Iron Deficiency Anemia in Pregnancy after Bariatric Surgery: Etiology, Risk Factors, and How to Manage It.

OBJECTIVE: Pregnancy after bariatric surgery is a reality of the 21st century and therefore is essential that all obstetricians know how to manage it. The most prevalent nutritional deficiency is iron deficiency and, consequently, anemia. Although bariatric surgery and pregnancy are already risk factors for anemia, we evaluated in our study if there were any other risk factors and actions to improve hemoglobin levels in this population. METHODS: We performed a retrospective cohort study, and performed frequency measurements and analyzes of odds ratio, X2 and Fisher exact test to evaluate the risk factors. RESULTS: We evaluated 44 pregnancies after bariatric surgery, with an incidence of anemia of 62%, and the only identifiable risk factor for anemia was being black. As for the treatment, the iron salt used for oral supplementation did not associate with anemia risk, and in 27% of the patients, the adjustment of the oral dosage was enough for improvement in hemoglobin levels, but in 36% supplementation with intravenous iron was necessary. CONCLUSION: Being black is a risk factor for anemia. The type of iron salt does not correlate with the incidence of anemia, and for the treatment and improvement of iron dosages, it seems an effective increase in iron intake.

OBJETIVO: A gestação após cirurgia bariátrica é uma realidade do século XXI e, portanto, é de suma importância que os obstetras saibam conduzir o pré-natal dessas gestantes. A deficiência nutricional mais prevalente nessa população é a deficiência de ferro, que tem como consequência a anemia. Apesar da própria gestação e da cirurgia serem fatores de risco para anemia ferropriva, realizamos um estudo para avaliar se existem outros fatores que são de risco e quais condutas podem melhorar os níveis de hemoglobina nessa população. MéTODOS: Trata-se de um estudo de coorte retrospectiva, e foram realizadas medidas de frequência e análise odds ratio, X2, e teste de exato de Fisher para a avaliação dos fatores de risco. RESULTADOS: Foram avaliadas 44 gestações após cirurgia bariátrica com incidência de anemia de 62%, sendo que o único fator de risco identificado foi a etnia preta. O sal de ferro utilizado na reposição não se associou com o risco de anemia. Em somente 27% das gestantes o ajuste da dose oral de ferro foi suficiente para corrigir a anemia, enquanto em 36% foi necessária a suplementação com ferro endovenoso. CONCLUSãO: Ser de etnia preta foi fator de risco para anemia após cirurgia bariátrica e o tipo de sal de ferro para suplementação não se correlacionou com a incidência de anemia. Para o tratamento da anemia, somente o ajuste da dose da medicação parece ser suficiente para a resolução desta.

Peripheral insulin resistance is early, progressive, and correlated with cachexia in Walker-256 tumor-bearing rats.

Insulin (INS) resistance is often found in cancer-bearing, but its correlation with cachexia development is not completely established. This study investigated the temporal sequence of the development of INS resistance and cachexia to establish the relationship between these factors in Walker-256 tumor-bearing rats (TB rats). INS hepatic sensitivity and INS resistance-inducing factors, such as free fatty acids (FFA) and tumor necrosis factor-α (TNF-α), were also evaluated. Studies were carried out on Days 2, 5, 8, and/or 12 after inoculation of tumor cells in rats. The peripheral INS sensitivity was assessed by the INS tolerance test and the INS hepatic sensitivity in in situ liver perfusion. TB rats with 5, 8, and 12 days of tumor, but not 2 days, showed decreased peripheral INS sensitivity (INS resistance), retroperitoneal fat, and body weight, compared to healthy rats, which were more pronounced on Day 12. Gastrocnemius muscle wasting was observed only on Day 12 of tumor. The peripheral INS resistance was significantly correlated (r = -.81) with weight loss. Liver INS sensitivity of TB rats with 2 and 5 days of tumor was unchanged, compared to healthy rats. TB rats with 12 days of tumor showed increased plasma FFA and increased TNF-α in retroperitoneal fat and liver, but not in the gastrocnemius, compared to healthy rats. In conclusion, peripheral INS resistance is early, starts along with fat and weight loss and before muscle wasting, progressive, and correlated with cachexia, suggesting that it may play an important role in the pathogenesis of the cachectic process in TB rats. Therefore, early correction of INS resistance may be a therapeutic approach to prevent and treat cancer cachexia.

Brazilian consensus for diagnosis, management and treatment of hereditary transthyretin amyloidosis with peripheral neuropathy: second edition.

Hereditary transthyretin amyloidosis with peripheral neuropathy (ATTRv-PN) is an autosomal dominant inherited sensorimotor and autonomic polyneuropathy with over 130 pathogenic variants identified in the TTR gene. Hereditary transthyretin amyloidosis with peripheral neuropathy is a disabling, progressive and life-threatening genetic condition that leads to death in ∼ 10 years if untreated. The prospects for ATTRv-PN have changed in the last decades, as it has become a treatable neuropathy. In addition to liver transplantation, initiated in 1990, there are now at least 3 drugs approved in many countries, including Brazil, and many more are being developed. The first Brazilian consensus on ATTRv-PN was held in the city of Fortaleza, Brazil, in June 2017. Given the new advances in the area over the last 5 years, the Peripheral Neuropathy Scientific Department of the Brazilian Academy of Neurology organized a second edition of the consensus. Each panelist was responsible for reviewing the literature and updating a section of the previous paper. Thereafter, the 18 panelists got together virtually after careful review of the draft, discussed each section of the text, and reached a consensus for the final version of the manuscript.

Polineuropatia amiloidótica familiar associada a transtirretina (ATTRv-PN) é uma polineuropatia sensitivo-motora e autonômica hereditária autossômica dominante com mais de 130 variantes patogênicas já identificadas no gene TTR. A ATTRv-PN é uma condição genética debilitante, progressiva e que ameaça a vida, levando à morte em ∼ 10 anos se não for tratada. Nas últimas décadas, a ATTRv-PN se tornou uma neuropatia tratável. Além do transplante de fígado, iniciado em 1990, temos agora 3 medicamentos modificadores de doença aprovados em muitos países, incluindo o Brasil, e muitas outras medicações estão em desenvolvimento. O primeiro consenso brasileiro em ATTRv-PN foi realizado em Fortaleza em junho de 2017. Devido aos novos avanços nesta área nos últimos 5 anos, o Departamento Científico de Neuropatias Periféricas da Academia Brasileira de Neurologia organizou uma segunda edição do consenso. Cada panelista ficou responsável por rever a literatura e atualizar uma parte do manuscrito. Finalmente, os 18 panelistas se reuniram virtualmente após revisão da primeira versão, discutiram cada parte do artigo e chegaram a um consenso sobre a versão final do manuscrito.

Brazilian consensus for diagnosis, management and treatment of hereditary transthyretin amyloidosis with peripheral neuropathy: second edition / Consenso brasileiro para o diagnóstico, manejo e tratamento da polineuropatia amiloidótica familiar associada à transtirretina: segunda edição

Abstract Hereditary transthyretin amyloidosis with peripheral neuropathy (ATTRv-PN) is an autosomal dominant inherited sensorimotor and autonomic polyneuropathy with over 130 pathogenic variants identified in the TTR gene. Hereditary transthyretin amyloidosis with peripheral neuropathy is a disabling, progressive and life-threatening genetic condition that leads to death in ~ 10 years if untreated. The prospects for ATTRv-PN have changed in the last decades, as it has become a treatable neuropathy. In addition to liver transplantation, initiated in 1990, there are now at least 3 drugs approved in many countries, including Brazil, and many more are being developed. The first Brazilian consensus on ATTRv-PN was held in the city of Fortaleza, Brazil, in June 2017. Given the new advances in the area over the last 5 years, the Peripheral Neuropathy Scientific Department of the Brazilian Academy of Neurology organized a second edition of the consensus. Each panelist was responsible for reviewing the literature and updating a section of the previous paper. Thereafter, the 18 panelists got together virtually after careful review of the draft, discussed each section of the text, and reached a consensus for the final version of the manuscript.

Resumo Polineuropatia amiloidótica familiar associada a transtirretina (ATTRv-PN) é uma polineuropatia sensitivo-motora e autonômica hereditária autossômica dominante com mais de 130 variantes patogênicas já identificadas no gene TTR. A ATTRv-PN é uma condição genética debilitante, progressiva e que ameaça a vida, levando à morte em ~ 10 anos se não for tratada. Nas últimas décadas, a ATTRv-PN se tornou uma neuropatia tratável. Além do transplante de fígado, iniciado em 1990, temos agora 3 medicamentos modificadores de doença aprovados em muitos países, incluindo o Brasil, e muitas outras medicações estão em desenvolvimento. O primeiro consenso brasileiro em ATTRv-PN foi realizado em Fortaleza em junho de 2017. Devido aos novos avanços nesta área nos últimos 5 anos, o Departamento Científico de Neuropatias Periféricas da Academia Brasileira de Neurologia organizou uma segunda edição do consenso. Cada panelista ficou responsável por rever a literatura e atualizar uma parte do manuscrito. Finalmente, os 18 panelistas se reuniram virtualmente após revisão da primeira versão, discutiram cada parte do artigo e chegaram a um consenso sobre a versão final do manuscrito.

Combined reverse osmosis and UV/H2O2 treatment of aqueous solutions of bisphenol A and 17α-ethinylestradiol: assessment of estrogenic activity.

Bisphenol-A (BPA) and 17α-ethinylestradiol (EE2) are considered endocrine disrupting compounds (EDC) and they may be harmful to the normal functioning of endocrine systems of humans and animals. Moreover, the presence of these compounds in superficial and groundwater may represent serious risks, even in low concentrations like ng·L-1. The objectives of this study were to remove BPA and EE2 from solutions containing a mixture of these compounds in ultrapure water at low concentrations through reverse osmosis (RO) membrane combined with a UV/H2O2 process. Furthermore, to assess the estrogenic activity reduction after such treatments, in vitro recombinant yeast-estrogen screen (YES) assay was used. The removal efficiencies of target micropollutants increased with the increase of H2O2 dosage. For RO permeate stream, they enhanced from 91% to 96% for EE2 and from 76% to 90% for BPA while, for the concentrate stream, from 70% to 81% for EE2 and 41% to 84% for BPA as the H2O2 concentration were increased from 100 to 1000 µg·L-1. The OH radicals' generation was the dominant factor in the degradation of EDC during the UV/H2O2 treatment since the photolysis itself was not enough to degrade BPA or EE2. The estrogenic activity reduction after UV/H2O2 treatment was high, ranging from 92% to 98% for the permeate stream and from 50% to 93% for the concentrate stream. The EE2 was responsible for the whole observed estrogenic activity since BPA does not present estrogenicity, by in vitro YES assay, in the concentrations observed.

New treatments for rare bone diseases: hypophosphatemic rickets/osteomalacia.

Phosphorus is one of the most abundant minerals in the human body; it is required to maintain bone integrity and mineralization, in addition to other biological processes. Phosphorus is regulated by parathyroid hormone, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], and fibroblast growth factor 23 (FGF-23) in a complex set of processes that occur in the gut, skeleton, and kidneys. Different molecular mechanisms - overproduction of FGF-23 by tumors responsible for oncogenic osteomalacia, generation of an FGF-23 mutant that is resistant to cleavage by enzymes, and impaired FGF-23 degradation due to a reduction in or loss of the PHEX gene - can lead to FGF-23-stimulating activity and the consequent waste of urinary phosphate and low levels of 1,25(OH)2D3. Conventional treatment consists of multiple daily doses of oral phosphate salts and vitamin D analogs, which may improve radiographic rickets but do not normalize growth. Complications of the conventional long-term treatment consist of hypercalcemia, hypercalciuria, nephrolithiasis, nephrocalcinosis, impaired renal function, and potentially chronic kidney disease. Recently, burosumab, an antibody against FGF-23, was approved as a novel therapy for children and adults with X-linked hypophosphatemia and patients with tumor-induced osteomalacia. Burosumab showed good performance in different trials in children and adults. It increased and sustained the serum phosphorus levels, decreased the rickets severity and pain scores, and improved mineralization. It offers a new perspective on the treatment of chronic and disabling diseases.

New treatments for rare bone diseases: hypophosphatemic rickets/osteomalacia

Abstract Phosphorus is one of the most abundant minerals in the human body; it is required to maintain bone integrity and mineralization, in addition to other biological processes. Phosphorus is regulated by parathyroid hormone, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], and fibroblast growth factor 23 (FGF-23) in a complex set of processes that occur in the gut, skeleton, and kidneys. Different molecular mechanisms - overproduction of FGF-23 by tumors responsible for oncogenic osteomalacia, generation of an FGF-23 mutant that is resistant to cleavage by enzymes, and impaired FGF-23 degradation due to a reduction in or loss of the PHEX gene - can lead to FGF-23-stimulating activity and the consequent waste of urinary phosphate and low levels of 1,25(OH)2D3. Conventional treatment consists of multiple daily doses of oral phosphate salts and vitamin D analogs, which may improve radiographic rickets but do not normalize growth. Complications of the conventional long-term treatment consist of hypercalcemia, hypercalciuria, nephrolithiasis, nephrocalcinosis, impaired renal function, and potentially chronic kidney disease. Recently, burosumab, an antibody against FGF-23, was approved as a novel therapy for children and adults with X-linked hypophosphatemia and patients with tumor-induced osteomalacia. Burosumab showed good performance in different trials in children and adults. It increased and sustained the serum phosphorus levels, decreased the rickets severity and pain scores, and improved mineralization. It offers a new perspective on the treatment of chronic and disabling diseases. Arch Endocrinol Metab. 2022;66(5):658-65

Stress fractures

ABSTRACT Stress fractures (SF) represent 10%-20% of all injuries in sport medicine. An SF occurs when abnormal and repetitive loading is applied on normal bone: The body cannot adapt quickly enough, leading to microdamage and fracture. The etiology is multifactorial with numerous risk factors involved. Diagnosis of SF can be achieved by identifying intrinsic and extrinsic factors, obtaining a good history, performing a physical exam, and ordering laboratory and imaging studies (magnetic resonance imaging is the current gold standard). Relative energy deficiency in sport (RED-S) is a known risk factor. In addition, for women, it is very important know the menstrual status to identify long periods of amenorrhea in the past and the present. Early detection is important to improve the chance of symptom resolution with conservative treatment. Common presentation involves complaints of localized pain, with or without swelling, and tenderness on palpation of bony structures that begins earlier in training and progressively worsens with activity over a 2- to 3-week period. Appropriate classification of SF based on type, location, grading, and low or high risk is critical in guiding treatment strategies and influencing the time to return to sport. Stress injuries at low-risk sites are typically managed conservatively. Studies have suggested that calcium and vitamin D supplementation might be helpful. Moreover, other treatment regimens are not well established. Understanding better the pathophysiology of SFs and the potential utility of current and future bone-active therapeutics may well yield approaches that could treat SFs more effectively.

No evidence of mineralization abnormalities in iliac bone of premenopausal women with type 2 diabetes mellitus.

OBJECTIVES: Patients with type-2 diabetes mellitus (T2DM) have increased risk for bone fractures which points towards impaired bone quality. METHODS: We measured bone mineralization density distribution (BMDD) and osteocyte lacunae section (OLS) characteristics based on quantitative backscattered electron images of transiliac biopsy samples from n=26 premenopausal women with T2DM. Outcomes were compared to those from reference cohorts as well as between T2DM subgroups defined by clinical characteristics. RESULTS: Comparison to references did not reveal any differences in BMDD (all p>0.05) but a lowered OLS-density in cancellous bone in T2DM (-14.9%, p<0.001). Neither BMDD nor OLS-characteristics differed in T2DM subgroups defined by HbA1c (<7% versus >7%). The average degree of bone mineralization (CaMean) was higher (0.44 wt%Ca in T2DM, 0.30 wt%Ca in reference) and consistently the calcium concentration between the tetracycline double labels (CaYoung) was higher (0.76 wt%Ca, all p<0.001) in cancellous versus cortical bone. CONCLUSIONS: Our findings suggest that bone matrix mineralization was neither affected by the presence nor by the glycemic control of T2DM in our study cohort. The intra-individual differences between cancellous and cortical bone mineralization gave evidence for differences in the time course of the early mineralization process in these compartments in general.

Performance of subjective global nutritional assessment in predicting clinical outcomes: Data from the Brazilian survey of pediatric oncology nutrition.

BACKGROUND: Methods for assessing nutritional status in children and adolescents with cancer is a difficult in clinical practice. The study aimed to evaluate the performance of Subjective Global Nutritional Assessment (SGNA) in predicting clinical outcomes in children and adolescents with cancer in Brazil. METHODS: This was a prospective cohort multicenter study. It was included 723 children and adolescents with cancer aged 2-18 years between March 2018 and August 2019. Nutritional assessment was performed according to World Health Organization recommendations and using SGNA within 48h of hospitalization. Unplanned readmission, length of hospital stay, and post-discharge death were analyzed. Cohen's kappa coefficient was used to ascertain the agreement between body mass index for age (BMI/A) and SGNA. The sensitivity, specificity, positive and negative predictive values, and accuracy of SGNA were estimated. Odds ratios (ORs) with 95% confidence intervals (CIs) were evaluated using multiple logistic regression. RESULTS: The mean patient age was 9.4 ± 4.9 years. SGNA showed that 29.7% (n = 215) and 6.5% (n = 47) patients had moderate and severe malnutrition, respectively. Considering the concurrent validity criterion, SGNA had an OR (95% CI) of 6.8 (3.1-14.9) for predicting low and very low weight for age at admission, with a sensitivity and specificity of 72.4% (59%-82.1%) and 72% (64.2%-78.9%), respectively. SGNA could predict death in children with severe/moderate malnutrition, with an accuracy of 63.8% (63%-65.1%). Logistic multivariate analysis showed that the adjusted effect of death; hematological tumor; living in the northeast, southeast, and midwest regions of Brazil; and older age was associated with malnutrition according to SGNA. CONCLUSION: Based on concurrent validity between SGNA and anthropometry, SGNA performed well and had a good ability to predict death in Brazilian children with cancer.

Assessment of trabecular and cortical parameters using high-resolution peripheral quantitative computed tomography, histomorphometry and microCT of iliac crest bone core in hemodialysis patients.

Patients with end-stage renal disease develop changes in bone quality and quantity, which can be assessed using different methods. This study aimed to compare and to correlate bone parameters obtained in vivo using high-resolution peripheral quantitative computed tomography (HR-pQCT) with those obtained by bone biopsy using histomorphometry and microcomputed tomography (microCT) analysis of the iliac crest core, and to evaluate if HR-pQCT is helpful in aiding with categorization of those with high turnover. Twenty hemodialysis patients, 13 females (7 postmenopausal), underwent bone biopsy from 2018 to 2020. The mean age was 48.5 ± 10.6 years, and the mean hemodialysis vintage was 15 years. Histomorphometry identified mineralization defects, low turnover, and high turnover in 65%, 45%, and 35% of the patients, respectively. The highest values of trabecular bone volume (BV/TV) were obtained by histomorphometry, while the highest values of cortical thickness (Ct.Th) were obtained by HR-pQCT at the distal tibia. Moderate correlations were found between BV/TV values obtained by microCT of the bone core and HR-pQCT at the distal radius (r = 0.531, p = 0.016) and at the distal tibia (r = 0.536, p = 0.015). BV/TV values obtained from the bone core by histomorphometry and microCT were also significantly correlated (r = 0.475, p = 0.04). Regarding Ct.Th, there was a strong correlation between the radius and tibia HR-pQCT (r = 0.800, p < 0.001), between bone core microCT and the distal radius HR-pQCT (r = 0.610, p < 0.01), as between histomorphometry and microCT (r = 0.899, p < 0.01). In groups classified by bone turnover, patients with high turnover presented lower BV/TV, Tb.N, Tb.Th, and Ct.Th than those with low turnover in peripheral sites using HR-pQCT. By this method, it was possible to identify low turnover from tibia BV/TV > 12,4% plus Tb.Sp ≤ 0.667 mm (AUC 0.810, 95% CI 0.575 to 0.948) and high turnover from total bone mineral density (BMD) ≤ 154.2 mg HA/cm3 (AUC 0.860, 95% CI 0.633 to 0.982, p < 0.001) and cortical BMD ≤ 691.6 mg HA/cm3 (AUC 0.840, 95% CI 0.609 to 0.963, p < 0.001). In conclusion, HR-pQCT had significant correlation with iliac crest bone in BV/TV and Ct.Th, which are known to provide bone strength. This method is quick and non-invasive and may be helpful in categorizing those with high versus low turnover in hemodialysis patients.

Osteosarcopenia and trabecular bone score in patients with type 2 diabetes mellitus

ABSTRACT Objective: To evaluate the prevalence of osteosarcopenia and the association of osteosarcopenia with trabecular bone score (TBS) in a group of patients with type 2 diabetes mellitus(T2DMG) compared with a paired control group (CG). Materials and methods: Cross-sectional study with men and women ≥ 50 years recruited by convenience. Patients in both groups answered questionnaires and underwent evaluation of bone mineral density (BMD), handgrip strength (HGS), and TBS. The T2DMG also underwent a gait speed (GS) test. Sarcopenia was defined as low lean mass plus low HGS or GS according to the Foundation for the National Institute of Health Sarcopenia Project, and osteosarcopenia was deemed present when sarcopenia was associated with osteopenia, osteoporosis, or low-energy trauma fractures. Results: The T2DMG (n = 177) and CG (n = 146) had, respectively, mean ages of 65.1 ± 8.2 years and 68.8 ± 11.0 years and 114 (64.4%) and 80 (54.7%) women. T2DMG versus the CG had higher rates of osteosarcopenia (11.9% versus 2.14%, respectively, p = 0.010), sarcopenia (12.9% versus 5.4%, respectively, p < 0.030), and fractures (29.9% versus 18.5%, respectively, p = 0.019), and lower HGS values (24.4 ± 10.3 kg versus 30.9 ± 9.15 kg, respectively, p < 0.001), but comparable BMD values. Mean TBS values were 1.272 ± 0.11 and 1.320 ± 0.12, respectively (p = 0.001). On multivariate analysis, age, greater waist circumference, fractures, and osteoporosis increased the risk of degraded TBS. Osteosarcopenia was associated with diabetes complications (p = 0.03), calcium and vitamin D supplementation (p = 0.01), and all components of osteosarcopenia diagnosis (p < 0.05). Conclusion: Compared with the CG, the T2DMG had a higher prevalence of osteosarcopenia, sarcopenia, and fractures and lower bone quality assessed by TBS.

Upregulation of RNA cap methyltransferase RNMT drives ribosome biogenesis during T cell activation.

The m7G cap is ubiquitous on RNAPII-transcribed RNA and has fundamental roles in eukaryotic gene expression, however its in vivo role in mammals has remained unknown. Here, we identified the m7G cap methyltransferase, RNMT, as a key mediator of T cell activation, which specifically regulates ribosome production. During T cell activation, induction of mRNA expression and ribosome biogenesis drives metabolic reprogramming, rapid proliferation and differentiation generating effector populations. We report that RNMT is induced by T cell receptor (TCR) stimulation and co-ordinates the mRNA, snoRNA and rRNA production required for ribosome biogenesis. Using transcriptomic and proteomic analyses, we demonstrate that RNMT selectively regulates the expression of terminal polypyrimidine tract (TOP) mRNAs, targets of the m7G-cap binding protein LARP1. The expression of LARP1 targets and snoRNAs involved in ribosome biogenesis is selectively compromised in Rnmt cKO CD4 T cells resulting in decreased ribosome synthesis, reduced translation rates and proliferation failure. By enhancing ribosome abundance, upregulation of RNMT co-ordinates mRNA capping and processing with increased translational capacity during T cell activation.

Bone Marrow Adiposity in Premenopausal Women With Type 2 Diabetes With Observations on Peri-Trabecular Adipocytes.

CONTEXT: No study has yet evaluated the relationships among bone marrow adiposity (BMA), bone histomorphometry (BH), and glycemic control in premenopausal women with type 2 diabetes (T2DM). OBJECTIVE: We aimed to assess the effect of glycemic control on BMA, correlate the parameters of BH with BMA, and correlate BMA with the use of hypoglycemic agents and with bone mineral density (BMD). METHODS: This was a cross-sectional study that evaluated 26 premenopausal women with T2DM who were divided into groups with HbA1c < 7% (good control [GC], n = 10) and HbA1c > 7% (poor control [PC], n = 16). BMA parameters (adipocyte number [Ad.N], total adipocyte perimeter [Ad.Pm], total adipocyte area [Ad.Ar], percentage adipocyte volume per marrow volume [Ad.V/Ma.V]) and peri-trabecular adipocyte number divided by bone surface (Ad.N/BS) were evaluated. BH static (bone volume fraction [BV/TV], osteoid thickness [O.Th], osteoid surface/bone surface [OS/BS]) and dynamic parameters and serum insulin-like growth factor-1 were measured. BMA data were compared between the GC and PC groups. Correlations were performed. RESULTS: Ad.N, Ad.Pm, and Ad.Ar were higher in PC (all, P = 0.04). HbA1c correlated positively with Ad.N/BS (P < 0.01) and Ad.N/BS correlated negatively with O.Th (P < 0.01) and OS/BS (P = 0.02). Positive and negative correlations were observed between insulin and metformin use, respectively, with all adipocyte parameters except Ad.N/BS (P < 0.05). Structural parameters were negatively correlated with the BMA. BMD of the femoral neck (r = -549, P < 0.01) and total femur (r = -0.502, P < 0.01) were negatively correlated with Ad.V/Ma.V. CONCLUSION: Poor glycemic control is associated with hyperplasia and hypertrophy of BMAs and with lower BV/TV. Ad.N/BS, a new BMA parameter, is correlated with HbA1c and negatively with O.Th. The use of insulin seems to stimulate the expansion of BMA while that of metformin has the opposite effect. These findings suggest that the increase in BMA may play a role in the T2DM bone disease; on the other hand, good glycemic control might help prevent it.

Association between fractures and traditional risk factors for osteoporosis and low bone mineral density in patients with obesity

ABSTRACT Objective: To evaluate the reasons for request of bone mineral density (BMD) evaluation and correlate the BMD results with previous fractures, risk factors for osteoporosis, and clinical characteristics in patients with obesity. Subjects and methods: Cross-sectional, retrospective, single-site study including adult patients with body mass index (BMI) ≥ 30 kg/m2 and BMD evaluation between January 2015 and May 2016 selected from a BMD database. Data on demographic characteristics, lifestyle habits, comorbidities, medications, risk factors, previous fractures, and indications for BMD evaluation were collected from the participants' medical records. Results: The study included 619 patients (89.9% women, mean BMI 34.79 ± 4.05 kg/m2). In all, 382 (61.7%), 166 (26.8%), and 71 (11.5%) patients had class 1, 2, and 3 obesity, respectively. The most frequent (29.9%) reason for BMD evaluation was for osteoporosis monitoring. In all, 69.4% of the patients had low BMD. Multivariate analysis showed that age, calcium supplementation, and previous osteoporosis or osteopenia were associated with low BMD, while age, vitamin D supplementation, use of proton pump inhibitors (PPIs), and low BMD were associated with previous fractures (p < 0.05 for all). Conclusions: Among patients with obesity identified from a tertiary hospital database, those with low bone mass and risk factors traditionally associated with fractures had an increased history of fractures. Patients with greater BMI had better bone mass and fewer fractures. These findings indicate that the association between reduced weight, risk factors for osteoporosis, and fractures remained despite the presence of obesity in our population.

Pterostilbene influences glycemia and lipidemia and enhances antioxidant status in the liver of rats that consumed sucrose solution.

AIMS: The present study investigated the potential effects of pterostilbene (PT) on glycemic and lipid profiles, fat storage, cardiovascular indices, and hepatic parameters of rats fed with sucrose solution. MAIN METHODS: 24 male Wistar rats received either drinking water or a 40% sucrose solution over a period of 140 days. After this period, animals were randomly allocated into four groups (n = 6): Control (C), C + Pterostilbene (PT), Sucrose (S), and S + PT. Pterostilbene (40 mg/kg) was given orally for 45 consecutive days. KEY FINDINGS: Pterostilbene did not influence morphometric and nutritional parameters. The insulin sensitivity index TyG was elevated in the C + PT group (p < 0.01) and reduced in S + PT group (p < 0.05). Basal glucose levels were lower in the S + PT group (p < 0.05), and the glycemic response was improved with PT treatment in glucose provocative tests. Conversely, rats from the C + PT group showed impaired glucose disposal during those tests. Lipid profile was partially improved by PT treatment. Hepatic oxidative stress in the S group was improved after PT treatment. In the C group, PT reduced SOD activity, glutathione levels, and increased catalase activity. Collagen content was reduced by PT treatment. SIGNIFICANCE: PT effects depends on the type of diet the animals were submitted. In rats fed with sucrose-solution, PT confirmed its positive effects, improving glucose and lipid profile, and acting as a potent antioxidant. The effects of PT on rats that consumed a normal diet were very discrete or even undesirable. We suggest caution with indiscriminate consume of natural compounds by healthy subjects.

Plinia cauliflora (Mart.) Kausel: toxicological assays, biological activities, and elemental analysis of organic compounds.

Jaboticaba, Plinia cauliflora (Mart.) Kausel, is a Brazilian berry traditionally used in folk medicine as treatment for some health conditions. Phenolic compounds such as flavonoids and anthocyanins have previously been detected in the fruit. This current study aimed to evaluate the toxicological effects of jaboticaba peel extract (JPE) on Artemia salina, L929, and MDA-MB-231 cell lines. Besides, JPE antioxidant, acetylcholinesterase, and antifungal activities, and elemental analysis CHNS were also tested. JPE had moderate toxicity (LD50 = 360.92 µg mL-1) on A. salina, non-toxic effect on L929 cell line, and decreased the viability of cancer cell line MDA at 1,000 µg mL-1 and 500 µg mL-1 concentrations. The antioxidant activity toward 2,2-diphenyl-1-picrylhydrazyl (DPPH) performed IC50 = 37.45 ± 0.17 µg mL-1, whereas 45.7% of acetylcholinesterase activity was inhibited. By its elemental composition, JPE is an alternative food supplement and dermocosmetic component. Antifungal potential toward Candida strains was not observed.

Prevention and treatment of oral adverse effects of antiresorptive medications for osteoporosis - A position paper of the Brazilian Society of Endocrinology and Metabolism (SBEM), Brazilian Society of Stomatology and Oral Pathology (Sobep), and Brazilian Association for Bone Evaluation and Osteometabolism (Abrasso)

ABSTRACT Antiresorptive therapy is the main form of prevention of osteoporotic or fragility fractures. Medication-related osteonecrosis of the jaw (MRONJ) is a relatively rare but severe adverse reaction to antiresorptive and antiangiogenic drugs. Physicians and dentists caring for patients taking these drugs and requiring invasive procedures face a difficult decision because of the potential risk of MRONJ. The aim of this study was to discuss the risk factors for the development of MRONJ and prevention of this complication in patients with osteoporosis taking antiresorptive drugs and requiring invasive dental treatment. For this goal, a task force with representatives from three professional associations was appointed to review the pertinent literature and discuss systemic and local risk factors, prevention of MRONJ in patients with osteoporosis, and management of established MRONJ. Although scarce evidence links the use of antiresorptive agents in the context of osteoporosis to the development of MRONJ, these agents are considered a risk factor for this complication. Despite the rare reports of MRONJ in patients with osteoporosis, the severity of symptoms and impact of MRONJ in the patients' quality of life make it imperative for health care professionals to consider this complication when planning invasive dental procedures.

Reference values of 25-hydroxyvitamin D revisited: a position statement from the Brazilian Society of Endocrinology and Metabolism (SBEM) and the Brazilian Society of Clinical Pathology/Laboratory Medicine (SBPC).

Hypovitaminosis D is a common condition with a negative impact on health. This statement, prepared by experts from the Brazilian Society of Endocrinology and Metabolism and the Brazilian Society of Clinical Pathology/Laboratory Medicine, includes methodological aspects and limitations of the measurement of 25-hydroxyvitamin D [25(OH)D] for identification of vitamin D status, and identifies individuals at increased risk for deficiency of this vitamin in whom 25(OH)D measurement is recommended. For the general population, 25(OH)D levels between 20 and 60 ng/mL are considered normal, while individuals with levels below 20 ng/mL are considered to be vitamin D deficient. This statement identifies potential benefits of maintaining 25(OH)D levels > 30 ng/mL in specific conditions, including patients aged > 65 years or pregnant, those with recurrent falls, fragility fractures, osteoporosis, secondary hyperparathyroidism, chronic kidney disease, or cancer, and individuals using drugs with the potential to affect the vitamin D metabolism. This statement also calls attention to the risk of vitamin D intoxication, a life-threatening condition that occurs at 25(OH)D levels above 100 ng/mL.

Reference values of 25-hydroxyvitamin D revisited: a position statement from the Brazilian Society of Endocrinology and Metabolism (SBEM) and the Brazilian Society of Clinical Pathology/Laboratory Medicine (SBPC)

ABSTRACT Hypovitaminosis D is a common condition with a negative impact on health. This statement, prepared by experts from the Brazilian Society of Endocrinology and Metabolism and the Brazilian Society of Clinical Pathology/Laboratory Medicine, includes methodological aspects and limitations of the measurement of 25-hydroxyvitamin D [25(OH)D] for identification of vitamin D status, and identifies individuals at increased risk for deficiency of this vitamin in whom 25(OH)D measurement is recommended. For the general population, 25(OH)D levels between 20 and 60 ng/mL are considered normal, while individuals with levels below 20 ng/mL are considered to be vitamin D deficient. This statement identifies potential benefits of maintaining 25(OH)D levels > 30 ng/mL in specific conditions, including patients aged > 65 years or pregnant, those with recurrent falls, fragility fractures, osteoporosis, secondary hyperparathyroidism, chronic kidney disease, or cancer, and individuals using drugs with the potential to affect the vitamin D metabolism. This statement also calls attention to the risk of vitamin D intoxication, a life-threatening condition that occurs at 25(OH)D levels above 100 ng/mL