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.

Genetics of osteoporosis: searching for candidate genes for bone fragility

ABSTRACT The pathogenesis of osteoporosis, a common disease with great morbidity and mortality, comprises environmental and genetic factors. As with other complex disorders, the genetic basis of osteoporosis has been difficult to identify. Nevertheless, several approaches have been undertaken in the past decades in order to identify candidate genes for bone fragility, including the study of rare monogenic syndromes with striking bone phenotypes (e.g. osteogenesis imperfecta and osteopetroses), the analysis of individuals or families with extreme osteoporotic phenotypes (e.g. idiopathic juvenile and pregnancy-related osteoporosis), and, chiefly, genome-wide association studies (GWAS) in large populations. Altogether, these efforts have greatly increased the understanding of molecular mechanisms behind bone remodelling, which has rapidly translated into the development of novel therapeutic strategies, exemplified by the tales of cathepsin K (CTSK) and sclerostin (SOST). Additional biological evidence of involvement in bone physiology still lacks for several candidate genes arisen from GWAS, opening an opportunity for the discovery of new mechanisms regulating bone strength, particularly with the advent of high-throughput genomic technologies. In this review, candidate genes for bone fragility will be presented in comprehensive tables and discussed with regard to how their association with osteoporosis emerged, highlighting key players such as LRP5, WNT1 and PLS3. Current limitations in our understanding of the genetic contribution to osteoporosis, such as yet unidentified genetic modifiers, may be overcome in the near future with better genotypic and phenotypic characterisation of large populations and the detailed study of candidate genes in informative individuals with marked phenotype.

Diagnosis and treatment of Paget's disease of bone: a mini-review / Diagnóstico e tratamento da doença de Paget dos ossos: uma minirrevisão

Paget's disease of bone (PDB) is a chronic progressive disorder of bone metabolism that may go undetected for many years, and endocrinologists should be alert to its clinical signs and promptly diagnose and treat PDB before it results in irreversible complications, such as deformity, fracture or neurological sequelae. Most commonly, PDB is suspected upon the incidental finding of elevated serum alkaline phosphatase levels or a radiographic abnormality in an otherwise healthy individual above 55 years of age. Some of these individuals may have symptoms such as bone pain or enlargement with increased warmth. In general, a basic laboratory evaluation of bone metabolism, plain radiographies of affected bones and bone scintigraphy are sufficient to corroborate the diagnosis. Antiresorptive therapy with bisphosphonates is the mainstay of treatment of symptomatic PDB, and intravenous zoledronic acid has emerged as an effective and safe treatment option, leading to sustained remission and improved quality of life. It is extremely important, though, to ensure calcium and vitamin D sufficiency before and during treatment in order to prevent hypocalcemia. The benefit of treating all asymptomatic patients is not clear, but treatment is warranted if the pagetic lesion is located in a site where progression to fracture, deformity, or compression would significantly impair the patient quality of life. This mini-review focuses on important aspects of the diagnosis and treatment of PDB.

A doença de Paget dos ossos (PDB) é uma doença progressiva e crônica do metabolismo ósseo que pode passar despercebida por muitos anos. Os endocrinologistas devem ficar alertas aos seus sinais clínicos e diagnosticar e tratar a PDB imediatamente, antes que ela gere complicações irreversíveis, como deformidade, fratura ou sequelas neurológicas. Mais comumente, suspeita-se da PBD após o achado incidental de níveis elevados de fosfatase alcalina no soro, ou anormalidades radiográficas em indivíduos aparentemente saudáveis com mais de 55 anos de idade. Alguns desses indivíduos podem apresentar sintomas, como a dor ou aumento ósseo com temperatura aumentada. Em geral, a avaliação laboratorial básica de metabolismo ósseo, radiografias simples dos ossos afetados e cintilografia óssea são suficientes para corroborar o diagnóstico. O tratamento antirreabsortivo com bifosfonatos é o principal tratamento da PDB sintomática, e o ácido zoledrônico intravenoso passou a ser uma opção de tratamento segura e eficiente, levando à manutenção da remissão e à melhora da qualidade de vida. É extremamente importante, entretanto, garantir níveis adequados de cálcio e vitamina D antes e durante o tratamento para se evitar a hipocalcemia. O benefício de se tratar todos os pacientes assintomáticos não está claro, mas o tratamento é recomendado se a localização da lesão pagética sugerir progressão para fratura, deformidade ou compressão que comprometam a qualidade de vida. Esta minirrevisão concentra-se em importantes aspectos do diagnóstico e tratamento da PDB.