Echocardiographic Alterations of Cardiac Geometry and Function in Patients with Familial Partial Lipodystrophy. / Alterações Ecocardiográficas da Geometria e da Função Cardíaca em Pacientes com Lipodistrofia Familiar Parcial.

BACKGROUND: Cardiomyopathy associated with partial lipodystrophy (PL) has not been well described yet. OBJECTIVE: To characterize cardiac morphology and function in PL. METHODS: Patients with familial PL and controls were prospectively assessed by transthoracic echocardiography and with speckle-tracking echocardiography (global longitudinal strain, GLS). The relationship between echocardiographic variables and PL diagnosis was tested with regression models, considering the effect of systolic blood pressure (SBP). Significance level of 5% was adopted. RESULTS: Twenty-nine patients with PL were compared to 17 controls. They did not differ in age (p=0.94), gender or body mass index (p= 0.05). Patients with PL had statistically higher SBP (p=0.02) than controls. Also, PL patients had higher left atrial dimension (37.3 ± 4.4 vs. 32.1 ± 4.3 mm, p= 0.001) and left atrial (30.2 ± 7.2 vs. 24.9 ± 9.0 mL/m2,p=0.02), left ventricular (LV) mass (79.3 ± 17.4 vs. 67.1 ± 19.4, p=0.02), and reduced diastolic LV parameters (E' lateral, p= 0.001) (E' septal, p= 0.001), (E/E' ratio, p= 0.02). LV ejection fraction (64.7 ± 4.6 vs. 62.2 ± 4.4 %, p= 0.08) and GLS were not statistically different between groups (-17.1 ± 2.7 vs. -18.0 ± 2.0 %, p= 0.25). There was a positive relationship of left atrium (ß 5.6, p<0.001), posterior wall thickness, (ß 1.3, p=0.011), E' lateral (ß -3.5, p=0.002) and E' septal (ß -3.2, p<0.001) with PL diagnosis, even after adjusted for SBP. CONCLUSION: LP patients have LV hypertrophy, left atrial enlargement, and LV diastolic dysfunction although preserved LVEF and GLS. Echocardiographic parameters are related to PL diagnosis independent of SBP.

FUNDAMENTO: A cardiomiopatia associada à lipodistrofia parcial (LP) ainda não foi bem descrita. OBJETIVO: Caracterizar a morfologia e a função cardíaca na LP. MÉTODOS: Pacientes com LP e controles foram avaliados prospectivamente por ecocardiografia transtorácica e ecocardiografia por speckle-tracking (Strain Longitudinal Global, SLG). A relação entre as variáveis ecocardiográficas e o diagnóstico de LP foi testada com modelos de regressão, considerando o efeito da pressão arterial sistólica (PAS). Adotou-se um nível de significância de 5%. RESULTADOS: Vinte e nove pacientes com LP foram comparados com 17 controles. Eles não se diferiram quanto à idade (p=0,94), sexo ou índice de massa corporal (p= 0,05). Os pacientes com LP apresentaram PAS estatisticamente mais alta (p=0,02) em comparação aos controles. Ainda, os pacientes com LP apresentaram maior dimensão do átrio (37,3 ± 4,4 vs. 32,1 ± 4,3 mm, p= 0,001) e maior volume atrial (30,2 ± 7,2 vs. 24,9 ± 9,0 mL/m2, p=0,02), massa do Ventrículo Esquerdo (VE) (79,3 ± 17,4 vs. 67,1 ± 19,4; p=0,02), e parâmetros sistólicos reduzidos do VE (E' lateral, p= 0,001) (E' septal, p= 0,001), (razão E/E', p= 0,02). A fração de ejeção do VE (64,7 ± 4,6 vs. 62,2 ± 4,4 %, p = 0,08) e o SLG não foram estatisticamente diferentes entre os grupos (-17,1±2,7 vs-18.0 ± 2,0%, p= 0,25). Observou-se uma reação positiva do átrio esquerdo (ß 5,6; p<0,001), espessura da parede posterior (ß 1,3; p=0,011), E' lateral (ß -3,5; p=0,002) e E' septal (ß -3,2; p<0,001) com o diagnóstico de LP, mesmo após o ajuste para a PAS. CONCLUSÃO: Os pacientes com LP apresentam hipertrofia do VE, aumento do átrio esquerdo, e disfunção diastólica do VE apesar de fração de ejeção do VE e SLG preservados. Os parâmetros ecocardiográficos estão relacionados com o diagnóstico de LP, independentemente da PAS.

Comprehensive analysis of morbidity and mortality patterns in familial partial lipodystrophy patients: insights from a population study.

Background: There is a lack of information on the clinical and molecular presentation of familial partial lipodystrophy (FPLD), a rare genetic disorder characterized by partial subcutaneous fat loss. Objective: This study aimed to provide a comprehensive assessment of the clinical, metabolic, and genetic features of FPLD in the Brazilian population. Methods: In a multicenter cross-sectional investigation we evaluated patients with FPLD across five Brazilian reference centers for lipodystrophies. Diagnosis of FPLD was made by clinical evaluation and genetic confirmation. Data on genetic, clinical, and metabolic characteristics were captured. Statistical analysis involved the utilization of the Kruskal-Wallis test to identify differences. Results: The study included 106 patients with genetic confirmation of FPLD. The mean age was 44 ± 15 years, and they were predominantly female (78.3%). LMNA pathogenic variants were identified in 85.8% of patients, PPARG in 10.4%, PLIN1 in 2.8%, and MFN2 in 0.9%. Diabetes mellitus (DM) was highly prevalent (57.5%), affecting 54 females (50.9%). Median triglycerides levels were 199 mg/dL (54-2724 mg/dL), severe hypertriglyceridemia (≥ 500 mg/dL) was found in 34.9% and pancreatitis in 8.5%. Metabolic-associated fatty liver disease (MAFLD) was observed in 56.6%, and cardiovascular disease in 10.4%. The overall mortality rate was 3.8%, due to cardiovascular events. Conclusion: This study presents an extensive cohort of Brazilian patients with FPLD, predominantly DM with several multisystem complications. A comprehensive characterization of lipodystrophy syndromes is crucial for effective patient management and care.

Latin-American consensus on the transition into adult life of patients with X-linked hypophosphatemia.

INTRODUCTION: X-linked hypophosphatemia is an orphan disease of genetic origin and multisystem involvement. It is characterized by a mutation of the PHEX gene which results in excess FGF23 production, with abnormal renal and intestinal phosphorus metabolism, hypophosphatemia and osteomalacia secondary to chronic renal excretion of phosphate. Clinical manifestations include hypophosphatemic rickets leading to growth abnormalities and osteomalacia, myopathy, bone pain and dental abscesses. The transition of these patients to adult life continues to pose challenges to health systems, medical practitioners, patients and families. For this reason, the aim of this consensus is to provide a set of recommendations to facilitate this process and ensure adequate management and follow-up, as well as the quality of life for patients with X-linked hypophosphatemia as they transition to adult life. MATERIALS AND METHODS: Eight Latin American experts on the subject participated in the consensus and two of them were appointed as coordinators. The consensus work was done in accordance with the nominal group technique in 6 phases: (1) question standardization, (2) definition of the maximum number of choices, (3) production of individual solutions or answers, (4) individual question review, (5) analysis and synthesis of the information and (6) synchronic meetings for clarification and voting. An agreement was determined to exist with 80% votes in favor in three voting cycles. RESULTS AND DISCUSSION: Transition to adult life in patients with hypophosphatemia is a complex process that requires a comprehensive approach, taking into consideration medical interventions and associated care, but also the psychosocial components of adult life and the participation of multiple stakeholders to ensure a successful process. The consensus proposes a total of 33 recommendations based on the evidence and the knowledge and experience of the experts. The goal of the recommendations is to optimize the management of these patients during their transition to adulthood, bearing in mind the need for multidisciplinary management, as well as the most relevant medical and psychosocial factors in the region.

Refining Evaluation of Bone Mass and Adipose Distribution in Dunnigan Syndrome.

Familial partial lipodystrophies (FPLD) are rare diseases characterized by selective loss of subcutaneous adipose tissue at different sites. This cross-sectional observational study aimed to estimate adipose tissue in the bone marrow (BMAT), intra (IMCL) and extra-myocyte lipids (EMCL), and define the bone phenotype in the context of FPLD2/Dunnigan syndrome (DS). The subjects comprised 23 controls (C) and 18 DS patients, matched by age, weight and height. Blood samples, dual-energy X-ray absorptiometry for bone mineral density (BMD) and trabecular bone score (TBS) and 1H-spectroscopy using magnetic resonance to estimate BMAT in the lumbar spine, IMCL, EMCL and osteoclastogenesis were assessed. The prevalence of diabetes mellitus was 78% in DS patients. Glucose, HbA1c, triglycerides, insulin and HOMA-IR levels were elevated in DS, whereas HDLc, 25(OH)D, PTH and osteocalcin levels were reduced. BMD was similar between groups at all sites, except 1/3 radius, which was lower in DS group. TBS was reduced in DS. DS presented increased osteoclastogenesis and elevated BMAT, with greater saturation levels and higher IMCL than the C group. HOMA-IR and EMCL were negatively associated with TBS; osteocalcin and EMCL were correlated negatively with BMD. This study contributes to refining the estimation of adipose tissue in DS by showing increased adiposity in the lumbar spine and muscle tissue. DXA detected lower TBS and BMD in the 1/3 radius, suggesting impairment in bone quality and that bone mass is mainly affected in the cortical bone.

Vitamin D deficiency contributes to the diabetic kidney disease progression via increase ZEB1/ZEB2 expressions.

BACKGROUND: Diabetic kidney disease (DKD) remains one of the main causes of end-stage renal disease (ESRD) and mortality in diabetic patients worldwide. Vitamin D deficiency (VitDD) is one of the main consequences of different chronic kidney disease (CKD) types and is associated with rapid progression to ESRD. Nevertheless, the mechanisms that lead to this process are poorly understood. This study aimed to characterize a model of diabetic nephropathy progression in VitDD and the epithelial-mesenchymal-transition (EMT) role in these processes. METHODS: Wistar Hannover rats received a diet with or without VitD before type 1 diabetes (T1D) induction. After this procedure, the rats were accompanied for 12 and 24 weeks after T1D induction and the renal function, structure, cell transdifferentiating markers and zinc finger e-box binding homeobox 1/2 (ZEB1/ZEB2) contribution to kidney damage were evaluated during the DKD progression. RESULTS: The results showed an increase in glomerular tuft, mesangial and interstitial relative areas and renal function impairment in VitD-deficient diabetic rats compared to diabetic rats that received a VitD-containing diet. These alterations can be associated with increased expression of EMT markers, ZEB1 gene expression, ZEB2 protein expression and TGF-ß1 urinary excretion. Decreased miR-200b expression, an important post-transcriptional regulator of ZEB1 and ZEB2 was also observed. CONCLUSION: Our data demonstrated that VitD deficiency contributes to the rapid development and progression of DKD in diabetic rats induced by increase ZEB1/ZEB2 expressions and miR-200b downregulation.

Association between vertebral fragility fractures, muscle strength and physical performance: A cross-sectional study.

BACKGROUND: Few studies have investigated the association between vertebral fragility fractures and lower limb muscle strength and physical performance in women with low bone mass. OBJECTIVES: To explore whether the presence of vertebral fracture is independently associated with poor physical performance and decreased lower limb muscle strength. To understand whether lower limb muscle strength is associated with physical performance in women with vertebral fracture. METHODS: Older women with low bone mass were divided into 2 groups: no vertebral fracture (NF) and presence of vertebral fragility fracture (VFF). Physical performance was evaluated using the Five Times Sit to Stand (5TSS) test, the Timed Up and Go (TUG) test and a 5m walk test (5MWT). Lower limb muscle strength was assessed using an isokinetic dynamometer. RESULTS: We included 94 women with low bone mass (mean age 71.6 [SD 5.7] years, time since menopause 24.4 [7.1] years, mean BMI 27.5 [5.1] kgm-2). VFF was only associated with low peak hip abductor torque (p = 0.001) after adjustments. In the VFF group (n= 47), each 1 Nmkg-1 increase: in knee extensor torque was associated with improved 5MWT (p = 0.005), TUG (p = 0.002) and 5TSS (p = 0.005) performances; in knee flexor torque was associated with improved 5MWT speed (p = 0.003) and TUG time (p = 0.006); in hip abductor torque was associated with improved 5MWT speed (p = 0.003); and in hip extensor torque with improved TUG time (p = 0.046). CONCLUSION: VFF was associated with reduced hip abductor strength in older women. However, the number of vertebral fractures influenced the association. Additionally, lower limb muscle strength was associated with physical performance, regardless of the clinical characteristics of the fractures. Therefore, strength and power training programs for the lower limbs could improve physical performance.

Contribution of Hip Abductors Muscles on Bone Mineral Density and Functionality in Older Women.

BACKGROUND: Despite the well-established role of muscle in maintaining bone mass and physical performance, there are still few studies that assess the relationship between muscle groups and specific bone sites and its contribution to physical function in older people. The aim of the study is to verify the association between hip and knee's muscle strength and bone mineral density of the femoral neck (BMD-FN) and investigated which muscle strength that are related with BMD-FN is associated with physical function in older women. METHODOLOGY: This is a cross-sectional study of 94 women over the age of 60 years, physically independent. Muscle strength of the hip and knee was evaluated using an isokinetic dynamometer (Biodex, USA) to obtain peak torque (PT). The BMD-FN was obtained using dual-energy x-ray absorption densitometry (DXA). Physical function was evaluated by the Timed Up and Go (TUG), gait speed (GS), five times stand to sit (5TSS) and single-leg stance (SS). To verify the association between muscle strength (independent variable) and the BMD-FN (dependent variable) and the relationship between muscle strength (independent variable) and clinical tests (dependent variable), the multiple linear regression was carried out, adjusted for age, time of menopause, height and level of physical activity. All of the analyses were carried out by the SPSS 17.0 software, with a level of p < 0.05 significance. RESULTS: We found an association between the hip abductors PT and the BMD-FN and between hip abductors PT and all clinical tests. CONCLUSION: We observe that hip abductor muscle strength contributes to BMD-FN and to performance in several clinical tests in older women. These findings reinforce the importance of this musculature not only for improving balance and gait, but also it can be a strategy to maintain/improve bone mass in the femoral neck in this population.

Paricalcitol Improves the Angiopoietin/Tie-2 and VEGF/VEGFR2 Signaling Pathways in Adriamycin-Induced Nephropathy.

Renal endothelial cell (EC) injury and microvascular dysfunction contribute to chronic kidney disease (CKD). In recent years, increasing evidence has suggested that EC undergoes an endothelial-to-mesenchymal transition (EndoMT), which might promote fibrosis. Adriamycin (ADR) induces glomerular endothelial dysfunction, which leads to progressive proteinuria in rodents. The activation of the vitamin D receptor (VDR) plays a crucial role in endothelial function modulation, cell differentiation, and suppression of the expression of fibrotic markers by regulating the production of nitric oxide (NO) by activating the endothelial NO synthase (eNOS) in the kidneys. This study aimed to evaluate the effect of paricalcitol treatment on renal endothelial toxicity in a model of CKD induced by ADR in rats and explore mechanisms involved in EC maintenance by eNOS/NO, angiopoietins (Angs)/endothelium cell-specific receptor tyrosine kinase (Tie-2, also known as TEK) and vascular endothelial growth factor (VEGF)-VEGF receptor 2 (VEGFR2) axis. The results show that paricalcitol attenuated the renal damage ADR-induced with antiproteinuric effects, glomerular and tubular structure, and function protection. Furthermore, activation of the VDR promoted the maintenance of the function and structure of glomerular, cortical, and external medullary endothelial cells by regulating NO production. In addition, it suppressed the expression of the mesenchymal markers in renal tissue through attenuation of (transforming growth factor-beta) TGF-ß1/Smad2/3-dependent and downregulated of Ang-2/Tie-2 axis. It regulated the VEGF/VEGFR2 pathway, which was ADR-deregulated. These effects were associated with lower AT1 expression and VDR recovery to renal tissue after paricalcitol treatment. Our results showed a protective role of paricalcitol in the renal microvasculature that could be used as a target for treating the beginning of CKD.

Calcitriol Reduces the Inflammation, Endothelial Damage and Oxidative Stress in AKI Caused by Cisplatin.

Cisplatin treatment is one of the most commonly used treatments for patients with cancer. However, thirty percent of patients treated with cisplatin develop acute kidney injury (AKI). Several studies have demonstrated the effect of bioactive vitamin D or calcitriol on the inflammatory process and endothelial injury, essential events that contribute to changes in renal function and structure caused by cisplatin (CP). This study explored the effects of calcitriol administration on proximal tubular injury, oxidative stress, inflammation and vascular injury observed in CP-induced AKI. Male Wistar Hannover rats were pretreated with calcitriol (6 ng/day) or vehicle (0.9% NaCl). The treatment started two weeks before i.p. administration of CP or saline and was maintained for another five days after the injections. On the fifth day after the injections, urine, plasma and renal tissue samples were collected to evaluate renal function and structure. The animals of the CP group had increased plasma levels of creatinine and of fractional sodium excretion and decreased glomerular filtration rates. These changes were associated with intense tubular injury, endothelial damage, reductions in antioxidant enzymes and an inflammatory process observed in the renal outer medulla of the animals from this group. These changes were attenuated by treatment with calcitriol, which reduced the inflammation and increased the expression of vascular regeneration markers and antioxidant enzymes.

Transtornos de ansiedade: histórico, aspectos clínicos e classificações atuais / Anxiety disorders: history, clinical features, and current classifications

Objetivos: contribuir para a compreensão do desenvolvimento histórico do conceito de ansiedade, das classificações dos transtornos ansiosos e suas manifestações clínicas, bem como para a atualização sobre o processo de avaliação diagnóstica. Métodos: todas as edições das classificações da Organização Mundial de Saúde (OMS) - CID e da Associação Psiquiátrica Americana (APA) - DSM foram examinadas, além de livros-texto de referência de psiquiatria clínica, de publicações sobre a história e a evolução desses diagnósticos e de publicações produzidas pelas equipes responsáveis pela revisão das classificações atuais. Resultados: entende-se por ansiedade um estado afetivo normal, como um sintoma ou um termo para nomear um grupo de transtornos mentais. Nas primeiras e subsequentes edições das classificações da OMS e da APA, entre 1948 e 1975, os quadros ansiosos faziam parte do grupo das psiconeurose/neuroses. A partir do DSM-III (1980), o grupo das neuroses foi fragmentado em diversos outros, entre os quais os transtornos de ansiedade, o que foi seguido pela CID-10 (1992), apesar de alguma distinção na composição dos subtipos. Para as últimas versões, houve um empenho de compatibilização entre as duas, contudo restaram diferenças: o DSM-5 (2013) adota critérios diagnósticos; a CID-11 (2019) utiliza descrições clínicas e diretrizes diagnósticas, além de abordagens dimensionais para alguns transtornos. Conclusão: ocorreram modificações nas classificações psiquiátricas atuais, no grupo dos transtornos de ansiedade, que precisam ser disseminadas e agregadas a estratégias de formação e qualificação profissionais, incrementando habilidades diagnósticas e permitindo uma comunicação mais uniforme e precisa na prática clínica.

Objectives: to contribute to the understanding of the historical development of the concept of anxiety, the classifications of anxiety disorders and their clinical manifestations, as well as to update on the diagnostic evaluation process. Methods: all editions of the classifications of the World Health Organization (WHO) - ICD and the American Psychiatric Association (APA) - DSM were examined, in addition to reference textbooks on clinical psychiatry, publications on the history and evolution of these diagnoses, and scientific articles produced by the teams responsible for reviewing the current classifications. Results: anxiety is understood as a normal affective state, as a symptom, or as a term to name a group of mental disorders. In the first and subsequent editions of the WHO and APA classifications, between 1948 and 1975, anxiety disorders were part of the psychoneuroses/neuroses group. As of DSM-III (1980) onwards, the neuroses group was fragmented into several others, including anxiety disorders, which was followed by ICD-10 (1992), despite some different choices of subtypes. For the latest versions, there was a compatibility effort between them. However, differences remained: DSM-5 (2013) adopts diagnostic criteria; ICD-11 (2019) uses clinical description and diagnostic guidelines, in addition to dimensional approaches for some disorders. Conclusion: modifications have occurred in current psychiatric classifications, in the group of anxiety disorders, which need to be disseminated and added to professional training and qualification strategies, increasing diagnostic skills and providing for more uniform and accurate communication in clinical practice.

Bone, fat, and muscle interactions in health and disease.

Energy metabolism is a point of integration among the various organs and tissues of the human body, not only in terms of consumption of energy substrates but also because it concentrates a wide interconnected network controlled by endocrine factors. Thus, not only do tissues consume substrates, but they also participate in modulating energy metabolism. Soft mesenchymal tissues, in particular, play a key role in this process. The recognition that high energy consumption is involved in bone remodeling has been accompanied by evidence showing that osteoblasts and osteocytes produce factors that influence, for example, insulin sensitivity and appetite. Additionally, there are significant interactions between muscle, adipose, and bone tissues to control mutual tissue trophism. Not by chance, trophic and functional changes in these tissues go hand in hand from the beginning of an individual's development until aging. Likewise, metabolic and nutritional diseases deeply affect the musculoskeletal system and adipose tissue. The present narrative review highlights the importance of the interaction of the mesenchymal tissues for bone development and maintenance and the impact on bone from diseases marked by functional and trophic disorders of adipose and muscle tissues.

Diabetes and bone.

Globally, one in 11 adults has diabetes mellitus of which 90% have type 2 diabetes. The numbers for osteoporosis are no less staggering: 1 in 3 women has a fracture after menopause, and the same is true for 1 in 5 men after the age of 50 years. Aging is associated with several physiological changes that cause insulin resistance and impaired insulin secretion, which in turn lead to hyperglycemia. The negative balance between bone resorption and formation is a natural process that appears after the fourth decade of life and lasts for the following decades, eroding the bone structure and increasing the risk of fractures. Not incidentally, it has been acknowledged that diabetes mellitus, regardless of whether type 1 or 2, is associated with an increased risk of fracture. The nuances that differentiate bone damage in the two main forms of diabetes are part of the intrinsic heterogeneity of diabetes, which is enhanced when associated with a condition as complex as osteoporosis. This narrative review addresses the main parameters related to the increased risk of fractures in individuals with diabetes, and the mutual factors affecting the treatment of diabetes mellitus and osteoporosis.

Definition and management of very high fracture risk in women with postmenopausal osteoporosis: a position statement from the Brazilian Society of Endocrinology and Metabolism (SBEM) and the Brazilian Association of Bone Assessment and Metabolism (ABRASSO).

Several drugs are available for the treatment of osteoporosis in postmenopausal women. Over the last decades, most patients requiring pharmacological intervention were offered antiresorptive drugs as first-line therapy, while anabolic agents were considered a last resource for those with therapeutic failure. However, recent randomized trials in patients with severe osteoporosis have shown that anabolic agents reduce fractures to a greater extent than antiresorptive medications. Additionally, evidence indicates that increases in bone mineral density (BMD) are maximized when patients are treated with anabolic agents first, followed by antiresorptive therapy. This evidence is key, considering that greater increases in BMD during osteoporosis treatment are associated with a more pronounced reduction in fracture risk. Thus, international guidelines have recently proposed an individualized approach to osteoporosis treatment based on fracture risk stratification, in which the stratification risk has been refined to include a category of patients at very high risk of fracture who should be managed with anabolic agents as first-line therapy. In this document, the Brazilian Society of Endocrinology and Metabolism and the Brazilian Association of Bone Assessment and Metabolism propose the definition of very high risk of osteoporotic fracture in postmenopausal women, for whom anabolic agents should be considered as first-line therapy. This document also reviews the factors associated with increased fracture risk, trials comparing anabolic versus antiresorptive agents, efficacy of anabolic agents in patients who are treatment naïve versus those previously treated with antiresorptive agents, and safety of anabolic agents.

Bone, fat, and muscle interactions in health and disease

Abstract Energy metabolism is a point of integration among the various organs and tissues of the human body, not only in terms of consumption of energy substrates but also because it concentrates a wide interconnected network controlled by endocrine factors. Thus, not only do tissues consume substrates, but they also participate in modulating energy metabolism. Soft mesenchymal tissues, in particular, play a key role in this process. The recognition that high energy consumption is involved in bone remodeling has been accompanied by evidence showing that osteoblasts and osteocytes produce factors that influence, for example, insulin sensitivity and appetite. Additionally, there are significant interactions between muscle, adipose, and bone tissues to control mutual tissue trophism. Not by chance, trophic and functional changes in these tissues go hand in hand from the beginning of an individual's development until aging. Likewise, metabolic and nutritional diseases deeply affect the musculoskeletal system and adipose tissue. The present narrative review highlights the importance of the interaction of the mesenchymal tissues for bone development and maintenance and the impact on bone from diseases marked by functional and trophic disorders of adipose and muscle tissues. Arch Endocrinol Metab. 2022;66(5):611-20

Diabetes and bone

Abstract Globally, one in 11 adults has diabetes mellitus of which 90% have type 2 diabetes. The numbers for osteoporosis are no less staggering: 1 in 3 women has a fracture after menopause, and the same is true for 1 in 5 men after the age of 50 years. Aging is associated with several physiological changes that cause insulin resistance and impaired insulin secretion, which in turn lead to hyperglycemia. The negative balance between bone resorption and formation is a natural process that appears after the fourth decade of life and lasts for the following decades, eroding the bone structure and increasing the risk of fractures. Not incidentally, it has been acknowledged that diabetes mellitus, regardless of whether type 1 or 2, is associated with an increased risk of fracture. The nuances that differentiate bone damage in the two main forms of diabetes are part of the intrinsic heterogeneity of diabetes, which is enhanced when associated with a condition as complex as osteoporosis. This narrative review addresses the main parameters related to the increased risk of fractures in individuals with diabetes, and the mutual factors affecting the treatment of diabetes mellitus and osteoporosis. Arch Endocrinol Metab. 2022;66(5):633-41

Definition and management of very high fracture risk in women with postmenopausal osteoporosis: a position statement from the Brazilian Society of Endocrinology and Metabolism (SBEM) and the Brazilian Association of Bone Assessment and Metabolism (ABRASSO)

ABSTRACT Several drugs are available for the treatment of osteoporosis in postmenopausal women. Over the last decades, most patients requiring pharmacological intervention were offered antiresorptive drugs as first-line therapy, while anabolic agents were considered a last resource for those with therapeutic failure. However, recent randomized trials in patients with severe osteoporosis have shown that anabolic agents reduce fractures to a greater extent than antiresorptive medications. Additionally, evidence indicates that increases in bone mineral density (BMD) are maximized when patients are treated with anabolic agents first, followed by antiresorptive therapy. This evidence is key, considering that greater increases in BMD during osteoporosis treatment are associated with a more pronounced reduction in fracture risk. Thus, international guidelines have recently proposed an individualized approach to osteoporosis treatment based on fracture risk stratification, in which the stratification risk has been refined to include a category of patients at very high risk of fracture who should be managed with anabolic agents as first-line therapy. In this document, the Brazilian Society of Endocrinology and Metabolism and the Brazilian Association of Bone Assessment and Metabolism propose the definition of very high risk of osteoporotic fracture in postmenopausal women, for whom anabolic agents should be considered as first-line therapy. This document also reviews the factors associated with increased fracture risk, trials comparing anabolic versus antiresorptive agents, efficacy of anabolic agents in patients who are treatment naïve versus those previously treated with antiresorptive agents, and safety of anabolic agents.

Official position of the Brazilian Association of Bone Assessment and Metabolism (ABRASSO) on the evaluation of body composition by densitometry: part I (technical aspects)-general concepts, indications, acquisition, and analysis.

OBJECTIVE: To review the technical aspects of body composition assessment by dual-energy X-ray absorptiometry (DXA) and other methods based on the most recent scientific evidence. MATERIALS AND METHODS: This Official Position is a result of efforts by the Scientific Committee of the Brazilian Association of Bone Assessment and Metabolism (Associação Brasileira de Avaliação Óssea e Osteometabolismo, ABRASSO) and health care professionals with expertise in body composition assessment who were invited to contribute to the preparation of this document. The authors searched current databases for relevant publications. In this first part of the Official Position, the authors discuss the different methods and parameters used for body composition assessment, general principles of DXA, and aspects of the acquisition and analysis of DXA scans. CONCLUSION: Considering aspects of accuracy, precision, cost, duration, and ability to evaluate all three compartments, DXA is considered the gold-standard method for body composition assessment, particularly for the evaluation of fat mass. In order to ensure reliable, adequate, and reproducible DXA reports, great attention is required regarding quality control procedures, preparation, removal of external artifacts, imaging acquisition, and data analysis and interpretation.

Does sensorimotor training influence neuromuscular responses, balance, and quality of life in diabetics without a history of diabetic distal polyneuropathy?

OBJECTIVE: To evaluate the effect of supervised and home sensorimotor training on static postural balance (SPB), quality of life (QL), and neuromuscular responses of Type 2 Diabetics (DM-2). DESIGN: Randomized controlled blind study with DM-2 patients, between 45 and 64 years old, of both sexes, divided into 3 groups: Control Group - CG (n = 27), Home Training Group - HTG (n = 27), and Supervised Training Group - STG (n = 26). The subjects were evaluated before and at the end of 3 months of treatment, with a four-week follow-up. The intervention was held twice a week, for 45 min, divided into three phases: warm-up, sensorimotor training, and cool-down. The primary outcome was SPB, using the force platform. Secondary outcome: questionnaires and clinical measures related to diabetic foot and knee flexor-extensors using isokinetic dynamometry. RESULTS: In the baseline, the characteristics were similar between groups and between times. Tactile and vibratory sensitivity demonstrated the absence of symptoms of peripheral neuropathy in diabetic patients. In the intra-group comparison, there was a significant increase in the classification without symptoms of diabetic distal polyneuropathy in the HTG and STG groups (p < 0.05) and there were no significant effects on other clinical outcomes and QL and SPB, muscle strength, and sense of knee joint position. CONCLUSION: The intervention showed no improvement in SPB, QL, and other clinical outcomes of DM-2 patients. Thus, no differences were found between the groups, considering that the patients did not present clinical characteristics of diabetic distal polyneuropathy.

Repetitive stress fracture: a warning sign of genetic susceptibility to fracture? A case report of a heterozygous variant in SERPINF1

SUMMARY The occurrence of fractures in young individuals is frequently overlooked by physicians, especially when associated with exercise or trauma. Nevertheless, multiple fractures should always be investigated since underlying conditions can predispose to such events. We describe here the case of a young, healthy woman who sustained multiple fractures in the lower limbs, which were initially considered to be "stress fractures". Further investigation, including a panel of genes associated with osteogenesis imperfecta, revealed that the patient is a heterozygous carrier of a SERPINF1 variant. According to criteria recommended by the American College of Medical Genetics and Genomics and the Association for Molecular Pathology, this variant is classified as likely benign (PM2, PP3, PP4, BP1, and BP4). The patient's mother and brother were also asymptomatic carriers of the variant and had sustained previous minor fractures. The patient had normal biochemical profile and bone density. This condition has been rarely described and is not associated with low bone mineral density or altered bone turnover markers. This case highlights the importance of investigating multiple fractures in young patients who are otherwise healthy since these may be a warning sign of rare genetic conditions associated with fragility fractures.

Repetitive stress fracture: a warning sign of genetic susceptibility to fracture? A case report of a heterozygous variant in SERPINF1.

The occurrence of fractures in young individuals is frequently overlooked by physicians, especially when associated with exercise or trauma. Nevertheless, multiple fractures should always be investigated since underlying conditions can predispose to such events. We describe here the case of a young, healthy woman who sustained multiple fractures in the lower limbs, which were initially considered to be "stress fractures". Further investigation, including a panel of genes associated with osteogenesis imperfecta, revealed that the patient is a heterozygous carrier of a SERPINF1 variant. According to criteria recommended by the American College of Medical Genetics and Genomics and the Association for Molecular Pathology, this variant is classified as likely benign (PM2, PP3, PP4, BP1, and BP4). The patient's mother and brother were also asymptomatic carriers of the variant and had sustained previous minor fractures. The patient had normal biochemical profile and bone density. This condition has been rarely described and is not associated with low bone mineral density or altered bone turnover markers. This case highlights the importance of investigating multiple fractures in young patients who are otherwise healthy since these may be a warning sign of rare genetic conditions associated with fragility fractures.