Department of Animal Physiology, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, ul. Akademicka 12, 20-950 Lublin, Poland.
Sub-Department of Internal Diseases of Farm Animals and Horses, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, ul. Głęboka 30, 20-612 Lublin, Poland.
Biomed Pharmacother. 2017 Oct;94:124-128. doi: 10.1016/j.biopha.2017.07.107. Epub 2017 Jul 28.
Physiological concentrations of thyroid hormones are crucial for skeletal growth and development, physiological bone turnover and bone homeostasis maintenance. Methimazole (1-methyl-2-mercaptoimidazole) is an antithyroid drug used for the treatment of the hyperthyroidism in humans and animals. The aim of the study was to determine effects of long-term oral methimazole treatment in male Wistar rats on biochemical bone metabolism markers, as well as morphological, geometric, densitometric and mechanical properties of femur and tibia. Experimental rats were subjected to 90-day-long oral treatment with 0.05% water solution of methimazole and were kept under identical environmental conditions and received the same diet ad libitum as the control group. Serum concentration of osteocalcin (OC) and C-terminal telopeptides of type I collagen (CTX-I) was determined. Femur and tibia were evaluated using quantitative computed tomography (QCT), peripheral QCT (pQCT) and three-point bending test. Final body weight of the experimental group was significantly decreased by 30% (P=0.01). Methimazole treatment significantly decreased serum OC concentration by 21% (P=0.02) and increased CTX-I concentration by 17% (P=0.06). Methimazole decreased morphological, geometric and densitometric parameters of femur and tibia in rats. Mechanical evaluation of bones has shown significantly decreased maximum elastic strength and ultimate strength of femur in rats treated with methimazole by 36% and 40% when compared to the control group (P<0.05). In conclusion, this study has shown that long-term treatment with methimazole inhibits bone formation and accelerates bone resorption processes. The observed negative effects of methimazole treatment on body weight gain and skeletal properties may be considered as additional possible side effects in living organisms to those reported in the previous studies. It may be suggested that long-term antithyroid treatment should be combined with prevention of the negative effects of methimazole on bone tissue and whole body metabolism.
甲状腺激素的生理浓度对骨骼生长和发育、生理骨转换和骨内稳态维持至关重要。甲巯咪唑（1-甲基-2-巯基咪唑）是一种抗甲状腺药物，用于治疗人类和动物的甲状腺功能亢进症。本研究旨在确定长期口服甲巯咪唑治疗对雄性 Wistar 大鼠生化骨代谢标志物的影响，以及对股骨和胫骨的形态、几何、密度和机械性能的影响。实验组大鼠接受 90 天的 0.05%水合甲巯咪唑口服治疗，并在相同的环境条件下饲养，给予与对照组相同的饮食。测定血清骨钙素（OC）和 I 型胶原 C 末端肽（CTX-I）浓度。使用定量计算机断层扫描（QCT）、外周 QCT（pQCT）和三点弯曲试验评估股骨和胫骨。实验组大鼠的最终体重显著下降 30%（P=0.01）。甲巯咪唑治疗使血清 OC 浓度显著降低 21%（P=0.02），CTX-I 浓度升高 17%（P=0.06）。甲巯咪唑降低了大鼠股骨和胫骨的形态、几何和密度参数。骨骼力学评估显示，与对照组相比，用甲巯咪唑治疗的大鼠股骨的最大弹性强度和极限强度分别显著降低了 36%和 40%（P<0.05）。综上所述，本研究表明，长期使用甲巯咪唑治疗可抑制骨形成并加速骨吸收过程。与以前的研究报道的结果相比，甲巯咪唑治疗对体重增加和骨骼特性的负面影响可能被认为是生物体内的另一种可能的副作用。建议长期抗甲状腺治疗应与预防甲巯咪唑对骨组织和全身代谢的负面影响相结合。
