Male osteoporosis

ABSTRACT Osteoporosis, a disease classically attributed to postmenopausal women, is underappreciated, underdiagnosed, and undertreated in men. However, it is not uncommon for osteoporotic fractures to occur in men. About 40% of fractures occur in men with an incidence that has increased over the years. After a first fracture, the risk of a subsequent episode, as well as the risk of death, is higher in the male than in the female population. Despite these facts, only 10% of men with osteoporosis receive adequate treatment. Up to half of the cases of male osteoporosis have a secondary cause, the most common being hypogonadism, excessive alcohol consumption, and chronic use of glucocorticoids. The International Society for Clinical Densitometry (ISCD) recommends using the female database for the diagnosis of osteoporosis by DXA (T-score ≤ −2.5 in men over 50 years old). In addition, osteoporosis can also be diagnosed independently of the BMD if a fragility fracture is present, or if there is a high risk of fractures by FRAX. Treatment is similar to postmenopausal osteoporosis, because the data regarding changes in bone density track closely to those in women. Data concerning fracture risk reduction are not as certain because the clinical trials have included fewer subjects for shorter period of time. In men with symptomatic hypogonadism, testosterone replacement, if indicated, can improve BMD.

Skeletal and nonskeletal consequences of hypoparathyroidism

ABSTRACT Hypoparathyroidism, despite the conventional therapy with calcium and active vitamin D, can lead to skeletal and nonskeletal abnormalities. Chronic hypoparathyroidism is associated with a significant reduction in bone remodeling, increases in areal and volumetric bone density, and improvement in trabecular microarchitecture and in trabecular bone score. Regardless of these advantages in bone mass and microarchitecture, recent data suggest an increased vertebral fracture risk in patients with nonsurgical hypoparathyroidism. Moreover, chronic hypoparathyroidism can lead to abnormalities in multiple organ systems, including the neurological, cardiovascular, renal, neuropsychiatric, ocular, and immune systems. Nephrocalcinosis, nephrolithiasis, and renal insufficiency, as well as decreased quality of life and cataracts, are common in patients with hypoparathyroidism. An increased incidence of hospitalization due to infections and a greater risk of cardiovascular diseases are observed in patients with hypoparathyroidism, particularly in those with nonsurgical disease. All these abnormalities may be because of the disease itself or complications of therapy. We herein reviewed the skeletal and nonskeletal consequences of hypoparathyroidism in patients conventionally managed with calcium and active vitamin D.

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.

Update on trabecular bone score

ABSTRACT Trabecular bone score (TBS) is an indirect and noninvasive measure of bone quality. A low TBS indicates degraded bone microarchitecture, predicts osteoporotic fracture, and is partially independent of clinical risk factors and bone mineral density (BMD). There is substantial evidence supporting the use of TBS to assess vertebral, hip, and major osteoporotic fracture risk in postmenopausal women, as well as to assess hip and major osteoporotic fracture risk in men aged > 50 years. TBS complements BMD information and can be used to adjust the FRAX (Fracture Risk Assessment) score to improve risk stratification. While TBS should not be used to monitor antiresorptive therapy, it may be potentially useful for monitoring anabolic therapy. There is also a growing body of evidence indicating that TBS is particularly useful as an adjunct to BMD for fracture risk assessment in conditions associated with increased fracture risk, such as type-2 diabetes, chronic corticosteroid excess, and other conditions wherein BMD readings are often misleading. The interference of abdominal soft tissue thickness (STT) on TBS should also be considered when interpreting these findings because image noise can impact TBS evaluation. A new TBS software version based on an algorithm that accounts for STT rather than BMI seems to correct this technical limitation and is under development. In this paper, we review the current state of TBS, its technical aspects, and its evolving role in the assessment and management of several clinical conditions.

Carcinoma de paratireoide: um relato de caso / Parathyroid carcinoma: case report

O carcinoma de paratireoide (CP) constitui entidade patológica incomum e detentora de peculiaridades propedêutico-terapêuticas. Em geral, apresenta-se como hiperparatireoidismo primário sintomático, no qual corresponde a somente 1% nesse subgrupo. O diagnóstico de CP é difícil, tanto clínico quanto histológico, devido à inconstância de critérios. Laboratorialmente, é comum apresentar hipercalcemia e PTH bastante acima do valor de referência. A cirurgia é o único tratamento curativo e efetivo para o carcinoma de paratireoide. Relato de caso: Paciente M.P.R.L., 48 anos, sexo feminino, melanodérmica, natural e procedente de Felisburgo ­ MG. Evoluíra há 02 anos com fraqueza progressiva, anemia, disfunção renal, dores crônicas e perda ponderal (cerca de 15 kg nos últimos cinco meses), associada a hipercalcemia PTH-dependente e declínio da função renal. Estudo ultrassonográfico (USG) de região cervical demonstrou presença de dois nódulos tireoideanos e cintilografia de paratireoides sem evidências de hiperplasia ou adenoma das glândulas. Foi admitida no Hospital Santa Casa de Belo Horizonte para seguimento propedêutico e terapêutico do quadro apresentado (AU)

Parathyroid carcinoma (PC) is an uncommon pathology which has propaedeutic and therapeutic peculiarities. In general, it presents as symptomatic primary hyperparathyroidism, that corresponds to only 1% in this subgroup. Both the clinical and histological diagnosis of PC are difficult due to inconsistent criteria. Laboratorial exams commonly present hypercalcemia and PTH well-above the reference value. Surgery is the only curative and effective treatment for parathyroid carcinoma. Case report: Patient M.P.R.L., 48 years old, female, melanodermic, native and from Felisburgo - MG. The disease had been progressing for 2 years with progressive weakness, anemia, renal dysfunction, chronic pain and weight loss (about 15 kg in last five months), associated with PTH-dependent hypercalcemia and renal function decline. A cervical study showed the presence of two thyroid nodules whereas a parathyroid scintigraphy showed no evidence of glands hyperplasia or adenoma. She was admitted to the Santa Casa Hospital of Belo Horizonte for a propaedeutic and therapeutic management of the presented profile. (AU)

Bone disease in primary hyperparathyroidism / Doença óssea no hiperparatiroidismo primário

Bone disease in severe primary hyperparathyroidism (PHPT) is described classically as osteitis fibrosa cystica (OFC). Bone pain, skeletal deformities and pathological fractures are features of OFC. Bone mineral density is usually extremely low in OFC, but it is reversible after surgical cure. The signs and symptoms of severe bone disease include bone pain, pathologic fractures, proximal muscle weakness with hyperreflexia. Bone involvement is typically characterized as salt-and-pepper appearance in the skull, bone erosions and bone resorption of the phalanges, brown tumors and cysts. In the radiography, diffuse demineralization is observed, along with pathological fractures, particularly in the long bones of the extremities. In severe, symptomatic PHPT, marked elevation of the serum calcium and PTH concentrations are seen and renal involvement is manifested by nephrolithiasis and nephrocalcinosis. A new technology, recently approved for clinical use in the United States and Europe, is likely to become more widely available because it is an adaptation of the lumbar spine DXA image. Trabecular bone score (TBS) is a gray-level textural analysis that provides an indirect index of trabecular microarchitecture. Newer technologies, such as high-resolution peripheral quantitative computed tomography (HR-pQCT), have provided further understanding of the microstructural skeletal features in PHPT.

A doença óssea no hiperparatiroidismo primário grave é representada pela osteíte fibrosa cística (OFC). Dor óssea, deformidades esqueléticas e fraturas patológicas são achados comuns na OFC. A densidade mineral óssea está, usualmente, extremamente diminuída na OFC, mas é reversível após a cura cirúrgica. Os sinais e sintomas da doença óssea grave incluem dor óssea, fraturas patológicas e fraqueza muscular proximal com hiper-reflexia. O comprometimento ósseo é tipicamente caracterizado pela aparência em “sal-e-pimenta” nos ossos do crânio, erosões ósseas e reabsorção das falanges, tumores marrons e cistos. Na radiografia, observam-se desmineralização difusa e fraturas patológicas especialmente nos ossos longos das extremidades. No hiperparatiroidismo primário (HPTP) sintomático grave, as concentrações séricas de cálcio e PTH estão usualmente bem elevadas e o comprometimento renal se caracteriza pela presença de urolitíase e nefrocalcinose. Uma nova tecnologia, recentemente aprovada para uso clínico nos Estados Unidos e na Europa, torna-se provável se difundir rapidamente, pois utiliza as imagens geradas pela densitometria DXA. O escore trabecular ósseo (TBS), obtido por meio da análise do nível da textura cinza das imagens dos corpos vertebrais, fornece informações indiretas sobre a microarquitetura trabecular. Novos métodos, como a tomografia de alta resolução quantitativa periférica computadorizada (HRpqCT), têm proporcionado conhecimentos adicionais sobre os achados da microarquitetura esquelética no HPTP.

Trabecular bone score: perspectives of an imaging technology coming of age / Escore de osso trabecular: perspectivas de um método de imagem em aprimoramento

The trabecular bone score (TBS) is a new method to describe skeletal microarchitecture from the dual energy X-ray absorptiometry (DXA) image of the lumbar spine. While TBS is not a direct physical measurement of trabecular microarchitecture, it correlates with micro-computed tomography (µCT) measures of bone volume fraction, connectivity density, trabecular number, and trabecular separation, and with vertebral mechanical behavior in ex vivo studies. In human subjects, TBS has been shown to be associated with trabecular microarchitecture and bone strength by high resolution peripheral quantitative computed tomography (HRpQCT). Cross-sectional and prospective studies, involving a large number of subjects, have both shown that TBS is associated with vertebral, femoral neck, and other types of osteoporotic fractures in postmenopausal women. Data in men, while much less extensive, show similar findings. TBS is also associated with fragility fractures in subjects with secondary causes of osteoporosis, and preliminary data suggest that TBS might improve fracture prediction when incorporated in the fracture risk assessment system known as FRAX. In this article, we review recent advances that have helped to establish this new imaging technology.

TBS (do inglês, “trabecular bone score”) é um novo método que estima a microarquitetura óssea a partir de uma imagem de densitometria óssea (DXA) da coluna lombar. Apesar de o TBS não ser uma medida física direta da microarquitetura trabecular, ele correlaciona-se com o volume ósseo, densidade da conectividade trabecular, número de trabéculas e separação trabecular medidos por microtomografia computadorizada (µCT), e com medidas mecânicas da resistência óssea vertebral em estudos ex vivo. Estudos em humanos confirmaram que o TBS associa-se a microarquitetura trabecular e resistência óssea medidas por tomografia computadorizada quantitativa periférica de alta resolução (HRpQCT). Estudos transversais e prospectivos, envolvendo um grande número de indivíduos, mostraram que o TBS é associado com fratura vertebral, de colo de fêmur e com outros tipos de fraturas osteoporóticas em mulheres na pós-menopausa. Dados em homens, apesar de escassos, mostram resultados semelhantes. Além disso, o TBS foi associado a fraturas por fragilidade em indivíduos com diversas causas secundárias de osteoporose e, dados preliminares, sugerem que o uso do TBS pode melhorar a previsão de fratura quando incorporado ao sistema de avaliação de risco de fratura (FRAX). Este artigo faz uma revisão de avanços recentes que têm ajudado a estabelecer esse novo método de imagem.

The burden of osteoporosis in Brazil / O ônus da osteoporose no Brasil

Osteoporotic fractures impose severe physical, psychosocial, and financial burden both to the patient and the society. Studies on the prevalence of osteoporosis and fragility fractures in Brazil show a wide variation, due to differences in sample size, the population studied, and methodologies. Few studies have been conducted in Brazil about the cost-effectiveness analyses of different intervention options aimed at the diagnosis and treatment of osteoporosis. Investigation and treatment strategies based on cost-effectiveness and scientific evidence are essential in the preparation of public health policies with the ultimate goal of reducing the incidence of fractures and, consequently, the direct and indirect costs associated with them. This article reviews the Brazilian burden of osteoporosis in terms of the prevalence and fractures attributable to the disease, the costs related to the investigation and management, as well as the impact of osteoporosis on the population as a whole and on affected individuals.

Fraturas osteoporóticas impõem graves entraves físicos, psicossociais e financeiros, tanto para o paciente quanto para a sociedade. Estudos sobre a prevalência de osteoporose e fraturas por fragilidade no Brasil mostram uma grande variação, em decorrência das diferenças no tamanho das amostras, da população estudada e da metodologia empregada. Poucos estudos têm sido realizados no Brasil sobre a análise de custo-efetividade das diferentes opções de intervenção que visam ao diagnóstico e ao tratamento da osteoporose. Estratégias de investigação e de tratamento com base na relação custo-eficácia e evidências científicas são essenciais para a elaboração de políticas de saúde pública, com o objetivo final de reduzir a incidência de fraturas e, consequentemente, os custos diretos e indiretos associados a elas. Este artigo faz uma revisão sobre o ônus da osteoporose no Brasil em termos de prevalência e fraturas atribuíveis à doença, de custos relacionados com a investigação, tratamento da osteoporose, bem como seu impacto na população como um todo e em indivíduos afetados.

Prevalência de deficiência e insuficiência de vitamina D e sua correlação com PTH, marcadores de remodelação óssea e densidade mineral óssea, em pacientes ambulatoriais / Prevalence of vitamin D deficiency and its correlation with PTH, biochemical bone turnover markers and bone mineral density, among patients from ambulatories

A deficiência de vitamina D (VD) leva ao raquitismo e à osteomalacia e sua insuficiência, caracterizada pelo hiperparatireoidismo secundário, pode resultar osteoporose. Apesar de amplamente prevalente, a insuficiência de VD ainda é pouco reconhecida e subtratada. Os autores estudaram 180 pacientes atendidos em ambulatório de endocrinologia em Belo Horizonte, que tiveram os níveis de 25(OH)VD mensurados, correlacionando-os com paratormônio (PTH), marcadores de remodelação óssea e densidade mineral óssea. Para caracterização de níveis insuficientes de VD, foram correlacionados os níveis de 25(OH)VD com os de PTH, definindo-se, nesta série, ponto de corte de 25(OH)VD de 32 ng/ml. Foi encontrada correlação inversa e significativa entre 25(OH)VD e PTH e entre 25(OH)VD e C-telopeptídeo. A prevalência de insuficiência de VD na população estudada foi de 42,4 por cento. Conclui-se que a insuficiência de VD tem alta prevalência entre pacientes que freqüentam nossos consultórios, alertando para a importância da sua investigação na prática clínica e na instituição de políticas para sua prevenção.

Consequences of VD deficiency include rickets and osteomalacia. However, marginal concentrations of 25-hydroxyvitamin D (25(OH)VD) are associated with secondary hyperparathyroidism and osteoporosis. In this context, levels of 25(OH)VD capable to elevate parathyroid hormone (PTH) could be considered as insufficient. The VD insufficiency, although widely prevalent, is still under-recognized and under-treated. The authors have studied 180 patients followed in a endocrinology clinic in Belo Horizonte, who had 25(OH)VD measured, correlating it with PTH, biochemical bone turnover markers and bone mineral density. To determine the sufficiency of VD, 25(OH)VD was correlated with PTH and the cutoff found was of 32ng/ml. CTX-1 and PTH were significantly negative correlated to 25(OH)VD and the prevalence of VD insufficiency was 42 percent. One concludes that the VD insufficiency is widely prevalent among patients who frequently come to our offices, alerting us for the importance to assess VD status more often and to practice politics for prevention of VD insufficiency.

Doença de cushing subclínica: relato de três casos e revisão da literatura / Subclinical cushings disease: presentation of three cases and critical review

Ao contrário da doença de Cushing subclínica, a síndrome de Cushing subclínica de origem adrenal é uma entidade amplamente conhecida. É definida como uma hiperprodução autônoma de cortisol, de leve intensidade, insuficiente para causar sinais clínicos específicos de hipercortisolismo, porém suficiente para levar a alterações bioquímicas detectáveis no eixo hipotálamo-hipófise-adrenal. Apesar de a doença de Cushing representar a grande maioria dos casos de hipercortisolismo, há poucos relatos na literatura sobre doença de Cushing subclínica. Neste trabalho são descritos três casos de doença de Cushing subclínica, causadas por macroadenomas hipofisários corticotróficos, confirmados por estudo imuno-histoquímico, despertando a atenção dos endocrinologistas clínicos para essa entidade e sugerindo que a investigação laboratorial do hipercortisolismo seja incluída em todos os casos de adenomas hipofisários.

Unlike subclinical Cushings disease, adrenal subclinical Cushings syndrome is widely recognized. It is defined as an autonomous cortisol hyperproduction of mild intensity not causing specific clinical signs, but detectable biochemically as derangements of the hypothalamic-pituitary-adrenal axis function. Although Cushings disease accounts for the majority of hypercortisolism states, subclinical Cushings disease has been rarely reported. Three cases of subclinical Cushings disease due to pituitary corticotrophic macroadenomas, confirmed by immunohistochemistry, are presented in order to underscore its recognition by clinical endocrinologists and to emphasize a diagnostic evaluation of hypercortisolism in all cases of pituitary adenomas.