TSH Prevents Bone Resorption and with Calcitriol Synergistically Stimulates Bone Formation in Rats with Low Levels of Calciotropic Hormones
TSH Prevents Bone Resorption and with Calcitriol Synergistically Stimulates Bone Formation in Rats with Low Levels of Calciotropic Hormones
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DOI：
10.1055/s-0033-1363989
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发表时间：
2014-05-01
影响因子：
2.2
通讯作者：
Vukicevic, S.
中科院分区：
文献类型：
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作者：
Dumic-Cule, I.;Draca, N.;Vukicevic, S.
促甲状腺激素对老年去卵巢大鼠和无促甲状腺激素受体小鼠的骨重塑具有抗吸收和合成代谢作用，临床结果表明，低促甲状腺激素水平与骨质流失增加有关。为了进一步探讨促甲状腺激素对骨代谢的影响，我们在此引入了一个切除甲状腺和甲状旁腺的大鼠模型，以获得低血清浓度的甲状腺和甲状旁腺激素、降钙素和1,25(OH)(2)D-3。手术导致低钙血症、甲状旁腺和甲状腺激素、1,25(OH)(2)D-3、c -端肽和骨钙素血清水平降低。间歇性给药促甲状腺激素导致血清钙进一步下降，血清c -末端肽水平下降，这是由于骨吸收受到抑制，而在同一动物中，血清骨钙素升高表明骨形成率增加。促甲状腺激素和1,25(OH)(2)D-3联合使用可显著提高血清Ca2+、c -末端肽和血清骨钙素值。股骨远端和胫骨近端显微ct分析显示，单独或联合促甲状腺激素治疗的大鼠骨小梁体积增加，骨小梁质量增强。生物力学测试显示，单独使用1,25(OH)(2)D-3或联合使用促甲状腺激素的大鼠，其骨小梁的最大负荷分别增加了105%和235%。我们认为，促甲状腺激素独立于促钙激素抑制骨吸收并刺激骨形成，而与1,25(OH)(2)D-3联合作用则协同作用于骨形成，导致骨体积增加。
Thyroid-stimulating hormone exerts both antiresorptive and anabolic effects on bone remodeling in aged ovariectomized rats and thyroid stimulating hormone-receptor null mice, supported by clinical results demonstrating that low thyroid-stimulating hormone level is associated with increased bone loss. To further explore the effect of thyroid-stimulating hormone on bone metabolism we introduced here a rat model with removed thyroid and parathyroid glands to obtain low serum concentrations of thyroid and parathyroid hormone, calcitonin and 1,25(OH)(2)D-3. Surgery resulted in hypocalcemia, low parathyroid and thyroid hormone, 1,25(OH)(2)D-3, C-telopeptide, and osteocalcin serum level. Intermittent administration of thyroid-stimulating hormone resulted in a further decrease of serum calcium and decreased level of serum C-telopeptide due to the suppression of bone resorption, while in the same animals osteocalcin in serum was higher indicating an increased bone formation rate. A combination of thyroid-stimulating hormone and 1,25(OH)(2)D-3 significantly increased the serum Ca2+, C-telopeptide and serum osteocalcin values. MicroCT analyses of the distal femur and proximal tibia showed that rats treated with 1,25(OH)(2)D-3 alone or in a combination with thyroid-stimulating hormone had an increased trabecular bone volume, and enhanced trabecular bone quality. Biomechanical testing of the trabecular bone showed an increased maximal load for 105% and 235%, respectively, in rats treated with 1,25(OH)(2)D-3 alone, or in a combination with thyroid-stimulating hormone. We suggest that thyroid-stimulating hormone independently of calciotropic hormones suppressed bone resorption and stimulated bone formation, while in combination with 1,25(OH)(2)D-3 acted synergistically on bone formation resulting in an increased bone volume.