during early postnatal development increases body mass, adiposity and serum lipids in adulthood associated with enhanced food intake and decreased metabolic activity in WAT, predisposing to obesity in adulthood.

Bone mineral density measurements, bone markers and serum vitamin D concentrations in men with chronic non-cirrhotic untreated hepatitis C.

INTRODUCTION: The high prevalence of chronic hepatitis C (CHC) and its consequent cirrhosis has been associated with bone fragility. Whether CHC may cause bone and mineral abnormalities in the absence of hepatocellular dysfunction is still unknown. In this study we aimed to determine the prevalence of osteoporotic vertebral fractures and low BMD measurements in men with non-cirrhotic CHC. Risk factors for low BMD and fractures were also investigated. METHODS: Morphometric vertebral fractures and BMD measurements were performed in 60 non-cirrhotic untreated men with CHC and 59 healthy controls, matched for age and gender, weight and current smoking. Serum CTx, calcium, phosphate, intact PTH, alkaline phosphatase and vitamin D (25OHD) concentrations were measured in all participants. Clinical risk factors for low BMD and fractures were evaluated by a structured questionnaire as well as details regarding HCV infection. RESULTS: Trochanter and total femur BMD were significantly lower in CHC patients as compared to healthy men (p = 0.04). In men 50 years and older, the prevalence of osteoporosis was significantly higher among CHC patients (p = 0.01). Lower levels of physical activities and more often report of prolonged immobilization were observed among CHC patients (p<0.05). Liver inflammation and fibrosis, viral load and genotype did not correlate with BMD measurements. Bone markers and 25OHD concentrations were similar in both groups. Only a few vertebral fractures were observed. CONCLUSIONS: Our results demonstrate that non-cirrhotic untreated CHC patients have lower BMD at the femur as compared to healthy men in spite of the absence of significant bone and mineral abnormalities.

Body composition parameters in healthy Brazilian women differ from white, black, and Hispanic American women reference range.

Body composition (BC) seems to vary between populations, suggesting the need for regional reference data. The objective of this study was to determine BC in Brazilian women. Five hundred healthy non-black Brazilian women aged 20 yr or older were included. Women with fractures, chronic diseases, medications affecting bone and mineral metabolism, coronary heart disease, pregnancy, silicone prosthesis, and Asians or Indians were excluded. BC by dual-energy X-ray absorptiometry (DXA) included total lean mass, appendicular lean mass, skeletal muscle index, and total body fat (BF). Reference values were made for 10-yr age groups. Lean mass decreased with age reaching the lowest values in women aged 80 yr and older. BF showed a bimodal distribution: increased with age until 50-59 yr, with a slight subsequent decrease. BF in Brazilian women did not differ from American women, except in the age groups 75-79 and 80-84 yr, where BF was lower (p < 0.05). Fat mass index was consistently higher between African and Hispanic American women (p < 0.05). Lean mass was consistently lower in Brazilian women compared with Americans in almost all age and ethnic groups (p < 0.05). BC in Brazilian women differs from American reference data. Our findings support the notion that BC varies according to ethnicity.

Higher prevalence of morphometric vertebral fractures in patients with recent coronary events independently of BMD measurements.

Cardiovascular disease and osteoporosis are important causes of morbi-mortality in the elderly and may be mutually related. Low bone mineral density (BMD) may be associated with increased risk of cardiovascular events. We investigated the prevalence of low bone mass and fractures in metabolic syndrome patients with acute coronary events. A case-control study was conducted with 150 individuals (30-80years-old) with metabolic syndrome. Seventy-one patients had had an acute coronary syndrome episode in the last 6months (cases) and the remaining 79 had no coronary event (controls). Cases and controls were matched for gender, BMI and age. DXA measurements and body composition were performed while spine radiographs surveyed for vertebral fractures and vascular calcification. Biochemical bone and metabolic parameters were measured in all patients. No statistically significant difference in BMD and the prevalence of osteopenia, osteoporosis and non-vertebral fractures was observed between cases and controls. The prevalence of vertebral fractures and all fractures was higher in the cases (14.1 versus 1.3%, p=0.003 and 22.5versus7.6%, p=0.010, respectively). Male gender (OR=0.22 95% CI 0.58 to 0.83, p=0.026) and daily intake of more than 3 portions of dairy products (OR=0.19 95% CI 0.49 to 0.75, p=0.017) were associated with lower prevalence of fractures. Cases had higher risk for fractures (OR=4.97, 95% CI 1.17 to 30.30, p=0.031). Bone mass and body composition parameters were not associated with cardiovascular risk factors or bone mineral metabolism. Patients with fragility fractures had higher OPG serum levels than those without fractures (p<0.001). Our findings demonstrated that patients with recent coronary events have a higher prevalence of vertebral fractures independently of BMD.

Percentage height of center of mass is associated with the risk of falls among elderly women: A case-control study.

Falls are a serious health problem for aged people, causing social and economic burden. Despite being an important determinant of balance, the positioning of the center of mass (COM) has not been evaluated as a risk factor for falls. This study examined the association between the percentage height of COM (%COM) and the risk of falls in the elderly. Healthy women aged 60 years and older were consecutively selected in a case-control study. Forty-eight individuals classified as "fallers" (having suffered two or more falls in the previous year) were the cases while 48 age and weight-matched women with one fall or no falls in the previous year were the controls ("non-fallers"). Body composition and bone mineral density (BMD) by DXA, 30-second chair stand test, abdominal circumference, Berg's balance scale and %COM using the reaction board method were evaluated in all participants. Body composition parameters were not significantly different between groups. Spine and hip BMD tended to be lower in the fallers, but the difference was significant only at the femoral neck (0.80±0.10g/cm(2) versus 0.87±0.76g/cm(2); p<0.01). Berg's balance scale scores were lower among fallers than non-fallers (p<0.05). Percentage height of COM was significantly higher among fallers (p<0.001) and this was associated with a higher number of fractures (p<0.05). Percentage height of COM is significantly higher in the elderly with frequent falls. Further work is needed in order to determine the value of board reaction measurements in a clinical setting to identify patients at high risk.

Kinin B1 receptor deficiency leads to leptin hypersensitivity and resistance to obesity.

OBJECTIVE: Kinins mediate pathophysiological processes related to hypertension, pain, and inflammation through the activation of two G-protein-coupled receptors, named B(1) and B(2). Although these peptides have been related to glucose homeostasis, their effects on energy balance are still unknown. RESEARCH DESIGN AND METHODS: Using genetic and pharmacological strategies to abrogate the kinin B(1) receptor in different animal models of obesity, here we present evidence of a novel role for kinins in the regulation of satiety and adiposity. RESULTS: Kinin B(1) receptor deficiency in mice (B(1)(-/-)) resulted in less fat content, hypoleptinemia, increased leptin sensitivity, and robust protection against high-fat diet-induced weight gain. Under high-fat diet, B(1)(-/-) also exhibited reduced food intake, improved lipid oxidation, and increased energy expenditure. Surprisingly, B(1) receptor deficiency was not able to decrease food intake and adiposity in obese mice lacking leptin (ob/ob-B(1)(-/-)). However, ob/ob-B(1)(-/-) mice were more responsive to the effects of exogenous leptin on body weight and food intake, suggesting that B(1) receptors may be dependent on leptin to display their metabolic roles. Finally, inhibition of weight gain and food intake by B(1) receptor ablation was pharmacologically confirmed by long-term administration of the kinin B(1) receptor antagonist SSR240612 to mice under high-fat diet. CONCLUSIONS: Our data suggest that kinin B(1) receptors participate in the regulation of the energy balance via a mechanism that could involve the modulation of leptin sensitivity.

Low peak bone mass and attenuated anabolic response to parathyroid hormone in mice with an osteoblast-specific deletion of connexin43.

Connexin43 (Cx43) is involved in bone development, but its role in adult bone homeostasis remains unknown. To overcome the postnatal lethality of Cx43 null mutation, we generated mice with selective osteoblast ablation of Cx43, obtained using a Cx43fl allele and a 2.3-kb fragment of the alpha1(I) collagen promoter to drive Cre in osteoblasts (ColCre). Conditionally osteoblast-deleted ColCre;Cx43-/fl mice show no malformations at birth, but develop low peak bone mass and remain osteopenic with age, exhibiting reduced bone formation and defective osteoblast function. By both radiodensitometry and histology, bone mineral content increased rapidly and progressively in adult Cx43+/fl mice after subcutaneous injection of parathyroid hormone (PTH), an effect significantly attenuated in ColCre;Cx43-/fl mice, with Cx43-/fl exhibiting an intermediate response. Attenuation of PTH anabolic action was associated with failure to increase mineral apposition rate in response to PTH in ColCre;Cx43-/fl, despite an increased osteoblast number, suggesting a functional defect in Cx43-deficient bone-forming cells. In conclusion, lack of Cx43 in osteoblasts leads to suboptimal acquisition of peak bone mass, and hinders the bone anabolic effect of PTH. Cx43 represents a potential target for modulation of bone anabolism.

Targeted expression of a dominant-negative N-cadherin in vivo delays peak bone mass and increases adipogenesis.

We studied the function of osteoblast cadherins in vivo by transgenic expression of a truncated N-cadherin with dominant-negative action, driven by an osteoblast-specific promoter (OG2-NcadDeltaC). During the first 3 months of life, bone mineral density was reduced, whereas percent body fat was increased in transgenic animals compared with wild-type littermates, with associated decreased bone formation rate and osteoblast number, but normal osteoclast number. Osteoblast differentiation was delayed in calvaria cells isolated from transgenic mice. Likewise, the number of osteoblast precursors in bone marrow stromal cells from OG2-NcadDeltaC mice was decreased compared with wild-type cultures, whereas the number of adipogenic precursors was increased. In vitro, a transcriptionally active beta-catenin mutant reversed the delay in osteoblast differentiation and the exuberant adipogenesis. Thus, in vivo disruption of cadherin function hinders osteoblast differentiation and favors, indirectly, bone marrow progenitor cell commitment to the alternative adipogenic lineage via interference with beta-catenin signaling. This results in decreased bone formation, delayed acquisition of peak bone mass and increased body fat.

Contribuição científica da reumatologia brasileira em nível internacional / International contribution of Brazilian rheumatology

A reumatologia brasileira é uma especialidade médica em expansão no Brasil. Um número crescente de profissionais reumatologistas tem sido formado, atendendo à necessidade de controle das doenças reumáticas no país. Além disso, atividades de pesquisa desenvolvidas nas escolas médicas têm contribuído para o desenvolvimento e reconhecimento da especialidade. Neste trabalho os autores avaliam a contribuição científica da reumatologia brasileira em nível internacional, analisando as publicações brasileiras nos encontros anuais do American College of Rheumatology-ACR no período de 1987 a 1997.