Glucocorticoid-induced osteoporosis: clinical and therapeutic aspects.

Glucocorticoid-induced osteoporosis (GIO) is the most common form of secondary osteoporosis. Fractures, which are often asymptomatic, may occur in as many as 30_50% of patients receiving chronic glucocorticoid therapy. Vertebral fractures occur early after exposure to glucocorticoids, at a time when bone mineral density (BMD) declines rapidly. Fractures tend to occur at higher BMD levels than in women with postmenopausal osteoporosis. Glucocorticoids have direct and indirect effects on the skeleton. They impair the replication, differentiation, and function of osteoblasts and induce the apoptosis of mature osteoblasts and osteocytes. These effects lead to a suppression of bone formation, a central feature in the pathogenesis of GIO. Glucocorticoids also favor osteoclastogenesis and as a consequence increase bone resorption. Bisphosphonates are the most effective of the various therapies that have been assessed for the management of GIO. Anabolic therapeutic strategies are under investigation. Teriparatide seems to be also efficacious for the treatment of patients with GIO

Therapy of Osteoporosis in Men with Teriparatide

Osteoanabolic therapy is an attractive therapeutic option for men with osteoporosis because it directly stimulates bone formation, an action not shared by any antiresorptive drug. Teriparatide (recombinant human PTH(1-34)) and PTH(1-84) are available in many countries but PTH(1-84) is not available in the United States. Only teriparatide is approved for the treatment of osteoporosis in men. It is also indicated in glucocorticoid-induced osteoporosis. Teriparatide is associated with major gains in bone density at the lumbar spine and, to a lesser extent, in the hip regions. Vertebral and nonvertebral fractures are reduced in postmenopausal women treated with teriparatide. Fracture reduction data in men are less secure because the number of study subjects is small and the studies have not been powered to document this endpoint. Nevertheless, observational data in men suggest a reduction in vertebral fractures with teriparatide. Attempts to show further beneficial effects of teriparatide in combination with antiresorptive agents have not been demonstrated yet to be superior to monotherapy with teriparatide alone. The duration of therapy with teriparatide is limited to 2 years. Thereafter, it is necessary to treat with an antiresorptive drug to maintain, and perhaps increase, densitometric gains. Teriparatide is well tolerated with a good safety profile

Primary hyperparathyroidism

Primary hyperparathyroidism (PHPT) is a common disorder in which parathyroid hormone (PTH) is excessively secreted from one or more of the four parathyroid glands. A single benign parathyroid adenoma is the cause in most people. However, multiglandular disease is not rare and is typically seen in familial PHPT syndromes. The genetics of PHPT is usually monoclonal when a single gland is involved and polyclonal when multiglandular disease is present. The genes that have been implicated in PHPT include proto-oncogenes and tumour-suppressor genes. Hypercalcaemia is the biochemical hallmark of PHPT. Usually, the concentration of PTH is frankly increased but can remain within the normal range, which is abnormal in the setting of hypercalcaemia. Normocalcaemic PHPT, a variant in which the serum calcium level is persistently normal but PTH levels are increased in the absence of an obvious inciting stimulus, is now recognized. The clinical presentation of PHPT varies from asymptomatic disease (seen in countries where biochemical screening is routine) to classic symptomatic disease in which renal and/or skeletal complications are observed. Management guidelines have recently been revised to help the clinician to decide on the merits of a parathyroidectomy or a non-surgical course. This Primer covers these areas with particular attention to the epidemiology, clinical presentations, genetics, evaluation and guidelines for the management of PHPT

Utility of the trabecular bone score (TBS) in secondary osteoporosis

Altered bone micro-architecture is an important factor in accounting for fragility fractures. Until recently, it has not been possible to gain information about skeletal microstructure in a way that is clinically feasible. Bone biopsy is essentially a research tool. High-resolution peripheral Quantitative Computed Tomography, while non-invasive, is available only sparsely throughout the world. The trabecular bone score (TBS) is an imaging technology adapted directly from the Dual Energy X-Ray Absorptiometry (DXA) image of the lumbar spine. Thus, it is potentially readily and widely available. In recent years, a large number of studies have demonstrated that TBS is significantly associated with direct measurements of bone micro-architecture, predicts current and future fragility fractures in primary osteoporosis, and may be a useful adjunct to BMD for fracture detection and prediction. In this review, we summarize its potential utility in secondary causes of osteoporosis. In some situations, like glucocorticoid-induced osteoporosis and in diabetes mellitus, the TBS appears to out-perform DXA. It also has apparent value in numerous other disorders associated with diminished bone health, including primary hyperparathyroidism, androgen-deficiency, hormone-receptor positive breast cancer treatment, chronic kidney disease, hemochromatosis, and autoimmune disorders like rheumatoid arthritis. Further research is both needed and warranted to more clearly establish the role of TBS in these and other disorders that adversely affect bone

Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1).

OBJECTIVE: The aim was to provide guidelines for evaluation, treatment, and genetic testing for multiple endocrine neoplasia type 1 (MEN1). PARTICIPANTS: The group, which comprised 10 experts, including physicians, surgeons, and geneticists from international centers, received no corporate funding or remuneration. PROCESS: Guidelines were developed by reviews of peer-reviewed publications; a draft was prepared, reviewed, and rigorously revised at several stages; and agreed-upon revisions were incorporated. CONCLUSIONS: MEN1 is an autosomal dominant disorder that is due to mutations in the tumor suppressor gene MEN1, which encodes a 610-amino acid protein, menin. Thus, the finding of MEN1 in a patient has important implications for family members because first-degree relatives have a 50% risk of developing the disease and can often be identified by MEN1 mutational analysis. MEN1 is characterized by the occurrence of parathyroid, pancreatic islet, and anterior pituitary tumors. Some patients may also develop carcinoid tumors, adrenocortical tumors, meningiomas, facial angiofibromas, collagenomas, and lipomas. Patients with MEN1 have a decreased life expectancy, and the outcomes of current treatments, which are generally similar to those for the respective tumors occurring in non-MEN1 patients, are not as successful because of multiple tumors, which may be larger, more aggressive, and resistant to treatment, and the concurrence of metastases. The prognosis for MEN1 patients might be improved by presymptomatic tumor detection and undertaking treatment specific for MEN1 tumors. Thus, it is recommended that MEN1 patients and their families should be cared for by multidisciplinary teams comprising relevant specialists with experience in the diagnosis and treatment of patients with endocrine tumors

Diagnóstico e manejo do hiperparatireoidismo primário: uma posição científica do Departamento de Metabolismo Ósseo, a Sociedade Brasileira de Endocrinologia e Metabolismo

OBJECTIVE: To conduct a literature review on the diagnosis and management of primary hyperparathyroidism including the classical hipercalcemic form as well as the normocalcemic variant. MATERIALS AND METHODS: This scientific statement was generated by a request from the Brazilian Medical Association (AMB) to the Brazilian Society for Endocrinology as part of its Clinical Practice Guidelines program. Articles were identified by searching in PubMed and Cochrane databases as well as abstracts presented at the Endocrine Society, Brazilian Society for Endocrinology Annual Meetings and the American Society for Bone and Mineral Research Annual Meeting during the last 5 years. Grading quality of evidence and strength of recommendation were adapted from the first report of the Oxford Centre for Evidence-based Medicine. All grades of recommendation, including D, are based on scientific evidence. The differences between A, B, C and D, are due exclusively to the methods employed in generating evidence. CONCLUSION: We present a scientific statement on primary hyperparathyroidism providing the level of evidence and the degree of recommendation regarding causes, clinical presentation as well as surgical and medical treatment.OBJETIVO: Conduzir uma atualização das últimas evidências científicas a respeito da apresentação, do diagnóstico e do manejo clínico e cirúrgico do hiperparatireoidismo primário clássico e normocalcêmico. MATERIAIS E MÉTODOS: Este documento foi concebido pelo Departamento de Metabolismo Ósseo da Sociedade Brasileira de Endocrinologia e Metabologia (SBEM) a partir daquele oriundo do Programa de Diretrizes da Associação Médica Brasileira (AMB) da SBEM. Realizamos uma revisão dos artigos mais relevantes obtidos nos bancos de dados PubMed e Cochrane, além de abstracts apresentados nos encontros anuais da Endocrine Society, da Sociedade Brasileira de Endocrinologia e da American Society for Bone and Mineral Research dos últimos cinco anos, e classificamos as evidências em níveis de recomendações de acordo com a força científica por tipo de estudo, adaptando o primeiro relato do Oxford Centre for Evidence-based Medicine. Todos os graus de recomendação, incluindo-se o D, foram basea-dos em evidência científica, sendo as diferenças entre o A, B, C e D devidas exclusivamente ao desenho empregado na geração da evidência. CONCLUSÃO: Apresentamos uma atualização científica a respeito do hiperparatireoidismo primário, classificando e graduando em níveis de recomendações as principais evidências científicas sobre as suas causas, as variadas formas de apresentação, seu diagnóstico e tratamento.University of Pernambuco Medical School Ministry of HealthFederal University of São Paulo Medical SchoolFederal University of Parana Medical SchoolUniversity of Brasilia Medical SchoolCatholic University of BrasiliaColumbia University College of Physicians & SurgeonsUNIFESP, Medical SchoolSciEL