The multiple effects of thyroid disorders on bone and mineral metabolism

Abstract

Differently from most hormones, which commonly are specialized molecules able to influence other cells, tissues and systems, thyroid hormones (TH) are pleiotropic peptides, whose primordial function is difficult to identify. The complex action of TH on human economy can be easily witnessed by examining the diverse consequences of TH excess and deficiency during development and after maturity. In particular, different manifestations in bone modeling and remodeling reflect the circumstantial consequences of thyroid disturbances, which are age dependent. While hyperthyroidism during childhood enhances bone mineralization and accelerates epiphyseal maturation, in adults it induces bone loss by predominant activation of osteoclast activity. Furthermore, the syndrome of TH resistance is a multifaceted condition in which different sites exhibit signs of hormone excess or deficiency depending on the configuration of the TH receptor isoform. The investigation of the impact of TH resistance on the skeleton still remains to be elucidated. We present here a thorough review of the action of TH on bone and of the impact of thyroid disorders, including hyper-and hypothyroidism and the syndrome of TH resistance, on the skeleton. Arq Bras Endocrinol Metab. 2014;58(5):452-63 Keywords Thyroid hormones; osteoporosis; thyrotoxicosis; hypothyroidism; thyroid hormone resistance ReSumoDiferentemente da maioria dos hormônios, que usualmente são moléculas especializadas capazes de influenciar outras células, tecidos e sistemas, os hormônios da tireoide (HT) são peptídeos pleiotrópicos, cuja função primordial é difícil de identificar. A ação complexa dos HT na fisiologia humana pode ser facilmente reconhecida ao observar as diversas consequências do excesso e da deficiência de HT durante e após o pleno desenvolvimento. Em particular as diferentes manifestações na modelação e remodelação óssea refletem que as consequências esqueléticas das disfunções tireoidianas dependem das circunstâncias e variam com a idade. Enquanto o hipertireoidismo durante a infância aumenta a mineralização óssea e acelera a maturação epifisária, em adultos induz a perda óssea pela ativação predominante da ação osteoclástica. Além disso, a síndrome de resistência ao HT é uma condição multifacetada na qual diferentes tecidos apresentam sinais de excesso ou deficiência hormonal, dependendo da predominância da expressão das diversas isoformas do receptor de HT. O impacto da resistência ao HT sobre o esqueleto ainda é motivo de investigação. Apresentamos aqui uma revisão abrangente sobre as ações ósseas dos HT e o impacto no esqueleto dos distúrbios da tireoide, incluindo hipo e hipertireoidismo e síndrome de resistência ao HT. Arq Bras Endocrinol Metab.

TSH-receptor antibodies may prevent bone loss in pre- and postmenopausal women with Graves' disease and Graves' orbitopathy

“…Triiodothyronine (T3) plays a primordial role in the skeletal homeostasis and stimulates osteoblast differentiation and activity by complex direct actions on TH-receptors and indirect mechanisms, involving diverse growth factors and cytokines (2). T3 also stimulates osteoclast differentiation and bone resorption, but it still remains unclear whether this effect results from direct action in osteoclasts or indirectly through RANK-RANKL system (3). Thyrotoxicosis is an established risk factor for secondary osteoporosis due to increased bone turnover (4).…”

Influence of experimental hypothyroidism on bone tissue metabolism and mineral exchange

“…2). Статиче-ски значимо снижается как уровень маркё-ров костной резорбции β-CTX, так и маркё-ра костеобразования -костной щелочной фосфатазы, отражая замедление процессов ремоделирования, что в конечном итоге приводит к снижению костной массы [3,9].…”

“…Тиреоидные гормоны оказы-вают сложное влияние на обмен фосфора, увеличивая фосфатурию и одновременно повышая его почечную реабсорбцию [9]. Не случайно данные литературы относи-тельно метаболизма фосфора при гиперти-реозе противоречивы.…”

“…Не случайно данные литературы относи-тельно метаболизма фосфора при гиперти-реозе противоречивы. Одни авторы сооб-щают, что тиреотоксикоз сопровождается гиперфосфатемией, другие устанавливали нормальные концентрации фосфора и даже гипофосфатемию [9,12].…”

“…Обращает внимание, что при интоксика-ции мерказолилом у животных с гипотире-озом увеличивается в сыворотке крови со-держание провоспалительных цитокинов: ИЛ-1β, ИЛ-6 и ФНОα. Провоспалительные цитокины в костной ткани индуцируют об-разование матриксных металлопротеиназ, тормозят синтез их ингибиторов, повыша-ют продукцию RANKL, тормозят мигра-цию остеобластов, вызывают апоптоз осте-оцитов и активируют остеокластогенез и функции остеокластов [9,15,16].…”