Endocrine Abstracts

Metabolic bone diseases encompass a large spectrum of disorders of bone strength, bone growth, or bone structure. Most of the disorders are caused by genetic defects and have onset prenatally or in childhood. The International classification of genetic skeletal disorders includes >450 disorders divided into 40 subgroups based on their clinical, radiographic and genetic features. The individual disorders are rare but collectively result in significant morbidity and pose a chall...

Genetic discoveries in patients and families with rare bone disorders have highlighted the complexity of molecular mechanisms and cellular pathways governing normal bone development and homeostasis. More than 400 different forms of skeletal dysplasia have been described. Most of them result from single-gene defects, involving genes that are of major importance for a particular cellular event in skeletal development. Studies aiming to identify the involved pathways can enable d...

Genetic factors play an important role in osteoporosis. Several monogenic forms of osteoporosis have been recognized. The most common of these is osteogenesis imperfecta (OI) in which dominantly inherited mutations in the genes encoding type I collagen (COL1A1 and COL1A2) are responsible for approximately 90% of the cases. Several rare autosomal recessive forms of OI have also been described. In these the defects lie in proteins involved in posttranslational modification of ty...

Juvenile primary osteoporosis, unless diagnosed as osteogenesis imperfecta, has previously been considered a sporadic and self-limiting disease. New genetic findings, including osteoporosis-causing mutations in the LDL-receptor related protein (LRP) 5 and LRP6 genes, challenge this view. The pathogenesis of juvenile osteoporosis still remains largely unknown. We describe findings in a three-generation pedigree with a new form of autosomal dominant osteoporosis.<p class="ab...

Mutations of the calcium-sensing receptor (CaSR), G-protein alpha-11 subunit (Gα11), and adaptor protein-2 sigma subunit (AP2σ) resulting in a loss-of-function, cause familial hypocalciuric hypercalcemia types 1-3 (FHH1-3), respectively. We investigated a family with FHH (four affected and two unaffected members) for CaSR, Gα11 and AP2σ mutations, and identified a heterozygous Gα11 missense mutation, Phe220Ser, which is predicted to disrupt a cluster o...

Introduction: Osteoporosis is a prevalent skeletal disease associated with increased fracture risk, morbidity, and mortality. Several meta-analyses have investigated the association between non-genetic, non-pharmacologic factors and osteoporosis risk.Purpose: We aimed to perform an umbrella review of the literature to systematically evaluate the available evidence.Methods: Meta-analyses of observational studies evaluating the assoc...

Pseudohypoparathyroidism (PHP) and related disorders lead to a wide spectrum of abnormal physical characteristics, neurocognitive and endocrine abnormalities that share a common PTH/PTHrP signaling pathway. The clinical and molecular overlap of PHP and related disorders lead to difficulties in clinical and molecular diagnosis which prompt to the possibility of incorrect management of these patients. PHP (including all subtypes), pseudoPHP, acrodysostosis and progressive osseou...