Meier Christian, Beat Müller, Guglielmetti Merih, Christ-Crain Mirjam, Staub Jean-Jacques, Kraenzlin Marius
Division of Endocrinology, Department of Medicine, University Hospitals, CH-4031, Basel, Switzerland.
Osteoporos Int. 2004 Mar;15(3):209-16. doi: 10.1007/s00198-003-1527-8. Epub 2004 Jan 16.
This study evaluated the effect of physiological l-thyroxine (L-T4) treatment on bone metabolism in patients with subclinical hypothyroidism. Sixty-six women with subclinical hypothyroidism (TSH 11.7 +/- 0.8 mIU/l) were randomly assigned to receive L-T4 or placebo for 48 weeks. Sixty-one of 66 patients completed the study. Individual L-T4 replacement (mean dosage 85.5 +/- 4.3 microg/day) was performed targeting euthyroid thyroid-stimulating hormone (TSH) levels. The primary outcome measure was 24- and 48-week change in markers of bone formation (total and bone alkaline phosphatase [ALP, bone ALP], osteocalcin [OC]) and resorption (pyridinoline [PYD] and deoxypyridinoline [DPD], C-terminal cross-linking telopeptide type I [CTX]). Secondary outcomes were 48-week changes in bone mineral density (BMD) of the lumbar spine and hip, measured by dual-energy X-ray absorptiometry. Compared with placebo, l-thyroxine ( n=31) resulted in significant activation of bone turnover. Overall, a significant treatment effect was observed for DPD (between-group difference 16.0%; 95%CI, 10.9 to 21.1), CTX (29.9%; 95%CI, 23.3 to 36.5), and bone ALP (13.2%; 95%CI, 6.6 to 19.7) after 24 weeks. At the end of the study, lumbar BMD in the both treatment groups differed by 1.3% (95%CI, -2.9 to 0.5) with lower levels in l-thyroxine treated women. Significant difference in BMD between groups was also observed at the trochanter. We conclude that physiological l-thyroxine treatment accelerates bone turnover reflecting early activation of bone remodeling units in the initial replacement of subclinical hypothyroidism. The observed bone loss could be interpreted as an adaptive mechanism on decreased bone turnover in preexistent hypothyroidism, and not as l-thyroxine-induced clinically important bone loss. However, long-term studies are needed to confirm this assumption.
本研究评估了生理剂量左甲状腺素（L-T4）治疗对亚临床甲状腺功能减退症患者骨代谢的影响。66例亚临床甲状腺功能减退症女性患者（促甲状腺激素[TSH]为11.7±0.8 mIU/l）被随机分配接受L-T4或安慰剂治疗48周。66例患者中有61例完成了研究。根据甲状腺功能正常时的促甲状腺激素（TSH）水平进行个体化L-T4替代治疗（平均剂量85.5±4.3μg/天）。主要观察指标为24周和48周时骨形成标志物（总碱性磷酸酶和骨碱性磷酸酶[ALP，骨ALP]、骨钙素[OC]）和骨吸收标志物（吡啶啉[PYD]和脱氧吡啶啉[DPD]、I型胶原C端交联肽[CTX]）的变化。次要观察指标为48周时采用双能X线吸收法测量的腰椎和髋部骨密度（BMD）变化。与安慰剂相比，左甲状腺素（n = 31）导致骨转换显著激活。总体而言，24周后观察到DPD（组间差异16.0%；95%CI，10.9至21.1）、CTX（29.9%；95%CI，23.3至36.5）和骨ALP（13.2%；95%CI，6.6至19.7）有显著治疗效果。在研究结束时，两个治疗组的腰椎BMD相差1.3%（95%CI，-2.9至0.5），接受左甲状腺素治疗的女性BMD水平较低。在转子部位也观察到组间BMD有显著差异。我们得出结论，生理剂量左甲状腺素治疗可加速骨转换，反映了亚临床甲状腺功能减退症初始替代治疗中骨重塑单位的早期激活。观察到的骨质流失可解释为对既往甲状腺功能减退症中骨转换降低的一种适应性机制，而非左甲状腺素诱导的具有临床意义的骨质流失。然而，需要长期研究来证实这一假设。
