Endocrine Abstracts

Thyroid hormones are essential for skeletal development and bone maintenance. Childhood hypothyroidism causes growth arrest with delayed bone maturation, whereas thyrotoxicosis accelerates growth and advances bone age. In adults, thyrotoxicosis causes osteoporosis and increased susceptibility to fracture. To investigate mechanisms of T3 action in bone, we analyzed T3 receptor (TR) mutant mice. TRα-null (TRα0/0) mice are euthyroid but display delayed ossification with...

Bisphosphonates are powerful inhibitors of bone resorption and have become blockbuster drugs in the treatment of metabolic bone diseases. Enormous progress has been made over the last few years in understanding exactly how bisphosphonate drugs act at the molecular level. After targeting bone and selective internalisation by osteoclasts, nitrogen-containing bisphosphonates potently inhibit FPP synthase. Inhibition of this enzyme disrupts the flux through the mevalonate pathway,...

Intact PTH [PTH(1–84)] measurements separate hypercalcaemic patients into 1) a parathyroid cause (usually 1°HPT) from 2) non-parathyroid causes (usually hypercalcaemia of malignancy). Improved sensitivity increases confidence in diagnosing hypoparathyroidism. PTH RIAs had problems with C-terminal PTH fragments and in renal failure circulating PTH (35–84) persists for hours giving high RIA PTH. Intact PTH is retained in renal failure and this resulted in new ap...

Vitamin D is a substrate for the active hormone, 1α, 25-dihydroxyvitamin D3, which binds to a single vitamin D receptor (VDR) belonging to the class of nuclear transcription factors.Ligand activated VDR regulates about 3 % the mouse/human genome and has a wide variety of physiologic actions. Its regulates calcium and bone homeostasis by increasing transepithelial calcium transport (intestine, kidney) and regulates the functions of bone an...