Advances in Our Understanding of Hyperthyroidism-associated Bone Loss

Abstract

Advances in Our Understanding of Hyperthyroidism-associated Bone LossOsteoporosis is characterized by low bone mass and deterioration of bone micro-architecture associated with increased bone fragility and susceptibility to fracture. In 2005 the incidence of osteoporotic fracture in the US was over two million, at a cost of nearly $17 billion. By 2025, annual fractures and costs are projected to rise by almost 50%, making this a major healthcare priority.1 Hyperthyroidism is an important cause of secondary osteoporosis 2 and the relationship between the hypothalamicpituitary-thyroid (HPT) axis and bone is an important factor to consider in the management of sub-clinical hyperthyroidism and differentiated thyroid cancer. This article discusses animal models that provide insight into the underlying mechanisms that result in hyperthyroidism-associated bone loss. It will then review the clinical data investigating effects of hyperthyroidism on the skeleton. alternatively, T3 and T4 may be inactivated irreversibly by a third deiodinase enzyme, D3, which catalyzes removal of the 5-iodine atom. Release of thyrotropin-releasing hormone (TRH) from the hypothalamus stimulates anterior pituitary thyrotrophs to secrete thyrotropin (TSH).The balance between activities of D2 and D3 enzymes within the target cell determines the amount of T3 available to the nuclear thyroid hormone receptors (TRs), which function as hormone-inducible transcription factors. 4 Several TR isoforms have been described. TRβ2 is expressed primarily in the hypothalamus and pituitary gland, where it mediates negative feedback inhibition of TRH and TSH synthesis. TRα1and TRβ1 are widely distributed in most tissues, but their relative levels of expression vary in temporo-spatial-specific patterns. Data from mutant mice suggest that TRα1 is the functionally predominant isoform expressed in the skeleton. 4Adult bone is a dynamic tissue that undergoes continuous re-modeling, a process mediated by the coupled activities of bone-resorbing osteoclasts and bone-forming osteoblasts. 5Precursors from the monocyte/macrophage cell lineage are activated and differentiate to mature bone-resorbing osteoclasts under the influence of macrophage colony-stimulating factor (MCS-F) and receptor activator of nuclear factor κB ligand (RANKL). RANKL and osteoprotegerin (OPG), a decoy receptor for RANKL, are secreted by osteoblasts and function as critical regulators of osteoclast differentiation, acting via a local paracrine pathway that facilitates communication between the two cell lineages.The bone re-modeling cycle consists of three consecutive phases. In the resorption phase, mature, differentiated osteoclasts adhere to the bone surface and remove mineral and bone matrix through secretion of digestive lysosomal enzymes. 6 Once resorption is complete there is a reversal phase in which osteoclasts undergo programmed cell death and mononuclear cells are seen on the bone surface. These cells may play a role in preparing the surface for osteoblasts to lay down new matrix and b...

Multiple Transduction Pathways Mediate Thyrotropin Receptor Signaling in Preosteoblast-Like Cells

“…If TSH exerts predominant actions to promote osteoblastogenesis and/or inhibit bone turnover, a question arises as to why individuals with Graves' hyperthyroidism are susceptible to osteoporosis and fracture ( 33 ). It would be predicted that high concentrations of circulating TSAbs in Graves' disease should protect patients from bone loss ( 34 ). However, the cumulative effect of the Graves' disease environment is most likely caused by the elevated levels of T 3 and T 4 , which directly stimulate excessive bone resorption ( 35 ).…”

Pengaruh Pemberian Kedelai Dan Susu Tinggi Kalsium Terhadap Fungsi Tiroid Dan Massa Tulang Pada Tikus Hipertiroid

“…8,12 Susu dan hasil olahannya seperti keju merupakan sumber kalsium yang utama, disamping itu serealia, kacang-kacangan dan hasil olahannya (tahu, tempe, dan lain-lain) juga merupakan sumber kalsium yang baik. 10,11 Fosfor terkandung dalam hampir semua jenis makanan, terutama bahan makanan yang mengandung protein tinggi seperti daging, ikan, telur, susu dan hasil olahannya, serta kacangkacangan dan serealia. Kebutuhan harian fosfor untuk remaja dan dewasa adalah 400-500 mg. 6 Kandungan fosfor dalam formula penelitian ini bersumber dari susu dan kedelai, dapat mencukupi ± 23 persen AKG fosfor dalam tubuh.…”

“…Hormon tiroid dihasilkan oleh kelenjar tiroid dalam bentuk tri-iodotiroinin (T3) dan tetra-iodotiroinin (T4/tiroksin). 9,10 Kondisi hipertiroid dimana kelenjar tiroid menghasilkan hormon tiroid dalam jumlah berlebih dapat meningkatkan metabolisme tubuh, termasuk metabolisme tulang dalam tubuh, ditandai dengan meningkatnya proses penggantian tulang hingga dua kali lipat sehingga menurunkan kepadatan tulang. Reseptor TSH dan hormon tiroid yang terdapat pada tulang menstimulasi langsung sel tulang dan meningkatkan resorpsi mineral tulang.…”