Zaidi Mone, Davies Terry F, Zallone Alberta, Blair Harry C, Iqbal Jameel, Moonga Surinder S, Mechanick Jeffrey, Sun Li
Mount Sinai Bone Program, Mount Sinai School of Medicine, New York, NY 10029, USA.
Curr Osteoporos Rep. 2009 Jul;7(2):47-52. doi: 10.1007/s11914-009-0009-0.
It has become accepted by virtue of rich anecdotal experience and clinical research that thyrotoxicosis is associated with high-turnover osteoporosis. The bone loss, primarily due to accelerated resorption that is not compensated by a coupled increase in bone formation, has been attributed solely to elevated thyroid hormone levels. Evidence using mice lacking the thyroid hormone receptors alpha and beta establishes a role for thyroid hormones in regulating bone remodeling but does not exclude an independent action of thyroid-stimulating hormone (TSH), levels of which are low in hyperthyroid states, even when thyroid hormones are normal, as after thyroxine supplementation and in subclinical hyperthyroidism. We show that TSH directly suppresses bone remodeling and that TSH receptor null mice have profound bone loss, suggesting that reduced TSH signaling contributes to hyperthyroid osteoporosis. TSH and its receptor could become valuable drug targets in treating bone loss.
基于丰富的轶事经验和临床研究，甲状腺毒症与高转换型骨质疏松症相关这一观点已被广泛接受。骨质流失主要是由于骨吸收加速，而骨形成的相应增加无法补偿这种加速，这一直被认为完全是甲状腺激素水平升高所致。使用缺乏甲状腺激素受体α和β的小鼠的研究证据表明甲状腺激素在调节骨重塑中起作用，但并不排除促甲状腺激素（TSH）的独立作用，在甲状腺功能亢进状态下，即使甲状腺激素正常，如补充甲状腺素后和亚临床甲状腺功能亢进时，TSH水平也较低。我们发现TSH直接抑制骨重塑，且TSH受体缺失的小鼠存在严重的骨质流失，这表明TSH信号减弱导致了甲状腺功能亢进性骨质疏松。TSH及其受体可能成为治疗骨质流失的有价值的药物靶点。
