Thyroid-stimulating hormone, thyroid hormones, and bone loss (original) (raw)
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TSH and Thyroid Hormones Both Regulate Bone Mass
Clinical Reviews in Bone and Mineral Metabolism, 2008
Thyrotoxicosis is associated with a high-turnover osteoporosis, which has been solely attributed to elevated thyroid hormone levels. Mice lacking the thyroid hormone receptors a and b establish a role for thyroid hormones in regulating bone remodeling. We show that TSH, which falls when thyroid hormones rise, directly suppresses bone remodeling, and that TSH receptor null mice have profound bone loss. We suggest that reduced TSH signaling contributes to hyperthyroid osteoporosis and that TSH and its receptor could become valuable drug targets.
The regulatory role of thyroid hormones in bone cell growth and differentiation
The Journal of nutrition, 1995
The clinical effects of thyroid hormones on bone in hypo- and hyperthyroidism are well known but their fundamental role in the regulation of bone remodeling is still poorly understood. In this review the current literature is summarized and experimental data from our laboratory are presented. The direct stimulation of bone resorption by thyroid hormones in organ culture, which in part is mediated by prostaglandins and TGF-beta, and the effect of different agents thereon are reviewed. More recent data concerning thyroid hormone action in the osteoblastic cell line MC3T3E1, are summarized. From their effect on proliferation and alkaline phosphatase activity, we conclude that thyroid hormones accelerate osteoblastic differentiation. The regulation of the transcriptional expression of certain genes by nuclear T3 receptors and their effect on osteoblastic target genes like IGF-I are reviewed. In addition a novel role of triiodothyronine as inhibitor of growth factor induced transcription...
Role of thyroid hormones in skeletal development and bone maintenance
Endocrine reviews, 2016
The skeleton is an exquisitely sensitive and archetypal T3-target tissue that demonstrates the critical role for thyroid hormones during development, linear growth, and adult bone turnover and maintenance. Thyrotoxicosis is an established cause of secondary osteoporosis, and abnormal thyroid hormone signaling has recently been identified as a novel risk factor for osteoarthritis. Skeletal phenotypes in genetically modified mice have faithfully reproduced genetic disorders in humans, revealing the complex physiological relationship between centrally regulated thyroid status and the peripheral actions of thyroid hormones. Studies in mutant mice also established the paradigm that T3 exerts anabolic actions during growth and catabolic effects on adult bone. Thus, the skeleton represents an ideal physiological system in which to characterize thyroid hormone transport, metabolism, and action during development, adulthood and in response to injury. Future analysis of T3 action in individua...
Bone remodeling and thyroid function
Many diseases are associated with more rapid bone loss and an increased risk of osteoporosis and fractures. Both hyperthyroidism and hypothyroidism as well as use of thyroid hormones or thyrosuppressant treatment influence bone turnover rates and may alter the risk of future fractures. Markers of bone remodeling are good indicators to determine bone turnover rates and potential bone loss, and correlate well with thyroid hormone levels. Untreated hyperthyroidism accelerates bone turnover resulting in net bone loss, while untreated hypothyroidism in adult humans slows down bone turnover resulting in net bone gain. In both cases, damage in bone microarchitecture occurs, leading to an increased relative risk of fractures. Effective therapies for both states are available, and in ideal case, full recovery of mineralized tissue may occur over time. Controversies are still present in patients receiving suppressive thyroxin treatment for thyroid carcinoma. It seems that suppressed thyroid...
Thyroid, 2011
Background: We have shown that thyroid-stimulating hormone (TSH) has a direct inhibitory effect on osteoclastic bone resorption and that TSH receptor (TSHR) null mice display osteoporosis. To determine the stage of osteoclast development at which TSH may exert its effect, we examined the influence of TSH and agonist TSHR antibodies (TSHR-Ab) on osteoclast differentiation from murine embryonic stem (ES) cells to gain insight into bone remodeling in hyperthyroid Graves' disease. Methods: Osteoclast differentiation was initiated in murine ES cell cultures through exposure to macrophage colony stimulation factor, receptor activator of nuclear factor kB ligand, vitamin D, and dexamethasone. Results: Tartrate resistant acid phosphatase (TRAP)-positive osteoclasts formed in *12 days. This coincided with the expected downregulation of known markers of self renewal and pluripotency (including Oct4, Sox2, and REX1). Both TSH and TSHR-Abs inhibited osteoclastogenesis as evidenced by decreased development of TRAP-positive cells (*40%-50% reduction, p ¼ 0.0047), and by decreased expression, in a concentrationdependent manner, of osteoclast differentiation markers (including the calcitonin receptor, TRAP, cathepsin K, matrix metallo-proteinase-9, and carbonic anhydrase II). Similar data were obtained using serum immunoglobulin-Gs (IgGs) from patients with hyperthyroid Graves' disease and known TSHR-Abs. TSHR stimulators inhibited tumor necrosis factor-alpha mRNA and protein expression, but increased the expression of osteoprotegerin (OPG), an antiosteoclastogenic human soluble receptor activator of nuclear factor kB ligand receptor. Neutralizing antibody to OPG reversed the inhibitory effect of TSH on osteoclast differentiation evidencing that the TSH effect was at least in part mediated by increased OPG. Conclusion: These data establish ES-derived osteoclastogenesis as an effective model system to study the regulation of osteoclast differentiation in early development. The results support the observations that TSH has a bone protective action by negatively regulating osteoclastogenesis. Further, our results implicate TSHR-Abs in offering skeletal protection in hyperthyroid Graves' disease, even in the face of high thyroid hormone and low TSH levels.