Use of aromatase inhibitors in patients with breast cancer is associated with deterioration of bone microarchitecture and density

ABSTRACT Objective: To evaluate changes in bone density and architecture in postmenopausal women with breast cancer (BC) and use of aromatase inhibitor (AI). Subjects and methods: Thirty-four postmenopausal women with BC, without bone metastasis, renal function impairment and who were not receiving bone-active drugs were selected from a population of 523 outpatients treated for BC. According to the presence of hormonal receptors, HER2 and Ki67, seventeen had positive hormonal receptors and received anastrozole (AI group), and seventeen were triple-negative receptors (non-AI group), previously treated with chemotherapy. Areal bone mineral density (aBMD) and vertebral fracture assessment (VFA) analyses were performed by DXA; vBMD and bone microarchitecture were evaluated by HR-pQCT. Fracture risk was estimated using the FRAX tool. Results: No patient referred previous low-impact fracture, and VFA detected one moderate vertebral fracture in a non-AI patient. AI patients showed lower aBMD and BMD T-scores at the hip and 33% radius and a higher proportion of osteoporosis diagnosis on DXA (47%) vs non-AI (17.6%). AI group had significantly lower values for vBMD at the entire, cortical and trabecular bone compartments, cortical and trabecular thickness and BV/TV. They also had a higher risk for major fractures and for hip fractures estimated by FRAX. Several HR-pQCT parameters evaluated at distal radius and distal tibia were significantly associated with fracture risk. Conclusion: AI is associated with alterations in bone density and microarchitecture of both the cortical and trabecular compartments. These findings explain the overall increase in fracture risk in this specific population.

Body composition, but not insulin resistance, influences postprandial lipemia in patients with Turner's syndrome

ABSTRACT Objective: The aim of the present study was to examine the influence of body composition and insulin resistance on the magnitude of postprandial lipemia in patients with Turner's syndrome receiving oral versus transdermal estrogen replacement. Subjects and methods: Twenty-five patients with Turner's syndrome receiving oral or transdermal estrogen replacement were evaluated for body mass index, waist-to-hip and waist-to-height ratios, fasting glycemia, insulin, body composition (dual-energy X-ray absorptiometry), and postprandial lipid metabolism. For statistical analysis, we used parametric tests to compare numeric variables between the two subgroups. Results: We observed no difference in postprandial triglyceride levels between patients receiving oral versus transdermal hormone replacement therapy. The postprandial triglycerides increment correlated positively with the percentage of total fat mass (p=0.02) and android fat mass (p=0.02) in the transdermal group. In the oral estrogen group, a positive correlation was observed between the increment in postprandial triglycerides and waist-to-hip (p=0.15) and waist-to-height (p=0.009) ratios. No association was observed between the estrogen replacement route and insulin resistance evaluated by the homeostatic model assessment-insulin resistance (HOMA-IR) index (p=0.19 and p=0.65 for the oral and transdermal groups, respectively). Conclusion: We concluded that body composition and anthropometric characteristics possibly affect the extent of postprandial lipemia independently from the route of estrogen replacement.

Diagnosis and treatment of hypoparathyroidism: a position statement from the Brazilian Society of Endocrinology and Metabolism.

Objective To present an update on the diagnosis and treatment of hypoparathyroidism based on the most recent scientific evidence. Materials and methods The Department of Bone and Mineral Metabolism of the Sociedade Brasileira de Endocrinologia e Metabologia (SBEM; Brazilian Society of Endocrinology and Metabolism) was invited to prepare a document following the rules set by the Guidelines Program of the Associação Médica Brasileira (AMB; Brazilian Medical Association). Relevant papers were retrieved from the databases MEDLINE/PubMed, LILACS, and SciELO, and the evidence derived from each article was classified into recommendation levels according to scientific strength and study type. Conclusion An update on the recent scientific literature addressing hypoparathyroidism is presented to serve as a basis for the diagnosis and treatment of this condition in Brazil.

Diagnosis and treatment of hypoparathyroidism: a position statement from the Brazilian Society of Endocrinology and Metabolism

ABSTRACT Objective To present an update on the diagnosis and treatment of hypoparathyroidism based on the most recent scientific evidence. Materials and methods The Department of Bone and Mineral Metabolism of the Sociedade Brasileira de Endocrinologia e Metabologia (SBEM; Brazilian Society of Endocrinology and Metabolism) was invited to prepare a document following the rules set by the Guidelines Program of the Associação Médica Brasileira (AMB; Brazilian Medical Association). Relevant papers were retrieved from the databases MEDLINE/PubMed, LILACS, and SciELO, and the evidence derived from each article was classified into recommendation levels according to scientific strength and study type. Conclusion An update on the recent scientific literature addressing hypoparathyroidism is presented to serve as a basis for the diagnosis and treatment of this condition in Brazil.

Calcium intake: good for the bones but bad for the heart? An analysis of clinical studies.

The proper dietary calcium intake and calcium supplementation, when indicated, are important factors in the acquisition of peak bone mass during youth and in the prevention of fractures in old age. In addition to its deposition in bone, calcium confers an increase in its resistance and exhibits important activities in different enzymatic pathways in the body (e.g., neural, hormonal, muscle-related and blood clotting pathways). Thus, calcium supplementation can directly or indirectly affect important functions in the body, such as the control of blood pressure, plasma glucose, body weight, lipid profile and endothelial function. Since one publication reported increased cardiovascular risk due to calcium supplementation, many researchers have studied whether this risk actually exists; the results are conflicting, and the involved mechanisms are uncertain. However, studies that have evaluated the influence of the consumption of foods rich in calcium have reported no increase in the cardiovascular risk, which suggests that nutritional intake should be prioritized as a method for supplementation and that the use of calcium supplements should be reserved for patients who truly need supplementation and are unable to achieve the recommended daily nutritional intake of calcium.

Calcium intake: good for the bones but bad for the heart? An analysis of clinical studies

ABSTRACT The proper dietary calcium intake and calcium supplementation, when indicated, are important factors in the acquisition of peak bone mass during youth and in the prevention of fractures in old age. In addition to its deposition in bone, calcium confers an increase in its resistance and exhibits important activities in different enzymatic pathways in the body (e.g., neural, hormonal, muscle-related and blood clotting pathways). Thus, calcium supplementation can directly or indirectly affect important functions in the body, such as the control of blood pressure, plasma glucose, body weight, lipid profile and endothelial function. Since one publication reported increased cardiovascular risk due to calcium supplementation, many researchers have studied whether this risk actually exists; the results are conflicting, and the involved mechanisms are uncertain. However, studies that have evaluated the influence of the consumption of foods rich in calcium have reported no increase in the cardiovascular risk, which suggests that nutritional intake should be prioritized as a method for supplementation and that the use of calcium supplements should be reserved for patients who truly need supplementation and are unable to achieve the recommended daily nutritional intake of calcium.

[Analysis of elderly outpatients in relation to nutritional status, sarcopenia, renal function, and bone density]. / Análise de idosos ambulatoriais quanto ao estado nutricional, sarcopenia, função renal e densidade óssea.

OBJECTIVES: To evaluate relationships between nutritional status, sarcopenia and osteoporosis in older women. SUBJECTS AND METHODS: We studied 44 women, 67-94 years, by mini-nutritional assessment (MAN), glomerular filtration corr. 1.73 m(2), body mass index (BMI), arm circumference and calf (CP and CB), bone mineral density and body composition, DXA (fat mass MG; lean MM). We gauge sarcopenia: IMM MM = MSS + MIS/height(2). We used the Pearson correlation coefficient, p < 0.05 as significant. RESULTS: MNA and IMM were positively correlated with BMI, CP, CB and MG. Age influenced negatively FG corr., BMI, FM, IMM and CP. Fourteen had a history of osteoporotic fractures. The lowest T-score was directly related to MAN and MG. CONCLUSIONS The aging caused the decline of FG, fat mass and muscle; the calf circumference, and brachial reflected nutritional status and body composition; and major influences on BMD were nutritional status and fat mass.

Análise de idosos ambulatoriais quanto ao estado nutricional, sarcopenia, função renal e densidade óssea / Analysis of elderly outpatients in relation to nutritional status, sarcopenia, renal function, and bone density

Objetivo : Avaliar relações entre estado nutricional, sarcopenia e osteoporose em idosas.Sujeitos e métodos : Estudamos 44 mulheres, 67-94 anos, mediante miniavaliação nutricional (MAN), filtração glomerular (FG) corr. 1,73 m2, índice de massa corporal (IMC), circunferência da panturrilha e braquial (CP e CB), densidade mineral óssea e composição corporal, DXA (massa gorda – MG; massa magra – MM). Aferimos sarcopenia: IMM = MM MSS + MIS/altura2. Utilizamos o coeficiente de correlação de Pearson, e p < 0,05 como significativo.Resultados : MNA e IMM se correlacionaram positivamente com IMC, CP, CB e MG. A idade influenciou negativamente FG corr., IMC, MG, IMM e CP. Quatorze tinham história de fraturas osteoporóticas. O mais baixo T-score foi diretamente relacionado a MAN e MG.Conclusões : O envelhecimento acarretou o declínio da FG, MG e massa muscular; a circunferência da panturrilha e braquial refletiu estado nutricional e composição corporal; e as grandes influências na DMO foram estado nutricional e MG. Arq Bras Endocrinol Metab. 2014;58(3):226-31.

Objectives : To evaluate relationships between nutritional status, sarcopenia and osteoporosis in older women.Subjects and methods : We studied 44 women, 67-94 years, by mini-nutritional assessment (MAN), glomerular filtration corr. 1.73 m2, body mass index (BMI), arm circumference and calf (CP and CB), bone mineral density and body composition, DXA (fat mass MG; lean MM). We gauge sarcopenia: IMM MM = MSS + MIS/height2. We used the Pearson correlation coefficient, p < 0.05 as significant.Results : MNA and IMM were positively correlated with BMI, CP, CB and MG. Age influenced negatively FG corr., BMI, FM, IMM and CP. Fourteen had a history of osteoporotic fractures. The lowest T-score was directly related to MAN and MG.Conclusions The aging caused the decline of FG, fat mass and muscle; the calf circumference, and brachial reflected nutritional status and body composition; and major influences on BMD were nutritional status and fat mass.Arq Bras Endocrinol Metab. 2014;58(3):226-31.

[Biochemical, hormonal and genetic evaluation of the families of two Brazilian patients with type 2 familial partial lipodystrophy]. / Avaliação bioquímica, hormonal e genética das famílias de duas pacientes brasileiras portadoras de lipodistrofia parcial familiar tipo 2.

OBJECTIVE: To evaluate clinical, biochemical, hormonal and genetic characteristics of relatives of two patients with familial partial lipodystrophy (FPLD) type 2. MATERIALS AND METHODS: Fifty subjects, members of two non-related Brazilian families from two different probands with FPLD phenotype, were evaluated. A mutation in exon 8 of LMNA gene was confirmed in 18 of them, and a heterozygous substitution at codon 482 was identified, predicting a p.R482W mutation. Based on the presence or absence of the mutation, subjects were classified in affected and unaffected, and compared in terms of clinical, biochemical and hormonal parameters. RESULTS: Affected subjects were 2.8 times more likely to manifest diabetes and PCOS, higher HOMA-IR, insulin and triglyceride levels, and lower levels of leptin. These changes preceded the onset of diabetes, because they were observed in diabetic and non-diabetic affected patients. A phenotypic heterogeneity was found among mutation carriers. CONCLUSION: A mutation in the LMNA gene is a determinant of clinical, biochemical and hormonal changes that imply in metabolic deterioration in mutation carriers.

Avaliação bioquímica, hormonal e genética das famílias de duas pacientes brasileiras portadoras de lipodistrofia parcial familiar tipo 2 / Biochemical, hormonal and genetic evaluation of the families of two Brazilian patients with type 2 familial partial lipodystrophy

OBJETIVO: Avaliar características clínicas, bioquímicas, hormonais e genéticas de familiares de duas pacientes portadoras de lipodistrofia parcial familiar (FPLD) tipo 2. MATERIAIS E MÉTODOS: Foram avaliados 50 indivíduos de duas famílias brasileiras não relacionadas a partir de dois propósitos com fenótipo de FPLD. Foi confirmada a mutação no éxon 8 do gene LMNA em 18 destes e identificada a substituição em heterozigose no códon 482, resultando na mutação p.R482W. Com base na presença ou não da mutação, os indivíduos foram separados em afetados e não afetados, e comparados quanto a parâmetros clínicos, bioquímicos e hormonais. RESULTADOS: Indivíduos afetados tiveram 2,8 vezes mais chance de manifestar diabetes e síndrome dos ovários policísticos (SOP), maiores índices HOMA-IR, níveis de insulina e de triglicérides e menores níveis de leptina. Essas alterações precedem o início do diabetes, pois foram evidenciadas nos afetados diabéticos e não diabéticos. Foi constatada heterogeneidade fenotípica entre os portadores da mutação. CONCLUSÃO: A mutação no gene da LMNA é determinante de alterações clínicas, bioquímicas e hormonais que implicam deterioração metabólica nos portadores da mutação.

OBJECTIVE: To evaluate clinical, biochemical, hormonal and genetic characteristics of relatives of two patients with familial partial lipodystrophy (FPLD) type 2. MATERIALS AND METHODS: Fifty subjects, members of two non-related Brazilian families from two different probands with FPLD phenotype, were evaluated. A mutation in exon 8 of LMNA gene was confirmed in 18 of them, and a heterozygous substitution at codon 482 was identified, predicting a p.R482W mutation. Based on the presence or absence of the mutation, subjects were classified in affected and unaffected, and compared in terms of clinical, biochemical and hormonal parameters. RESULTS: Affected subjects were 2.8 times more likely to manifest diabetes and PCOS, higher HOMA-IR, insulin and triglyceride levels, and lower levels of leptin. These changes preceded the onset of diabetes, because they were observed in diabetic and non-diabetic affected patients. A phenotypic heterogeneity was found among mutation carriers. CONCLUSION: A mutation in the LMNA gene is a determinant of clinical, biochemical and hormonal changes that imply in metabolic deterioration in mutation carriers.

Factors associated with low bone mineral density in a Brazilian cohort of vertically HIV-infected adolescents.

OBJECTIVE: To assess the prevalence and factors associated with low bone mineral density (BMD) in HIV-infected adolescents. METHODS: This was a cross-sectional study of a Brazilian cohort of vertically HIV-infected adolescents. Body composition and lumbar spine (LS) and total body (TB) BMD were estimated by dual-energy X-ray absorptiometry (DXA). Low BMD was considered for a Z-score ≤-2 standard deviations. Pubertal development, anthropometric data, laboratory measurements, antiretroviral regimen, and time of immunological and virological recovery were evaluated as factors associated with a low BMD. RESULTS: Seventy-four adolescents aged 17.3 ± 1.8 years were studied. Low BMD was present in 32.4% of them. LS and TB BMD Z-scores were positively correlated with weight, body mass index (BMI), BMI Z-score, total body fat, and nutritional status. Patients on tenofovir had lower LS and TB BMD Z-scores. Time on tenofovir was indirectly correlated with LS and TB BMD Z-scores. No difference was found regarding levels of calcium, parathyroid hormone, or 25-hydroxyvitamin D according to BMD status. CONCLUSIONS: Control of the HIV infection, especially before the initiation of puberty, might have a positive influence on bone gain. Body composition and nutritional status had a positive influence on BMD that was more evident in females, suggesting that nutritional intervention may have a positive impact on BMD.

Osteoporosis and inflammation.

Several inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, celiac disease, cystic fibrosis and chronic obstructive pulmonary disease have been associated to bone resorption. The link between osteoclast, macrophage colony stimulating factor and pro-inflammatory cytokines, especially tumor necrosis factor-alpha and interleukin-1 explain the association between inflammation and osteoporosis. These diseases are related to osteoporosis and high fracture risk independent of other risk factors common to inflammatory diseases such as reduced physical activity, poor nutritional status, hypovitaminosis D, decrease in calcium intake and glucocorticoid treatment. Erythrocyte sedimentation rate and C-reactive protein should always be performed, but the indication about when to perform the densitometry test should be analyzed for each disease. Bisphosphonates are nowadays the best choice of therapy but new medications such as denosumab, IL-1 receptor antagonist, and TNF-alpha antibody have risen as new potential treatments for osteoporosis secondary to inflammation.

Osteoporosis and inflammation / Osteoporose e inflamação

Several inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, celiac disease, cystic fibrosis and chronic obstructive pulmonary disease have been associated to bone resorption. The link between osteoclast, macrophage colony stimulating factor and pro-inflammatory cytokines, especially tumor necrosis factor-α and interleukin-1 explain the association between inflammation and osteoporosis. These diseases are related to osteoporosis and high fracture risk independent of other risk factors common to inflammatory diseases such as reduced physical activity, poor nutritional status, hypovitaminosis D, decrease in calcium intake and glucocorticoid treatment. Erythrocyte sedimentation rate and C-reactive protein should always be performed, but the indication about when to perform the densitometry test should be analyzed for each disease. Bisphosphonates are nowadays the best choice of therapy but new medications such as denosumab, IL-1 receptor antagonist, and TNF-α antibody have risen as new potential treatments for osteoporosis secondary to inflammation.

Diversas doenças inflamatórias têm sido associadas à reabsorção óssea, como a artrite reumatoide, o lúpus eritematoso sistêmico, a doença inflamatória intestinal, a doença celíaca, a fibrose cística e a doença pulmonar obstrutiva crônica. A ligação entre osteoclastos, fator estimulador de colônia de macrófagos e citocinas pró-inflamatórias, principalmente o fator de necrose tumoral-α e interleucina-1, explica a associação entre a inflamação e a osteoporose. Essas doenças estão relacionadas com osteoporose e aumento do risco de fratura, independentemente de outros fatores de risco comuns às doenças inflamatórias, tais como redução da atividade física, estado nutricional, hipovitaminose D, diminuição da ingestão de cálcio e uso de glicocorticoides. A velocidade de hemossedimentação e proteína C-reativa devem ser sempre realizadas, mas a indicação do exame de densitometria óssea deve ser analisada em cada doença. Os bisfosfonatos são atualmente a melhor opção de terapia, mas novos medicamentos, tais como denosumabe, antagonista do receptor de IL-1 e anticorpos anti-TNF-α, surgem como novos potenciais tratamentos para a osteoporose secundária à inflamação.

Densitometric analysis of femoral region in men older than 50 years old from an ambulatory of urology / Análise densitométrica da região femoral de homens acima de 50 anos oriundos de um ambulatório de urologia

Introdução: A osteoporose em homens ainda é pouco diagnosticada. O objetivo deste estudo é mensurar a densidade mineral óssea (DMO) e a prevalência de osteoporose em uma amostra de homens. Pacientes e métodos: Cento e cinquenta e um homens de 50 a 93 anos, em boas condições clínicas, oriundos de um ambulatório de rotina de Urologia, realizaram a medida da densidade óssea da coluna lombar e da região femoral. Resultados: A idade teve influência negativa na DMO e no T-Score femoral (rs = 0,49 e 0,73, respectivamente, P ≤ 0,0001), utilizando o coeficiente de correlaçãode Spearman. Detectamos osteoporose na região femoral em 25,16% (n = 38). A maioria (81,56%) dos pacientes osteoporóticos tinha mais de 70 anos, sendo uma parcela expressiva (47,37%) muito idosa, ou seja, homens com 80 anos ou mais. Além da idade, hipogonadismo induzido por análogo de GNRH ou acetato de ciproterona para tratamento de câncer de próstata, uso crônico de anticoagulante, histórico de revascularização miocárdica e uso de álcool foram fatores de risco encontrados em cerca de 18% da população osteoporótica. Conclusão: Todos os homens acima de 70 anos e também os mais jovens com fatores de risco devem realizar densitometria óssea.

INTRODUCTION: Men osteoporosis remains poorly diagnosed. The objective of this study was to measure bone mineral density (BMD) and the prevalence of osteoporosis in a group of men. PATIENTS AND METHODS: 151 men (ages 50-93 years) in good health, from an outpatient clinic for routine urologic evaluation performed the measurement of bone density of lumbar spine and femoral regions. RESULTS: Age had a negative influence on femoral neck BMD and T-Score (rs = 0.49 and 0.73, respectively, P < 0.0001) using the Spearman's rank correlation coefficient. Femoral neck osteoporosis was detected in 25.16% (n = 38). Most of the osteoporotic patients (81.56%) were over 70 years old, and 47.37% of them were very old (aged 80 years or more). Beside age, hypogonadism induced by GnRH analogues and cyproterone acetate for treatment of prostate cancer, anticoagulants, coronary revascularization history and alcohol were risk factors identified in about 18% of the osteoporotic group. CONCLUSION: All men over 70 years old and younger men with risk factors for osteoporosis should be submitted to a bone densitometry.

Aspectos genéticos, influência do eixo GH/IGF1 e novas possibilidades terapêuticas na osteoporose idiopática / Genetics aspects, GH/IGF1 axis influence and advance therapeutic alternatives in idiopathic osteoporosis

A osteoporose idiopática é uma condição rara que afeta ambos os sexos, mulheres durante o menacme e homens antes dos 65 anos. O diagnóstico somente pode ser considerado depois de serem descartadas todas as causas conhecidas de osteoporose. A apresentação clínica é heterogênea, variando desde o achado de osteoporose à densitometria em paciente pouco sintomático até múltiplas fraturas por fragilidade, principalmente de corpos vertebrais. A remodelação óssea encontra-se geralmente no limite inferior da normalidade, mas a reabsorção óssea sempre excede a formação, resultando em perda óssea. A disfunção osteoblástica, descrita na maioria dos artigos, tem sido relacionada a baixas concentrações do fator de crescimento insulina-simile (IGF-1) no sangue e na matriz óssea. Fatores genéticos e hormonais parecem envolvidos na etiopatogenia. Drogas anti-reabsortivas, como os bisfosfonatos, são úteis em reduzir a taxa de fraturas. Drogas anabólicas, tais como o hormônio de crescimento, o IGF-1 e mais recentemente a teriparatida (PTH recombinante), são mais promissoras, uma vez que elas realmente aumentam a massa óssea e melhoram a qualidade do osso. A proposta deste artigo é rever aspectos da fisiopatologia da osteoporose idiopática, rotina diagnóstica e alternativas terapêuticas.

Funçäo tireoideana pós-tireoidectomia em doença de Basedow-Graves / Thyroid function post-thyroidectomy in Basedow-Graves disease

A doença de Graves é a causa mais comum de hipertireoidismo, devendo-se primariamente á produçäo de auto-anticorpos que se ligam ao receptor do TSH nas células foliculares da tireóide, estimulando-os. Drogas antireoideanas, iodorradiotivo e cirurgia säo usados no tratamento desta doença, cada um com vantagens e desvantagens. A cirurgia para doença de Grave tem como indicaçöes : grande bócio com sintomas compressivos, presença concomitante de nódulo frio, preferência do paciente, näo adesäo ao tratamento medicamentoso.Suas principais complicaçöes säo lesäo do nervo laríngeo recorrente, ,hipoparatireoidismo e hipotireoidismo pós-operatório, devido geralmente á extensäo da tireidectomia. O objetivo deste estudo foi avaliar a evoluçäo pós operatória de tireoidectomia , correlacionando, quando possível, com dosagem de anticorpos antitireoglobulina e antimicrossomal. Materiais e metodos : estudamos 106 prontuários de pacientes submetidos à tireoideectomia para tratamento de doença de Graves no HUCFF, no período de 1978 a 1996. Obtivemos dados clínicos e laboratoriais com relaçäo à funçäo tireoidedana e, em 40 deste pacientes, pudemos avaliar a presença de anticorpos antitireoglobulina e antimicrossomal. Resultados : 37 pacientes evadiram no pós-operatório imediato. A funçäo tireoideana foi avaliada nos 69 pacientes restantes. Consideramos hipotireoidismo definitivo os pacientes com confirmaçäo clínica e laboratorial e com acompanhamento pós-tireoidectomia mínimo de um ano. Quarenta e um pacientes desenvolveram hipotireoidismo. Näo observamos correlaçäo entre a positividaded de anticorpos e a evoluçäo pós-operatóra.(au)