Greenspan S L, Greenspan F S, Resnick N M, Block J E, Friedlander A L, Genant H K
Division of Gerontology, Beth Israel Hospital, Massachusetts 02215.
Am J Med. 1991 Jul;91(1):5-14. doi: 10.1016/0002-9343(91)90066-7.
The impact of long-term L-thyroxine replacement therapy on skeletal integrity is a growing concern because of the large number of women receiving thyroid hormone therapy. The purpose of this study was to examine the hypothesis that long-term L-thyroxine therapy in which the free thyroxine index (FT4I) is maintained within a physiologic range has minimal impact on vertebral or femoral bone mineral density in both premenopausal and postmenopausal women.
We measured hip integral and spinal trabecular and integral bone densities in 28 premenopausal and 28 postmenopausal women who had been receiving L-thyroxine therapy for a median of 12 and 15 years, respectively, and in whom therapy was titrated to keep the FT4I within the normal range. The relationship between bone density parameters and thyroid hormone status was examined using univariate and multivariate statistical methods.
Seventy-nine percent of the premenopausal women and 86% of the postmenopausal women had FT4I values in the normal range at the time of bone density determination. Moreover, throughout the study's duration, the majority of annually measured values were in the normal range for more than 80% of subjects. Premenopausal women had slightly lower bone density than would be expected for age: -6.7% (z = -0.39 +/- 0.74 [mean +/- SD], p less than 0.01), -3.1% (z = -0.22 +/- 0.78, p = 0.15), and -5.1% (z = -0.36 +/- 0.74, p less than 0.02) for spinal trabecular, spinal integral, and hip integral bone density, respectively. Postmenopausal women likewise had slightly lower bone density values that were significant only at the hip: -0.2% (z = -0.01 +/- 1.01, p = 0.95), -1.0% (z = -0.05 +/- 1.11, p = 0.80), and -6.2% (z = -0.39 +/- 0.80, p less than 0.02) for spinal trabecular, spinal integral, and hip integral bone density, respectively. When patients with previously treated Graves' disease (n = 4 in each group) were eliminated, the differences in bone density at the hip were no longer seen. Correlation analysis revealed only weak and generally nonsignificant relationships between parameters of thyroid hormone status and bone density at any site in either subgroup. Results of multiple regression analysis among the pooled data of all subjects showed that age provided a consistently significant contribution (R2 = 0.18 to 0.66) to the variability in bone density at the spine and the hip, but parameters of thyroid hormone status did not.
These data provide the first supportive evidence that long-term L-thyroxine therapy that maintains the FT4I in the physiologic range is associated with a statistically significant, but clinically minimal, decrement in spinal and hip bone density in both premenopausal and postmenopausal women. The decrement at the hip was entirely due to the inclusion of patients with treated Graves' diseases. Thus, the changes in bone density in women receiving long-term L-thyroxine therapy are minimal at most and should not be a contraindication to therapy.
由于接受甲状腺激素治疗的女性数量众多，长期左甲状腺素替代治疗对骨骼完整性的影响日益受到关注。本研究的目的是检验以下假设：在绝经前和绝经后女性中，将游离甲状腺素指数（FT4I）维持在生理范围内的长期左甲状腺素治疗对椎体或股骨骨密度的影响最小。
我们测量了28名绝经前和28名绝经后女性的髋部整体、脊柱小梁和整体骨密度，这些女性分别接受左甲状腺素治疗的中位时间为12年和15年，且治疗时将FT4I调整至正常范围内。使用单变量和多变量统计方法研究骨密度参数与甲状腺激素状态之间的关系。
在进行骨密度测定时，79%的绝经前女性和86%的绝经后女性FT4I值在正常范围内。此外，在整个研究期间，超过80%的受试者每年测量的大多数值都在正常范围内。绝经前女性的骨密度略低于预期年龄：脊柱小梁、脊柱整体和髋部整体骨密度分别低-6.7%（z=-0.39±0.74[均值±标准差]，p<0.01）、-3.1%（z=-0.22±0.78，p=0.15）和-5.1%（z=-0.36±0.74，p<0.02）。绝经后女性同样骨密度略低，仅在髋部有显著性差异：脊柱小梁、脊柱整体和髋部整体骨密度分别低-0.2%（z=-0.01±1.01，p=0.95）、-1.0%（z=-0.05±1.11，p=0.80）和-6.2%（z=-0.39±0.80，p<0.02）。当排除先前患有格雷夫斯病的患者（每组4例）后，髋部骨密度差异不再明显。相关性分析显示，在任何一个亚组中，甲状腺激素状态参数与任何部位的骨密度之间仅存在微弱且通常无显著性的关系。所有受试者汇总数据的多元回归分析结果表明，年龄对脊柱和髋部骨密度的变异性始终有显著贡献（R2=0.18至0.66），但甲状腺激素状态参数没有。
这些数据首次提供了支持性证据，即在生理范围内维持FT4I的长期左甲状腺素治疗与绝经前和绝经后女性脊柱和髋部骨密度在统计学上有显著但临床上极小的降低有关。髋部骨密度降低完全是由于纳入了患有格雷夫斯病的患者。因此，接受长期左甲状腺素治疗的女性骨密度变化至多极小，不应成为治疗的禁忌证。
